HOSPITAL KUALA KUBU BHARU PHARMACY BULLETIN

HOSPITAL KUALA KUBU BHARU
PHARMACY BULLETIN
1st edition /Jun2015
DIS HKKB 03-60641333 ext 279
ISSUE OF THE MONTH : RAMADHAN IS HERE AGAIN!
(PAGE 1-5)



Self monitoring blood glucose during fasting
Dosage adjustment for Oral Antidiabetic and insulin during
fasting
Updated list of medication that cannot be taken by muslim
during fasting.
CURRENT ISSUES (PAGE 6-7)



Accepted abbreviations for prescription writing in HKKB
Abbreviation that should be avoided
Tamiflu (Children)
A GLANCE OF PHARMACEUTICAL SCIENCE (PAGE 9-12)

Introduction to Pharmacokinetics : ADME process

The workflow of Therapeutic Drugs Monitoring (TDM) service
in HKKB
KNOW YOUR MEDICINE (PAGE 13-16)

Asthma & Medication
PHARMACY EDUCATION (PAGE 17-19)

Idiopathic nephrotic Syndrome in Children
EDITORIAL BOARD
ADVISOR : Ratna Suny Mohamed Esa
CHIEF EDITOR : Noor Haslina Zainor Abidin
EDITOR : Ainur Fadlina Nadzir
Nurzafirah Mustafa Kamal
CONTRIBUTORS:
1)
2)
3)
4)
Tan Hwei Yuin
Syazyanti Izyanti Mohd Ariffin
Azwa Abdullah
Mohamad Shafawie Mohamad Sidik
RAMADHAN
&
DIABETES
Ramadhan is the 9th month in the Islamic calendar. In this month, Muslims worldwide perceives thismonth as the fasting month. The practice of fasting lasts for 29-30 days. During this month, Muslims will
fast from dawn until dusk daily. Fasting is believed to clean the soul by freeing it from harmful impurities
and inculcate the practice of self-discipline, self-control, sacrifice, and compassion for those who are less
fortunate. Thus, Muslims are encouraged to practice the act of generosity and charity especially during
Ramadhan.
The practice of fasting during Ramadhan is compulsory for all Muslims once puberty is reached. However,
there are certain exceptional like those with chronic diseases such as diabetes mellitus. Fasting in diabetec
patients may be associated with adverse outcomes like dehydration, hypoglycaemia and hyperglycaemia.
Thus, diabetic patients are required to be monitored and given necessary medical advice if patient insist to
fast. However, there are certain diabetic patients who are not encouraged to fast as they have higher risk of
developing the adverse effects than other normal diabetic patients [refer Table 1].
Table 1:
The criteria that FORBIDS Diabetic patients to fast:
1. Uncontrolled diabetes (may lead to various complication– dehydration, infection and coma)
2. Non compliance to diet restrientions and medication
3. Suffering from serious diabetes complications (Coronary heart disease and uncontrolled hypertension)
4. History of severe diabetes complication with 3 months prior to fasting
 Ketoacidosis
 Hyperosmolar hypoglycemic coma
 Recurrent hypoglycemia
5. Suffering bacterial infection
6. Elderly who lives alone
7. Pregnant women who is suffering from Gestational Diabetes Mellitus
8. Children under the age of 12 years old. (Haven’t reached puberty)
9. Type 1 Diabetes patient
By : TAN HWEI YUIN
1
Pathophysiology of Fasting during Ramadhan
Owing to the abstaining from eating, drinking and smoking from predawn to sunset during the
Ramadhan period, the metabolism of glucose is altered from the normal physiology. When fasting,
the body will finish up the available glucose storage (glycogen) in the liver and gradually transit to
fat as the main source of energy. During fasted state, liver glycogen will deplete within the first 18
to 24 hours via glycogenolysis. Once glycogen stores are depleted, fats will be mobilized in the form
of triglycerides and subjected to lipolysis for generation of energy. After a prolonged period of fasting (days-weeks), protein becomes the next source of energy via catabolism of muscle.
However, Ramadan fast only last from dawn till dusk, thus; there is ample opportunity to replenish energy stores at pre-dawn and dusk meals. Therefore, this will ensure sufficient supply of
glycogen or fats as the source of energy, and prevents the breakdown of muscle for protein.
Pathophysiology of fasting in diabetes patient
2
To Known the Signs of Hypoglycemia, Hyperglycemia and Dehydration
Signs of HYPOGLYCEMIA:
Fatigue
Shivering
Cold
Sweats
Hungry
Palpitation

Pale

Coma
Anxious
Signs of HYPERGLYCEMIA:
Frequent
urination
Extreme
thirst
Drowsiness
Decrease
healing
Signs of DEHYDRATION:
Extreme
thirst
Very dry skin
& tongue
Patients are encouraged to self-monitor blood glucose during fast, sugguested at the following time :
Time
Target
Pre-sahur
4.4 - 6.1 mmol/L
2 hours post SAHUR
4.4 – 8 mmol/L
Midday
4.4 - 6.1 mmol/L
2 hours post IFTAR
4.4 - 6.1 mmol/L
Right before IFTAR
4.4 - 6.1 mmol/L
Stop fasting IMMEDIATELY if :

Experiencing signs of hypoglycemia or blood glucose <3.3mmol/L



Blood glucose <3.9mmol/L in the first few hours of fasting [especially in
patient taking sulfonylureas, meglitinides or insulin]
Blood glucose >16.7 mmol/L
Sick (fever, infections etc)
3
Dose ADJUSTMENT for Oral AntiDiabetic and insulin during Ramadhan
Medicine Name and Strength
Metformin 500mg
(Biguanides)
Regime for Ramadhan month
 Once/Twice daily
No dosage adjustment required
 Three times daily
Take 2/3 from the TOTAL DAILY DOSE during IFTAR
Take1/3 from the TOTAL DAILY DOSE during SAHUR
(Max dose: 1g)
Eg: T. Metformin 500mg three times daily
* Metformin 1g during IFTAR, 500mg during SAHUR
Gliclazide / Glibenclamide
(Sulphonylureas)


Eg: T. Gliclazide 80mg twice daily
* Gliclazide 40mg during SAHUR, 80mg during IFTAR
Gliclazide MR
(Sulphonylureas)

No dosage adjustment required (Take during IFTAR)

No dosage adjustment required (Take during IFTAR)

No dosage adjustment required. Omit midday dose.
No dosage adjustment required during IFTAR
Reduce or omit during SAHUR
Eg: T. Gliclazide MR 60mg once daily
Rosiglitazone / Pioglitazone
(Thiazolidinediones)
Eg: T. Rosiglitazone 4mg once daily
Acarbose
(Alpha-glucosidase inhibitors)
Eg: T. Acarbose 50mg three times daily
Repaglinide/Nateglinide
(Rapid acting insulin secretagogues)
Eg: T. Repaglinide 2mg per meal (maximum
4 meal)
Sitagliptin
(Dipeptidyl peptidase-4-inihibitors)
Acarbose 50mg during SAHUR, 50mg during IFTAR. Midday
dose can be omitted during fasting
 Twice daily
No dosage adjustment required during IFTAR
Take HALF dose during SAHUR

No dosage adjustment required
Eg: T. Sitagliptin 100mg once daily
Insulatard®, Humulin N®, Lantus®,
Levemir® , Insuman Basal®
(Basal insulin)

Mixtard® 30/70, Humulin® 30/70, Novomix® 30, Insuman Comb 30®
(Pre-mixed insulin)

Eg: S/C Mixtard® 30/70– 30unit morning
& 20 unit evening
* S/C Humulin 30/70 10 unit during SAHUR, 30unit during
IFTAR
Actrapid®, Humulin ®, Insuman Rapid®
(Rapid acting insulin)

No dosage adjustment required . (Inject before going to
bed)
 Can reduce 20% (2unit) of the normal dose if
hypoglycaemia had occurred before


Eg: S/C Humulin® 16unit three times daily 
Reverse dose—Morning dose take during IFTAR dan
evening dose at SAHUR
Evening dose can be reduced from 20-50% based on the individualized blood glucose level
No changes or REDUCE SAHUR dose up to 50% if one is
suffering from hypoglycemia.
Midday dose can be omitted during fasting
No changes during IFTAR
 S/C Humulin® 16unit BEFORE SAHUR and 16unit
BEFORE IFTAR
4
Types of Drug that ALLOW/CANCEL Fasting
Medication that DOES NOT BREAK Fast

Tablet
condition of not reaching the base of eardrum,

Syrup
throat)

Inhaler


Eyedrop, Eardrop & nasal spray (with the
Medication that BREAK Fast
Sublingual tablet (under the tongue); with the 
Pessary (Including vaginal wash)
condition of not swallowing
Suppository & Enema (any medicine that is

All forms of injection

Topical (cream/ointment) and plaster

Mouthwash gargle

Local anesthetic

inserted into anus

General anesthetic (involves inhaling gas)
REFERENCES:
1. Puasa & Ubat,2015, Bahagian Perkidmatan Farmasi, Kementerian Kesihatan
Malaysia.
2. Prof Nor Azmi Kamaruddin. Pengurusan Diabetes Ketika Berpuasa. Peroncean
Endocrin & Metabolisma Malaysia (MEMS). 2015.
3. Kementerian Kesihatan Malaysia & MEMS. Practical Guide to Diabetes Management
in Ramadan. 2015.
5
Current Issues
ACCEPTED ABBREVIATIONS IN PRESCRIPTION WRITING, HKKB
Abbreviation
Intended meaning
Example of prescribing
Stat.
Immediate
T. Captopril 50mg stat.
PRN
When necessary
Oint. Methyl salicylate PRN X 1/52
Syr.
Syrup
Syr. Paracetamol 120mg tds X 1/52
Gutt.
Eye drop
Gutt. Gentamicin 0.3% 1 drop tds, BE X 1/12
Oint.
Ointment
Oint. Methyl salicylate PRN X 1/52
Mist.
od
Mixture
Once a day
Mist. Potassium Citrate 10ml tds X 1/52
T. Prednisolone 30mg od x 5/7
bd
tds
Twice daily
Three times a day
T. Metformin 1g bd X 1/12
T. Nifedipine 10mg tds X 1/12
mg
Milligram
T. Amlodipine 10mg od X 1/12
mcg
ml
OM
ON
microgram
Milliliter
Morning
Night
T. Levothyroxine 50mcg od X 1/12
Mist. Potassium Citrate 10ml tds X 1/52
ORS
Oral Rehydration Salt
ORS per purge X 3/7
Vit.
Vitamin
T. Vit. C 100mg od X 1/52
GTN
Glyceryl Trinitrate
T. GTN 1tab PRN X 1/12
T. Valproic acid 200mg OM, 400mg ON X 1/12
ACCEPTED SYMBOLS IN PRESCRIPTION WRITING, HKKB
Symbol
Meaning
↑
↓
Increase or high
Decrease or low
@
X
At
Times
6
Current Issues
ABBREVIATIONS THAT SHOULD BE AVOIDED
Abbreviation
Intended meaning
Suggestion for prescribing
St.
stat (immediate)
stat
cc
Milliliter
ml
BVC
Betamethasone
Reason
Not a standard abbrevia-
tion
May be mistaken as ‘oo’
Betamethasone cream for
if poor handwriting
Not a standard abbrevia-
LA
tion
Not a standard abbrevia-
HCTZ
Hydrochlorothia-
T. Hydrochlorothiazide
tion. May be confused
zide
25mg od
with Hydrocortisone
(HCT)
MVT
Multivitamin
CMC
Chloramphenicol
MTF
Metformin
CPZ
Chlorpromazine
BE/Bena
Diphenhydramine
ASA
Acetylsalicylic Acid
OMS
HCT
Ointment Methyl
salicylate
Hydrocortisone
Syr. Multivitamin 5ml od
Gutt. Chloramphenicol 2
drop tds
T. Metformin 500mg bd
May be confused with
MMT
Not a standard abbreviation
Not a standard abbrevia-
T. Chlorpromazine 100mg
tion
May be confused with
ON
carbamazepine (CBZ)
Syr. Diphenhydramine 10ml
Not a standard abbrevia-
tds
T. Acetylsalicylic Acid
tion
Not a standard abbrevia-
150mg od
tion
Oint. Methyl salicylate PRN
IV Hydrocortisone 100mg
QID
May be confused with
ORS
May be confused with
Hydrochlorthiazide
(HCTZ)
7
Compounding of oral suspension from
Tamiflu 75mg Capsule
Carefully open one capsule and pour all the powder into the
bowl. (Handle the powder carefully as it may cause irritation to
skin and eyes).
1) Add 5ml of water to the bowl and mix it with powder for 2
minutes.
2) Add 7.5ml of Syrup Simplex to the bowl.
3) Stir the mixture well before giving the dose (Please refer
the table below for dose measurement).
Note :
WEIGHT
< 15kg
16-23 kg
24-40 kg
≥41 kg
NOTE
Final concentration : 6mg/ml.
Preparation is to be made for each dose, not in bulk.
Shake well before use.
Store the capsules below 25ºC and protect from moisture.
PROPHYLAXIS
(7 DAYS)
TREATMENT
(5 DAYS)
DOSE
DOSE
30mg OD
45mg OD
60mg OD
75mg OD
<3 months old :
not recommended
3 months – 1 year
old : 3mg/kg/dose OD
30mg
45mg
60mg
75mg
BD
BD
BD
BD
VOLUME
(ML)
5.00
7.50
10.00
12.50
< 1 year old :
3mg/kg/dose BD
Antiviral Medication Recommended for Treatment of Influenza
References :
www.cdc.gov : Influenza Antiviral Medications: Summary for Clinicians
Product Leaflet : Osmivir Capsule 75mg (Royce ™)
8
A GLANCE OF PHARMACEUTICAL SCIENCE
BY : SYAZYANTI IZYANTI MOHD ARIFFIN
THERAPEUTIC DRUG MONITORING
What is
pharmacokinetics?
Study of absorption,
distribution, metabolism
and excretion of drugs
in the body
Measurement of drug concentration in body fluids to
aid in optimizing drug therapy.
Why is it necessary?




Certain drugs have narrow therapeutic range
In concentrations above the upper limit of the
range, the drug can be toxic
In concentrations below the lower limit of the
range, the drug can be ineffective
Not all patients have same response at
similar doses
PHARMACOKINETIC TERMS
Volume
distribution (Vd)
The amount of blood, per Kg
body weight necessary to
contain all of the body burden of drug at equilibrium
concentration
Steady state
The point at which drug
intake and elimination reach
an equilibrium, and the
height of the peak and the
depth of the trough are
predictable
Half Life (T1/2)
Time required for the drug
concentrations to
Decrease by to 50%
9
GUIDELINES OF SAMPLING TIME
Drug
Time to steady state
Sampling time
Digoxin
(Oral)
Without LD: 7-14 days
(ESRF: 15-20days)
With LD: 24 hours
30 minutes or just before the
next dose
Theophylline
(Oral)
Oral: 2days
LD IV: 24hours
IV: 2days
30 minutes or just before the
next dose
Phenytoin
Without LD: 7 days
With LD: 12-24hours
30 minutes or just before the
next dose
Carbamazepine
2-3 weeks
(Induction phase)
30 minutes or just before the
next dose
4-7 days (MD)
Valproic acid
3-5 days
30 minutes or just before the
next dose
Phenobarbitone
Adult: 1 month
Children: 2 weeks
30 minutes or just before the
next dose
REFERENCES
1.
Laryn A. Bauer (2006) The Mc-Graw Hill companies, Clinical Pharmacokinetic Handbook, United
States
2. Therapeutic Drug Monitoring, Clinical Guide. Accessed online on 24th May 2014 at: https://
www.abbottdiagnostics.com/enus/staticAssets/learningGuide/public/
IA_09_23773v2_Ther_Drug_Guide_120910_E_Brochure.pdf
3. Therapeutic Drug Monitoring, An Educational Guide. Accessed online on 24th May 2014 at:
http://www.healthcare.siemens.com/siemens_hwem-hwem_ssxa_websites-context-root/wcm/idc/groups/
public/@global/@clinicalspec/documents/download/mdaw/mtu3/~edisp/tdm_guide_final-00028657.pdf
10
Flow Chart of Clinical Pharmacokinetic Service
(From In-Patient Department)
Receive TDM request form from ward/ verbal
request from Dr/ informed by ward BEFORE
blood is taken
Screen the request and conduct
initial patient assessment in the
ward (CLERK CASE)
Clinical Pharmacist
HKKB (EXT 209)
Consult the requester
and rectify the problem
Yes
Any
problem?
No
Send specimen together with the TDM
form to Pathology Lab HKKB for registration, serum extraction & preservation
Collect the pink copy of the TDM
Pathology
Lab HKKB
Keep pink copy of the TDM form before
dispatch to Selayang Hospital
Register the request with HKKB
Pharmacy Reference Number
Dispatch the specimen together with the
TDM form (original and yellow copy) to
Biochemical Lab Selayang Hospital for
analysis
Obtain the results from Biochemical Lab Selayang Hospital via
phone call; obtain the original copy
from Pathology Lab HKKB
Register the request
Pharmacy
HKKB
Interpret the results
Biochemical
Lab Selayang
Hospital
Prepare carousel, reagent and sample for
assay
Run the assay
Keep the yellow copy and return the
original copy with results to HKKB
Discuss the results and recommendations with the prescriber
Send the original copy of the
TDM form to the requester, record & file the pink copy
11
Flow Chart of Clinical Pharmacokinetic Service
(From out-Patient Department, a&e and out of
working hour)
Receive specimen & TDM
request form
Screen the request
Consult the
requester and rectify the problem
Yes
Any
problem?
Pathology Lab
HKKB
No
Register the request, extract and preserve the serum
Pathology Lab
Keep pink copy of the TDM form
before dispatch to Selayang Hospital
Dispatch the specimen together with
the TDM form (original and yellow
copy) to Biochemical Lab Selayang
Hospital for analysis
Biochemical
Lab Selayang
Hospital
Collect the pink copy of the
TDM form
Register the request with HKKB
Register the request
Obtain the results from Biochemical Lab Selayang Hospital via
phone call; obtain the original
copy from Pathology Lab HKKB
Prepare carousel, reagent and sample
Interpret the results
Run the assay
Discuss the results and recommendations with the prescriber
Keep the yellow copy and return the
original copy with results to HKKB
Pharmacy
HKKB
Send the original copy of the
TDM form to the requester,
record & file the pink copy
12
KNOW YOUR MEDICINE
BY : AZWA BT ABDULLAH
ASTHMA & METERED DOSE INHALERS
(MDI) : WHAT YOU SHOULD KNOW?
Asthma is a chronic (long-term) inflammation disorder of the lung where the airways become inflamed, swollen, narrowing and very sensitive. Cells in the airway might produce
more mucus than usual. Mucus is a sticky, thick liquid that can further narrow the airways.
Asthma causes recurring periods of wheezing (a whistling sound while breathing), chest
tightness, shortness of breath, and coughing. The coughing often occurs at night or early in
the morning.
The location of the lungs and airways in the body. Figure B shows a cross-section of a normal airway.
Figure C shows a cross-section of an airway during asthma symptoms.
Two types of inhaler
Asthma is usually treated with inhalers. Inhaler is a device that will deliver the drug
straight into the lungs. There are many type of inhalers that works in a slightly different
way but briefly it can be divided into two categories as follow ;.
RELIEVER (“PELEGA”)
Quick relief of asthma symptoms
PREVENTER (“PENCEGAH”)
Take longer time to show effect on asthma
symptoms
Relax the muscle around the narrowed Reduce airway sensitivity , redness and
airway that will open the airway wider swelling and help to dry up mucus
and make the patient breathe easier
Short term treatment
Long term treatment
13
RELIEVER (“PELEGA”)
PREVENTER (“PENCEGAH”)
Reliever should not be used regularly, if patient use them three or more times a week it
indicates patient asthma condition is
worsening.
Preventers need to be taken every day to
reduce symptoms and asthma attacks, and
it may take a few weeks before they reach
their full effect.
There are two main categories of reliever
medication:
Short-acting beta-agonists

Salbutamol

Levobuterol
Anticholinergics

Ipratropium bromide (usually
use in COPD)

Tiotropium bromide
Preventer consist of inhaled corticosteroid

Budesonide

Beclomethasone

Fluticasone

Triamcinolone acetonide
Possible side effects include:

Increased heart rate (felt as palpitations)

Muscle tremor (shaking, especially
in the hands), and/or

slight feelings of anxiety or nervousness

Upset stomach (rare)

Sleeping troubles (rare)
Possible side effect:

Candiasis/ oral trush – rinse mouth
after use

Sore throat

Hoarse voice

skin bruising (rare)

cataract (rare)

glaucoma (rare)

adrenal suppression (rare)

growth suppression (rare)
Differences between available Meter Dose Inhaler (MDIs) in HKKB
VENTOLIN/
BUVENTOL
EASYHALER
BUDESONIDE/
FLIXOTIDE/
BECLOMET
EASYHALER
BERODUAL
SERETIDE
Salbutamol 100
mcg/puff
Salbutamol 200
mcg/puff
(Easyhaler)
Budesonide 200 mcg /puff
Fluticasone 125 mcg/puff
Beclomethasone 200
mcg/puff (Easyhaler)
Ipratropium bromide 21 mcg and
Fenoterol hydrobromide 50 mcg
Salmeterol 25mcg
and Fluticasone
Propionate 50mcg
Inhalation
Example
Content
14
VENTOLIN
BUDESONIDE/
FLUTICASONE
MOA
Short acting beta
2 agonist
How to
use
Inhaled
corticosteroid
SERETIDE
Anticholinergic
Short acting beta 2
and
agonist and inLong acting beta 2 haled corticosteragonist
oid
1.
Remove the mouthpiece cover. Remain standing/seated upright to obtain the full dose of each actuation.
2. Shake the inhaler 3-5 times in up-down motion
3. Prime new inhalers
4. To administer 1 puff:

Hold the inhaler in a upright position.

Breathe out fully

Place the mouthpiece between the teeth and close the lip (Do not
bite the pump). Ensure that lip fully cover the mouthpiece.

Begin to breathe in and press down on the canister simultaneously. Continue inhalation 3-5 minutes.

Hold breathe for 10 second

Remove pump and exhale through mouth.
5.
If the dose is two puffs, patient need to repeat procedure no (4). Do not
press two times simultaneously. Wait a few second between this two puffs.
6.
Close the cover and keep inhaler in dry place.
7.
Clean the MDIs every week.
Addition- In acute attack:
al
counsel After 5 minutes of first dose (2
ling point
puffs) patient are allowed to take
another 2 puffs.
When to
use
BERODUAL

Then if the symptoms still not resolved in 5 minutes, patient may
take another 2 puff.

But however highly recommended
to consult doctor in nearest hospital.
When necessary


MUST rinse mouth after use.
Use every day and do not stop without doctor’s instruction.
Every day with the Both – when nec- Every day with the
dose prescribed essary and/or eve- dose prescribed by
by doctor
ry day
doctor
15
Other types of inhaler available in Malaysia
Type
Picture
Example
Easyhaler

Budesonide Easyhaler
(Giona)
Turbohaler

Symbicort turbohaler
(Budesonide &
Salmeterol)
Pulmicort Turbohaler
(Budesonide)

Accuhaler
Handihaler
Seretide Accuhaler
Flixotide Accuhaler



Spiriva (Tiotropium
bromide)
References

Lexicomp drug information handbook 23rdedition (2014-2015)

Pharmacotherapy Handbook

Mims Malaysia

Product leaflet

British Guideline on the Management of Asthma May 2011

http://www.nhlbi.nih.gov/health/health-topics/topics/asthma/

http://www.medicalnewstoday.com/info/asthma/

http://www.asthmaaustralia.org.au/preventers.aspx
16
PHARMACY EDUCATION
BY : MOHAMAD SHAFAWIE BIN MOHAMAD SIDIK
Nephrotic syndrome is a clinical syndrome of massive proteinuria
defined by :

Oedema

Proteinuria > 40mg/m²/hour (>1g/m²/day) or an early morning urine protein
creatinine index of >200 mg/mmol

Hypoalbuminaemia <25g/l

Hypercholesterolameia
WHAT IS IDIOPHATIC NEPHROTIC SYNDROME?
Idiophatic (primary) nephrotic syndrome is one class of nephrotic syndrome which include
minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and diffuse
mesangial proliferation (DMP)
Common definitions to define the coarse of nephrotic syndrome
Nephrotic syndrome
Oedema, hypoalbuminaemia, proteinuria, hypercholesterolameia
Relapse
Urinary protein excretion > 40mg/m²/h; ≥ 3+ by dipstick for 3 consecutive day
Remission
Urinary protein excretion < 40mg/m²/h; nil or trace by dipstick on spot sample for 3
consecutive day
Frequent relapse
Two or more relapse in 6 months of initial response; 4 or more relapse in any 12
month period
Steroid dependence
Occurrence of 2 consecutive relapse during steroid therapy or within 2 weeks of its
cessation
Steroid resistance
Failure to achieve remission after 4 weeks of daily therapy with oral prednisolone
at a dose of 2mg/kg/day
TREATMENT OF INITIAL PRESENTATION OF NEPHROTIC SYNDROME
Prednisolone dose:

60mg/m²/day for 4 weeks (maximum 80mg)

40mg/m²/on alternate day for 4 weeks (maximum 60mg)

Reduce dose by 5-10mg/m² each week for another 4
weeks then stop
Prednisolone can be given as a single dose in the morning with food, or as divided dose during the day. If
prednisolone cause gastric irritation, start ranitidine 2mg/kg twice daily for the duration of steroid treatment.
Response to treatment:
 A remission occur when urinary protein excretion < 40mg/m²/h; nil or trace by dipstick on spot sample for 3 consecutive day.
 Treatment is contimued for a total of 12 weeks
 If proteinuria persists beyond the first 4 weeks of steroid treament , patient should be referred for
renal biopsy
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TREATMENT OF RELAPSES IN NEPHROTIC SYNDROME
Prednisolone induction dose:

60mg/m²/day (maximum 80mg) until remission followed by

40mg/m²/on alternate day (maximum 60mg) for 4 weeks
Breakthrough proteinuria may occur with intercurrent infection and usually does not require corticosteroids induction if the child has no oedema, remain well and proteinuria remits with the
resolution of the infection. However, if proteinuria persists, treat as relapse
FREQUENTLY RELAPSING NEPHROTIC SYNDROME THERAPHY OPTIONS




Prednisolone 2mg/kg per day until proteinuria normalize for 3 consecutive days followed by 1.5 mg/
kg on alternate days for 4 weeks, then taper over 2
months by 0.5 mg/kg on alternate days
Oral cyclophosphamide 2mg/kg per day for 12
weeks (cumulative dose : 168 mg/kg) based on ideal
body weight started during prednisolone induced
remission, decrease prednisolone to 1.5mg/kg on
alternate days for 4 weeks then taper over 4 weeks
Mycophenolate mofetil 25-36mg/kg per day
(maximum 2g/day) divided twice daily for 1 to 2
years with a tapering dose of prednisolone
Cyclosporine A 3 to 5 mg/kg per day divided in
BID for an average of 2 to 5 years
Malaysian Pediatric Protocol 2013 only recommend prednisolone as treatment of frequent relapses and later is commonly use in
steroid dependent nephrotic syndrome.
Prednisolone induction dose:

60mg/m²/day (maximum 80mg) until
remission followed by

40mg/m²/on alternate day (maximum
60mg) for 4 weeks
 Taper prednisolone dose every 2 weeks
and keep on as low an alternate day dose
as possible for 6 months. Should child
relapse while on low dose alternate day
prednislone, the child should be reinduced with prednisolone as for relapse
TREATMENT OF STEROID DEPENDENT NEPHROTIC SYNDROME





Glucocorticoids are preferred treatment in the absence of steroid toxicity
Cytotoxic drugs ex : cyclophosphamide, chlorambucil
Levamisole
Calcineurin inhibitor ex: Cyclosporine, Tacrolimus
Mycofenolate Mofetil
STEROID-RESISTANT NEPHROTIC SYNDROME MANAGEMENT


Goal of therapy : complete resolution of proteinuria 

and preservation of kidney function
3 major categories of therapy for SRNS :

-Immunosuppressive
-Immunostimulatory
-Nonimmunosuppressive
Kidney biopsy
Tailor therapeutic regimen according to
kidney histology
Supportive therapy
Immunosuppresive
 The most commonly used immunosuppressive therapy include calccineurin inhibitor, MMF,
pulse intravenous methylprednisolone and cytotoxic agent
 Less commonly used include plasma exchange and immunoabsorption
Immunostimulatory
 The only reported immunostimulatory is levamisole however it is not universally available
Nonimmunosuppressive
 Consider as supportive treatment and include ACE-I, ARB and vitamin E
 ACE-I and ARB reduce proteinuria by decreasing the transcapillary glomerular hysrostatic
pressure and altering glomerular permeability
 ACE-I decrease synthesis of transforming growth factor (TGF)-β and plasminogen activator
inhibitor (PAI)-1. TGF-β and PAI-1 are important profibrotic cytokines promoting glomerulosclerosis
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THIAZOLIDINEDIONES
RITUXIMAB
GALACTOSE
ADALIMUMAB
MONITORING RECOMMENDATIONS FOR
CHILDREN WITH NEPHROTIC SYNDROME
SOURCES : S. Gipson, D., F. Massengill, S., Yao, L., Nagaraj, S., E. Smoyer, W., D. Mahan, J., Wigfall, D., Miles, P., Poswell, L., Lin,
J., Trachtman, H. and A. Greenbaum, L. 2008. Management of Childhood Onset Nephrotic Syndrome. Journal of The American Acedemy of Pediatrics, 27 (124), p. 747
REFERENCES
1.
2.
3.
4.
5.
6.
Bangga, A. and Mantan, M. 2005. Nephrotic syndrome in children. Indian J Med Res, 122 pp. 13-28.
Kodner, C. 2009. Nephrotic Syndrome in Adults : Diagnosis and Management. A merican Family Physician,
80 (10)
A. Greenbaum, L., Benndorf, R. and E. Smoyer, W. 2012. Childhood nephrotic syndrome-current an future
therapies. Nature Reviews Nephrology, 8 pp. 445-448
Guideline for Management of Nephrotic Syndrome, Renal unit Royal Hospital for Sick Children Yorkhill Division
S. Gipson, D., F. Massengill, S., Yao, L., Nagaraj, S., E. Smoyer, W., D. Mahan, J., Wigfall, D., Miles, P.,
Poswell, L., Lin, J., Trachtman, H. and A. Greenbaum, L. 2008. Management of Childhood Onset Nephrotic
Syndrome. Journal of The A merican Acedemy of Pediatrics, 27 (124), p. 747
Paediatric protocols for Malaysian Hospitals 3rd Edition
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