therapeutics manual

Transcription

therapeutics manual

Methodist Healthcare – Memphis Hospitals
THERAPEUTICS
MANUAL
Sixth Edition
THERAPEUTICS MANUAL, 6th EDITION ‐ TABLE OF CONTENTS ‐ METHODIST SPECIFIC GUIDELINES Guidelines for Electrolyte Replacement: Magnesium, Phosphate , Potassium Initiating Peripheral and Total Parenteral Nutrition (TPN) 1‐5 6‐10 Automatic IV to PO Conversion Criteria 11‐13 Factor IX Products 14‐15 Epoetin guidelines 16‐17 Warfarin guidelines 18 Summary of Consensus Guidelines 19‐21 Cardiovascular Hyperlipidemia Therapy (NCEP) 22‐24 Hypertension Therapy (JNC‐VII) 25‐30 CONSENSUS GUIDELINES VTE Prophylaxis and Treatment (ACCP) 31‐33 Perioperative Management of Warfarin 34‐36 Congestive Heart Failure Therapy (ACC/AHA) 37‐41 Acute Myocardial Infarction Therapy (ACC/AHA) 42‐45 Respiratory Asthma Guidelines (NHLBI) Acute Asthma Management (NHLBI) 46‐48 Chronic Obstructive Pulmonary Disease (NHLBI/WHO) 49‐50 Diabetes Diabetes Mellitus Guidelines (ADA) 51‐60 Diabetic Ketoacidosis Management 61‐63 Infectious Disease Bacterial Endocarditis, Prevention Guidelines 64‐65 Empiric Fungal Therapy Guidelines 66‐67 Acute Ischemic Stroke Guidelines 68‐70 General Pain Guidelines 71‐76 77‐79 Fentanyl Conversion and Pharmacist Checklist 83‐84 Opioid Cross Allergenicity 85‐86 Corticosteroid Equivalents 87 IV Push Rates 88‐90 91 Category D and X Drugs in Pregnancy 92‐95 Common Calculations 96 ACLS Guidelines 97‐100 Other TABLES Therapeutic Drug Monitoring Guidelines Opioid Analgesic Dose Equivalents Vancomycin Dosing Guidelines 80‐82 MISCELLANEOUS MANAGEMENT OF HYPOMAGNESEMIA
CAUSES: Dietary deficiency/malnutrition, intestinal loss (diarrhea, laxative use),
alcoholism, drug-induced renal losses (amphotericin B, cisplatin, diuretics,
aminoglycosides)
SIGNS/SYMPTOMS:
Muscle weakness, vertigo, ataxia, seizures, anxiety, psychosis, confusion,
paresthesias, cardiac arrhythmias
GUIDELINES FOR REPLACEMENT*
Serum Magnesium
IV Supplementation
Concentration
Severe
Hypomagnesemia
(Mg < 1mEq/L)
Symptomatic
 If life threatening cardiac
arryhythmia, 2gm Mg sulfate may be
pushed over 1 min in 10 ml of NS.
Oral
Supplementation
Not
Recommended
 If non emergent, give 4 gm IVPB
over 2-4 hours. (Repeat x 1 if still
symptomatic). Repeat serum Mg
level in 8 hours, add 2-4 gm Mg
sulfate to IVF daily, and monitor Mg
level daily until stable.
Asymptomatic
 4 gm Mg sulfate IVPB over 4-6
hours. Repeat Mg level in 8 hours.
Repeat serum Mg level in 8 hours,
add 2-4 gm Mg sulfate to IVF daily,
and monitor Mg level daily until
stable.
Not recommended
1
Mod.
Hypomagnesemia
(Mg 1-1.4 mEq/L)
Symptomatic
 Give 2-4 gm Mg sulfate IVPB over
2-4 hours and repeat if still
symptomatic. Add 2-4 gm to IVF
daily.
Not recommended
Asymptomatic
 2-4 gm Mg sulfate IVPB over 8
hours
 Give 2 g Mg sulfate IVPB over 8
hours
Mg Oxide 400 mg
BID-TID
Mg Oxide 400 mg
daily-BID
Mild
Hypomagnesemia
(Mg 1.5-1.8 mEq/L)
*In patients with normal renal function. If renal insufficiency is present, magnesium should be
administered at ½ recommended dose to avoid magnesium toxicity.
TREATMENT:
IV replacement is recommended for the acute replacement of magnesium
deficiency. Oral replacement is used primarily for maintenance therapy
due to the poor PO absorption of magnesium and the likelihood of inducing
diarrhea with excessive oral magnesium. Up to 50% or more of a dose of
IV magnesium will be excreted in the urine, making repeat dosing and
serum concentration monitoring necessary. Slower infusion time will
decrease urinary wastage.
MONITOR:
Serum concentrations q8-12h during initial tx phase if severe, then q24h
following stabilization (Mg>1.4 mEq/L). Full stabilization should occur
within 7 days.
DISCONTINUE TX:
Discontinue therapy if patient develops hypotension (SBP < 80 mmHg),
bradycardia (<60 bpm), hypermagnesemia, or absence of deep tendon
reflexes.
2
MANAGEMENT OF HYPOPHOSPHATEMIA
CAUSES: Refeeding syndrome, intracellular shifts (glucose administration,
insulin therapy, corticosteroid therapy), phosphorous deficiency (chronic
alcoholism, vitamin D deficiency), decreased absorption (antacids,
sucralfate), increased excretion (diuretics, hyperparathyroidism)
SIGNS/SYMPTOMS:
Cardiac dysrhythmias, respiratory failure, muscle weakness, numbness,
tingling, confusion, lethargy, seizures, immune dysfunction, osteomalacia
(chronic deficiency)
Serum Phosphorous
IV Supplementation
Oral
Concentration
(NaPhos or Kphos)
Supplementation
PO4 < 1.0 mg/dL
0.64 mmol/kg Phos over 6-8 hours
Not recommended
PO4 1.0-2.4 mg/dL
2 packets Phos-NaK
K or Phos-NaK BID
(if no IV access)
PO4 2.5-3.0 mg/dL
1 packet (Phos-NaK
K or Phos-NaK) BID
* In patients with normal renal function. If renal insufficiency is present, ½ recommended replacement
dose should be given.
** Round PO4 doses to the nearest increment of 3. Typical doses are 15, 21, 30, or 45 mmol. **
** Each 15mmol PO4 should be infused over 2 hours.**
PHOSPHOROUS PRODUCTS:
IV:
Na Phosphate (3 mmol PO4 and 4 mEq Na per ml)
K Phosphate (3 mmol PO4 and 4.4 mEq K per ml)
Oral: Phos-NaK (8 mmol PO4, 7 mEq Na, and 7 mEq K)
3
MONITOR:
Serum phosphorous and calcium concentrations q12-24 hours during initial
therapy, then every 1-3 days following stabilization. Concentrations may
increase rapidly with IV replacement; thus, serum phosphorus levels should
be measured prior to additional dosing.
DISCONTINUE TX:
Discontinue therapy if the patient develops hypocalcemia and/or
hyperphosphatemia. Monitor Ca x Phos product. (If [Ca++] x [Phos] >70,
the patient is at increased risk for metastatic calcification and organ
damage.) Phosphorus should be replaced more cautiously if concomitant
hypercalcemia is present.
4
MANAGEMENT OF HYPOKALEMIA
CAUSES: GI losses (nasogastric suction, vomiting, diarrhea, laxative use), renal
losses (Mg depletion, diuretics, levodopa, steroids, amphotericin),
intracellular shift (metabolic alkalosis, albuterol, insulin)
SIGNS/SYMPTOMS:
Cardiac dysrhythmias, muscle weakness/cramps, paralysis, respiratory
distress, ileus, urinary retention, constipation
TREATMENT:
Per Methodist policy, infusion rates should not exceed 10 mEq/hr without
concurrent ECG monitoring (A higher rate of 20 mEq/hr may be used with
monitoring. In emergency situations only, a 40 mEq/hr rate can be used
with continuous ECG monitoring).
Hypomagnesemia should also be corrected during potassium replacement.
Serum Potassium
IV Supplementation
Oral
Concentration
Supplementation1
K+ < 3.0 mEq/L
40 mEq IV KCl X 2; repeat K+ level
N/A
2-4 hours after the last infusion
+
K 3.0-3.2 mEq/L
30 mEq IV KCl X 2
40 mEq x 2
+
K 3.2-3.5 mEq/L
40 mEq IV KCl X 1
20-40 mEq x 2
*
In patients with normal renal function. If renal insufficiency is present, more cautious replacement
with ½ of the recommended doses should be given.
1
Oral supplementation can replace IV supplementation if patient is asymptomatic and can take PO. If
there is ongoing K+ losses (diuretic therapy, NG suction, etc), patients may require maintenance oral
or IV supplementation after they are adequately replaced.
MONITOR:
Serum K+ concentrations q6-12h during early phases of tx if initial
K+ <3.0 meq/L, and then q12-24h following stabilization (> 3.5
mEq/L). Stabilization should occur in 24-48 hours. In patients with
serum K+ <2.5 mEq/L, amount K+ given should not be > 80 mEq
without repeated measurements of serum K+ concentrations.
5
Guidelines for Initiating Peripheral and
Total Parenteral Nutrition
Parenteral nutrition (PN) is indicated for patients with nonfunctional GI
t r a c t s o r those unable to ingest adequate calories or a l l y o r e n t e r a l l y . P N
s h o u l d b e c o n s i d e r e d i f a p a t i e n t i s a n tic ipa te d to be NPO f or gr e a te r tha n 7
days or if adequate calories cannot be provided via the enteral route.
I n i t i a l or de r s f o r c en t r al p a r en t e r al n u t r i t i o n ( T PN) mus t b e w r i t t e n o n t h e
a p p r o v e d p r e p r i n t e d o r d e r f o r m . T h e N u t r i t i o n Su p p o r t T e a m i s
a u t o ma t i c a l l y c o ns ul t e d o n al l n e w T P N p at i e n t s . T P N o r d e r s mu s t b e w r i t t e n
a n d e n t e r e d i n t o c o m p o u n d e r b y 1 3 0 0 , a n d a ll TPNs a r e hung a t 2100 da ily .
Recommended Monitoring:

C MP , Mg, & P O 4 d a y # 1 ; B M P , M g , & P O 4 d a y s # 2 - 4 ;
t h e n C M P / B M P , M g , & P O 4 a t l e a st t w i c e w e e k l y t h e r e a f t e r

B l ood glucose monitoring with s l i d i n g s c a l e r e g u l a r
insulin Q6H. More frequent m o n i t o r i n g ma y b e n e c e s s a r y
fo r d i a b e t i c s , c ri t i ca l l y i l l pat i e nt s , a nd p a t i e nt s o n s t e r oid s .

Baseline and weekly serum triglycerides (hold lipids for
levels >250)

B a s e l i n e n i t r o ge n ba l a n c e ( 24 h r U U N ) e x c e pt i n a c u t e a nd c h r o n i c
renal failure (ARF/CRF)

I n i t i a l a nd w e e k l y p r e a l b u mi n l e v e l s ( n o t v a l i d i n c ri t i c a l l y i l l )

D a i l y w e i g h t s , a n d d a i l y input and output (I/O)

R e l e v a n t c l i n i c a l i n f o r ma t i o n a f f e c t i n g n u t r i t i o n s u p p o r t , s u c h a s
me d i c a t i o n c h a n g e s ( s t e r o i d s , i n s u l i n , d i u r e t i c s , p r o p o f o l , o r a l
electrolyte supplements, etc), fl uid sta tus ( I V f luids, NG output,
v o mi t i n g , d i a r r h e a , e t c ) , othe r nutr ition sour c e s (initiation of tube
feeding or oral di et), decreased o r i n c r e a s e d a c ui t y o f i l l n e ss , w o u n d
h e a l i n g i ss u e s , c l i n i c a l c o ur s e ( s u r g e r y , r a d i o l o g y f i n d i n g s , t e mp e r a t u r e
curve)
C a l o r i e Re q u i r e m e n t s :

M o s t p a t i e n t s r e q u i r e 2 5 - 3 5 k c a l / kg/day depending on acui t y o f i l l ne s s
a n d baseline nutritional sta tus. Ca lor ic goa ls should be ba se d on
T O TA L kcal, not nonpr otein calories (NPC)

Ca lories should be based o n t h e p a t i e n t ’ s a c t u a l b o d y
w e i g h t ( AB W) i f a c t u a l w e i g h t i s 1 0 0 -1 3 0 % o f I B W. I f a c t u a l w e i g h t i s
> 1 3 0 % t h e n a n a d j u s t e d w e i g h t s h o u l d b e u s e d . I f a c t u a l we i g h t i s
< I B W, t h e n i d e a l w e i g h t s h o u l d b e u s e d .
Males: IBW(kg) = 50 + (2.3 x inches >5 ft)
F e males: IB W(k g) = 45.5 + ( 2.3 x inc he s > 5 f t )
6





A d j u s t e d wt ( k g ) = ( A B W - I B W ) 0 . 4 + I B W
Hypocaloric feeding: Critical l y i l l o b e s e p a t i e n t s ( > 1 3 0 % I B W) s h o u l d
r e c e i v e 2 2 - 2 5 k c a l / k g / d ( I BW) wi t h i n c r e a s e d p r o t e i n p r o v i s i o n .
P e r mi s s i v e u n d e r f e e d i n g : A l l c r i t i c a l l y i l l pt s ma y b e n e f i t f r o m mi l d
u n derfeeding ( ≤ 8 0% g o a l cal o r i e s ) u nt i l pt s t a bi l i z e s .
D e x t r o s e p r o v i s i o n o f g o a l f o r mu l a s h o u l d h a v e a g l u c o s e i n f u s i o n r a t e
( G I R ) o f < 5 mc g / k g / mi n .
L i p i d s s h o u l d p r o v i d e 2 0 - 3 0 % o f a p at i e n t ’ s t ot al c a l or i es . G o a l l i pi d
p r o v i s i o n s h o u l d b e < 1 g / k g / d a y i n mo s t p a t i e n t s .
Calculation of calories:
Dextrose: 3.4 kcal/gram
Protein: 4 kcal/gram
Lipid: 10 kcal/gram (20% l i p i d e mu l s i o n 2 5 0 ml = 5 0 0 k c a l )
P r o t e i n Re q u i r e m e n t s
P r o t e i n r e q u i r e me n t s f o r mos t p a t i e n t s a r e 1 - 1 . 5 g m/ k g / d a y . S e v e r e l y
i l l / st r e sse d patients ma y requir e up to 2 g m/ k g / d . P a t i e n t s w i t h a c u t e r e n a l
f a i l u r e o r e n d - s t a g e h e p a t i c d i s e a s e r e quir e pr ote in restriction (0.6-1
g m/ k g / d ) . P a t i e n t s w i t h c h r o n i c r e n a l i n s u f f i c i e n c y s h o u l d r e c e i v e 0 . 6 - 0 . 8
g m/ k g / d , u n l e s s r e c e i v i n g h e m o d i a l y s i s ( 1 . 2 - 1 . 4 g m/ k g / d ) . P a t i e n t s r e c e i v i n g
c o n t i n u o u s r e n a l r e p l a c e me n t t h e ra pie s ( CRRT) ma y r e quir e up to
2 . 5 g m/ k g / d . H y p o c a l o r i c a l l y f e d o b e s e p t s ( > 1 3 0 % I B W) ma y r e q u i r e 2 2 . 5 g m/ k g I B W/ d . M o n i t o r o n g o i n g B U N a n d s e r u m c r e a t i n i n e t o a s s e s s f o r
p r o t e i n r e q u i r e me n t .
Lipid Requirements
I n t r a l i p i d s h o u l d b e g i v e n t o m o s t p a t i e nts r e c e iving PN if t o l e r a t e d . L i p i d s
ma y b e a d mi n i s t e r e d t w i c e we e k l y , e v e r y other day, or daily. Lipids ma y be
g i v e n i n the T PN (3-in-1) o r a s a s e p a r a t e p i g g y b a c k (2-in-1). Lipids should
b e h e l d f o r t r i g l y c e r i d e l e v e l s > 2 5 0 . Pa tie nts r e c e iving pr opof ol inf usions
( 1 0 % l i p i d e mu l s i o n = 1 . 1 k c a l / ml ) s h o u l d not receive IV li pids, a nd pa tie n ts
w h o a r e t o l e r a t i n g s o me p o i n t a k e b e yo n d c l e a r l i q u i d s m a y n o t r e q u i r e I V
l i p i d s. I n order to avoid essentia l f a t t y a c i d d e fi c i e n c y ( EF A ) , t h e l e n g t h o f
t i me w i t h o u t a n y nut r i t i o n a l s o u r c e o f l i p i d s ( P O o r I V ) s ho u l d n o t e x c e e d 3 4 w e e k s . 2 0 % I n t r a l i p i d 2 5 0 ml ( 5 0 g = 5 0 0 k c a l ) g i v e n t w i c e w e e k l y i s
s u f f i c i e n t t o p r e v e n t E F A . I f l i p i d s a re g i v e n a s a s e p a r at e p i g g y b a c k ( n o t
a d d e d t o t h e T P N b a g ) , e a c h b a g s h o u l d b e i n f u s e d o v e r 12 h o u r s .
General TPN Guidelines
The hospital preprinted TPN order form includes a standard adult TPN
f o r mu l a . T h i s f o r m u l a i s n o t a c c e p t a b l e f o r a l l pa t i e nt s , e sp e c i al l y pa t i e nt s
with renal insufficiency; therefore, the for mula should be modified as
n e c e s s a r y.
7
Standard Adult TPN Formula
Dextrose
20%
A mi n o A c ids
4.25%
NaCl
4 0 mEq / L
NaAcetate
2 0 mEq / L
KCl
2 0 mEq / L
2 0 mEq / L
KPO 4
M a g n e s i u m 8 mEq / L
Ca Gluc
5 mEq/L
MVI
1 0 ml / d a y
MTE-5
3 ml / d a y

C e n t r a l v e n o u s a c c e s s s h o u l d b e c o n f i r me d a n d d o c u me n t e d o n t h e T P N
order form. TPN s olutions should be initiated at rates of 40-50 mL/ hr
a n d a d v a n c e d t o w a r d g o a l r a t e d a i l y i n i n c r e me n t s o f 2 0 - 3 0 ml / h r a s
t o l e r a t e d . A l t e r n a t i v e l y , T P N ma y b e i n i t i a t e d at g o a l r at e , b u t w i t h a
decreased dextrose final concentra t i o n ( 1 0 - 1 2 % ) . I n t h i s c a s e , t h e
dextrose final concentration should be advanced daily by 4-5% per day
a s t o l e r a t e d . ( P r o t e i n c o n c e n t r ation can be started at goal.)

D i a b e t i c a n d g l u c o s e i n t o l e r a n t p at i e n t s ( p a n c r e a t i t i s , st e r o i d t h e r a py ,
p o s t o p h y p e r g l y c e mi a ) s h o u l d b e s t a r t e d a t a l o w e r i n f u s i o n r a t e ( o r
l o w e r d e xt r o s e c on ce n t r at i o n) to a sse ss tole r a nc e a nd a void
h y p e r g l y c e mi c a d v e r s e e v e n t s .

A n a c c e p t a b l e b l o od g l u c o s e ( B G ) w h i l e o n T P N i s 1 0 0 - 1 50 mg / d L .
TPN rate or dextrose should not be i n c r e a s e d i n p a t i e n t s w i t h b l o o d
g l u c o s e mo n i t o r i n g c o n s i s t e n t l y a b o v e 2 0 0 mg / d L .

I n s u l i n ma y b e a d d e d t o t h e T P N s o l u t i o n t o h e l p ma n a g e
h y p e r g l y c e mi a . O r d e r s f o r i n s u l i n mu s t b e w r i t t e n i n u n i t s / L . T h e
t y p i c a l s t a r t i n g d o s e o f i n s u l i n i s 1 0 - 2 0 u n i t s / L ( ma x 1 0 0 u n i t s / L) w i t h
a d j u s t me n t a s n e e d e d b a s e d o n b l o o d g l u c o s e l e v e l s .

P a t i e n t s a t r i s k f o r v o l u me o v e r l oa d ( i . e . A R F / C R F , c o n g e s t i v e h e a r t
f a i l u r e) m a y r e q u i r e mor e c o n c e n t r a te d T P N for m u l a s t o del i v er t h ei r
r e q u i r e d c a l o r i e s i n a s ma l l e r f l u i d volume. TPN infusion rate should
b e d i s c u s s e d w i t h t h e r e s p o n s i b l e p h y s ician if questions regarding fluid
r e s t r i ct i on a r i s e .

Malnourished patients at risk fo r R e f e e d i n g S y n d r o me r e q u i r e g r e a t e r
t h a n s t a n d a r d a mo u n t s o f p o t a s s i u m, p h o s p h o r u s , a n d ma g n e s i u m i n t h e
i n i t i a l T PN f o r mu l a s . T P N s h o u l d b e initiated at a low rate or a low
f i n a l c o n c e n t r a t i o n o f d e x t r o s e (1 0 % ) , a n d e l e c t r o l y t e s mu s t b e
monitored closely and replaced as indic a te d. TPN r a te or f or mula
s h o u l d n o t b e a d v a n c e d u n t i l e l e ct r o l y t e s a r e w i t h i n n o r ma l l i mi t s .

Patients with ARF/CRF (and not on HD) generally need 0-50%
of the
s t a n d a r d p o t a s s i u m, p h o s p h o r u s , a n d ma g n e s i u m i n T P N .
The standard
e l e c t r o l y t e o r d e r s a r e n o t a p pr o p r i at e i n t h e s e p a t i e nt s . E l e c t r o l y t e l e v el s
should be monitored closely.

P a t i e n t s w i t h A R F / C R F , c o n g e s tive heart failure (CHF),
a n d h e p a t i c d i s e a s e w i t h a s c i t e s a re of te n volume ove r loa de d a nd hav e
i n c r e a s e d t o t a l b o d y N a (e v e n t h o u g h s e r u m N a m a y b e l o w o r
n o r m a l ) . P a t i e nt s w i t h t h e se d i s e a s e st ates should start with 0-50% of
8

s t a n d a r d N a i n t h e i r T P N , a s N a ma y e x a c e r b a t e t h e i r c o n di t i o n .
M o n i t o r s e r u m N a a n d d a i l y I / O s c l o s e l y . * N o t e : 1 / 4 N S ~ 4 0 me q N a / L ;
1 / 2 N S ~ 8 0 me q N a / L ; N S ~ 1 6 0 me q N a / L . * Tot al N a ( a l l sa l t s) i n TPN
s h o u l d n ot e x c e e d 16 0 me q / L . L o w N a l e v e l s s h ou l d r e s p on d t o
c h a n g e s i n N a c o n t e n t o r t o t a l v o l ume of IV fluids and/or TPN and
should not be “bolused” as they are usually a reflection of positive
f l u i d b a l a n c e a n d n o t a t r u e N a d ef ic ie nc y. Fluid sta tus should be
e v a l u a t e d c a r e f u l l y a n d d i s c u ssed with physician if needed.
E l e c t r o l y t e s i n t h e T P N f o r m u l a s h o u l d b e o r d e r e d i n mEq / L .
E s t i m a t e d e l e c t r o l y t e n e e d s ( a s s u m i ng n o o r g a n d y s f u n c t i o n ) :
E l e c t r ol yt e
Calcium
Magnesium
Phosphate
Sodium
Potassium
Acetate
Chloride
Standard Intake (Daily)
10-15 mE q/day
8 - 2 0 mEq / d a y
20-40 mmol/day
1 - 2 mEq / k g / d a y + s o d i u m l o s s e s
1 - 2 mEq / k g / d a y
A s n e e d e d t o ma i n t a i n a c i d- b a s e b a l a nce
A s n e e d e d t o ma i n t a i n a c i d - b a s e b a l a n c e
PPN Guidelines
T h e h o s p i t a l s u p p l i e s a p r e mi x e d P P N f o r mu l a ( o r d e r e d a s C l i n i mi x ) w h i c h
c a n b e u t i l i z e d f o r s h o r t - t e r m n u t r i t i o n al s u p p o r t ( 5 - 7 d a y s ) , o r a s a n a d j u n c t
t o l e s s t h a n g o a l i n t a k e o f p o o r e n t e r a l d i e t . P P N i s n o t recommende d when
c e n t r a l v e i n a c c e s s i s f e a si bl e b e c a u s e P P N i s a s s o c i a t e d w i t h t h r om b o p h l e b i t i s a n d v o l u me o v e r l o a d .
Clinimix Composition*
Dextrose
10%
Ca
4.5 mEq/L
Amino Acids 4.25%
Acetate
70 mEq/L
Na
35 mEq/L
Cl
39 mEq/L
15 mMol/L
K
30 mEq/L
PO 4
Mg
5 mEq/L
(Total calories = 510 kcal/L, Protein = 42.5g/L)
* C l i n i mi x a l s o a v a i l a b e WI T H O U T e l e c t r o l y t e s

D u e t o l a ck o f s t a b i l i t y d at a an d o s mo l a r i t y i s s u e s , a d d i t i o n o f
i n g r e d i e n t s t o p r e mi x e d s o l u t i o n s i s s t r o n g l y d i s c o u r a g e d .
9

I f a d d i t i on a l a d d i t i v e s a r e des i r e d , an i n d i v i d u al i z e d P P N / T P N fo r m u l a
should be written.
P a t i e nt s r e c e i vi n g P P N a s s o l e s o u r c e o f n u t r i t i o n s h o u l d a l s o r e c e i v e
l i p i d s ( i .e. 2 0 % I n t ra l i pi d – 2 5 0 ml d a i l y o r 2 - 3 t i me s p e r w e e k ) t o
p r o v i d e ad d i t i o na l c a l o ri e s an d p r e v e nt e s s e nt i al fa t t y a c i d d e fi c i e n cy .
1 . G u i d e l i n e s f o r t h e p r o v i s i o n a n d a s s e s s me n t o f n u t r i t i o n s u p p o r t t h e r a p y i n
t h e a d u l t c r i t i c a l l y i l l pa t ie n t . J P E N 2 0 0 9 ; 3 3 ( 3 ) : 2 7 7 - 3 1 6 .
2 . S t a n d a r d f o r s p e c i a l i z e d n u t r i t i o n s u p p o r t : a d u l t h o s p i t al i ze d p a t i e n t s .
N u t r i t i o n i n C l i n i c al P r a c t i c e 2 0 0 2 ; 1 7 : 3 8 4 - 3 9 1 .
3 . G u i d e l i n e s f o r t h e u s e o f p a r e n t e r a l a n d e n t e r a l n u t r i t io n i n a d u l t a n d
p e d i a t r i c p a t i e n t s . JPEN 2 0 0 1 ; 2 6 ( 1 s u p p l e me n t ) .
10
Automatic IV to PO Conversion Criteria and Eligible Drugs
Background:
Studies have shown that switching a patient from IV to oral therapy early on can decrease the length of
stay in the hospital, and it may also improve patient outcomes. An IV to PO antibiotic procedure has been
in place for several years.
The policy is being changed to reflect additional drugs (gatifloxacin and linezolid), the updated American
Thoracic Society (ATS) guidelines, and to appoint new personnel. The criteria below will be implemented
primarily by clinical or other well-trained pharmacists, to change patients from IV to PO medications.
ANTIBIOTICS
1) Patient is receiving intravenous therapy with one or more of the following antibiotics:
 azithromycin
 ciprofloxacin
 clindamycin
 fluconazole
 levofloxacin
 linezolid
 metronidazole
 moxifloxacin
 ofloxacin
 trimethoprim-sulfamethoxazole (exception: AIDS patient)
 voriconazole
2) Patient shows some improvement of signs and symptoms of infection, which were present when
therapy was started.
3) Patient is afebrile (<37.5 C orally) on two occasions 8 h apart.
3
4) White blood cell count (WBC) <15,000/mm . Patients with white blood cell counts lower that
3
4,000/mm is exempt from the protocol.
5) Patient has a functioning GI tract, as indicated by one of the following: receiving scheduled medications
prescribed orally or tolerating a diet or tube feeding.
Exclusions:
Pharmacy will not independently initiate an IV-to-PO change on any patient with the following
characteristics:
• AIDS patient.
• Patient who is neutropenic (ANC < 1,500)
• Organ transplant patient.
• Patient with known malabsorption syndrome.
• Continuous oro- or nasogastric suction
• Physician exemption to the protocol
Note: If patient with exclusions meeting criteria is receiving other oral systemic anti-infectives (except
oral metronidazole or vancomycin), conversion may occur in the presence of exclusions.
Procedure:
If a patient is receiving one of the listed IV antibiotics, a pharmacist can examine the duration of therapy.
If IV therapy has been continued for at least 1 day (non ICU) or 2 days (ICU) as defined above, a checklist
will be completed. If all criteria are met, an order will be initiated in the chart for conversion to oral
therapy; the conversions are listed below:
11
IV Antibiotic Dose Equivalent PO Dose
IV antibiotic dose
Equivalent PO antibiotic dose
Azithromycin 500mg q24h
azithromycin 500mg q24h
Ciprofloxacin any dose
125% of dose and same interval
Clindamycin 900mg q8h
clindamycin 450mg q6h
600mg q8h
300mg q6h
Fluconazole any dose
equivalent dose & interval
Levofloxacin any dose
Linezolid any dose
Metronidazole any dose
Moxifloxacin any dose
Ofloxacin any dose
TMP/SMX any dose
Voriconazole 4 mg/kg q12h
voriconazole 200mg q12h (>40kg)
References:
1. Vfend package insert. New York, NY: Pfizer Inc.; 2002 May.
2. American Thoracic Society Guidelines for the Management of Adults with Community-acquired
Pneumonia: Diagnosis, Assessment of Severity, Antimicrobial Therapy, and Prevention. Am J Respir
Crit Care Med. 2001;163:1730-1754.
IV to PO Folic Acid
1. Convert from the IV to the oral route if the patient is receiving at least one routinely administered
oral medication.
2. Convert the IV to the same dose of oral.
3. Folic acid tabs may be crushed and administered via a feeding tube.
IV to PO H2 Antagonists
Convert from the IV to the oral route if all of the following criteria are met:
1. The patient is receiving a parenteral H2 antagonist
2. The patient may be in any area of the hospital
3. The patient is receiving at least one routinely-administered oral medication
4. The patient is receiving and tolerating any form of oral feedings
IV to PO Levetiracetam:
After 24 hours, interchange to oral levetiracetam (equivalent dose) if:
1. The patient is receiving other oral medications by mouth, OR
2. The patient has enteral access and is receiving other medications through the tube
IV to PO Lacosamide:
The pharmacist will be able to automatically convert the patient from IV to oral lacosamide therapy using
an equivalent daily dosage and frequency as the IV administration if: The patient is receiving other oral
medications by mouth OR the patient has enteral access and is receiving other medications per tube.
IV to PO Proton Pump Inhibitors:
1. If the patient receiving other oral medications by mouth or has enteral access and is receiving
other medications through the tube, interchange to oral pantoprazole
2. If continuous dosing, wait 72 hours, and assess for IV to PO criteria. If patient does NOT meet
the criteria (below), contact the physician for assessment of continuation of continuous infusion
Assessment for IV to PO Conversion after Continuous infusion:
a. The patient is NOT receiving active nasogastric suction
12
b. The patient IS receiving other routinely scheduled oral medications or enteral feeds
c. If the patient meets the criteria (yes to a. & b.), IV may be changed to PO pantoprazole
IV to PO Thiamine
1. After one dose if IV, convert from the IV to the oral route if the patient is receiving at least one
routinely administered oral medication
2. If the patient is not on other orals, implement a 3-day automatic stop with an interchange to
injectable multivitamin on the fourth day
3. Convert the IV to the same dose of oral
IV to PO Metoclopramide
The patient is receiving oral medications by mouth or has enteral access
 The patient is not receiving nasogastric suction
 The patient has not vomited in the last 24 hours
Exclusions: Do not convert from IV metoclopramide to oral if:
 The patient is an oncology patient
 Metoclopramide IV is being used for gastroparesis
13
Review of “Factors”: Alphanate ®, Bebulin®, Benefix®, Mononine®,
NovoSeven®
What you should know
Each of these products is different! They cannot be interchanged.
Some situations to think about:
 You receive an order for Factor IX 2000 units IV STAT. Which product
should you use? First, check to see which products we have in stock then
call the physician to determine which product he/she wants then select the
product in PharmNet.
 You receive an order for Bebulin 500 units IV STAT. When you check the
refrigerator you notice we are out of Bebulin. Should you substitute
Benefix or Mononine? No! Call the physician and let him/her know that we
are out of Bebulin and ask which product he/she would like to use.
 Note below that really only 2 products have been studied for lifethreatening bleeding due to warfarin: Bebulin VH® and NovoSeven®.
Alphanate® (Factor VIII Complex, Antihemaphilic Factor/von Willebrand
Factor Complex)
 Human derived, this product is a combination of Factor VIII and von
Willebrand Factor. It may also be referred to as Humate-P®
 Dosed in international units of either Factor VIII (FVIII:C) or von Willebrand
Factor Complex (vWF:RC). Vials have varying amounts of vWF:RC so the
number of units per vial will be indicated on the box and/or vial.
 Indicated for the prevention and treatment of hemorrhagic episodes in
patients with hemophilia A or acquired factor VIII deficiency, prophylaxis
with surgical and/or invasive procedures in patients with von Willebrand
disease, treatment of spontaneous or trauma-induced bleeding, as well as
prevention of excessive bleeding during and after surgery, in patients with
vWD (mild, moderate, or severe).
Bebulin VH® (Factor IX Complex, Vapor Heated)
 Obtained from human plasma, this product is a concentrate of the vitamin
K dependent clotting factors, II, VII (low levels), IX, and X. It may also be
referred to as Prothrombin Complex Concentrate (PCC).
 Dosed in international units of factor IX. Note that vials may contain
varying amounts of factor IX, and the number of units per vial will be
labeled on the box and/or vial.
 Indicated for use of hemorrhage in hemophilia B patients but has become
popular for off-label use of reversal of warfarin in life-threatening bleeding.
It should be combined with FFP and vitamin K in the treatment of warfarin
toxicity due to its short duration of action.
14
Benefix® (Coagulation Factor IX, Recombinant)
 This product is a recombinant form of factor IX and is not obtained from
human plasma.
 Dosed in international units of factor IX, each vial usually contains 250,
500, or 1000 international units.
 Indicated for the treatment and prevention of hemorrhage in patients with
hemophilia B. It has not been studied for the off-label use of warfarin
reversal.
Mononine® (Coagulation Factor IX, Human)
 This product is a concentrate of factor IX from human plasma.
 It contains nondetectable levels of factors II, VII, and X, and therefore,
should not be used for the treatment of warfarin toxicity.
 It is dosed in international units of factor IX, when reconstituted correctly;
each mL contains 100 international units.
 Indicated for the prevention and control of bleeding in hemophilia B
NovoSeven® (Coagulation Factor VIIa, Recombinant)
 This product is the recombinant form of activated factor VII
 At MUH, we stock the 4.8 mg vial although it is available as 1.2 mg and
2.4 mg vials. The 4.8 mg vial costs approximately $4000 and expires in 3
hours after reconstitution. When used for warfarin toxicity, it should also
be combined with FFP and Vitamin K.
 Indicated for the treatment and prevention of bleeding in Hemophilia A or
B patients with inhibitors to factors VIII or IX and also in patients with
congenital deficiencies of factor VII. It has been studied for hemorrhage
due to warfarin toxicity,spontaneous intracerebral hemorrhage and trauma
15
Erythropoietin Stimulating Agents (ESAs)
Dosing Guidelines and Procedures
Note: Fill out ESA checklist to determine eligibility for erythropoietin stimulating
agent. Communicate with physician as appropriate and document on ESA checklist.
Outpatient orders must be on approved order sheet.
Therapeutic Interchange
Darbepoetin Alpha
Epoetin Alpha
2,000 units TIW (IP)
25 mcg Qweek
OR
6,000 units Qweek (OP)
40 mcg Qweek
OR
60 mcg Qweek
OR
100 mcg Qweek
OR
OR
200 mcg q14day
150 mcg Qweek
OR
OR
300 mcg q14day
500 mcg q21day
OR
Dosing and Administration Guidelines:
Chose a product based on whether or not patient is
dialysis or non-dialysis for coding purposes
Interchange Weekly/Biweekly All doses should be trice weekly except for one time
Doses
orders
Calculation example:
- Order received is 10,000 units once weekly
- Divide by 10,000 by 3 = 3333 units
- Round to nearest 1000
- Interchange to 3000 units TIW
- 40,000 units weekly would be 10,000 units TIW
Dose Cap
25,000 units TIW
Any doses greater than that should be interchanged
to 25,000 units TIW.
One time orders
Interpret as usual – one time orders may be given
Administration
Route: SQ only
Location: Nursing floor. Not to be given in dialysis
Scheduling: Put doses written on Tuesday (T),
Thursday (Th), or Saturday (Sa) on a TThSa
schedule. Any other day will be a MWF schedule.
Doses other than 10,000,
Should be drawn up from the 20,000 unit MDV
20,000, or 40,000 units
Stability of syringe
7 days under refrigeration
Product Selection
16
Dose changes
Patient Education
Informed consent
None allowed with in 72 hours of initial ESA order
Each patient must receive an education leaflet from
the nursing staff and have documentation of
education. Enrollment in REMS program is
mandatory.
All oncology patients that receive an ESA must
receive an informed consent.
Current Epoetin guidelines are available on MOLLI. These further describe what
criteria must be met before epoetin is ordered and given.
17
Warfarin Dosing Guidelines




A warfarin dosing service is provided by the pharmacy department upon
consult by a physician. Pharmacists who provide the service will complete a
competency program annually. Warfarin dosing service guidelines used are
found below.
Routine use of genetic testing for variations in CYP2C9 and VCORC1 in order
to guide warfarin dosing is not recommended.
The maximum daily starting dose of warfarin is 10 mg. Initial doses of
warfarin that exceed 10 mg daily will be automatically interchanged to 10 mg
daily unless clearly documented that the patient has required a higher dose
previously.
Warfarin is dispensed as a unit dose product and administered at a standard
time once daily at 1800. (Stat or Now doses will be administered at the
ordered time).
INR MONITORING:








The results of a baseline INR will be available prior to dispensing the initial
dose. If no INR has been drawn in the previous 48 hours, a computerized rule
will generate an order for an INR. The pharmacist may order the INR during
computer down-times.
For patients admitted taking warfarin at home, an INR will be drawn on
admission. If an INR is not ordered by the physician, a Pharmacist will order
an INR, and the results will be reviewed prior to dispensing.
The INR will be drawn daily beginning after the first dose and continued until
the INR is in the appropriate therapeutic range for 2 days.
After the INR has been stable in the therapeutic range for 2 days, the
frequency of INR monitoring may be reduced to no less than three times a
week.
After the INR has been stable for at least 2 weeks with three times a week
testing, the INR monitoring may be reduced to not less than once weekly.
If the patient’s clinical condition changes, a significant drug interaction occurs,
or the dose is changed, INR monitoring will begin again daily until the INR is
in the therapeutic range for 2 days.
The pharmacist will place an order for the INR in the chart if not done
according to the above standards. Therapy will not be interrupted or delayed
while waiting for these results (unless the order is for a baseline INR).
Nurses will call the prescriber if INR > 3.5.
o Vitamin K guidelines are available for appropriate warfarin reversal.
o Pharmacy will automatically interchange intramuscular orders for
vitamin K to the IV route. If the patient has no IV access, the
pharmacist will contact the prescriber to recommend the oral route if
possible or the subcutaneous route if necessary.
CBC MONITORING: CBC monitoring will be done at least every 3 days during the first
two weeks of therapy.
Patient/Family Education: Patients receiving warfarin will have warfarin education
(generally provided by pharmacy personnel) prior to discharge.
18
Summary of “Consensus” Guidelines
In view of the growing complexity of medical care and the proliferation of trials related to management of patients,
many organizations are choosing to invest significant efforts in an evidence-based approach to define guidelines
for care. The following is a partial list of publications available which help to define “best approach” to the use of
drugs for prevention and/or treatment of various disorders. Other guidelines are developed in greater detail in other
sections of this handbook. The National Guideline Clearinghouse (www.guideline.gov) may also be referred to for
Internet links to various organizations/publications.
Guideline/Disorder
Organization
Reference
Anemia: Cancer- and Treatment- National Comprehensive Cancer
www.nccn.org
Related
Network
Antithrombotic therapy
American College of Chest Physicians www.chestnet.org
`
Chest 2004;126(3):s1-696.
Atrial Fibrillation
American College of Physicians
Ann Intern Med 2003;139:1009-17
Benign Prostatic Hypertrophy
American Urological Association
http://www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines.cfm
Chronic Kidney Disease
National Kidney Foundation
http://www.kidney.org/professionals/KDOQI/
Community-acquired Pneumonia American Thoracic Society
Am J Respir Crit Care Med
2001;163:1730-54
Community-acquired Pneumonia Infectious Diseases Society of America Clin Infect Dis 2003;37:1405-33
COPD, Acute Exacerbations
ACP-ASIM/ACCP
Ann Intern Med 2001;134:600-20
Dementia
American Academy of Neurology
Neurology 2001;56:1143-66
Depression
Texas Medication Algorithm Project
http://www.pbhcare.org/pubdocs/upload/documents/TMAP%20Depression%202010.pdf
Diabetes Mellitus
American Diabetes Association
http://professional.diabetes.org
Am. Assoc.of Clinical Endocrinologists
www.aace.com/publications/guidelines
19
GERD
Hematopoietic ColonyStimulating Factors
Hepatitis
American Gastroenterological Association
http://www.gastro.org/practice/medical-position-statements
American Society of Clinical Oncology JCO Oct 20 2000;3558-3585
American Association for the Study
http://www.aasld.org/practiceguidelines
Of Liver Diseases
HIV/AIDS, Antiretroviral Therapy US Dept. Health & Human
www.aidsinfo.nih.gov
HIV/AIDS, Prevention Opp.
CDC/USPHS
www.aidsinfo.nih.gov
Infections
Hormone Therapy
American Congress of Obstetricians
http://www.acog.org/
And Gynecologists
Hypertension
National Heart, Lung, and Blood
www.nhlbi.nih.gov
Institute
American Heart Association-HTN
http://hyper.ahajournals.org/
Infectious Diseases
Infectious Diseases Society of America www.idsociety.org
Intravascular Catheter
Infectious Diseases Society of America
http://www.cdc.gov
Lipid Management
National Cholesterol Education Program JAMA 2001;285(5/16):2486-97
Management of Menopause
Am. Assoc. of Clinical Endocrinology Endocrine Practice 2006;12:315-77
Myocardial Infarction
ACC/AHA
www.acc.org
Neutropenic Fever, Cancer
Infectious Diseases Society of America www.nccn.org
Patients
Obesity
Center for Nutrition Policy and Promotion
http://www.cnpp.usda.gov/
Osteopososis
American College of Rheumatology
http://www.rheumatology.org/practice/clinical/guidelines/index.asp
Sepsis
Society of Critical Care Medicine
http://www.survivingsepsis.org/
Sinusitis
Sinus/Allergy Health Partnership
OtolaryngolHead Neck Surg
2000;123 (supplement 1)
Surgical Infection Prophylaxis
National Surgical Infection Prevention Clin Infect Dis 2004;38:1706-15
Project & Centers for Medicare Svcs
Thyroid disease
Am. Assoc. of Clinical Endocrinologists
www.aace.com/publications/guidelines
20
Tuberculosis
American Thoracic Society
Am J Resp Crit Care Med
2003;167:603-67.
Unstable Angina
ACC/AHA
www.acc.org
Urinary Tract Infections Society for Healthcare Epidemiology
Infect Cont Hosp Epidemiol
Long-term Care
Of America
2001; 22(3):167-75
Urinary Tract Infections-Women Infectious Diseases Society of America Clin Infect Dis 1999;29:745-58
Vaccinations
CDC ACIP
http://www.cdc.gov/vaccines/recs/acip/default.htm
21
Hyperlipidemia Therapy (NCEP Guidelines)
Risk Category1
Very high risk*:
LDL Goal
< 70 mg/dL
High risk:
CHD or CHD risk
equivalents**
Moderately high risk:
2 + risk factors
(10-year risk 10-20%)
Moderate risk:
2+ risk factors
(10-year risk <10%)
Lower risk:
0-1 risk factor
< 100 mg/dL
Lifestyle Changes
> 100 mg/dL
Drug Therapy
> 100 mg/dL
(if <100 mg/dL, drug
tx optional)
< 130 mg/dL
> 130 mg/dL
> 130 mg/dL
(100-129 mg/dL,
consider drug tx)
< 130 mg/dL
> 130 mg/dL
> 160 mg/dL
< 160 mg/dL
> 160 mg/dL
> 190 mg/dL
(160-189 mg/dLdrug tx optional)
*
Very high risk factors include: CHD + either (1) multiple major risk factor (especially diabetes), (2)
severe and poorly controlled risk factors (especially cigarette smoking), (3) multiple risk factors of the
metabolic syndrome, (4) patients with acute coronary syndrome.
**
CHD equivalents include: peripheral artery disease, abdominal aortic aneurysm, symptomatic carotid
artery disease, diabetes mellitus, multiple risk factors that confer a 10-year risk for CHD >20%.
Major Risk Factors That Modify LDL Goals2
 Current cigarette smoking
 Hypertension
 Low HDL cholesterol (< 40 mg/dL)
 Family history of premature Coronary Heart Disease (CHD)
(CHD in male first-degree relative < 55 years; CHD in female first-degree relative
<65 years)
 Age (Male > 45 years; Female > 55 years)
Negative risk factor (remove one risk factor if present)
 High HDL cholesterol (> 60 mg/dL)
1
Grundy SM, Cleeman JI, et al. Implications of recent clinical trials for the National Cholesterol
Education Program Adult Treatment Panel III Guidelines. Circulation 2004;110:227-239.
2
Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection,
Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA
2001;285:2486-2497.
22
LIPID LOWERING AGENTS
Drug Class
HMG-CoA reductase
inhibitors
(Statins)
Lipid Effects
LDL 18-62%
HDL  5-15%
TG  7-30%
Aspirin + statin
See above
Bile acid sequestrants
LDL
HDL
TG
LDL
HDL
TG
LDL
HDL
TG
 15-30%
 3-5%
/
 5-25%
 15-35%
 20-50%
 30-42%
 20-30%
 32-44%
LDL
HDL
TG
LDL
HDL
TG
 17-18%
 1%
 7-9%
 45-60%
 6-10%
 23-31%
Nicotinic acid
Nicotinic acid + statin
Absorption inhibitor
Absorption inhibitor
+ statin
Available Agents
Lovastatin (Mevacor)*
Pravastatin (Pravachol)*
Simvastatin (Zocor)*
Fluvastatin (Lescol)
See individualized Atorvastatin (Lipitor)
table on next page. Rosuvastatin (Crestor)
Dosing range
10-80 mg/day
10-80 mg/day
5-80 mg/day
20-80 mg/day
10-80 mg/day
5-40 mg/day
ASA + pravastatin (Pravigard PAC)
Cost
$
$
$-$$
$$$$$$
$$$$$$
$$$$$$
81/20-325/80
mg/day

4-24 gm/day
Cholestyramine (Questran )*

5-30 gm/day
Colestipol (Colestid )*

3.75-4.375 gm/day
Colesevelam (WelChol )
Immediate/sustained-release niacin* 1.5-6 gm/day
1-2 gm/day
Niacin extended-released

(Niaspan )*
500/20-2000/40
Niacin extended-release + lovastatin

mg/day
(Advicor )
Niacin extended-release + simvastatin
(Simcor)
10 mg/day
Ezetimibe (Zetia)
$$$$$$
Ezetimibe + simvastatin (Vytorin)
$$$$$$
10/10-10/80
mg/day
$$$
$$$
$$$$$$$
$-$$
$$-$$$$
$$$$$$$
$$$$$$
23
Fibric acids
LDL  5-20%
HDL  10-20%
TG  20-50%
Fenofibrate (Tricor, Triglide,
Fenoglide, Lipofen, Lofibra tabs*)
Fenofibrate micronized (Antara,
Lofibra caps*)
Fenofibric acid (Trilipix)
Varies by product
$$$$$$$$$$
Gemfibrozil (Lopid)*
1200mg/day
$
* Generic available
MH-MH formulary medications (in bold)
COMPARISON CHART OF STATIN POTENCY
% LDL
reduction
25-32
31-39
37-45
48-52
55-60
60-63
Fluvastatin
(Lescol)
40mg
80mg
-----
Lovastatin
(Mevacor)
20mg
40mg
80mg
----
Pravastatin
(Pravachol)
20mg
40mg
80mg
----
Simvastatin
(Zocor)
10mg
20mg
40mg
80mg
---
Atorvastatin
(Lipitor)
-10mg
20mg
40mg
80mg
--
Rusuvastatin
(Crestor)
--5mg
10mg
20mg
40mg
24
Hypertension Therapy
JNC-VII Recommendations
CATEGORY
Normal
Prehypertension
Hypertension, Stage 1
Hypertension, Stage 2
SYSTOLIC BP, mm Hg
< 120
120-139
140-159
> 160
DIASTOLIC BP, mm Hg
< 80
80-89
90-99
> 100
Algorithm for Treatment of Hypertension
Lifestyle Modifications
Not at Goal BP (<140/90 mm Hg or <130/80 mm Hg
for those with diabetes or chronic kidney disease)
Initial Drug Choice
Hypertension without
compelling indications
Hypertension with
compelling indications
Stage 1 Hypertension
Stage 2 Hypertension
Thiazide-type diuretic for
most. May consider ACE
inhibitor, ARB, -blocker,
calcium channel blocker, or
combination
2-Drug combo for most
(Usually Thiazide-type
diuretic and ACE-I, or
ARB, or -blocker, or
Calcium channel blocker)
Drug(s) for the
compelling indication
Other antihypertensive
drugs as needed
Not at Goal BP
Optimize dosages or add additional drugs until goal blood pressure is achieved
25
General Principles of Initiating Therapy:
1. Initiate therapy with the lowest dose possible, slowly titrating upward.
2. Optimal formulation should provide 24 hour efficacy with once daily dosing to
enhance compliance, lower cost and allow for a more constant lowering of blood
pressure.
3. Most patients with hypertension will require 2 or more antihypertensive medications
to achieve their BP goals.
4. When BP is more than 20/10 mm Hg above goal, initiating therapy with 2 drugs
should be considered.
Compelling Indications for Individual Drug Classes
Compelling Indication
Initial Therapy Options
Heart Failure
Thiazide diuretic,  blocker, ACE inhibitor,
ARB, Aldosterone receptor blocker
Post-myocardial infarction
 blocker, ACE inhibitor, Aldosterone
receptor blocker
High risk for coronary disease
Calcium channel blocker
Diabetes
ARB, Calcium channel blocker
Chronic kidney disease
ACE inhibitor, ARB
Recurrent stroke prevention
Thiazide diuretic, ACE inhibitor
Pregnancy
Methyldopa,  blocker, Vasodilator
DRUG
 BLOCKERS
INITIAL DOSE
TARGET DOSE
Atenolol (Tenormin)†
Bisoprolol (Zebeta)†
Metoprolol tartrate
(Lopressor)†
Metoprolol succinate
(Toprol XL)
Pindolol (Visken)†
25-50 mg daily
2.5-5 mg daily
50-100 mg bid
Propranolol (Inderal,
Inderal LA)†
40 mg bid,
60-80 mg daily
50-100 mg daily
5 mg bid
50-100 mg daily
2.5-20 mg daily
100-450 mg in 2-3
divided doses
100-400 mg daily
MAXIMUM
DOSE
100 mg daily
40 mg daily
450 mg/day
400 mg daily
10-30 mg in 2-3
60 mg/day
divided doses
160-480 mg in divided 640 mg/day
doses,120-160 mg/day
† Available in generic preparations. *Only formulary products are listed.
26
DRUG
ACE INHIBITORS
INITIAL DOSE
TARGET DOSE
Benazepril (Lotensin)† 5-10 mg daily
20-40 mg daily or in
divided doses

12.5-25 mg bid or 50 mg tid
Captopril (Capoten )†
tid

5 mg daily
Enalapril (Vasotec )†
divided doses

Fosinopril (Monopril )† 10 mg daily
divided doses

10 mg daily
20-40 mg daily
Lisinopril (Prinivil ,

Zestril )†
7.5 mg daily
7.5-30 mg daily or in
Moexipril (Univasc)
divided doses

4 mg daily
4-8 mg daily
Perindopril (Aceon )

Quinapril (Accupril )† 10 mg daily
divided doses

2.5-5 mg daily
2.5-20 mg daily or in
Ramipril (Altace )
divided doses

1-2 mg daily
2-4 mg daily
Trandolapril (Mavik )
MAXIMUM
DOSE
80 mg/day
150 mg tid
40 mg/day
80 mg/day
80 mg daily
30 mg/day
16 mg daily
80 mg/day
20 mg/day
8 mg daily
† Available in generic preparations
*All ACE inhibitors are on formulary.
ANGIOTENSIN II RECEPTOR BLOCKERS (ARB)
DRUG
INITIAL DOSE
TARGET DOSE
MAXIMUM
DOSE

25-50 mg daily
25-100 mg daily or in 100 mg/day
Losartan (Cozaar )
divided doses

80-160 mg daily 80-320 mg daily or in 320 mg/day
Valsartan (Diovan )
divided doses
*Only formulary ARBs are listed.
27
RENIN INHIBITOR
INITIAL DOSE TARGET DOSE
DRUG
Aliskiren (Tekturna)
150 mg daily
Increase as needed
DIURETICS
DRUG
Thiazide Diuretics
Chlorthalidone †
Hydrochlorothiazide †
Metolazone
(Zaroxolyn)†
Loop Diuretics*
Bumetanide (Bumex)†
MAXIMUM
DOSE
300 mg daily
MAXIMUM
DOSE
25 mg daily
25-100 mg daily
12.5 mg daily
25-100 mg daily
1.25-2.5 mg daily 5-10 mg daily
100 mg daily
200 mg daily
10 mg daily
Increase as needed
10 mg/day
Furosemide (Lasix)†
0.5-2 mg 1-2
times/day
10-40 mg daily
240 mg bid
Torsemide (Demadex)†
5-10 mg daily
Increase by 20-40
mg as needed
Double the dose as
needed
50-100 mg daily
25-200 mg daily or
in divided doses
100 mg daily
200 mg/day
Aldosterone Receptor Blockers
50 mg daily
Eplerenone (Inspra)
Spironolactone
25 mg daily

(Aldactone )†
200 mg daily
*
Furosemide 40 mg=10-20 mg of torsemide=1 mg of bumetanide
All listed agents are formulary.
DRUG
CALCIUM CHANNEL BLOCKERS
(Not short acting, immediate release agents)
Nondihydropyridines
Diltiazem
(Cardizem†, Tiazac†)
Verapamil (Calan,
30 mg tid,
240-360 mg in 3-4
180-240 mg daily doses, 240-360 mg
daily
40 mg bid,
80 mg tid,
MAXIMUM
DOSE
360 mg/day
360 mg/day
28
Isoptin, Verelan)†
Dihydropyridines
Amlodipine (Norvasc)†
Nifedipine (Adalat CC)†
Nisoldipine (Sular)
120 mg daily
120-240 mg daily
2.5-5 mg daily
30 mg daily
20 mg daily
5-10 mg daily
30-60 mg daily
20-40 mg daily
10 mg daily
120-180 mg daily
60 mg daily
† Available in generic preparations. *Only formulary calcium channel blockers are listed.
29
DRUG
Doxazosin (Cardura)†
Terazosin (Hytrin)†
-BLOCKERS
(Not Initial Monotherapy)
INITIAL DOSE
TARGET DOSE
1 mg daily
1 mg qhs
1-16 mg daily
1-5 mg qhs
MAXIMUM
DOSE
16 mg daily
20 mg qhs
Only formulary alpha blockers are listed.
CENTRAL -AGONISTS and Other Centrally Acting Drugs
(Not Initial Monotherapy)
DRUG
INITIAL DOSE
TARGET DOSE
MAXIMUM
DOSE

0.2-1.2 mg bid,
2.4 mg/day
Clonidine (Catapres †, 0.05-1 mg bid,

0.1 mg patch
0.1-0.3 mg every week 0.6 mg/week
Catapres TTS )
every week
Methyldopa
250 mg bid-tid
500 mg-2 g in 2-4
3 g/day

divided doses
(Aldomet )†

1-3 mg qhs
3 mg qhs
Guanafacine (Tenex )† 1 mg qhs
Reserpine †
0.05-0.1 mg daily 0.1-0.25 mg daily
0.5 mg daily
† - Available in generic preparations
DRUG
Hydralazine
(Apresoline)†
Minoxidil (Loniten)†
DIRECT VASODILATORS
(Not initial Monotherapy)
INITIAL DOSE
TARGET DOSE
10 mg qid
25-50 mg qid
MAXIMUM
DOSE
300 mg daily
2.5-5 mg daily
10-40 mg daily
100 mg daily
† - Available in generic preparations.
Adapted from The Seventh Report of the Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure. JAMA 2003;289:2560-2572;May 21, 2003.
30
VTE Prophylaxis and Treatment:
Selected Recommendations from ACCP
Indication
VTE Prophylaxis
Do not use aspirin for VTE prophylaxis
Use mechanical methods (GCS or IPC) if
bleeding risk is high
Laparoscopic procedures + VTE risk factors
Minor surgery, age <40, no risk factors)
General surgery (moderate risk)*
General surgery (high risk)**
General surgery (very high risk)***
Gynecologic surgery (no risk)
Gynecologic surgery (major surgery)
Gynecologic surgery (major surgery with
malignancy)
Urologic surgery (low or no risk)
Urologic surgery (major, open)
Urologic surgery (with multiple risk factors)
Hip replacement/ hip fracture surgery
Elective knee replacement
Neurosurgery
Trauma, Spinal cord injury
Ischemic stroke
General medical patient (admitted for CHF or
resp. illness or confined to bed and have
additional risk factors)
ICU patients
Therapy
LDUFH or LMWH, IPC or GCS
Early and aggressive mobilization
LDUFH q8h or LMWH
LDUFH q8h or LMWH
LMWH or LDUFH q8h + IPC/GCS
Early and aggressive mobilization
LDUFH q12h or LMWH or IPC
LDUFH q8h or LMWH, consider
adding IPC/GCS
None recommended
LDUFH or LMWH or GCS or IPC
GCS +/- IPC with LDUFH or LMWH
LMWH or fondaparinux or warfarin
(INR 2-3) for at least 10 days.
Consider using extended prophylaxis
for up to 28-35 days post-operatively.
LMWH or fondaparinux or warfarin
(target INR 2.5, range 2-3)
IPC or LMWH or LDUH q12h
LMWH continued through
rehabilitation
LDUFH or LMWH
LDUFH or LMWH
LDUFH or LMWH
31
Indication
Treatment of Thromboembolism
Therapy
Begin anticoagulation while awaiting
test results when clinical suspicion is
high.
LMWH or UFH IV for at least 5 days.
Overlap with warfarin until INR is in
therapeutic range and stable.
UFH is preferred in severe renal
insufficiency.
LMWH for the first 3-6 months should
be considered for patients with VTE
and cancer.
Elastic compression stockings for 2
years after an episode of DVT reduces
risk for post-thrombotic syndrome.
Indication
Atrial Fibrillation
Prior TIA or Stroke or systemic embolism
One or more of the following: Age >75 years,
History of hypertension or diabetes or systolic
heart failure or mitral stenosis or rheumatic
mitral valve disease
Age  75years and no other risk factors
Therapy
Warfarin (target INR 2.5, range 2-3)
ASA 325 mg/day
32
Indication
Prosthetic Heart Valves
Aortic bileaflet or tilting disk valves
Aortic bileaflet valves + atrial fibrillation
Mitral bileaflet or tilting disk valves
Caged ball or caged disk valves
Mechanical valves + MI or left atrial
enlargement or hypercoagulable state or low
ejection fraction
Mechanical valves + atrial fibrillation or
hypercoagulable state or low ejection fraction
or atherosclerotic disease or systemic
embolism despite therapeutic INR
Bioprosthetic valves (aortic)
Bioprosthetic valves (mitral)
Indication
Ischemic Stroke/TIA
Secondary Prevention
Non-cardioembolic stroke
Therapy
Warfarin (target INR 3, range 2.5-3.5)
+ ASA 50-100 mg/day
ASA 50 to 100 mg/day
Warfarin (target INR 2.5, range 2-3) x
3 months then either no anticoagulation
or ASA 50 to 100 mg/day
Therapy
ASA 50-100 mg daily or the
combination of ASA 25 mg and
extended release dipyridamole 200 mg
BID or clopidogrel 75 mg.
VTE = venous thromboembolism, LDUFH = low-dose-unfractionated heparin, LMWH = lowmolecular-weight heparin, ASA = aspirin, GCS = graduated compression stockings, IPC =
intermittent pneumatic compression
*
**
***
Moderate Risk: Minor surgery in patients with additional risk factors; non-major
surgery in patients aged 40-60 years, with no risk factors; major surgery and age
<40 with no risk factors
High Risk: Non-major surgery in patients > 60 or with additional risk factors;
major surgery in patients > 40 years or with additional risk factors
Very High Risk: Major surgery in patients > 40 and history of VTE, cancer,
hypercoagulable state; major trauma, spinal cord injury
Adapted from Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians
Evidenced-Based Clinical Practice Guidelines (8th Edition). 2008; 133(6): 67S-887S.
33
Perioperative Management of Patients Who Require Discontinuation of Warfarin

For elective procedures, discontinue warfarin 5 days prior to procedure, allowing the INR to
return to normal by the time of the procedure. If INR is still elevated (> 1.5) 1 to 2 days prior
to procedure, consider administering low dose oral Vitamin K (~2.5mg).

For non-elective procedures where rapid reversal is needed, may give Vitamin K 1-2mg IV
infusion. Note: high doses of IV Vitamin K may result in warfarin resistance post procedure.

Bridge with heparin therapy, if indicated, based on risk stratification. See table below.
Risk of
Thromboembolism
High annual risk
(>10%)
Moderate
(4-10%)
Low
(<4%)
Indication for warfarin therapy
Recommendation
Mechanical Valve
-Any MVR
-Caged-ball or tilting disc AVR
- Recent CVA/TIA < 6mo
Afib
-CHADS2 = 5-6
-Recent CVA/TIA < 3mo
-Rheumatic valvular heart dz
VTE
-Recent event < 3mo
-Known major thrombophilia
(PC, PS, AT III, APA, multiple)
Therapeutic-dose LMWH or IV
UFH
Mechanical Valve
-Bileaflet AVR + 1 CHADS2 risk
factor
Afib
-CHADS2 = 3-4
VTE
-Recent event ~3-12 mo
-Known minor thrombophilia
(hetero FVL, hetero 20210)
-Recurrent VTE
-Active cancer
Therapeutic-dose LMWH, IV
UFH, or low-dose LMWH
Mechanical Valve
-Bileaflet AVR and no afib or
CHADS2 risk factor
Afib
-CHADS2 = 0-2, and no CVA
VTE
-Single event >12 mo prior
and no other risk factors
Low-dose LMWH or no bridge
LMWH preferred
(as may be done outpatient)
Therapeutic-dose LMWH
preferred
34

Last dose of LMWH should be administered 24 hrs prior to procedure;
IV UFH should be continued up to 4 hrs prior to procedure

Restart warfarin 12-24 hrs post procedure once there is adequate hemostasis

Restart therapeutic-dose heparin (if indicated):
~24 hrs post minor surgery/procedure and adequate hemostasis
~48-72 hrs post major surgery/procedure and adequate hemostasis
Perioperative Management of Antiplatelet Therapy
Patients at high risk for
CV events
Surgical procedure
Recommendation
MI <3mo
Non-cardiac surgery or
CABG
Continue ASA
Hold clopidogrel >5 d
(preferably 10d)
PCI
Continue all antiplatelet tx
Any
Continue ASA &
clopidogrel
Do NOT bridge w/ UFH,
LMWH, DTI or
glycoprotein IIb/IIIa
inhibitor
Recent coronary stent:
-Bare metal < 6 wks
-DES < 12 mo
Douketis JD, Berger PB, Dunn AS, et al. The Perioperative Management of Antithrombotic
Therapy. Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians
Evidenced-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:299-339S.
MH-MH Vitamin K guidelines. P&T approved 05/08
35
Vitamin K Guidelines
INR
Clinical Setting
4.5-10
No bleeding
Therapeutic Options
Hold warfarin until INR in therapeutic range,
vitamin K not recommended
Rapid reversal
Hold warfarin and give vitamin K 1-5 mg IV
required
infusion
> 10
No bleeding
Hold warfarin until INR in therapeutic range and
give vitamin K 5 mg PO
May repeat q24h as necessary
Rapid reversal
required
infusion.
May repeat q12-24 hours as needed
Any INR Serious or life
threatening
Prothrombin Complex Concentrate (PCC)
bleeding
Repeat as necessary.
Intravenous Vitamin K will be given as an IV infusion over 30 minutes.
36
HEART FAILURE THERAPY (ACC/AHA)
New York Heart Association Functional Classification:
Class I:
Patients with cardiac disease but without limitations of physical
activity. Ordinary physical activity does not cause undue fatigue,
dyspnea or palpitation.
Class II:
Patients with cardiac disease that results in slight limitations of physical
activity. Ordinary physical activity results in fatigue, palpitation,
dyspnea or angina.
Class III:
Patients with cardiac disease that results in marked limitation of
physical activity. Although patients are comfortable at rest, less than
ordinary activity will lead to symptoms.
Class IV:
Patients with cardiac disease that results in an inability to carry
on physical activity without discomfort. Symptoms of congestive heart
failure are present at rest. With any physical activity, increased
discomfort is experienced.
Criteria Committee, New York Heart Association, Inc. Diseases of the Heart and Blood Vessels.
Nomenclature and Criteria for Diagnosis, 7th ed. Boston, Little, Brown, 1973.
Classification Based on Disease Progression- 2005 Guidelines
Stage A: Patient at high risk for developing heart failure but has no structural heart
disease (Examples: HTN; CAD; DM; Obesity; Metabolic syndrome; History of
cardiotoxins; Family history of cardiomyopathy).
Stage B: Patient with structural heart disease who has never developed symptoms of
heart failure (Examples: Previous MI; Left ventricular hypertrophy and low ejection
fraction; Asymptomatic valvular heart disease).
Stage C: Patient with known structural heart disease and prior or current symptoms of
heart failure.
Stage D: Patient with marked symptoms at rest despite maximal medical therapy (e.g.
those who are frequently hospitalized or cannot be safely discharged without specialized
interventions such as mechanical circulatory support, continuous inotropic therapy,
cardiac transplantation or hospice care).
*This classification is intended to complement but not replace the New York Heart Association
functional classification, which primarily gauges the severity of symptoms in patients who are in Stage
C or D.
37
Therapy
Stage A:
1. Control blood pressure (angiotensin converting enzyme (ACE) inhibitors and beta
blockers preferred).
2. Lifestyle modifications- smoking cessation, exercise, discourage alcohol and illicit
drug use, control metabolic syndrome.
3. Treat lipid abnormalities in accordance with recommended guidelines.
4. Begin ACE inhibitors in patients with a history of atherosclerotic vascular disease,
diabetes mellitus, or hypertension and associated cardiovascular risk factors.
Stage B:
1. Same recommendations as Stage A.
2. Initiate ACE inhibitor (ARB may be used if intolerant of ACE inhibitor) and beta
blocker therapy post-myocardial infarction.
Stage C:
1. Same recommendations as Stage A and B.
2. Drugs for routine use: ACE inhibitors, beta blockers, diuretics.
3. Potential therapies: aldosterone antagonists, digoxin, angiotensin receptor blockers
(ARBs), hydralazine + isosorbide dinitrate.
Stage D:
1. Same recommendations as Stage A-C.
2. Possible IV inotropic therapy, heart transplantation, ventricular assist devices, and/or
hospice care.
ACE Inhibitors (ACEI) should be used in all patients with current or prior symptoms
of HF and reduced LVEF, unless contraindicated. Absolute contraindications include:
angioedema, pregnancy, bilateral renal artery stenosis. Relative contraindications
include: cough, SCr > 3.0, significant hyperkalemia.
Beta blockers (BB) should be used in all stable patients with current or prior symptoms
of HF and reduced ejection fraction, unless contraindicated. Recommended beta
blockers include bisoprolol, metoprolol succinate (sustained release) and carvedilol.
Absolute contraindications include: HR <50, SBP < 90 mm Hg, and second or third
degree heart block without a pacemaker. Relative contraindications include:
bronchoconstrictive disease.
38
Diuretics should be prescribed for all patients with current or prior symptoms of heart
failure and reduced ejection fraction who have evidence of fluid retention. Diuretics
should not be used alone even if the symptoms of heart failure are well controlled.
Loop diuretics are the preferred diuretic agents for use in most patients with heart
failure. If a patient experiences a 1-2 kg weight gain, double the loop diuretic dose. If
this fails, metolazone can be added for several days. If hypotension or azotemia is
observed, the rapidity of diuresis should be decreased. Overdosing of diuretics can lead
to volume depletion, which may increase the likelihood of hypotension with ACE
inhibitors and risk of renal insufficiency. Nonsteroidal anti-inflammatory drugs may
cause diuretic resistance and should be avoided in patients with heart failure.
Angiotensin Receptor Blockers (ARBs) that are approved for HF (candesartan,
valsartan) are a reasonable alternative in patients who are ACEI intolerant. They should
not be used in patients who have no prior use of an ACEI or in patients who are
tolerating an ACEI. At this time, ARBs should be considered in patients who
experience cough while receiving an ACEI. Use with caution in patients with a history
of angioedema to ACEI. If a patient is taking an ARB for another indication the use of
an ARB over ACEI can be considered.
The combination of hydralazine and isosorbide dinitrate is recommended to improve
outcomes for patients self-described as African-Americans, with moderate-severe
symptoms on optimal therapy with ACEI, BB and diuretics. This combination can be
considered when ACEI are not tolerated because of angioedema, renal insufficiency,
hyperkalemia or cough.
Aldosterone antagonists (spironolactone, eplerenone) are recommended in select
patients with moderately severe-severe (Class III/IV) symptoms of HF and reduced
LVEF who can have careful monitoring of potassium and SCr levels. SCr should be
less than 2.5 mg/dL for men or less than 2 mg/dL for women. Potassium should be less
than 5 mEq/L.
Digoxin can be beneficial to reduce hospitalizations in patients with current or prior
symptoms of HF and reduced LVEF. In this setting, digoxin should be added to a
standard HF regimen of ACEI, BB and loop diuretic. Goal digoxin level for heart failure
is 0.5-0.8 ng/ml. Digoxin levels above 1 ng/ml are associated with an increased risk of
mortality.
Amlodipine and felodipine are the only calcium channel blockers that can be safely
used in patients with heart failure.
39
Therapy for Diastolic Dysfunction:
Goals: control BP, HR, blood volume and ischemia.
Therapy: ACE inhibitors, beta blockers.
DRUG
Captopril (Capoten)
Enalapril (Vasotec)
Fosinopril (Monopril)
Lisinopril (Zestril,
Prinivil)
Quinapril (Accupril)
Ramipril (Altace)
DRUG
Candesartan
(Atacand)
Valsartan (Diovan)
ACE INHIBITORS
INITIAL DOSE
TARGET
DOSE
6.25 mg tid
50 mg tid
2.5 mg bid
10-20 mg bid
5-10 mg daily
20-40 mg daily
5 mg daily
20-40 mg daily
MAXIMUM COST/
DOSE
Month
100 mg tid
$
20 mg bid
$
40 mg daily
$
40 mg daily
$
5 mg bid
20-40 mg bid
1.25-2.5 mg daily 10 mg daily
40 mg bid
10 mg daily
ANGIOTENSIN RECEPTOR BLOCKERS
INITIAL DOSE
TARGET
MAXIMUM
DOSE
DOSE
4 mg daily
4-16 mg daily 32 mg daily
DRUG
Bisoprolol (Zebeta)
Carvedilol (Coreg)
Metoprolol XL
(Toprol)
DRUG
Eplerenone (Inspra)
Spironolactone
(Aldactone)
40 mg bid
40-160 mg bid 160 mg bid
BETA BLOCKERS
INITIAL DOSE
TARGET
DOSE
1.25 mg daily
2.5-10 mg
daily
3.125 mg bid
25 mg bid
12.5-25 mg daily 200 mg daily
$
$$$
COST/
Month
$$$$$
$$$$$$$
MAXIMUM COST/
DOSE
Month
10 mg daily
$$$
50 mg bid
200 mg daily
$
$$$
ALDOSTERONE ANTAGONISTS
INITIAL DOSE
TARGET
MAXIMUM COST/
DOSE
DOSE
Month
25 mg daily
50 mg daily
50 mg daily
$$$$$
25 mg daily
25-50 mg daily 50 mg daily
$
40
DRUG
HYDRALAZINE & ISOSORBIDE DINITRATE
INITIAL DOSE
TARGET
MAXIMUM
DOSE
DOSE
10-25 mg bid
75 mg tid
100 mg tid
Hydralazine
(Apresoline)
Isosorbide dinitrate
Hydralazine/isosorbide
(BiDil)
DRUG
Hydrochlorothiazide
Loop Diuretics
Bumetanide (Bumex)
Furosemide (Lasix)
10 mg tid
37.5/20 mg tid
40 mg tid
80 mg tid
37.5/20 mg- 75/40 mg tid
75/40 mg tid
COST/
Month
$
$
$$$$$$$
DIURETICS
INITIAL DOSE
TARGET
DOSE
MAXIMUM
DOSE
12.5 mg daily
25-100 mg
daily
200 mg daily
0.5-2 mg daily
(1 mg= 40 mg
furosemide)
10-40 mg daily
As needed, inc. 4-8 mg daily
by 1-2 mg
$$
As needed, inc. 240 mg bid
by 20-40 mg
Double the
200 mg daily
dose as needed
$
Torsemide (Demadex) 10-20 mg daily
(Equal to 40 mg
furosemide)
Miscellaneous Diuretics
2.5 mg daily
Metolazone

(Zaroxolyn )
5-10 mg daily
10 mg daily
COST
(30 D
supply)
$
$$$$
$$$
*All listed agents are formulary with the exception of Atacand.
Adapted from 2009 Focused update: ACCF/AHA Guidelines update for the diagnosis and management
of chronic heart failure in adults. A report of the American College of Cardiology/ American Heart
Association Task Force on Practice Guidelines. www.acc.org; www.americanheart.org
41
Acute Coronary Syndrome (UA/NSTEMI/STEMI)1,2,3
Drug
Aspirin
Clopidogrel
Prasugrel
Class of Recommendation
I.
1. Initial dose of 162-325 mg orally.
2. Continued indefinitely at a daily dose of 75-162 mg for patients with
UA/NSTEMI managed medically without stenting.
3. After bare metal stenting, aspirin 162-325 mg should be prescribed
for at least 1 month, then continued indefinitely at a dose of 75-162
mg.
4. After stenting with drug eluting stents, aspirin 162-325 mg should be
prescribed for 3-6 months, then continued indefinitely at a dose of
75-162 mg.
IIa. For patients considered high risk of bleeding, a lower initial aspirin
dose (75-162 mg) after PCI can be considered.
I.
1. In patients who have had a PCI procedure, regardless of stent type,
clopidogrel or prasugrel should be given in combination with aspirin
for at least 12 months in patients who are not at high risk for
bleeding.
2. If the risk of bleeding outweighs the anticipated benefit, earlier
discontinuation should be considered.
3. For UA/NSTEMI patients who are treated medically, clopidogrel
should be given (in combination with aspirin) for at least 1 month
and ideally up to 12 months.
4. For STEMI patients treated with thrombolytic therapy or PTCA
alone, clopidogrel should be given (in combination with aspirin) for
at least 14 days and up to 1 year.
5. In patients in whom CABG is planned, withhold clopidogrel for at
least 5 days and at least 7 days for patients receiving prasugrel.
6. Alternative to aspirin in patients with hypersensitivity or major
gastrointestinal intolerance.
IIa. Continuation of clopidogrel or prasugrel beyond 15 months may be
considered after drug eluting stent placement.
42
Reperfusion I.
therapy1. Generally preferred if STEMI patient presents to a hospital without
Thrombolysis
PCI capability who cannot be transferred to a PCI center within 90
minutes of arrival. Therapy should be given within 30 minutes of
arrival.
2. In the absence of contraindications, preferred time frame for
consideration is within 12 hours of symptom onset.
IIa. Reasonable to administer to STEMI patients presenting 12-24 hours
after symptom onset.
III.
1. Greater than 24 hours after symptom onset and pain resolved.
2. NSTEMI patients
Heparin
I.
1. IV in patients undergoing percutaneous revascularization or medical
management.
2. IV in STEMI patients treated with selective thrombolytics (alteplase,
reteplase, tenecteplase).
3. DVT prophylaxis for at least 48 hours in patients treated with a
conservative strategy.
4. Monitor platelet counts daily.
Enoxaparin
I. Alternative to heparin.
1. STEMI patients managed with fibrinolytic therapy for up to 8 days.
2. UA/NSTEMI patients with planned invasive or conservative strategy.
Beta Blockers I.
1. Oral beta blocker therapy within the first 24 hours for patients who
do not have any of the following: signs of heart failure, evidence of
low output state, increased risk of cardiogenic shock or relative
contraindication. Continue indefinitely.
2. Therapy should be re-evaluated in patients not given beta blocker
within 24 hours of presentation.
IIa. Reasonable to give an IV beta blocker at the time of presentation to
patients who are hypertensive and do not have any of the following;
signs of heart failure, evidence of low output state, increased risk of
cardiogenic shock or relative contraindication.
ACE
I.
Inhibitors
1. Oral ACEI within the first 24 hours to patients with pulmonary
congestion or LVEF < 40%, without hypotension or
contraindications.
2. Patients with LVEF < 40% and for those with hypertension, diabetes
or chronic kidney disease unless contraindicated.
43
IIa. Oral ACEI within the first 24 hours can be useful to patients without
pulmonary congestion or LVEF < 40%, without hypotension or
contraindications.
III. An IV ACE inhibitor should not be given within the first 24 hours
due to risk of hypotension.
ARB
I. Administer to patients who are intolerant of ACE inhibitors who
have clinical or radiological signs of HF or EF < 40%.
Aldosterone I. Patients without significant renal dysfunction or hyperkalemia who
blocker
are receiving therapeutic doses of ACE inhibitor and beta blocker,
have LVEF < 40% and symptomatic heart failure or diabetes.
Nitroglycerin I.
1. SL 0.4 mg every 5 minutes for a total of 3 doses for patients with
ongoing ischemic discomfort.
2. IV within the first 48 hours for persistent ischemia, hypertension or
pulmonary congestion.
3. Oral or topical nitrates are useful beyond the first 48 hours for
treatment of recurrent angina if their use does not preclude therapy
with beta blockers and ACE inhibitors.
III.
1. SBP < 90 mm Hg or > 30 mm Hg below baseline, severe
bradycardia, tachycardia, or suspected RV infarction.
2. Phosphodiesterase inhibitor use within the last 24 hours.
Calcium
I. Verapamil or diltiazem in patients with contraindications to beta
Channel
blocker or when beta blockers are not successful.
Blockers
IIa. Reasonable for use for recurrent ischemia in the absence of
contraindications after beta blockers and nitrates have been used.
III. Nifedipine (short acting) is contraindicated.
Lipid
See lipid lowering guidelines
Therapy
Obtain lipid panel within 24 hours of admission.
Warfarin
I. In patients requiring warfarin, clopidogrel and aspirin therapy, an INR
goal of 2-2.5 is recommended with low dose aspirin (75-81 mg).
NSAIDs/
I. These agents should be discontinued upon hospital presentation.
Celecoxib
III. Should not be administered during hospitalization for ACS.
1. Anderson JL, Adams CD, Antman EM, et al. ACC/AHA Guidelines for the management of patients
with unstable angina/non-ST-elevation myocardial infarction. www.acc.org.
2. Antman EM, Hand M, Armstrong PW, et al. 2007 focused update of the ACC/AHA 2004
guidelines for the management of patients with ST-elevation myocardial infarction. www.acc.org.
3. Kushner FG, Hand M, Smith SC Jr, et al. 2009 focused updates: ACC/AHA guidelines for the
management of patients with ST-elevation myocardial infarction (updating the 2004 guideline and
44
2007 focused update) and ACC/AHA/SCAI guidelines on percutaneous coronary intervention
(updating the 2005 guideline and 2007 focused update). www.acc.org
The ACC/AHA classification system for procedures and treatments:
Class I:
Evidence and/or general agreement that treatment is beneficial, useful, and
effective.
Class II:
Conflicting evidence and/or a divergence of opinion about the
usefulness/efficacy.
Class IIa: Weight of evidence/opinion is in favor of usefulness/efficacy.
Class IIb: Usefulness/efficacy is less well established by evidence/opinion.
Class III: Evidence and/or general agreement that treatment is not useful/effective
and in some cases may be harmful.
45
Acute Asthma Management
The main therapies in the emergency department and hospital: supplemental oxygen, inhaled
short acting beta2-agonists (SABA), systemic corticosteroids, and ipratropium (dose and
frequency vary with severity). Long acting beta2-agonists (LABA) are not to be used as
monotherapy for long-term control of asthma.
Albuterol 1 unit dose = 2.5 mg albuterol
Ipratropium 1 unit dose = 0.5 mg ipratropium
Initial Assessment
 FEV1 or PEF >40% (mild to moderate)
-Oxygen to achieve O2 saturation >90%
-Inhaled SABA by nebulizer or MDI with valved holding chamber, up to 3 doses in first
hour (Albuterol 10-15 mg continuous nebulization over 1 hr OR 2.5-5 mg nebulization Q
20 minutes)
-Oral steroids if no immediate response or if patient recently on oral steroids (Prednisone
40-80 mg po now & daily; may give Solu-Medrol 40 mg IV if unable to take po)
 FEV1 or PEF<40% (severe)
-Oxygen to achieve O2 saturation  90%
-Inhaled SABA (Albuterol 10-15 mg continuous nebulization over 1 hr OR 2.5-5 mg
nebulization Q 20 minutes) and anticholinergic (Ipratropium 0.5-1 mg continuous
nebulization over 1 hr or 0.25-0.5 mg nebulization Q 20 minutes) Can also be given by
MDI with valved holding chamber, up to 3 doses in first hour.
-Oral steroid (Prednisone 40-80 mg po now & daily; may give Solu-Medrol 40 mg IV if
unable to take po)
Repeat Assessment (after 1 hr of treatment)
 Moderate exacerbation (FEV1 or PEF 40-69%)
-Inhaled SABA (Albuterol 2.5-5 mg continuous nebulization over 1 hr)
-If oral steroids not already given, administer Prednisone 40-80 mg po now & daily; may
give Solu-Medrol 40 mg IV if unable to take po
-Continue treatment 1-3 hours, provided there is improvement; make admit decision in <4
hours
 Severe exacerbation (FEV1 or PEF <40%)
-Inhaled SABA (Albuterol 2.5-5 mg continuous nebulization over 1 hr) + inhaled
anticholinergic (Ipratropium 0.25-0.5 mg continuous nebulization over 1 hr)
-Systemic steroid (Prednisone 40-80 mg po now & daily; may give Solu-Medrol 40 mg
IV if unable to take po)
46
Repeat Assessment (after 1 hr of treatment)
 Good response (FEV1 or PEF  70%)
-Discharge home: continue treatment with inhaled beta2-agonist; consider inhaled
corticosteroid; continue course of oral corticosteroid; patient education
 Incomplete response (FEV1 or PEF 40-69%)
-Admit to hospital: inhaled beta2-agonist; systemic corticosteroid; oxygen to maintain O2
saturation >90%
 Poor response (FEV1 or PEF <40%; PCO2 >42 mmHg)
-Admit to hospital Intensive Care
-Inhaled beta2-agonist hourly or continuously
-IV corticosteroid
-Possible intubation and mechanical ventilation
Medications for Acute Asthma Exacerbations
INHALED SHORT-ACTING BETA2-AGONISTS
MEDICATIONS
DOSAGES
COMMENTS
Albuterol
Nebulizer solution
2.5 - 5 mg q 20 min for 3 Only selective beta2-agonists are
recommended. For optimal delivery, dilute
(5 mg/mL)
doses, then 2.5 - 10 mg
q 1-4 hours prn, or 10-15 aerosols to minimum of 3 mL at gas flow of
6-8 L/min
mg/hour continuously
HFA MDI (90 mcg/puff) 4-8 puffs q 20 min up to As effective as nebulized therapy if patient
4 hours, then q 1-4 hours is able to coordinate inhalation maneuver.
(Use spacer)
prn
Levalbuterol
1.25-2.5 mg q 20 min for Typically reserved for albuterol intolerance,
Nebulizer solution
3 doses, then 1.25 –5 mg failures, or tachycardia
(1.25mg/3ml)
0.63 mg of levalbuterol is equivalent to 1.25
q 1-4 hours prn
mg of albuterol
HFA MDI (45 mcg/puff) 1-2 puffs q 4-6 hours
Typically reserved for albuterol intolerance,
failures, or tachycardia
Pirbuterol
MDI (200 mcg/puff)
See albuterol dose.
Has not been studied in severe asthma
exacerbations.
47
SYSTEMIC (INHALED) BETA-AGONISTS
MEDICATIONS
DOSAGES
COMMENTS
Epinephrine 1:1000
0.3-0.5 mg q 20 min for No proven advantage of systemic
(1 mg/mL)
3 doses sq
therapy over aerosol
Terbutaline
0.25 mg q 20 min for 3
No proven advantage of systemic
(1 mg/mL)
doses sq
therapy over aerosol
MEDICATIONS
Ipratropium bromide
Nebulizer solution
(0.25 mg/mL)
MDI (18 mcg/puff)
MEDICATIONS
Prednisone
Methylprednisolone
Prednisolone
ANTICHOLINERGICS
DOSAGES
COMMENTS
0.5 mg q 20 min for 3
doses then q 2-4 hours
prn
8 puffs q 20 min prn up
to 3 hours
May mix in same nebulizer with
albuterol. Should not be used as
first-line therapy; should be added
to short acting beta2-agonist
therapy for more severe cases.
The addition of ipratropium has
not been shown to provide further
benefit once the pt is hospitalized.
Dose delivered from MDI is low
and has not been studied in
asthma exacerbations.
CORTICOSTEROIDS
DOSAGES
COMMENTS
For outpatient “burst” use 40-60
40-80 mg/day in 1-2
divided doses until PEF mg/day in single or divided doses
for adults (children –1-2
reaches 70% of
mg/kg/day, maximum 60 mg/day)
predicted or personal
for 3-10 days.
best.
Adapted from the Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma. NIH
Publication No 02-5074. 8/07
48
Chronic Obstructive Pulmonary Disease (COPD) Classifications*
Stage
Characteristics
I: Mild
FEV1/FVC < 70%;
FEV1 80% predicted
With or without chronic symptoms (cough,
sputum)
II: Moderate
FEV1/FVC < 70%;
50% ≤ FEV1 < 80% predicted
SOB on exertion; with or without chronic
symptoms (cough, sputum)
III: Severe
FEV1/FVC < 70%;
30% ≤ FEV1 < 50% predicted
Increased shortness of breath, reduced exercise
capacity, fatigue, and repeated exacerbations
IV: Very Severe
FEV1/FVC < 70%;
FEV1 < 30% predicted or
FEV1 < 50% plus chronic respiratory failure or
clinical signs of right heart failure
*Based on Post-Bronchodilator FEV1
49
COPD Therapy Based on Classification*
Stage
Therapy
I: Mild
-Short-acting bronchodilator as
needed
II: Moderate
-Regular treatment with one or
more bronchodilators
-Pulmonary rehabilitation
III: Severe
-Inhaled glucocorticosteroids if repeated
exacerbations (>3 in 3 years)
IV: Very Severe
-Inhaled glucocorticosteroids if repeated
exacerbations (>3 in 3 years)
-Long-term oxygen therapy if respiratory
failure
-Consider surgical options
NOTE: See asthma section for a list of medications and doses
Adapted from the recommendations of the NHLBI/WHO: Global Initiative for Chronic
Obstructive Lung Disease. 2009 Update
50
Diabetes Mellitus Guidelines
Table 1 Criteria for the Diagnosis of Diabetes Mellitus1
1. A1C >6.5%
OR
2. Fasting plasma glucose (FPG) > 126mg/dl (fasting >8 hours) – impaired fasting
glucose (IFG)
OR
3. Two-hour plasma glucose (PG) >200 mg/dl following a 75g oral glucose tolerance
test (OGTT) – impaired glucose tolerance (IGT)
OR
4. Random plasma glucose >200 mg/dl (fasting not required) accompanied by classic
symptoms hyperglycemia or hyperglycemic crisis (increased thirst, urination and
unexplained weight loss)
1
In the absence of unequivocal hyperglycemia, criteria 1-3 should be confirmed by repeat testing.
Table 2 Categories of Increased Risk for Diabetes2
1. FPG 100-125 mg/dl
2. Two-hour PG on the 75g OGTT 140-199 mg/dl
3. A1C 5.7-6.4%
2
For all three tests, risk is continuous, extending below the lower limit of the range and becoming disproportionately greater at higher
ends of the range. These are risk factors for future diabetes and cardiovascular disease.
Table 3 Criteria for Testing for Diabetes in Asymptomatic Adult Individuals
1. Adults who are overweight (BMI >25 kg/m2*) with additional risk factors:
a. physical inactivity
b. 1st degree relative with diabetes
c. members of high-risk ethnic population (Latino, Pacific Islander, or African-, Native-, AsianAmerican
d. women who delivered a baby weighing >9 lb or were diagnosed with gestational diabetes
mellitus (GDM)
e. hypertension (>140/90 mmHg or on therapy for hypertension)
f. HDL cholesterol level <35 mg/dl and/or triglyceride level >250 mg/dl
g. women with polycystic ovary syndrome (PCOS)
h. A1C >5.7%, IGT, or IFG on previous testing
i. other clinical conditions associated with insulin resistance (e.g. severe obesity, acanthosis
nigricans)
j. history of CVD
2. Begin testing at age 45 years if above criteria are absent
3. Repeat testing every 3 years if results are normal. Consider more frequent testing
based on initial results and risk status
*
At-risk BMI may be lower in some ethnic groups
51
Table 4 Screening for and Diagnosis of GDM
 Diabetes risk assessment at the first prenatal visit
Low-Risk Assessment
Very High-Risk Assessment






(ALL characteristics must be present)
Age <25 years
Weight normal before pregnancy
Member of an ethnic group with low
prevalence of diabetes
No known diabetes in 1st degree relatives
No history of abnormal glucose tolerance
No history of poor obstetrical outcome





(Any characteristic present)
Severe obesity
Prior history of GDM or delivery of largefor-gestational-age infant
Presence of glycosuria
Diagnosis of PCOS
Strong family history of type 2 diabetes
 Low-risk status does not require GDM screening
 Very high-risk patients should be screened as soon as possible following pregnancy
confirmation using standard diagnostic testing (Table 1)
 Unless low-risk, all women should undergo GDM screening at 24-28 weeks of
gestation using one of the following approaches
Two-Step Approach
One-Step Approach
 Initial Screening:
 Preferred in clinics with high
 50g OGTT (fasting not required)
prevalence of GDM
 One-hour plasma or serum glucose
 Diagnostic 100g OGTT on morning
 >140 mg/dl – captures 80% of all
after overnight fast >8 hours
women with GDM
 >130 mg/dl – captures 90% of all
women with GDM
 Follow-up Screening (separate day)
 If initial screening threshold exceeded,
perform diagnostic 100g OGTT on
morning after overnight fast >8 hours
Diagnostic plasma glucose values for GDM
– At least two must be present during test:
 Fasting >95 mg/dl
 1-hour >180 mg/dl
Table 5 Recommendations for Glycemic Control in Pregnant Women
Glucose Testing
GDM
Pre-Existing Type 1or 2 DM
Preprandial
<95 mg/dl
60-99 mg/dl
1-hour post meal
<140 mg/dl
2-hour post meal
<120 mg/dl
Peak postprandial
100-129 mg/dl
Bedtime/Overnight
60-99 mg/dl
A1C
<6%
52
Table 6 Recommendations for Non-Pregnant Adults with Diabetes Mellitus
Glycemic Control
A1C
<7%
Preprandial plasma glucose
70-130 mg/dl
3
Peak postprandial plasma glucose
<180 mg/dl
Key Concepts in Setting Glycemic Goals
 AlC is the primary target for glycemic control
 Goals should be individualized based on:
o
o
o
o
o
o
duration of diabetes
age/life expectancy
comorbid conditions
known CVD or advanced microvascular complications
hypoglycemia unawareness
individual patient considerations
 More or less stringent glycemic goals may be appropriate for individual patients
 Postprandial glucose may be targeted if A1C goals are not met despite reaching
preprandial glucose goals
Hypertension/Blood Pressure Control
Systolic Blood Pressure
<130 mm/Hg
Diastolic Blood Pressure
<80 mm/Hg
4
Dyslipidemia/Lipid Control
LDL
<100 mg/dl – no overt CVD
<70 mg/dl – overt CVD5
Triglycerides
<150 mg/dl
HDL
>40 mg/dl – men
>50 mg/dl – women
4
Statin therapy should be added to lifestyle therapy for patients with overt CVD or over age 40 years with CVD risk factors
In very-high-risk individuals with overt CVD, a lower LDL cholesterol goal of <70 mg/dl is an option
5
Table 7 Correlation of A1C with Mean Plasma Glucose
A1C (%)
mg/dl
6
126
7
154
8
183
9
212
10
240
11
269
12
298
mmol/l
7
8.6
10.2
11.8
13.4
14.9
16.5
53
Figure 1 Algorithm for the Metabolic Management of Type 2 Diabetes*
Tier 1:
At diagnosis:
Lifestyle
+
Metformin1
STEP 1
Lifestyle + Metformin
+
Basal Insulin
+
Intensive Insulin
+
Sulfonylurea2
STEP 2
Tier 2:
*
Well-Validated Core Therapies
GOAL IS TO ACHIEVE AND
MAINTAIN A1C <7% AND
CHANGE INTERVENTIONS AT
AS RAPID A PACE AS
TITRATION OF MEDICATION
ALLOWS WHEN TARGET
GLYCEMIC GOALS ARE NOT
BEING ACHIEVED.
Amylin agoinsts, α-glucosidase
inhibitors, megiltinides, and DPP-4
inhibitors are not included in the two
tiers of preferred agents owing to
their lower or equivalent overall
glucose-lowering effectiveness
compared with other agents and/or
their limited clinical data or relative
expense. However, they may be
appropriate choices in select patients.
STEP 3
Less Well-Validated Therapies
+
Pioglitazone
No hypoglycemia
Oedema/CHF
Bone Loss
+
GLP-1 agonist3
No hypoglycemia
Weight loss
Nausea/Vomiting
+
Pioglitazone
+
Sulfonylurea2
+
Basal Insulin
1
See Table 8 for Titration of Metformin. 2Sulfonylureas other than glyburide or chlorpropamide are preferable for ↓ risk of hypoglycemia. 3Insufficient clinical use to be confident regarding
54
Figure 2 Initiation and Adjustment of Insulin Regimens*
Start with bedtime intermediate-acting insulin or bedtime or morning
long-acting insulin (can initiate with 10 units or 0.2 units/kg)
Check fasting glucose (fingerstick) usually daily and increase dose, typically by 2 units every 3
days until fasting levels are consistently in target range (70-130 mg/dl). Can increase dose in
larger increments, e.g., by 4 units every 3 days, if fasting glucose is >180mg/dl
If hypoglycemia
occurs, or fasting
glucose level <70
mg/dl, reduce
bedtime dose by 4
units or 10% whichever is
greater
Continue
regimen.
Check
A1C every
3 months
NO
A1C >7% after 2 – 3 months
YES
NO
If fasting BG is in target range
(70-130 mg/dl), check BG
before lunch, dinner, and bed.
Depending on BG results, add
second injection as below. Can
usually begin with ~4 units and
adjust by 2 units every 3 days
until BG is in range
Pre-lunch BG
out of range.
Add rapid acting insulin
at breakfasta
Pre-dinner BG out of
range. Add NPH
insulin at breakfast or
rapid-acting insulin at
lunch
Pre-bed BG
out of range.
Add rapid
acting insulin
at dinnera
A1C >7% after 3 months
YES
Recheck pre-meal BG levels and if out of range,
may need to add injection. If A1C continues to
be out of range, check 2-hour postprandial levels
and adjust preprandial rapid-acting insulin
*
This algorithm can only provide basic guidelines for initiation and adjustment of insulin
a
Premixed insulins not recommended during adjustment of doses; however, they can be used conveniently, usually before breakfast and/or
dinner, if proportion of rapid- and intermediate-acting insulins is similar to the fixed proportions available.
55
Table 8 Titration of Metformin
1. Begin with low-dose metformin (500mg) taken once or twice per day with meals
(breakfast and/or dinner) or 850mg once per day.
2. After 5-7 days, if gastrointestinal side effects have not occurred, advance dose to
850, or two 500mg tablets, twice per day (medication to be taken before breakfast
and/or dinner).
3. If gastrointestinal side effects appear as doses advanced, decrease to previous lower
dose and try to advance the dose at a later time.
4. The maximum effective dose can be up to 1,000 mg twice per day but is often 850
mg twice per day. Modestly greater effectiveness has been observed with doses up
to about 2,500 mg/day. Gastrointestinal side effects may limit the dose that can be
used.
5. Based on cost considerations, generic metformin is the 1st choice of therapy. A
longer-acting formulation is available in some countries and can be given once per
day.
56
Table 9 Non-Insulin Agents for Diabetes Mellitus Type 2
Biguanides
Mechanism
of Action
Oral
Sulfonylureas
↑ insulin
secretion
Side Effects
↓BG
GI
Effect on Fasting
Plasma Glucose
Effect on A1C
lowers
60-70mg/dl
lowers
1-2%
N/A
Effect on Weight
Advantages
Alphaglucosidase
Inhibitors
↓ digestion
of CHOs in
small
intestines
TZDs
Meglitinide
GLP-1
Agonist
Amylin
Agonist
DPP-4
Inhibitor
↑ muscle,
fat, and liver
sensitivity
to insulin
↑ insulin
secretion
↓ gastric
motility,
inhibit
glucagon
production
↑ insulin
secretion,
↓ glucagon
secretion
GI
fluid
retention
↓BG
↑ insulin
secretion,
↓ glucagon
secretion,
↓ gastric
motility
GI1, ↑
pancreatitis
reported
lowers
60-70mg/dl
lowers
1-2%
 LDL, TG
 HDL
lowers
20-30mg/dl
lowers
0.5-0.8%
N/A
lowers
60-70 mg/dl
lowers
0.5-1.5%
N/A
lowers
15-20 mg/dl
lowers
0.5-1%
N/A
data
unavailable
lowers
0.5-1%
data
unavailable

rapidly
effective
neutral
↓BG is rare
neutral
↓BG is rare

rapidly
effective
↓
↓BG is rare
↓
↓BG is rare
Disadvantages
Severe
hypoglycemia
possible
GI effects
can limit
dosing
tid dosing,
expensive,
↑GI effects
tid dosing,
expensive
Price
$-$$$
$$-$$$$
$$$$$+
lowers
35-40 mg/dl
Lowers
0.5-1.4%
 TG,
 HDL,
LDL

improved
lipid profile,
↓BG is rare
↑CHF risk,
adipose
tissue, bone
fractures,
possibly MI
$$$$$$+
bid injections,
↑GI effects,
expensive,
?long-term
safety
$$$$$$$
Effect on Lipids
↓ hepatic
glucose
output
$$$$$$$
GI3
↑ respiratory
infection,
pancreatis
reported
lowers
20mg/dl
lowers
0.5-0.8%
data unavailable
neutral
tid injections, ?long term safety,
↑GI effects,
expensive
?long term
safety,
expensive
$$$$$$$
$$$$$$$
Abates with time of therapy
CHOs – carbohydrates, TZDs – thiazolidinediones, TG = triglycerides, LDL = low-density lipoprotein, HDL = high-density lipoprotein
1
57
Table 10 Comparison Chart of Orally Administered Hypoglycemic Agents
First Generation
Oral Sulfonylureas
Chlorpropamide*
Starting Dose
(mg/day)
Dosing Range
100-250 mg
# Daily Doses
1
Elimination
Half-life
Onset
Comments
Pregnancy
Category
Contraindication
100-500 mg
Glipizide
(Glucotrol,
(Glucotrol® XL)
2.5-5 mg
5-40 mg
XL 20 mg
1-2 (divide if
dose >15 mg)
Second Generation
Oral Sulfonylureas
Glyburide (Diabeta,
Glynase1, Pres Tab1)
Biguanides
Glimepiride
(Amaryl)
1.25-5 mg
micronized 0.75-3 mg
1.25-20 mg
micronized 0.75-12 mg
1-2 (divide if dose >10
mg [6 mg micronized])
1-2 mg
renal, fecal
10 hours
micronized 4 hours
15-60 minutes
peak 2-4 hours
renal, fecal
5-9 hours
1-8 mg
1
renal
36 hours
renal, fecal
2-5 hours
1 hour
peak 3-6 hours
peak 1-3 hours
XL 6-12 hours
Take 30 min before
meals
Take 30 min
before meals,
XL with
breakfast
Take with meals at the
same time each day
Give with
1st main
meal
C
C
C
Type 1 DM, DKA
Type 1 DM,
DKA
B/C
(vary by manufacturer)
Type 1 DM, DKA,
concomitant use with
bosentan
peak
2-3 hours
DKA
Metformin
(Glucophage)
(Glucophage XR)
850-1000 mg
XR 500 mg
1000-2550 mg
XR 2000 mg
2-3 (3 if dose >2000
mg)
XR: 1-2
renal
4-9 hours
peak
2-3 hours
XR 4-8 hours
Take with meals at
same time each day, do
not crush/break/chew
XR, monitor CBC &
renal function
B
SCr >1.5 mg/dl males,
>1.4 mg/dl, abnormal
CrCl, metabolic
acidosis
Alpha-glucosidase
Inhibitors
Acarbose
Miglitol

(Precose )
(Glyset)
25-75 mg
75 mg
75-300 mg
75-300 mg
3
3
fecal, renal
2 hours
renal
2 hours
peak
1 hour
peak
2-3 hours
Give with
first bite of
meal
Give with
first bite of
meal
B
B
IBD, DKA, IBD, DKA,
cirrhosis,
colonic
colonic
ulceration,
ulceration,
intestinal
intestinal
obstruction
obstruction
Non-formulary agent
Micronized formulation – not bioequivalent to conventional glyburide tablets
IBD – Inflammatory Bowel Disease, DKA – Diabetic Ketoacidosis
*
1
58
Table 10 Comparison Chart of Orally Administered Hypoglycemic Agents, cont.
Starting Dose
(mg/day)
Dosing Range
# Daily Doses
Elimination
Half-life
Onset
Comments
Pregnancy
Category
Contraindication
Thiazolidinediones
(TZD)
Pioglitazone
Rosiglitazone

(Actos )
(Avandia)
15-30 mg
4 mg
15-45 mg
1
renal, fecal
4-8 mg
1-2 (divide if dose
>4 mg)
renal, fecal
3-7 hours (parent)
3-4 hours
16-24 hours (total)
delayed
delayed
peak 2 hours
peak 1 hour
Obtain liver
Obtain liver
enzymes at
enzymes at
initiation and
initiation and
periodically during periodically during
treatment, take
treatment, take
with or without
with or without
food
food
C
C
NYHA Class
III/IV HF –
initiation of
therapy
NYHA Class
III/IV HF –
initiation of
therapy
Meglitinides
Repaglinide
(Prandin)
1.5-6 mg
Nateglinide
(Starlix)
180-360 mg
Dipeptidyl Peptidase
(DPP-4)Inhibitor
Sitagliptin
(Januvia®)
100 mg
1.5-12 mg
2-4
180-360 mg
2-4
25-100 mg
1
fecal, renal
renal, fecal
renal, fecal
1 hour
1.5 hours
12 hours
15-60 minutes
peak 1 hour
Take 15-30 min
before meals –
skip dose if skip
meal, if meal
added, add dose
20 minutes
peak 1 hour
Take 1-30 min
before meals –
skip dose if skip a
meal; if meal
added, add dose
peak
1-4 hours
Take with or without
food
C
C
B
Type 1 DM,
DKA, concurrent
gemfibrozil use
Type 1 DM, DKA
Type 1 DM, DKA
HF – heart failure, DM – diabetes mellitus, DKA – diabetic ketoacidosis, IBD – inflammatory bowel disease
59
Table 11 Insulin Products Comparison
Brand
Generic
Rapid Acting
HumaLOG®
Lispro
®
*NovoLOG
Aspart
Short Acting (Only insulin that can be given IV/IM)
HumuLIN® R
Regular
®
*NovoLIN R
Intermediate Acting
HumuLIN® N
NPH
*NovoLIN® N
Long Acting
Lantus®
Glargine
*Levemir
Detemir
Mixtures
HumuLIN® 70/30 70% NPH/30% regular
*NovoLIN®
insulin
70/30
HumaLOG®
50% lispro protamine/50%
Mixture 50/50
lispro
®
*HumaLOG
75% lispro protamine/25%
Mixture 75/25
lispro
®
70% aspart
*NovoLOG
Mixture 70/30
protamine/30%aspart
Onset (hr)
Duration (hr)
Comments
0.25 - 0.5
0.2 - 0.3
<5
3-5
Administer 30 min. before meals; clear and colorless
SQ 0.5 - 1
4 - 12
Administer 30-60 min. before meals; clear and
colorless
1-2
14 - 24
3-4
3-4
10.8 - >24
6 - 23
0.5
18-24
Administer 30-45 min. before meal; cloudy suspension;
do not mix with other insulin
0.25-0.5
14-24
0.25-0.5
14-24
0.1-0.2
18-24
Administer 15 min. before meals; cloudy suspension;
Cloudy suspension
Clear suspension; Do not mix with any other insulin
Clear suspension; Do not mix with any other insulin
*Formulary Agent
SQ – Subcutaneous
Adapted from:
1. UK Prospective Diabetes Study Group: Intensive blood-glucose control with sulfonylureas or insulin compared with conventional treatment and risk of complications in type 2
diabetes (UKPDS 33). Lancet. 1998; 352: 837-53.
2. UK Prospective Diabetes Study Group: Effect of intensive blood-glucose control with metformin on patients with type 2 diabetes (UKPDS 34). Lancet. 1998; 352: 854-65.
3. Nathan DM, Buse JB, Davidson MB, et al.: Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a
consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009;32:193-203.
4. American Diabetes Association: Standards of Medical Care in Diabetes – 2010. Diabetes Care. 2010;33 (supplement 1):S11-61.
5. Lexi-Comp® Online [Intranet database]. Hudson, OH: Lexi-Comp, Inc
60
Diabetic Ketoacidosis (DKA) Management
Patient Assessment and Initial Work Up:
1. History and physical exam with emphasis on the following:
a. Precipitating factors (infection, omission or inadequate use of insulin,
new onset diabetes, etc)
b. Airway patency
c. Level of consciousness
d. Volume status
2. Initial work up includes the following:
a. Blood chemistries
b. Blood glucose (finger stick)
c. Blood and urine ketones
d. CBC with differential
e. ABG
f. Urinalysis
g. If appropriate, obtain chest film, ECG, and blood cultures to evaluate the cause
while patient is being hydrated.
3. Diagnosis
a. Hyperglycemia (serum glucose > 250 mg/dL)
b. Low bicarbonate (HCO3 < 15 mEq/L)
c. Low pH (pH < 7.3)
d. Ketonemia 1:2 dilution
e. Ketonuria: moderate
61
Protocol for DKA managment
62
Protocol for management of HHS
Kitabchi AE, Umpierrez GE, Murphy MB, et al. Hyperglycemic crises in diabetes. Diabetes Care 2006
Dec; 29 (12): 2379-2748
63
Prevention of Bacterial Endocarditis
Endocarditis prophylaxis recommended only for:
- high risk categories listed below PLUS
- dental procedures that involve manipulation of the gingival tissue
or the periapical region of teeth or perforation of the oral mucosa
 High risk categories
1. Prosthetic cardiac valve or prosthetic material used for cardiac valve
repair
2. Previous bacterial endocarditis
3. Congenital heart disease (CHD)
- Unrepaired cyanotic CHD, including palliative shunts and conduits
- Completely repaired congenital heart defect with prosthetic
material or device, whether placed by surgery or by catheter
intervention, during the first 6 months after the procedure
- Repaired CHD with residual defects at the site or adjacent to the
site of a prosthetic patch or prosthetic device (which inhibit
endothelialization)
4. Cardiac transplantation recipients who develop cardiac valvulopathy
 Endocarditis prophylaxis not recommended for:
- Any other form of CHD not listed above
- GI or GU procedures
64
Prophylactic regimens for dental procedures
Situation
Medication
Regimen
Oral
Amoxicillin
2 gm PO 1 hour before procedure
Unable to take oral
Ampicillin
2 gm IM or IV
medications
or
Cefazolin or 1 gm IM or IV
ceftriaxone
30 min before procedure
Penicillin allergy--oral
Cephalexin
2 gm PO 1 hour before procedure
Clindamycin 600 mg PO 1 hour before procedure
Azithromycin 500 mg PO 1 hour before procedure
or
Clarithromycin
Penicillin allergic and
Cefazolin or 1 gm IM or IV 30 min before
unable to take PO
ceftriaxone
procedure
medications
Clindamycin 600 mg IM or IV 1 hour before
procedure
Adapted from Wilson W, Taubert KA, Gewitz M, Lockhart PB, Baddour LM, et al. Prevention of infective
endocarditis. Circulation 2007;116:1736-1754.
65
Drug Treatment for Fungal Infections
For the latest guidelines please refer to: http://www.idsociety.org
Empiric Treatment for suspected candidal infections may be considered in febrile
patients with the following risk factors:
 Prolonged use of antibacterial antibiotics
 Immunosuppression
 Colonization by candida of multiple nonsterile sites
 Central venous catheters
 Hyperalimentation
 Surgery (especially surgery that transects the gut wall)
 Prolonged ICU stay
 Urinary tract instrumentation
 Advanced Age
Typical Antifungal Doses
Antifungal
Fluconazole
Itraconazole
Voriconazole*
Posaconazole#
Caspofungin
(NF)
Daily Dose (range)
Dose Adjustment with
Renal Impairment
IV or PO: 400 mg (200-800) Administer 50% of dose
for CrCl < 50 ml/min.
200 mg (100-400)
Intravenous use not
recommended with a CrCl
< 30 ml/min
IV:6 mg/kg q12h x 2 doses, Intravenous use not
then 4 mg/kg q12h
recommended with a CrCl
PO: 200 mg bid
< 30 ml/min
200 mg tid
70 mg x 1, then 50 mg daily
No
No
Dose Adjustment with
Hepatic Impairment
No
No
Moderate hepatic
insufficiency: reduce
maintenance dose by
50%
No
Moderate hepatic
insufficiency: initial
loading dose of 70mg
then 35 mg/day
No
No
Amphotericin B 0.5 mg/kg (0.25-1.5)
No
Amphotericin B 5 mg/kg
No
lipid complex
Anidulafungin
IV: 200mg x1 then 100mg
No
No
(NF)
daily
Micafungin□
50 mg-150 mg IV daily
No
No
*
Restricted to ID, Critical Care/Pulmonary, and Heme/Onc
#
Restricted to ID and Heme/Onc
□Restricted to Attending physicians in the subspecialty groups of Infectious Disease,
Pulmonary/Critical Care, Solid Organ Transplant, and Hematology/Oncology
66
References:
1. Pappas PG, et al. Clinical Practice Guidelines for the Management of Candidiasis. 2009 Update by the
Infectious Disease Society of America. CID 2009; 48:503-535.
2. O’Grady, et al. Practice Guidelines for evaluating new fever in critically ill adult patients. CID 1998;
26:1042-59.
3. Slain DS, et al. Intravenous itraconazole. Ann Pharmacother 2001; 35:720-729.
4. Prescribing Information. Http://www.sporanox.com
67
Acute Ischemic Stroke Guidelines
1.
2.
Fever is associated with increased morbidity/mortality. The source of any
fever following stroke should be ascertained and treated with antipyretics.
Optimal management of hypertension remains controversial. Blood pressure
may fall spontaneously if patient is allowed to rest in a quiet room, bladder
is emptied, and headache or pain controlled. There is no proven benefit for
lowering blood pressure in patients with acute ischemic stroke, and
antihypertensive agents should be withheld unless DBP > 120 or SBP
>220 mmHg. When treatment of blood pressure is necessary, a reasonable
goal would be to lower blood pressure by ~15% during the first 24 hours. In
particular, “prn” orders for oral antihypertensives should be avoided.
Consider one of the following options:
 Labetalol 10-20 mg IV prn SBP >220 OR DBP>120. May repeat or
double dose every 10 min until max. of 300 mg OR Labetalol 10 mg IV
followed by an infusion of 2-8 mg/min to achieve 15% reduction in BP
 Nicardipine 5 mg/hour IV infusion. Titrate by 2.5 mg/hr every 5 min. to
max. of 15 mg/hr until 15% reduction in BP (NOTE: cost ~ $300 per
day!)
 If DBP>140: Nitroprusside 0.25 mcg/kg/min IV infusion, titrate to
achieve a 15% reduction in BP.
 In patients who have preexisting hypertension and are neurologically
stable, antihypertensive medications should be restarted at ~24 hours
unless a specific contraindication exists.
 Criteria for use of IV rtPA 0-3 hours after stroke onset and 3-4.5 hours
after stroke onset are listed below per protocol. Potential complications
of IV rtPA include bleeding and angioedema. If the patient posseses ALL
of the inclusion criteria and NONE of the exclusion criteria, IV alteplase
therapy should be considered. These Inclusion/Exclusion Criteria may
need to be adapted to meet the needs of a specific patient.
0-3 hours after stroke onset
INCLUSION
EXCLUSION






Age greater than or equal to 18 years
Clinical diagnosis of ischemic stroke
causing a measurable neurological deficit
Clinical diagnosis of ischemic stroke by
MD
Non-contrast CT of head assessed by MD
Time of onset of stroke less than 3 hours


Symptoms minor or rapidly improving
(NIHSS < 4, except isolated aphasia or
isolated hemianopsia)
Non-contrast CT of head demonstrating
intracranial hemorrhage
recent multilobar infarction (hypodensity
more than 1/3 of middle cerebral artery
68














territory) or mass effect
Seizure at onset of stroke
Other stroke or serious head trauma within
past 3 months
Major surgery or serious trauma within last
14 days
Known history of intracranial hemorrhage
Bacterial endocarditis or percarditis
History of myocardial infarction within 3
months
Sustained SBP > 185 mmHg or DBP > 110
mmHg despite pharmacological
intervention.
Symptoms suggestive of subarachnoid
hemorrhage
Gastrointestinal or urinary tract
hemorrhage within 21days
Arterial puncture at noncompressible site
or spinal tap within 7 days
Received heparin within 48 hours with
PTT > mean control value
Current use of anticoagulants with PT > 15
seconds or INR > 1.7
Platelet count < 100,000/mm³
Blood glucose < 50mg/dl or > 400 mg/dl
3-4.5 hours after stroke onset
INCLUSION
EXCLUSION






Age 18 to 80 years
Clinical diagnosis of ischemic stroke
causing a measurable neurological deficit
Clinical diagnosis of ischemic stroke by
MD
Non-contrast CT of head assessed by MD
Time of onset of stroke between 3 and 4.5
hours







Symptoms minor or rapidly improving
(NIHSS < 4 except isolated aphasia or
isolated hemianopsia).
NIHSS score greater than 25
intracranial hemorrhage
recent multilobar infarction (hypodensity
more than 1/3 of middle cerebral artery
territory) or mass effect
Seizure at onset of stroke
Other stroke or serious head trauma within
past 3 months
Combination of previous stroke and
diabetes mellitus
Major surgery or serious trauma within
69











3.
4.
5.
6.
7.
8.
9.
10.
past 3 months
Known history of intracranial hemorrhage
Bacterial endocarditis or pericarditis
History of myocardial infarction within 3
months
Sustained SBP > 185 mmHg or DBP > 110
mmHg despite pharmacological
intervention.
Symptoms suggestive of subarachnoid
hemorrhage
Gastrointestinal or urinary tract
hemorrhage within 21 days
Arterial puncture at noncompressible site
or spinal tap within 7 days
Received heparin within 48 hours with
PTT greater than mean control value
Oral anticoagulant treatment
Platelet count < 100,000/ mm³
Blood glucose < 50 mg/dl or > 400 mg/dl
Use of intra-arterial thrombolysis is an option for patients with major stroke of less than 6
hours duration due to large vessel occlusions of the MCA. Use in patients with basilar
artery occlusion should be individualized.
Evidence indicates that persistent hyperglycemia (>140 mg/dL) during the first 24 hours
after stroke is associated with poor outcomes, and thus hyperglycemia should be treated
in patients with acute ischemia stroke.
Low dose subcutaneous heparin or LMWH or IPC is strongly recommended to prevent
DVT in immobilized patients (grade A recommendation).
Published guidelines specifically state that anticoagulation with full doses of heparin or
LMWH is NOT recommended for patients with acute ischemic stroke (grade A).
ASA 325 mg should be given within 24-48 hours after stroke onset.
The administration of clopidogrel alone or in combination with aspirin is not
recommended for the treatment of acute ischemic stroke.
Early mobilization and comprehensive rehabilitation measures are strongly
recommended.
Corticosteroids are not recommended for the management of cerebral edema and
increased ICP following ischemic stroke.
Parenteral anticoagulation should not be prescribed until a brain imaging study has excluded the
possibility of a primary intracranial hemorrhage. The level of anticoagulation should be closely
monitored if a patient is receiving one of these medications.
Stroke. 2007;38:1655-1711
70
Guidelines for Pain Management
Non-opioid analgesics (e.g., acetaminophen, NSAIDs) are useful in both acute and
chronic pain. They are recommended in most analgesic regimens for patients unless
the patient has a contraindication to using them.1
 Acetaminophen
o Little/no anti-inflammatory effect and does not damage the gastric mucosa1
o Food and Drug Administration (FDA) maximum recommended dose is 4
grams/day2
o Based on recent evidence, the American Liver Foundation recommends a
maximum dose of 3 grams/day3
o Not recommended in neutropenic patients
 NSAIDs1 (Examples include: ketorolac, ibuprofen, naproxen, and ketoprofen)
o NSAIDs may cause gastrointestinal disturbances including nausea, vomiting,
heartburn, heartburn, dyspepsia, ulceration, GI bleed
o In patients where protection against ulcers is warranted, consider a proton
pump inhibitor
o Use the lowest possible dose for the shortest amount of time
 Ketorolac (Toradol®) use should be limited to 5 days because of
increased risk for GI hemorrhage
o NSAIDs can induce renal insufficiency; monitor use in patients with renal
dysfunction
Add an opioid analgesic to a non-opioid in a patient with acute, chronic cancerrelated or chronic non-cancer pain if the pain is not controlled.1
 Some opioids are available in combination with non-opioids (e.g, oxycodone with
acetaminophen)
CAUTION: be vigilant of the amount of acetaminophen being consumed by the
patient (i.e. combination opioid products, over-the-counter cough/cold products
and other acetaminophen containing products)
 All opioids are metabolized by the liver and are generally cleared through the
kidneys. Opioids should be used with caution in patients with moderate-to-severe
liver impairment, impaired ventilation, bronchial asthma, increased intracranial
pressure, moderate-to-severe renal impairment and paralytic ileus.
The route, dosage, and schedule of the analgesic needs to be individualized.1
 Opioids are available in a variety of formulations and may be administered by a
variety of routes. Routes of administration include oral, buccal/transmucosal,
sublingual, intramuscular, intravenous, subcutaneous, epidural, intrathecal,
transdermal, topical, and rectal.
 The oral route is preferable for analgesic administration (oral, transmucosal and
sublingual).
 The intramuscular route has the disadvantages of painful administration and wide
fluctuations in absorption.
 The intravenous route provides a most rapid onset for analgesia in about 5 minutes.
Intravenous infusion route may be used to provide steady state blood concentrations
71





of opioids and may be helpful in chronic pain conditions. Use extreme caution in
opioid-naïve patients.
The subcutaneous route provides analgesia similar to intravenous administration.
Epidural and intrathecal administration of opioids may be required in those patients
with pain syndromes unable to be controlled by conventional methods. Uses of these
routes of administration are usually managed by anesthesiology.
Transdermal route provides effective analgesia for patients with chronic pain. Due to
the extended half-life of the transdermal fentanyl patch (t1/2 17 hrs) it is not intended
for management of acute pain. (see fentanyl conversions for further information)
 fentanyl patch (Duragesic®)
Rectal administration is the least favored option but can be useful in providing
patients with a steady serum concentration of opioids when other alternatives are
exhausted.
PCA: See PCA protocol on pages 19 and 23 of the therapeutics manual.
If the pain is present most of the day, then analgesics should be administered on a
regular basis (not PRN).1
 Around-the-clock opioid adminstration provides better pain control when pain
persists for an extended period of time.
 a PRN order for a supplementary opioid should be used if necessary for breakthrough
pain
 Opioid titration should be individualized and adjusted to patient tolerance or
emergence of adverse effects.
Familiarize yourself with dose and time course of opioids1
 Sustained release regimens: To determine a sustained-release regimen, treat patient
for 24-48 hours with an immediate-release opioid to determine the total daily dose of
opioid required. Once the total daily dose of opioid is determined, prescribe 2/3 of
the total daily opioid dose as sustained release preparation and provide the remainder
of the dose as PRN immediate-release opioid.
To change to a new opioid or different route, use the opioid equianalgesic table and
instructions for conversions between opioids.
Be able to recognize and treat the side effects of opioids.1
 The most common side effects of opioids include sedation, constipation, nausea,
vomiting, itching, respiratory depression (especially in opioid naïve patients) and
pinpoint pupils. Patients generally gain tolerance to most opioid-induced adverse
effects following several days of therapy with the exception of constipation and
pinpoint pupils.
 Ways to manage side effects include:
o Change the dosing regimen or route of the drug in order to aim for more
constant blood levels
o Use a different opioid
o Use multidrug and multimodal therapy
72

o
o
o
o
o
E.g., utilize an NSAID or an adjunct medication in order to reduce the
dose of the opioid
 Use another drug that counteracts the adverse effect of the opioid
Sedation
 May be partially counteracted with a stimulant for patients receiving
chronic opioid therapy (e.g., caffeine, dextroamphetamine, or
methylphenidate).
Constipation (Patients NEVER gain tolerance to this adverse effect).
 Ensure that patient is on an appropriate bowel prophylaxis regimen, a
stimulant +/- softner is generally recommended. **A stool softener
alone is not sufficient **
Nausea and Vomiting
 Consider rotating to another opioid OR
 For opioid induced nausea and vomiting consider adding a
phenothiazine (prochlorperazine) or prokinetic agent
(metoclopramide)
 For motion-exacerbated nausea (due to vestibular disturbance)
consider an antiemetic with antihistamine properties such as meclizine
or scopolamine
 For more severe or uncontrolled nausea consider a 5HT3
antagonist (e.g., ondansetron)
Itching
 Consider rotating to another opioid OR
 Manage with antihistamines (e.g., diphenhydramine, promethazine,
hydroxyzine, loratadine)
Respiratory depression
 Typically most common in opioid naïve patients, occurs rarely in
patients with chronic use of opioids
 Monitor patient closely for respiratory depression and if needed, use
an opioid antagonist (e.g, naloxone)
Meperidine is NOT recommended for chronic use in pain management and should
generally be avoided in elderly patients and patients with renal insufficiency.
Be aware of the potential risks of psychomimetic effects with mixed agonistantagonists (e.g., pentazocine).1
Adjunctive agents
 Glucocorticoids (e.g, dexamethasone)1
o May decrease pain caused by edema or bone pain due to metastases
 Bisphosphonates such as pamidronate and zoledronate and radionuclides such as
strontium may be useful as adjuncts for metastatic bone pain1
 Anticonvulsants1
o Useful in neuropathic pain states (e.g., postherpetic neuralgia and trigeminal
neuralgia)
73





o Examples include gabapentin, pregabalin, phenytoin, carbamazepine, sodium
valproate, clonazepam, topiramate, oxycarbazapine, lamotrigine, and
zonisimade
Tricyclic antidepressants1
o May be useful in diabetic neuropathy and postherpetic neuralgia
o Relatively contraindicated in patients with coronary artery disease because
they can worsen arrhythmias
o Examples include nortriptyline, desipramine, amitriptyline, and imipramine
SNRI (Serotonin/norepinephrine reuptake inhibitor)4
o Examples include Cymbalta® (duloxetine) and Effexor® (venlafaxine)
 May be useful for the management of neuropathic pain
Local anesthetics (e.g., EMLA cream, lidocaine patches)1
o EMLA cream (lidocaine and prilocaine) may be useful for topical dermal
anesthesia or post-herpetic neuralgia
o Topical lidocaine patches may be useful for postherpetic neuralgia
Skeletal muscle relaxants/antispasmodic agents (e.g., carisoprodol, cyclobenzaprine)1
o May be useful for acute muscle injury
Topical Agents (e.g., capsaicin)1
o May be useful in peripheral neuropathic pain and arthritic pain
o Most patients are NOT able to tolerate the burning sensation associated with
application of this medication
Terminology:1
 Tolerance:
 A state of adaptation in which being exposed to a drug induces changes that cause
a decrease in one or more of the drug’s effects over the course of time
 Physical dependence:
 A state of adaptation in which withdrawal symptoms may occur after abruptly
stopping, quickly decreasing the dose, decreasing the blood level of a drug, and/or
by administering an opioid antagonist. Withdrawal symptoms may be prevented
by slowly tapering a patient off of the opioid.
o Symptoms of withdrawal include anxiety, tachycardia, and sweating
 Dependence is NOT addiction and this natural phenomena can occur with other
classes of medications (e.g., antihypertensives)
 Addiction: Continued use of a medication despite harm (to self or others)
 A chronic, neurobiologic disease with genetic, psychosocial, and environmental
factors that influence its manifestations
 Behaviors involved include: impaired control of drug use, compulsive use of the
drug, craving of the drug, and drug-seeking behavior
 Pseudoaddiction
o A term used to describe behaviors that a patient may exhibit when their
pain is under treated.
o These behaviors generally resolve when a patient’s pain is effectively
treated.
74
References:
1. Principles of analgesic use in the treatment of acute pain and cancer pain.
American Pain Society. Fifth edition.
2. Letter from the Department of Health and Human Services. October 2005.
www.fda.gov. Accessed August 24, 2007.
3. American Liver Foundation Issues Warning on Dangers of Excess
Acetaminophen. http://www.liverfoundation.org/about/news/33/ Accessed
August 22, 2007.
4. Adapted table from: principles of analgesic use in the treatment of acute pain and
cancer pain. American Pain Society. Fifth edition.
75
Table 1: Selected Opioids that are morphine-like agonists4
Opioid
Oral
Parenteral
Precautions/Contraindications
equianalgesic
equianalgesic
dose (mg)
dose (mg)
Morphine
30
10
-May accumulate in renal
impairment-has active
metabolites
Hydromorphone 7.5
1.5
impairment-NO active
metabolites
Oxycodone
20
Not applicable
impairment-has some active
metabolites
Methadone*
Not applicable
Not applicable
-Dose titration should be done
Contact
Contact
cautiously-takes about 4-5 days
pharmacy for
pharmacy for
to reach steady state levels
dosing
dosing
-Caution in older adults
Oxymorphone
10
Not applicable
impairment-has some active
metabolites
* Dosing is dependent on individual patient characteristics.
 Tramadol is a weak opioid agonist that also inhibits the reuptake of serotonin and
norepinephrine. Tramadol lowers the seizure threshold; therefore, do not use in
doses greater than 400 mg per day.1
 Fentanyl is available in a transdermal patch, lozenge, buccal tablet, iontophorectic
transdermal system, and IV formulations. The patch is not intended for acute pain
which includes post-operative pain.1
76
Therapeutic Drug Monitoring
DRUG
Amikacin
SAMPLING
TIME
Trough:
30 minutes
before the dose
Peak: 30 minutes
after the infusion
has ended
Carbamazepine Trough
concentration
Digoxin
6 h after dose
Gentamicin
Lidocaine
THERAPEUTIC
RANGE
Trough:
4-8 mcg/ml
Peak:
15-30 mcg/ml
MAJOR
SERUM
COMMENTS
ROUTE OF
HALF
ELIMINATION LIFE (nl)
Renal: 100%
1.5-3 h
Persistent high levels may
increase incidence of
ototoxicity and
nephrotoxicity.
4-12 mcg/ml
Hepatic: 99%
8-20 h
Renal: 75-85%
Hepatic: 15%
Renal: 100%
36-44 h
1.5-3 h
ototoxicity and
nephrotoxicity.
Hepatic: > 90%
Renal: < 10%
1.2-2.2 h
Protein binding changes in
MI leads to elevated
concentration; metabolite
accumulates in renal
failure.
CHF: 0.5-0.8 ng/ml
Afib: 0.5-2.0 ng/ml
Trough:
Trough:
0.5-2 mcg/ml
30 minutes
Peak:
before the dose
Peak: 30 minutes 3-10 mcg/ml
after infusion
has ended
6-24 h after start 1.5-5 mcg/ml
of infusion
Active metabolite is
eliminated renally.
77
DRUG
SAMPLING
TIME
Lithium
12 h after evening
dose
Phenobarbital
Trough
concentration
Phenytoin
Trough
concentration
Procainamide
(PCA)
1 h after loading
dose then every
24 h until stable
Quinidine
Trough
concentration
THERAPEUTIC
RANGE
Acute mania:
0.6-1.2 mEq/L
Bipolar:
0.8-1 mEq/L
Adults:
20-40 mcg/ml
Infants/children:
15-30 mcg/ml
Adults/children:
10-20 mcg/ml
Neonates:
8-15 mcg/ml
Free level 1-2
mcg/ml
PCA:
4-10 mcg/ml
NAPA:
15-25 mcg/ml
2-5 mcg/ml
MAJOR
SERUM
COMMENTS
ROUTE OF
HALF
Renal: 90%
14-28 h
Fluid and electrolyte
manipulations may cause
variations in steady-state
concentrations.
Hepatic: 80%
60-150 h Half-life is decreased in
Renal: 20%
children and is elevated in
cirrhosis, elderly, and by
valproic acid.
Therapeutic range for total
Hepatic: >95%
Dose &
concentra- phenytoin concentration
decreases in ESRD and
tion
dependent hypoalbuminemia.
Renal: 50%
Hepatic: 50%
2.5-5 h
Hepatic: 60-80%
Renal: 10-30%
5-7 h
Active metabolite, NAPA,
is eliminated in urine 90%
unchanged. NAPA
accumulates in renal
failure.
Hepatic cirrhosis & CHF
decrease clearance;
phenobarbital and
phenytoin increase
clearance.
78
DRUG
SAMPLING
TIME
Theophylline
IV: 30 min after
load, then 12-18 h
after maintenance
PO: Trough conc.
Tobramycin
Trough:
30 minutes before
the dose
Peak: 30 minutes
after the infusion
has started
Trough
concentration
Valproic acid
Vancomycin
Trough:
immediately
before dose
THERAPEUTIC
RANGE
MAJOR
SERUM
ROUTE OF
HALF
6-8 h
COPD and asthma Hepatic: > 90%
Renal: < 10%
5-15 mcg/ml
Neonatal apnea:
6-13 mcg/ml
Pregnancy:
3-12 mcg/ml
Renal: 100%
1.5-3 h
Trough:
< 0.5-2 mcg/ml
Peak:
3-10 mcg/ml
Epilepsy:
50-100 mcg/ml
Mania:
50-125 mcg/ml
Hepatic: 95%
10 h
Trough:
10-20 mcg/ml
Renal: 90%
2.5-6 h
COMMENTS
Half-life is influenced by
factors affecting hepatic
enzymes.
ototoxicity and
nephrotoxicity.
Carbamazepine and
phenytoin decrease halflife; protein binding is
dependent on serum
concentration.
Monitor trough for possible
accumulation in renal
failure. Avoid checking
peak concentrations
(frequent errors).
79
Methodist Healthcare – Memphis Hospitals
Therapeutics Manual
Opioid Analgesic Dose Equivalents Table and Examples Update
Opioid Equianalgesic Dosing for Select Opioids
Used in Moderate to Severe Chronic Pain in Adults1,2
Opioid
Common Proprietary
Starting
Usual Dosing
Oral
Parenteral
Names
Dose (PO)
Interval (hrs) Equianalgesic
Equianalgesic
Dose (mg)
Dose (mg)
3–4
Morphine
Immediate release:
MSIR, Roxanol®
8 – 12
Sustained release:
MSContin®, Kadian®,
and Avinza®
15 – 30 mg
12 – 24
30
10
®
Lortab (combination
5 – 10 mg
30
N/A
Hydrocodone
w/acetaminophen)
4–6
20
N/A
Oxycodone
Immediate release:
®
®
OxyIR , Roxicodone ,
10 – 20 mg
4–6
OxyFast®, Percocet®
(combo with
acetaminophen)
Sustained release:
OxyContin®
10 – 20 mg
8 – 12
4 – 8 mg
PO: 3 – 6
7.5
1.5
HYDROmorphone Dilaudid®
IV: 2 – 3
10
1
Oxymorphone
Immediate release:
Opana®
5 – 10 mg
4–6
Sustained release:
5 – 10 mg
Opana ER®
12
®
* Meperidine (Demerol ) is NOT recommended by the American Pain Society for management of chronic pain
due to accumulation of the toxic metabolite, normeperidine.
Please Note:


When converting scheduled doses of opioids, decrease the amount of the new doses by at least 25 –
50 % to account for incomplete cross-tolerance. Reduction is not necessary when converting PRN
doses.
Always provide patients with long-acting pain medications a breakthrough or rescue dose of a
short-acting pain medication.
The following formula may be used to convert between certain opioids:
Cross multiply and solve for X (TDD of new opioid).
Example Calculations:
80
Example 1: Pt was getting morphine 2 mg IV every 2 hrs PRN (using about 8 doses per day) for pain. Calculate
an equivalent dose of PRN oxycodone for the patient.
Step 1: Calculate the TDD of opioid used in the last 24 hrs.
Answer: 2 mg x 8 = 16 mg IV morphine
Step 2: Check the chart for the equianalgesic dose for IV morphine to ORAL oxycodone.
Answer: 10 mg IV morphine is equal to 20 mg PO oxycodone
Step 3: Use the equation to solve for the TDD of the new opioid, X.
=
X = 32 mg PO oxycodone (TDD)
Step 4: Divide the TDD into the appropriate frequency of administration.
Answer: The drug may be given every 2 – 6 hrs (either OxyIR® or Percocet®). An appropriate dose would be
oxycodone 5 mg PO every 4 hours PRN pain.
Example 2: The patient’s pain was well controlled with MS Contin 30 mg PO every 8 hours with MSIR 15 mg
PO every 2 hours PRN (using 3 doses per day) at home. New onset renal insufficiency admitted with mental
status changes. You recommend switching to oxycodone for continued pain control and less risk of metabolite
accumulation in renal insufficiency.
Step 1: Calculate TDD of PO morphine.
Answer: (30 mg x 3) + (15 mg x 3) = 135 mg PO morphine
Step 2: Use chart to determine equianalgesic dose of ORAL morphine to ORAL oxycodone.
Answer: 30 mg morphine = 20 mg oxycodone
Step 3: Plug values into equation and solve for X.
=
X = 90 mg PO oxycodone (TDD)
Step 4: Decrease the TDD by 25% to account for incomplete cross-tolerance of the opioids.
Answer: 90 – 25% (22.5 mg) = 67.5 mg
Round the dose down to a TDD 60 mg PO oxycodone
Step 5: Divide the TDD into the appropriate frequency of administration.
Answer: Sustained release oxycodone (OxyContin®) may be administered every 8 – 12 hrs. Give the dose as
either 30 mg PO every 12 hrs or 20 mg PO every 8 hours.
References:
1. Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain. American Pain Society.
Fifth edition. 2003.
81
Fentanyl Conversion
Transdermal Fentanyl Conversion
(Duragesic® 25, 50, 75, 100 mcg patch)
Duragesic® Equivalent
PO Morphine
(mg/24 hr)
(mcg/hr)
45-134
25
135-224
50
225-314
75
315-404
100
405-494
125
495-584
150
585-674
175
675-764
200
765-854
225
855-944
250
945-1034
275
1035-1124
300
Allow 12 to 16 hrs for patch to be effective.
Patches may be changed every 48 - 72 hrs.
Transmucosal fentanyl products have
duration of action of approximately 4 – 5
hrs.




Oral transmucosal fentanyl citrate (OTFC)
(Actiq®)
Actiq® is available in the following dosage strengths:
200, 400, 600, 800, 1200 and 1600 mcg
The usual starting dose is 200 mcg and a maximum of 2
doses may be given for each pain episode with no more
than 4 units used in a 24 hr period.
Transmucosal buccal tablet (Fentora®)
Fentora® tablet is available in the following dosage
strengths: 100, 200, 300, 400, 600 and 80 mcg
The usual starting dose is 100 mcg, an additional dose
may be given within 30 min if needed; maximum 2
doses per pain episode.
Transmucosal buccal film (OnsolisTM)
OnsolisTM is available in the following dosage
strengths: 200, 400, 600, 800, and 1200 mcg
The usual starting dose is 200 mcg, an additional dose
may be given per pain episode up to a maximum of 4
applications per day.
The manufacturer recommendations for conversion between the transmucosal lozenge and the
transmucosal buccal tablet are listed below:
Lozenge dose 200 – 400 mcg, then buccal tablet 100 mcg
Conversion to the buccal film from other transmucosal products should start at 200 mcg and may
be titrated to effect.
Oral transmucosal fentanyl products are NOT interchangeable and should never be substituted mcg
for mcg.
Oral transmucosal fentanyl products are intended for use as breakthrough pain medications for
patients with chronic pain and on long acting pain medications.
Reference: Lexi-Comp Online: Fentanyl. Last accessed on 4/22/10.
82
Pt. Name_________________
Date ____________________
FIN#____________________
MD_____________________
RPh:____________________
Fentanyl Transdermal Patch (Duragesic®) Pharmacist Checklist
Form should be completed prior to processing medication. If order is a continuation of
patients’ home medication and dose, do not complete form and proceed with order entry.
Verify that patient was still receiving fentanyl patch at home.
Instructions:
Complete one of the two sections below. For new fentanyl transdermal orders, complete
the “Starting Dose” section. For transdermal fentanyl dose increases, complete the "Dose
Increase” section. If the answer is “YES” to each question in the appropriate section,
proceed with order processing. If any question is marked “NO”, the physician must be
contacted. If the order will not be processed by pharmacy, inform nursing not to apply
patch.
Starting dose: If not a starting dose, move to “Dose increase” section.
YES
NO Is fentanyl transdermal being prescribed for chronic pain?
(Contraindicated for the management of acute, mild, post-operative, or
intermittent pain) If transdermal fentanyl prescribed for acute pain, inform
physician of the contraindication and that pharmacy may not process the
order.
YES
NO Is the patient opioid-tolerant? Opioid-tolerant is defined as patients
who have been taking, for a week or longer, the equivalent of (see Table B):
• Oral morphine 60 mg per day
• Oral oxycodone 30 mg per day
• Oral hydromorphone (Dilaudid) 8 mg per day
If transdermal fentanyl prescribed for patient who is not opioid tolerant, inform
physician of patient’s opioid intake and package labeling for opioid nontolerant patients. Recommend maximizing use of PRN medications and to
consider prescribing patch in future if patient meets opioid-tolerant definition.
YES
NO Is the prescribed transdermal fentanyl dose lower than or equal to the
calculated equianalgesic patch dose? (See “Dose Conversion Guidelines” for
instructions on how to calculate the transdermal fentanyl starting dose using
long-acting and PRN opioids.)
If answer is “NO,” contact physician and recommend lower dose of patch per
calculated in Table A. If starting dose is >100 mcg patch, contact clinical
pharmacy specialist on-call to verify calculations and dose.
Dose increase: For patients already receiving transdermal fentanyl.
YES
NO For dose increases after the initial patch, has there been at least 3
days since the patch was initially placed? For other dose increases, has
it been at least 6 days?
If the answer is “NO,” contact physician and suggest maximizing PRN
medications. Fentanyl transdermal has a 17 hour t½ and should not be titrated
more frequently than listed above. Contact the clinical pharmacy specialist oncall if there are specific questions.
Was Physician contacted? No Yes
___________________________________________________________________
If physician contacted, leave order clarification/telephone order in chart after discussion
with physician (D/C fentanyl, lower patch dose, etc.).
83
Dose Conversion Guidelines*
To convert patients from oral or parenteral opioids to transdermal fentanyl, use
the following steps:
1. Determine the opioid requirements from the previous 24 hours (including scheduled and
PRN opioid medications). Use the MAR to add the amount of PRN opioid doses the
patient has received.
2. If only one opioid (e.g. morphine) has been used over the last 24 hours, use Table A
below to determine the transdermal fentanyl requirements. If patient has received more
than one opioid (e.g. oxycodone plus hydromorphone, other combinations), use Table B
to determine the total daily oral morphine equivalents and then oral morphine in Table
A to determine the equianalgesic transdermal fentanyl dose.
Current
Analgesic
Oral morphine
IV morphine
Oral oxycodone
Oral codeine
Oral
hydromorphone
IV
hydromorphone
IV meperidine
Recommended
transdermal
fentanyl dose
TABLE A:*
Dose Conversion Guidelines
Daily Dosage (mg/day)
60-134
10-22
30-67
150-447
8-17
135-224
23-37
67.5-112
448-747
17.1-28
225-314
38-52
112.5-157
748-1047
28.1-39
315-404
53-67
157.5-202
1048-1347
39.1-51
>404
>67
>202
>1347
>51
1.5-3.4
3.5-5.6
5.7-7.9
8-10
>10
75-165
⇓
25 mcg/hr
patch
166-278
⇓
50 mcg/hr
patch
279-390
⇓
75 mcg/hr
patch
391-503
⇓
100 mcg/hr
patch
>503
⇓
Consult
clinical
specialist
TABLE B:*
Equianalgesic Potency Conversion
Equianalgesic Dose
(mg)
Name
IV
PO
Morphine
10
30
Hydromorphone
1.5
7.5
Oxycodone
20
Meperidine
75
-Codeine
130
200
*The dose conversion tables listed above should not be used to convert transdermal
fentanyl to oral or parenteral opioids.
84
Opioid Allergy
Scenario 1: Patient has an intolerance – not an allergy:
The following signs do NOT suggest an allergy:
 Flushing
 Itching
 Sneezing
 Sweating
This reaction is most likely a result of histamine release from mast cells, a common side
effect of opioids and not an allergy.
Analgesic options include:
1. Switch to a nonopioid analgesic (NSAID, APAP)
2. Dose reduce the opioid
3. Dose reduce the opioid, and add/increase dose of nonopioid analgesic
4. Premedicate and concurrently medicate with an antihistamine (diphenhydramine 2550mg) and possibly an H2 blocker (famotidine 20 mg)
5. If the opioid is intravenously administered, reduce rate of infusion
6. Switch to an opioid that is less likely to cause a histamine release
Opioid
Codeine
Morphine
Meperidine
Fentanyl
Methadone
Propoxyphene
Hydrocodone
Hydromorphone
Oxycodone
Oxymorphone
Buprenorphine
Nalbuphine
Chemical Source
Natural
Natural
Synthetic
Synthetic
Synthetic
Synthetic
Semi-synthetic
Semi-synthetic
Semi-synthetic
Semi-synthetic
Semi-synthetic
Semi-synthetic
Histamine Releasing Ability
High
High
High
Low
Low
Unknown
Unknown
Low
Low
Low
Unknown
Unknown
Scenario 2: Patient has a TRUE allergy:
The following signs DO suggest an allergy:
 Hypotension (BP <90/60mmHg)
 Hives, maculopapular rash, erythema multiforme, pustular rash
 Difficulty breathing, speaking, or swallowing (i.e. bronchospasm)
 Swelling of face, lips, mouth, tongue, pharynx, or larynx (i.e. angioedema)
This reaction is likely a true allergy.
Analgesic options include:
1. Switch to a nonopioid analgesic (NSAID, APAP)
2. The risk of cross-allergenicity between the chemical classes of opioids is low. If an
opioid is necessary, choose an opioid in a different class from the one that caused
the allergic reaction. For example, if meperidine, which is in class A, caused an
allergic reaction, try an opioid listed under class B or C instead.
85
a. Closely monitor the patient as it is possible to be allergic to more than one
class of opioids.
b. Note that Ultram (tramadol) and Ultracet (tramadol/APAP) are contraindicated
in patients allergic to ANY opioid.
Class A
meperidine
fentanyl
Class B
methadone
propoxyphene
propoxyphene/APAP
Class C
morphine
codeine
hydrocodone
oxycodone
oxymorphone
hydromorphone
nalbuphine
butorphanol
Example Situations:
1. You think the morphine drip is causing your patient to itch. It is possible the
morphine is causing a histamine release. What can you do?
Call the physician and ask him to order diphenhydramine 25-50mg PO q6-8 hours
while the patient is on the morphine drip, or, call the physician and ask him to d/c
the morphine and switch the patient to an equianalgesic dose of oxycodone which
doesn’t typically cause as much itching.
2. A patient presents in acute sickle cell crisis. He reports that “morphine gives me
hives all over my body”. What is your suggestion for pain control?
To control his pain, do not prescribe any opioids listed in the same class as
morphine. Try using an opioid from class A or B (see the above table for opioid
classes). It is still important to watch him closely in case he develops signs and
symptoms of an allergic reaction.
References:
1. Analgesic Options for Patients with Allergic-Type Opioid Reactions. Pharmacist’s
Letter/Prescriber’s Letter 2006;22(2):220201
2. Salijoughian M. Opioids: Allergy vs. Pseudoallergy. US Pharmacist. 2006;7:HS-5-HS9
3. Li, Fanny. Pharmacologically Induced Histamine Release: Sorting Out
Hypersensitivity Reactions to Opioids. Drug Therapy Topics. 2006;35(4):13-15
86
Glucocorticoid Comparison
Agent
Equivalent dose
Route of
(approximate mg) administration
Short-Acting
Cortisone
25
PO
Hydrocortisone
20
IM, IV, PO
Intermediate-Acting
Methylprednisolone 4
IM, IV, PO
Prednisolone
5
PO
Prednisone
5
PO
Long-Acting
Betamethasone
0.6-0.75
IM, IV, PO
Dexamethasone
0.75
IM, IV
Biologic half-life
(hours)
8-12
8-12
18-36
18-36
18-36
36-54
36-54
Conversion Example
Methylprednisolone
dose (example)
40 mg Q6H
60 mg Q6H
80 mg Q6H
125 mg Q6H
Equivalent
dexamethasone dose
8 mg Q6H
12 mg Q6H
16 mg Q6H
24 mg Q6H
Equivalent
hydrocortisone dose*
200 mg Q6H
300 mg Q6H
400 mg Q6H
625 mg Q6H
*Hydrocortisone has significant mineralocorticoid potency and may cause significant fluid
retention
References:
1. Dixon JS. Second-line Agents in the Treatment of Rheumatic Diseases. Informa Health
Care, 1991. (456).
2. Meikle AW and Tyler FH. Potency and duration of action of glucocorticoids. Am J of
Med 1977;63;200.
3. Webb R, Singer M. Oxford Handbook of Critical Care. Oxford ; New York : Oxford
University Press, 2005.
4. Brunton LL, ed. Goodman & Gilman's The Pharmalogical Basis of Therapeutics. 11th
Edition (2006).
87
IV Push Rates for Adult Patients
MUST USE FILTER NEEDLE WHEN AMPULE IS USED
Drug
Rate of Administration
Diluent
Dilute each 500 mg in 5 mL
Acetazolamide
100-500 mg/min
SWI
Over 1-2 seconds followed
Adenosine
Undiluted
by 5 mL NS flush
Atropine
0.4 mg/min
Undiluted
Undiluted in ventricular
Bretylium
Over 1 min*
fibrillation
Bumetanide
Over 1-2 min*
Undiluted
Calcium chloride
MAX 1mL/min
Undiluted
Calcium gluconate
MAX 1mL/min
Undiluted
Dexamethasone
Over 1 min*
Undiluted
(≤ 10 mg)
D50W
3 ml/min
Undiluted†
Diazepam
MAX 5 mg/min
Undiluted
Digoxin
Undiluted or with NS (4 fold)
 5 min
Diphenhydramine
25 mg over 1 min
Undiluted
Droperidol
1.25 mg over 1-2 min
Undiluted
Enalaprilat
Over 5-10 min*
Undiluted
Epinephrine
0.1 mg/min
1:10,000 solution: Undiluted
Bolus over 1-2 min, then
Eptifibatide
Undiluted
continuos infusion
Famotidine
Over 2 min*
20 mg diluted with 5-10 mL NS
Flumazenil
Over 15-30 seconds*
Undiluted
1.5-25 mg PE/mL, in NS or D5W,
Fosphenytoin
MAX 150 PE/min
Furosemide
MAX 20 mg/min
Undiluted
Test dose:
1,000 units/min
Heparin
Undiluted
After test dose:
5,000 units/min
Hydralazine
5 mg/1-5 min
Undiluted
Hydrocortisone
500 mg/min
Dilute to 50 mg/mL
Hydromorphone
Over 2-3 min*
Undiluted†
Test dose over 30 sec
Iron Dextran
Undiluted (test dose only)
MAX 50 mg/min
Isoproterenol
2-10 mcg/min
Dilute with 10 mL NS
Ketorolac
Over at least 15 sec
Undiluted
88
Labetalol
Lidocaine
Lorazepam
Mannitol
Meperidine
Methylprednisolone
succinate
20 mg over 2 min
25-50 mg/min
MAX 2 mg/min
200 mg/kg over 3-5 min
Over 4-5 min*
Metoclopramide
2 min
Metoprolol
5 mg over 1-2 min
Midazolam
Over 2 min*
Morphine
Naloxone
Ondansetron
Phenobarbital
Over 4-5 min*
0.4 mg over 15 sec
2 mcg/kg (bolus) over 60
seconds, followed by
continuos infusion
Over 2-5 min
MAX 60 mg/min
Phentolamine
5 mg/min
Phenytoin
MAX 50 mg/min
Procainamide
20-50 mg/min
Prochlorperazine
MAX 5 mg/min
Promethazine
Each 25 mg over 1 min
MAX 25 mg/min
Propranolol
Protamine
Sodium Bicarbonate
Verapamil
1 mg/min
Max 50 mg/10 min
1 mEq/kg over 1-3 min
5 mg over 2 min
Nesiritide
500 mg over 2-3 min
Undiluted
Undiluted
Dilute with equal volume of NS
Undiluted†
Dilute to 10 mg/mL
Reconstitute as directed: 40-125
mg/mL
Undiluted (for doses 10 mg or
less)
Undiluted
Dilute 1 and 5 mg/mL with NS
Max Concentration 0.5 mg/mL
Undiluted
Undiluted in an emergency
Draw loading dose (6 mcg/mL)
from continuos infusion bag
Undiluted
Use a minimum of 3 mL of SWI
Dissolve 5 mg with 1 mL of
SWI
Undiluted
Dilute each 100 mg with 5-10
mL of D5W
Undiluted
Avoid IV route if possible (use
IM or oral). Inject IV into freely
flowing IV infusion set. If
patient complains of pain,
immediately stop injecting.
Undiluted†
Undiluted
Undiluted†
Undiluted through Y-tube
*Assume all doses are safe over time period when not specified.
†
Dilution not specified as required; assume undiluted.
D5W=dextrose 5% in water; SWI=sterile water for injection; NS=0.9% sodium chloride (normal
saline)
89
90
Recommended Initial Vancomycin Dosing
Weight
(kg)
50
55
60
65
70
75
80
85
90
95
100
105
>110
20
†
750q48h
750q48h
750q48h
1000q48h
1000q48h
1250q48h
1250q48h
1250q48h
1500q48h
1500q48h
1500q48h
1750q48h
1750q48h
30
40
50
750q24h
750q24h
750q24h
1000q24h
1000q24h
1250q24h
1250q24h
1250q24h
1500q24h
1500q24h
1500q24h
1750q24h
1750q24h
750q24h
750q24h
1000q24h
1000q24h
1000q24h
1250q24h
1250q24h
1250q24h
1500q24h
1500q24h
1500q24h
1750q24h
1750q24h
750q24h
750q24h
1000q24h
1000q24h
1000q24h
1250q24h
1250q24h
1250q24h
1500q24h
1500q24h
1500q24h
1750q24h
1750q24h
CrCl (mL/min)
60
70
750q12h
750q12h
1000q12h
1000q12h
1000q12h
1250q12h
1250q12h
1250q12h
1500q12h
1500q12h
1500q12h
1750q12h
1750q12h
750q12h
750q12h
1000q12h
1000q12h
1000q12h
1250q12h
1250q12h
1250q12h
1500q12h
1500q12h
1500q12h
1750q12h
1750q12h
80
90
100
>110
750q12h
750q12h
1000q12h
1000q12h
1000q12h
1250q12h
1250q12h
1250q12h
1500q12
1500q12h
1500q12h
1750q12h
1750q8h
750q12h
750q12h
1000q12h
1000q12h
1000q12h
1250q12h
1250q12h
1250q12h
1500q12h
1500q12h
1500q12h
1750q12h
1750q12h
750q8h
750q8h
750q8h
1000q8
1000q8h
1000q8h
1000q8h
1000q8h
1250q8h
1250q8h
1250q8h
1500q8h
1500q8h
750q8h
750q8h
750q8h
1000q8h
1000q8h
1000q8h
1000q8h
1000q8h
1250q8h
1250q8h
1250q8h
1500q8h
1500q8h
**Dose is in mg
**Vancomycin Troughs should be drawn 30 min prior to the 3rd dose
**Vancomycin dose and interval should be individualized based on serum concentration monitoring.
†
CrCl < 20: pulse dose based on levels after initial dose
91
CATEGORY D AND X DRUGS IN PREGNANCY
**Non-inclusive list**
Not all listed products are formulary items.
FDA CATEGORIES D AND X FOR DRUG USE IN PREGNANCY1
Category D:
There is positive evidence of fetal risk but there may be certain
situations where the benefit might outweigh the risk (lifethreatening or serious diseases where other drugs are ineffective or
carry a greater risk).
Category X:
There is definite fetal risk based on studies in animals or humans or
based on human experience and the risk clearly outweighs any
benefit in pregnant women.
1
From Federal Register 1980;44:37434-37467.
Valsartan (D)
ACE Inhibitors
Benazepril (D)
Captopril (D)
Enalapril (D)
Fosinopril (D)
Lisinopril (D)
Moexipril (D)
Perindopril (D)
Quinapril (D)
Ramipril (D)
Trandolapril (D)
Angiotensin II
Receptor Antagonists
Candesartan (D)
Eprosartan (D)
Irbesartan (D)
Losartan (D)
Olmesartan (D)
Telmisartan (D)
Antiarrhythmics
Amiodarone (D)
Dronedarone (X)
See Beta Blockers
Antibiotics
Amikacin (D)*
Demeclocycline (D)
Chlortetracycline (D)
Doxycycline (D)
Methacycline (D)
Minocycline (D)
Kanamycin (D)
Streptomycin (D)
Sulfonamides (D)
Tetracycline (D)
Tobramycin (D)*
Anticonvulsants
Bromides (D)
Carbamazepine (D)
Ethotoin (D)
Phenytoin (D)
Phenobarbital (D)
Primidone (D)
Trimethadione (D)
Valproic Acid (D)
Antidepressants
Imipramine (D)
Nortriptyline (D)
Anti-Infectives
Trimetrexate (D)
Quinine (X)*
Ribavarin (X)
Povidone-Iodine (D)
Antifungals
Voriconazole (D)
92
Antilipemic Agents
Atorvastatin (X)
Fluvastatin (X)
Lovastatin (X)
Pitavastatin (X)
Pravastatin (X)
Rosuvastatin (X)
Simvastatin (X)
Antineoplastics
See specialized reference
Bendamustine (D)
Everolimus (D)
Oxaliplatin (D)
Pazopanib (D)
Pralatrexate (D)
Romidepsin (D)
Temozolomide (D)
Barbiturates
Amobarbital (D)
Butalbital (D)
Mephobarbital (D)
Pentobarbital (D)
Phenobarbital (D)
Secobarbital (D)
Benzodiazepines
Alprazolam (D)
Chlordiazepoxide (D)
Clonazepam (D)
Clorazepate (D)
Diazepam (D)
Estazolam (X)
Flurazepam (X)
Lorazepam (D)
Midazolam (D)
Quazepam (X)
Beta Blockers
Acebutolol (D)
Atenolol (D)
Betaxolol (D)
Bisoprolol (D)
Carteolol (D)
Carvedilol (D)
Celiprolol (D)
Labetalol (D)
Mepindolol (D)
Metoprolol (D)
Nadolol (D)
Oxyprenolol (D)
Penbutolol (D)
Pindolol (D)
Propranolol (D)
Sotalol (D)
Timolol (D)
Central Nervous
System Drugs
Oxazepam (D)
Temazepam (X)
Triazolam (X)
Colchicine (D)
Primidone (D)
Imipramine (D)
Phencyclidine (X)
Levorphanol (D)**
Lithium (D)
Pentazocine (D)**
Meprobamate (D)
Methaqualone (D)
Chelating Agents
Penicillamine (D)
Diuretics
(D if used in gestational
hypertension)
Amiloride (B/D)
Bendroflumethiazide
(C/D)
Bumetanide (C/D)
Chlorothiazide (C/D)
Chlorthalidone (B/D)
Ethacrynic Acid (B/D)
Furosemide (C/D)
Hydrochlorothiazide
(B/D)
Indapamide (B/D)
Methyclothiazide (B/D)
Metolazone (B/D)
Polythiazide (C/D)
Spironolactone (C/D)
Triamterene (C/D)
Gastrointestinal Agents
Sulfasalazine (D)‡
Misoprostol (X)
Paregoric (D)**
Hematological Agents
Coumarin Derivatives
(X)*
Dicumarol (D)
Warfarin (X)*
Hormones/Steroids
Betamethasone (D)
Cortisone (D)
Clomiphene (X)
Danazole (D)
Dexamethasone (D)
Estradiol (X)
Estrogens, Conjugated
(X)
93
Estrone (X)
Ethinyl Estradiol (X)
Ethynodiol (D)
Fluoxymesterone (X)
Hormonal Pregnancy
Test Tablets (X)
Hydrocortisone (D)
Hydroxyprogesterone
(D)
Leuprolide (X)
Levonorgestrel (X)
Medroxyprogesterone
(D)
Mestranol (X)
Methimazole (D)
Methyltestosterone (X)
Mifepristone (X)
Norethindrone (X)
Norgestrel (X)
Oral Contraceptives (X)
Prednisolone (D)
Prednisone (D)
Propylthiouracil (D)
Tamoxifen (D)
Testosterone (X)
Triamcinolone (D)
Immunosuppressants
Azathioprine (D)
Miscellaneous
Aliskeren (C/D)
Bosentan (X)
Chlorpropamide (D)
Cigarette Smoking (X)
Cyclazocine (D)
Diethylstilbestrol (X)
Dihydroergotamine (X)
Efavirenz (D)
Ergotamine (X)
Ethanol (D/X)†
Iodinated Glycerol (X)
Iodine (D)
Levallorphan (D)
Methylene Blue (D)
Nalorphine (D)
Norepinephrine (D)
Leflunomide (X)
Quinidine (X)
Reserpine (D)
Thalidomide (X)
NSAIDS/Pain
Medications
Alfentanil (D)**
Aspirin (D)
Butorphanol (D)**
Celecoxib (D)
Codeine (D)**
Diclofenac (D)
Diflunisal (D)
Dihydrocodeine (D)**
Etodolac (D)
Fenoprofen (D)
Fentanyl (D)**
Flurbiprofen (D)
Hydrocodone (D)**
Hydromorphone (D)**
Ibuprofen (D)
Indomethacin (D)
Ketoprofen (D)
Ketorolac (D)
Meclofenamate (D)
Mefenamic Acid (D)
Meloxicam (D)
Meperidine (D)**
Methadone (D)**
Morphine (D)**
Nalbuphine (D)**
Nabumetone (D)
Naproxen (D)
Oxaprozin (D)
Oxycodone (D)**
Oxymorphone (D)**
Pentazocine (D)**
Phenylbutazone (D)
Piroxicam (D)
Propoxyphene (D)
Remifentanil (D)**
Sufentanil (D)
Sulindac (D)
Tolmetin (D)
Radiopharmaceuticals
Sodium Iodide I125 (X)
Sodium Iodide I131 (X)
Serums, Toxoids, &
Vaccines
Measles (X)
Mumps (X)
Rubella (X)
Smallpox (X)
TC-83 Venezuelan
Equine Encephalitis (X)
Yellow Fever (D)
Vitamins
Acitretin (X)
Calcifediol (C/D)***
Calcitriol (C/D)***
Cholecalciferol
(C/D)***
Dihydrotachysterol
(A/D)***
Ergocalciferol (A/D)***
Etretinate (X)
94
Isotretinoin (X)
Menadione (C/X)***
Tretinoin (systemic) (D)
Vitamin A (A/X)***
Vitamin D (A/D)
Most severe rating adapted from Briggs GG, Freeman RK, Yaffe SJ. Drugs in
Pregnancy and Lactation. Baltimore, Williams & Wilkins, 2005. See Briggs for further
information.
* Manufacturer’s rating
** If used for prolonged periods or high doses at term.
*** If used in doses above the recommended daily allowance.
†If used in large amounts or prolonged periods.
‡If given near term.
95
Common Calculations
Anion Gap
Anion gap = sodium - (chloride + HCO3)
Body Surface Area
BSA (m2) =
Ht (in) x Wt (lb)
or BSA (m2) =
Ht (cm) x Wt (kg)
3131
3600
Corrected Calcium for Albumin Level
[(Normal albumin - patient’s albumin) x 0.8] + measured serum calcium
Corrected Sodium 1
Corrected Na+ = measured Na+ + [1.6 x {(glucose - 100) ÷ 100}]
Correction of Serum Phenytoin Concentration for Albumin Level
 Adjusted concentration = measured concentration ÷ [(0.25 x albumin) + 0.1]
(normal renal function)
 Adjusted concentration = measured concentration ÷ [(0.1 x albumin) + 0.1]
(CrCl <10 ml/min)
Creatinine Clearance
CrCl (male) = (140-age) x IBW (kg)
72 x serum creatinine
CrCl (female) = CrCl (male) x 0.85
Dosing Weight (For use when ABW is > 1.2 x IBW)
Dosing Weight = 0.4 x (ABW - IBW) + IBW
Ideal Body Weight 2,3
IBW (male) = 50 + (2.3 x height in inches over 5 feet)
IBW (female) = 45.5 + (2.3 x height in inches over 5 feet)
Theophylline/Aminophylline Conversion
Aminophylline dose x 0.8 = Theophylline dose
Serum Osmolality 4
Serum Osmolality = (2 x Na[mEq/L]) + (Glucose[mg/dL] ÷ 18) +( BUN [mg/dL] ÷ 2.8)
References:
1. Hillier TA, Abbott RD, and Barrett EJ. "Hyponatremia: Evaluating the Correction Factor for Hyperglycemia." Am
J Med , 1999, 106(4):399-403.
2. Devine BJ, "Gentamicin Therapy." Drug Intell Clin Pharm , 1974, 8:650-5.
3. Robinson JD, Lupkiewicz SM, Palenik L, et al. "Determination of Ideal Body Weight for Drug Dosage
Calculations." Am J Hosp Pharm , 1983, 40(6):1016-9.
4. Kraft MD, Btaiche IF, Sacks GS, et al. ”Treatment of electrolyte disorders in adult patients in the intensive care
unit.” Am J Health Syst Pharm. 2005 Aug 15;62(16):1663-82.
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therapeutics manual

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