CitraNatal® Visual Highlights

Transcription

CitraNatal Visual Highlights
®
Product Logo
Alternate Product Logo
Product Packaging
CitraNatal® 90 DHA
Multivitamin • 75 mg B6
pick the
Lets you
one for
just-right
tient’s
ever y pa
needs
nutritional
Choose the calming option
for additional vitamin B6
Multivi
tamin
& gelcap
•
Combination single pill • 250 mg DHA • Stool softener
eption,
onc
ition for prec
Gentle nutr
ation
cy, and lact
pregnan
90 mg
iron •
300 mg
DHA •
n For many women, nausea and vomiting
can be serious concerns9
Stool soft
ener
n Vitamin B6 may reduce symptoms of severe
nausea and vomiting safely and effectively10
n CitraNatal B-Calm provides gentle GI
calming all day, with 25 mg B6 every 8 hours
®
n Signature CitraNatal formula contains
gentle ingredients for mom and strong
nutrition for baby, including
— Calcium
citrate—to avoid
Choose the
prenatal
nutrition
gas and bloating
Multivitamin & gelcap • 300 mg DHA • Stool softener
in tune with her life
2
— Carbonyl iron—gentle absorption
for better tolerability and safety1
p
in & gelca
Multivitam • Stool softener
300 mg DHA
iron
p • 90 mg
in & gelca
Multivitam • Stool softener
300 mg DHA
n Trusted, gentle formula—the proven comfort of
calcium citrate helps minimize gas and bloating2
n Gentle carbonyl iron—known for tolerability,
absorption, and safety with “less gastrointestinal
toxicity than iron salts”4
CitraNatal comfort with
Choose
prenatal vitamin
gentle GIthe
calming
n Constipation relief—gentle docusate sodium
helps ease the constipation that often
accompanies pregnancy3
that babies them both
n 250 mg life’sDHA™ optimizes benefits for baby
with pure, preformed,
vegetable-source DHA
n With Ferr-Ease™, a patented dual-iron delivery
CitraNatal B-Calm®
CitraNatal Harmony®
e pill
tion singl
ner
Combina
• Stool softe
250 mg DHA
Choose
patients the gentle op
tio
need
addition n when
deficien
al iron
cy ane
neurode
mia has
velo
n Iron
been linke
pmental
conseq
d
uences 6-8 to fetal
n Citra
Natal ®
90 con
made
up of both tains a full
90 mg
carbony
of iron
l iron and
with FerrEase™,
ferrous
comfort
glucona
of calc
than othe
te
ium citra
r calcium
te—for
less gas
salts 2
and bloa
n Doc
ting
usate
sodium
constipa
to relie
ve the
tion duri
frequen
ng preg
t prob
nancy 3
lem of
n Opt
imized
life’sDHA with 300 mg
vegetab
™—mee
le-base
for preg
ts worl
d, pure
dwide
nancy
, preform
consens
and lact
us reco
ed
ation 5
mmend
ations
n The
with both carbonyl iron and ferrous gluconate
Multivitam
B6
Its gentle nature
and bloating than other calcium salts2
is its strength.
cause of fatal
is a leading
In
ing products
CHILDREN.
iron-contain OUT OF THE REACH OF
overdose of
immediately.
PRODUCT
Accidental
6. KEEP THIS
control center
WARNING:
children under call a doctor or poison
poisoning in
se,
ntal overdo
case of accide
n Docusate sodium to relieve the frequent
problem of constipation during pregnancy3
n Optimized with 300 mg vegetable-based,
pure, preformed life’sDHA™—meets worldwide
consensus recommendations for pregnancy
and lactation5
The first and only
single-pill prenatal vitamin with
comfortable calcium citrate
The prenatal vitamin
where comfort for mom meets
optimized nutrition for baby.
Professional Campaign
Rx only - Please see full prescribing information provided.
WARNING: Accidental overdose of iron-containing products is a leading
cause of fatal poisoning in children under 6. KEEP THIS PRODUCT OUT
OF THE REACH OF CHILDREN. In case of accidental overdose, call a
doctor or poison control center immediately.
Images shown not actual size.
Copyright © 2012 Mission Pharmacal Company. All rights reserved.
CitraNatal Assure®
ming
losso
Our b
ntle
of ge
ily
ins…
fam
vitam
atal
pren
in • 75 mg
n Easygoing simplicity—just one vanilla-scented gel
cap, once a day, n
helps
enhance
compliance
The comfort
of calcium
citrate—for less gas
Extra iron
in
comprehensivea formulation that’s
and comfor
table
CitraNatal® Visual Highlights
Product Logos by Brand
Product Packaging
INDICATIONS: CitraNatal Assure® is a multivitamin/mineral
prescription drug indicated for use in improving the nutritional status
of women prior to conception, throughout pregnancy, and in the
postnatal period for both lactating and nonlactating mothers.
DESCRIPTION: CitraNatal Harmony® is a prescription prenatal/
postnatal multivitamin/mineral soft gelatin capsule. The prenatal vitamin
is a purple, opaque soft gelatin capsule containing a greenish-gray
liquid to semi-solid fill. The capsule is printed “0798” in white ink.
Each prenatal capsule contains:
Calcium (Calcium citrate)............................................ 104 mg
Iron (Carbonyl iron)...................................................... 30 mg
Vitamin D3 (Cholecalciferol)........................................ 400 IU
Vitamin E (dl-alpha tocopheryl acetate)....................... 30 IU
Vitamin B6 (Pyridoxine HCl)........................................ 25 mg
Folic Acid ................................................................ 1 mg
Docusate Sodium....................................................... 50 mg
Docosahexaenoic Acid (DHA
40% from 650 mg Algal Oil).......................................... 260 mg
INDICATIONS: CitraNatal Harmony® is a multivitamin/mineral
prescription drug indicated for use in improving the nutritional status
of women prior to conception, throughout pregnancy, and in the
postnatal period for both lactating and nonlactating mothers.
CONTRAINDICATIONS: This product is contraindicated in patients
with a known hypersensitivity to any of the ingredients.
WARNING: Accidental overdose of iron-containing products is a
leading cause of fatal poisoning in children under 6. KEEP THIS
PRODUCT OUT OF THE REACH OF CHILDREN. In case of accidental
overdose, call a doctor or poison control center immediately.
WARNING: Ingestion of more than 3 grams of omega-3 fatty acids per
day has been shown to have potential antithrombotic effects, including
an increased bleeding time and INR. Administration of omega-3 fatty
acids should be avoided in patients on anticoagulants and in those
known to have an inherited or acquired bleeding diathesis.
WARNING: Folic acid alone is improper therapy in the treatment of
pernicious anemia and other megaloblastic anemias where vitamin
B12 is deficient.
WARNING: Accidental overdose of iron-containing products is
a leading cause of fatal poisoning in children under 6. KEEP THIS
PRODUCT OUT OF THE REACH OF CHILDREN. In case of accidental
overdose, call a doctor or poison control center immediately.
WARNING: Ingestion of more than 3 grams of omega-3 fatty acids
per day has been shown to have potential antithrombotic effects,
including an increased bleeding time and INR. Administration of
omega-3 fatty acids should be avoided in patients on anticoagulants
and in those known to have an inherited or acquired bleeding
diathesis.
B12 is deficient.
PRECAUTIONS: Folic acid in doses above 0.1 mg daily may obscure
pernicious anemia in that hematologic remission can occur while
neurological manifestations progress.
ADVERSE REACTIONS: Allergic sensitization has been reported
following both oral and parenteral administration of folic acid.
DOSAGE AND ADMINISTRATION: One tablet and one capsule daily
or as directed by a physician.
STORAGE: Store at 20-25°C (68-77°F)
NOTICE: Contact with moisture can discolor or erode the tablet.
HOW SUPPLIED: Six child-resistant blister packs of 5 tablets and
5 capsules each - NDC 0178-0893-30
To report a serious adverse event or obtain product information, call
(210) 696-8400.
WARNING: Accidental overdose of iron-containing products is a
leading cause of fatal poisoning in children under 6. KEEP THIS PRODUCT
OUT OF THE REACH OF CHILDREN. In case of accidental overdose, call a
CAUTION: Exercise caution to ensure that the prescribed dosage of
DHA does not exceed 1 gram (1000 mg) per day.
Store at controlled room temperature.
NOTICE: Contact with moisture can discolor or erode the capsule.
HOW SUPPLIED: Bottles of 30 capsules each - NDC 0178-0798-30.
(210) 696-8400.
DESCRIPTION: CitraNatal Assure® is a prescription prenatal/
postnatal multivitamin/mineral tablet with Ferr-Ease®, a patented
dual-iron delivery comprising both a quick release and slow release
iron, and a capsule of an essential fatty acid. The prenatal vitamin
is a white, coated, oval multivitamin/mineral tablet. The tablet
is debossed “0893” on one side and is blank on the other. The
essential fatty acid DHA capsule is caramel colored and contains a
light yellow to orange semi-solid mixture.
Each prenatal capsule contains:
Vitamin C (Ascorbic acid)............................................... 120 mg
Calcium (Calcium citrate)............................................... 125 mg
Iron (Carbonyl iron, ferrous gluconate)........................... 35mg
Vitamin D3 (Cholecalciferol)........................................... 400 IU
Vitamin E (dl-alpha tocopheryl acetate)......................... 30IU
Thiamin (Vitamin B1)....................................................... 3mg
Riboflavin (Vitamin B2)................................................... 3.4 mg
Niacinamide (Vitamin B3)............................................... 20mg
Vitamin B6 (Pyridoxine HCl)........................................... 25mg
Folic Acid........................................................................ 1mg
Iodine (Potassium iodide)............................................... 150 mcg
Zinc (Zinc oxide)............................................................. 25mg
Copper (Cupric oxide).................................................... 2mg
Docusate Sodium........................................................... 50mg
Each DHA gelatin capsule contains:
Docosahexaenoic Acid
(DHA, 40% from 750 mg Algal Oil).............................. 300mg
Eicosapentaenoic Acid (EPA) ................ Not more than 0.750 mg
Other ingredients in DHA gelatin capsule: High Oleic Sunflower
Oil, Sunflower Lecithin, Rosemary Extract, Tocopherols, Ascorbyl
Palmitate.
INDICATIONS: CitraNatal® 90 DHAis a multivitamin/mineral prescription
drug indicated for use in improving the nutritional status of women prior
to conception, throughout pregnancy, and in the postnatal period for both
lactating and nonlactating mothers.
CONTRAINDICATIONS: This product is contraindicated in patients with
a known hypersensitivity to any of the ingredients.
DOSAGE AND ADMINISTRATION: One capsule daily or as directed
by a physician.
DESCRIPTION: CitraNatal® 90 DHA is a prescription prenatal/postnatal
multivitamin/mineral tablet with Ferr-Ease®, a patented dual-iron delivery
comprising both a quick release and slow release iron, and a capsule
of an essential fatty acid. The prenatal vitamin is a scored, white, oval
multivitamin/mineral tablet.The tablet is debossed “CN 90” on one side
and “08” bisect “29” on the other. The essential fatty acid DHA capsule
is caramel colored and contains a light yellow to orange semi-solid
mixture.
Each prenatal tablet contains:
Vitamin C (Ascorbic acid)....................................................... 120 mg
Calcium (Calcium citrate)....................................................... 160 mg
Iron (Carbonyl iron, ferrous gluconate)................................... 90 mg
Vitamin D3 (Cholecalciferol).................................................... 400 IU
Vitamin E (dl-alpha tocopheryl acetate)................................. 30 IU
3 mg
Thiamin (Vitamin B1)............................................................... Riboflavin (Vitamin B2)............................................................ 3.4 mg
Niacinamide (Vitamin B3)........................................................ 20 mg
Vitamin B6 (Pyridoxine HCl).................................................... 20 mg
Folic Acid................................................................................ 1 mg
Iodine (Potassium iodide)....................................................... 150 mcg
Zinc (Zinc oxide)..................................................................... 25 mg
Copper (Cupric oxide)............................................................ 2 mg
Docusate Sodium................................................................... 50 mg
Each DHA gelatin capsule contains:
Docosahexaenoic Acid
(DHA, 40% from 750 mg Algal Oil)........................................300mg
Eicosapentaenoic Acid (EPA) ....................... Not more than 0.750 mg
Other ingredients in DHA gelatin capsule: High Oleic Sunflower Oil,
Sunflower Lecithin, Rosemary Extract, Tocopherols, Ascorbyl Palmitate.
DESCRIPTION: CitraNatal B-Calm® is a prescription prenatal
multivitamin/mineral tablet with B6, along with two vitamin B6 tablets.
The prenatal tablet contains Ferr-Ease®, a patented dual-iron delivery
comprising both a quick release and slow release iron. The prenatal
tablet is white, coated, modified oval, and is debossed with “0832”
on one side and is blank on the other. The B6 25 mg tablets are white
to off-white, uncoated, round, and are debossed with “B” on one side
and “6” on the other.
Each prenatal tablet contains:
Vitamin C (Ascorbic acid)....................................................120 mg
Calcium (Calcium citrate)....................................................120 mg
Iron (Carbonyl iron, ferrous gluconate)................................20 mg
Vitamin D3 (Cholecalciferol)................................................400 IU
Vitamin B6 (Pyridoxine HCl)................................................25 mg
Folic Acid............................................................................. 1 mg
Each vitamin B6 tablet contains:
Vitamin B6 (Pyridoxine HCl)................................................25 mg
INDICATIONS: CitraNatal B-Calm® is a multivitamin/mineral
prescription drug indicated for use in improving the nutritional status of
women prior to conception, throughout pregnancy, and in the postnatal
period for both lactating and nonlactating mothers. CitraNatal B-Calm®
may be used in conjunction with a physician prescribed regimen to
help minimize pregnancy related nausea and vomiting.
WARNING: Accidental overdose of iron-containing products is
a leading cause of fatal poisoning in children under 6. KEEP THIS
AND ALL DRUGS OUT OF THE REACH OF CHILDREN. In case
of accidental overdose, call a doctor or poison control center
immediately.
B12 is deficient.
PRECAUTION: Folic acid in doses above 0.1 mg daily may obscure
pernicious anemia, in that hematologic remission can occur while
neurological manifestations remain progressive.
DOSAGE AND ADMINISTRATION: One tablet every eight hours,
beginning with “Tablet 1”, or as directed by a physician.
WARNING: Ingestion of more than 3 grams of omega-3 fatty acids per
day has been shown to have potential antithrombotic effects, including
an increased bleeding time and INR. Administration of omega-3 fatty
acids should be avoided in patients on anticoagulants and in those
known to have an inherited or acquired bleeding diathesis.
pernicious anemia and other megaloblastic anemias where vitamin B12
is deficient.
DOSAGE AND ADMINISTRATION: One tablet and one capsule daily or
as directed by a physician.
HOW SUPPLIED: Six child-resistant blister packs of 5 tablets and
5 capsules each - NDC 0178-0829-30
(210) 696-8400.
CitraNatal Harmony®:
Capsules are MADE IN CANADA
CitraNatal Harmony® contains
life’sDHA™ .
To report a serious adverse event or obtain product information, call (210)
696-8400.
Ferr-Ease
®
Dual-iron delivery
Trademark of Mission Pharmacal Company
U.S. Patent No. 6,521,247
Trademark of Martek Biosciences Corporation
DHA capsules manufactured for:
MISSION PHARMACAL COMPANY
San Antonio, TX USA 78230 1355
Prenatal tablets manufactured by:
NOTICE: Contact with moisture can discolor or erode tablets.
HOW SUPPLIED: Six child-resistant blister packs of 5 multivitamin/
multimineral tablets and 10 vitamin B6 tablets each - NDC 0178-0832-30.
CitraNatal Assure®, CitraNatal B-Calm
and CitraNatal® 90DHA contain
Ferr-Ease®.
Copyright © 2012 Mission Pharmacal
Company. All rights reserved.
CNP-49_Rev 0212
CitraNatal Assure® and CitraNatal®
90DHA contain life’sDHA™.
Trademark of Martek Biosciences Corporation
citranatal.com
missionpharmacal.com
Urocit -K 15 mEq
Visual Highlights
®
Product Logo
Product Packaging
Product
Take the pain out of stone therapy dosing
with
Simplify the dose.
Strengthen the compliance.
Urocit®-K 15 mEq—a maximum-strength alkalinizing
agent for simple BID dosing in the treatment
of recurrent nephrolithiasis.
Medication management is a proven tool
for inhibiting stone formation. Yet patient
adherence to multitablet, multidose therapy
regimens remains a significant challenge.8,9
Powerful dosage strength—Urocit-K 15 mEq
Welcome simplicity—more concentrated
contains 50% more active ingredient than Urocit-K 10 mEq
formula simplifies complex dosing schedules
Streamlined control—maintain targeted urinary
Condition
– Hypercalciuria
(urinary Ca > 250 mg/day)
– Hyperuricosuria
citrate and urinary pH levels with fewer daily tablets
Enhanced compliance—in clinical
studies, less frequent dosing regimens
demonstrate better compliance10
– Relative hypocitraturia
Proven efficacy—potassium citrate has been
Comfortable formula—slow-release
wax-matrix delivery system for extended
release in the GI tract enhances tolerability
and provides uniform increases in urinary
citrate levels4,11
– Hypocitraturia
proven to inhibit formation of calcium oxalate and uric
acid stones,1,2,3 with a clinical success rate of more
than 90%4,5,6
Long-term studies demonstrate that
potassium citrate significantly decreases
the rate of kidney stone formation7
(urinary UA > 700 mg/day, pH > 5.50)
15 mEq Tablet
Dosage
BID
1 tablet AM
2 tablets PM
BID
1 tablet AM
1 tablet PM
(urinary Citrate 320-500 mg/day)
(urinary Citrate < 320 mg/day)
– Idiopathic uric acid nephrolithiasis
(urinary pH < 5.50 on both random and restricted diets)
BID
1-2 tablets AM
1-2 tablets PM
Urocit -K 15 mEq should be taken with meals or within 30 minutes
after meals or bedtime snack.
®
Objective: To restore normal urinary citrate (greater than 320 mg/day
and as close to the normal mean of 640 mg/day as possible), and to
increase urinary pH to a level of 6.0 to 7.0.
• Severe hypocitraturia (urinary citrate < 150 mg/day): therapy should
be initiated at 60 mEq per day; a dose of 30 mEq two times per
day or 20 mEq three times per day with meals or within 30 minutes
after meals or bedtime snack
• Mild to moderate hypocitraturia (urinary citrate >150 mg/day):
therapy should be initiated at 30 mEq per day; a dose of 15 mEq
two times per day or 10 mEq three times per day with meals or
within 30 minutes after meals or bedtime snack
Image at right is an artistic representation and not an actual tablet.
The strength to simplify .
®
Kidney
stones
hurt.
Nonco
mplian
ce
Contraindications
• Patients with hyperkalemia, peptic ulcer disease, active urinary tract infection, and renal insufficiency
• Conditions predisposing patients to hyperkalemia, including chronic renal failure, uncontrolled diabetes mellitus, acute dehydration,
strenuous physical exercise in unconditioned individuals, adrenal insufficiency, and extensive tissue breakdown
Warnings and Precautions
• Hyperkalemia: In patients with impaired mechanisms for excreting potassium, Urocit-K administration can produce hyperkalemia and
cardiac arrest. Potentially fatal hyperkalemia can develop rapidly and be asymptomatic. The use of Urocit-K in patients with chronic
renal failure, or any other condition which impairs potassium excretion such as severe myocardial damage or heart failure, should be
avoided
• Gastrointestinal lesions: If there is severe vomiting, abdominal pain or gastrointestinal bleeding, Urocit-K should be discontinued immediately and the possibility of bowel perforation or obstruction investigated
Please see full Prescribing Information.
rt m
can hu
ore.
Patient Counseling Information
Administration of Drug
• Patients should be told to take Urocit-K 15 mEq without crushing, chewing, or sucking the tablet
• Patients should be told to take Urocit-K 15 mEq only as directed, especially if the patient is also taking both diuretics and digitalis preparations
• Patients should be told to check with the doctor if they experience difficulty swallowing the tablet or it seems to stick in the throat
• Patients should be told to check with the doctor at once if they notice tarry stools or other signs of gastrointestinal bleeding
• Patients should be advised that regular blood tests and electrocardiograms will be performed to ensure safety
Patient Monitoring Information
Hyperkalemia
• Patients with impaired mechanisms for excreting potassium should be closely monitored for signs of hyperkalemia with periodic blood tests
and ECGs
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
Urocit®-K safely and effectively. See full prescribing information
for Urocit®-K.
Urocit®-K (Potassium Citrate) Extended-release tablets for oral use
Initial U.S. Approval: 1985
------------------------RECENT MAJOR CHANGES--------------------Dosage and Administration, Urocit®-K 15 mEq (2.2, 2.3)
12/2009
Dosage Forms and Strengths, Urocit®-K 15 mEq (3)
12/2009
®
Description, Urocit -K 15 mEq (11)
12/2009
Clinical Studies (14)
12/2009
®
How Supplied/Storage and Handling, Urocit -K 15 mEq (16)
12/2009
------------------------ INDICATIONS AND USAGE --------------------Urocit®-K is a citrate salt of potassium indicated for the management of:
• Renaltubularacidosis(RTA)withcalciumstones(1.1)
• Hypocitraturiccalciumoxalatenephrolithiasisofanyetiology(1.2)
• Uricacidlithiasiswithorwithoutcalciumstones(1.3)
--------------------- DOSAGE AND ADMINISTRATION -----------------Objective:Torestorenormalurinarycitrate(greaterthan320mg/dayandas
closetothenormalmeanof640mg/dayaspossible),andtoincreaseurinary
pHtoalevelof6.0to7.0.
• Severehypocitraturia(urinarycitrate<150mg/day):therapyshouldbe
initiated at 60 mEqperday;adoseof30mEqtwotimesperdayor
20mEqthreetimesperdaywithmeals or within 30 minutes after meals
orbedtimesnack(2.2)
• Mildtomoderatehypocitraturia(urinarycitrate>150mg/day):therapy
shouldbeinitiatedat30mEqperday;adoseof15mEqtwotimesper
dayor10mEqthreetimesperdaywithmealsorwithin30minutes aftermealsorbedtimesnack(2.3)
--------------------DOSAGE FORMS AND STRENGTHS ---------------Tablets:5mEq,10mEqand15mEq(3)
-------------------------- CONTRAINDICATIONS ----------------------• Patientswithhyperkalemia(orwhohaveconditionspredisposingthem
tohyperkalemia).Suchconditions include chronic renal failure,
uncontrolled diabetesmellitus,acutedehydration,strenuousphysical exerciseinunconditionedindividuals,adrenalinsufficiency,extensive tissuebreakdown(4)
• Patientsforwhomthereiscauseforarrestordelayintabletpassage through the gastrointestinal tract suchasthosesufferingfromdelayed
gastricemptying,esophagealcompression,intestinalobstruction
or stricture (4)
• Patientswithpepticulcerdisease(4)
• Patientswithactiveurinarytractinfection(4)
• Patientswithrenalinsufficiency(glomerularfiltrationrateoflessthan
0.7ml/kg/min)(4)
--------------------- WARNINGS AND PRECAUTIONS -----------------• Hyperkalemia:Inpatientswithimpairedmechanismsforexcretingpotas-
sium, Urocit®-Kadministrationcanproducehyperkalemiaandcardiac
arrest.Potentiallyfatalhyperkalemiacandeveloprapidlyandbe
asymptomatic.TheuseofUrocit®-K in patients with chronic renal failure,
oranyotherconditionwhichimpairspotassiumexcretionsuchas severemyocardialdamageorheartfailure,shouldbeavoided(5.1)
• Gastrointestinallesions:ifthereisseverevomiting,abdominalpainor
gastrointestinalbleeding,Urocit®-Kshouldbediscontinuedimmediately
andthepossibilityofbowelperforationorobstructioninvestigated(5.2)
-------------------------- ADVERSE REACTIONS ----------------------Somepatientsmaydevelopminorgastrointestinalcomplaintssuchas
abdominaldiscomfort,vomiting,diarrhea,loosebowelmovementsornausea.
Thesemaybealleviatedbytakingthedosewithmealsorsnacksorby
reducing the dosage (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Mission
Pharmacal Company at 1-800-298-1087 or FDA at 1-800-FDA-1088
or www.fda.gov/medwatch
-------------------------- DRUG INTERACTIONS ----------------------Thefollowingdruginteractionsmayoccurwithpotassiumcitrate:
• Potassium-sparingdiuretics:concomitantadministrationshouldbe avoidedsincethesimultaneousadministration of these agents can
produceseverehyperkalemia(7.1)
• Drugsthatslowgastrointestinaltransittime:Theseagents(suchas anticholinergics)canbeexpectedtoincreasethegastrointestinalirritation
producedbypotassiumsalts(7.2)
--------------------- USE IN SPECIFIC POPULATIONS -----------------• Pregnantwomen:PregnancyCategoryC;animalreproductionstudies
havenotbeenconducted.ItisnotknownwhetherUrocit®-K can cause
fetal harm when administered to a pregnant woman or can affect
reproductioncapacity.Urocit®-Kshouldbegiventoapregnantwoman
onlyifclearlyneeded(8.1)
• Nursingmothers:Thenormalpotassiumioncontentofhumanmilkisabout
13mEq/L.Itisnotknownif Urocit®-K has an effect on this content. Urocit®-K
shouldbegiventoawomanwhoisbreastfeedingonlyifclearlyneeded(8.3)
• PediatricUse:Safetyandeffectivenessinchildrenhavenotbeen
established(8.4)
See 17 for PATIENT COUNSELING INFORMATION
Revised: 04/2010
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
1.1 Renaltubularacidosis(RTA)withcalciumstones
1.2 Hypocitraturiccalciumoxalatenephrolithiasisofanyetiology
1.3 Uric acid lithiasis with or without calcium stones
2 DOSAGE AND ADMINISTRATION
2.1 DosingInstructions
2.2 Severehypocitraturia
2.3 Mildtomoderatehypocitraturia
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Hyperkalemia
5.2 Gastrointestinallesions
6 ADVERSE REACTIONS
6.1 PostmarketingExperience
7 DRUG INTERACTIONS
7.1 PotentialEffectsofPotassiumcitrateonOtherDrugs
7.2 PotentialEffectsofOtherDrugsonPotassiumcitrate
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy
8.3NursingMothers
8.4PediatricUse
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1MechanismofAction
14 CLINICAL STUDIES
14.1Renaltubularacidosis(RTA)withcalciumstones
14.2Hypocitraturiccalciumoxalatenephrolithiasisofanyetiology
15 REFERENCES
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
17.1AdministrationofDrug
*Sectionsorsubsectionsomittedfromthefullprescribinginformationare
not listed
FULL PRESCRIBING INFORMATION
1.1 Renal tubular acidosis (RTA) with calcium stones
Potassiumcitrateisindicatedforthemanagementofrenal
tubularacidosis[see Clinical Studies (14.1)].
1.2 Hypocitraturic calcium oxalate nephrolithiasis of any etiology
PotassiumcitrateisindicatedforthemanagementofHypocitraturic calciumoxalatenephrolithiasis[see Clinical Studies (14.2)].
PotassiumcitrateisindicatedforthemanagementofUricacidlithiasis
with or without calcium stones [see Clinical Studies (14.3)].
2.1 Dosing Instructions
Treatmentwithextendedreleasepotassiumcitrateshouldbeaddedto
aregimenthatlimitssaltintake(avoidanceoffoodswithhighsaltcontent
andofaddedsaltatthetable)andencourageshighfluidintake(urine
volumeshouldbeatleasttwolitersperday).Theobjectiveoftreatmentwith
Urocit®-KistoprovideUrocit®-Kinsufficientdosagetorestorenormalurinary
citrate(greaterthan320mg/dayandasclosetothenormalmeanof640
mg/dayaspossible),andtoincreaseurinarypHtoalevelof6.0or7.0.
Monitorserumelectrolytes(sodium,potassium,chlorideandcarbon
dioxide),serumcreatinineandcompletebloodcountseveryfourmonthsand
morefrequentlyinpatientswithcardiacdisease,renaldiseaseoracidosis.
Performelectrocardiogramsperiodically.Treatmentshouldbediscontinuedif
thereishyperkalemia,asignificantriseinserumcreatinineorasignificantfall
inbloodhemocritorhemoglobin.
2.2 Severe Hypocitraturia
Inpatientswithseverehypocitraturia(urinarycitrate<150mg/day),
therapyshouldbeinitiatedatadosageof60mEq/day(30mEqtwotimes/
dayor20mEqthreetimes/daywithmealsorwithin30minutesaftermeals
orbedtimesnack).Twenty-fourhoururinarycitrateand/orurinarypHmeasurementsshouldbeusedtodeterminetheadequacyoftheinitialdosage
andtoevaluatetheeffectivenessofanydosagechange.Inaddition,urinary
citrateand/orpHshouldbemeasuredeveryfourmonths.DosesofUrocit®-K
greaterthan100mEq/dayhavenotbeenstudiedandshouldbeavoided.
2.3 Mild to Moderate Hypocitraturia
Inpatientswithmildtomoderatehypocitraturia(urinarycitrate>150
mg/day)therapyshouldbeinitiatedat30mEq/day(15mEqtwotimes/day
or10mEqthreetimes/daywithin30minutesaftermealsorbedtimesnack).
Twenty-fourhoururinarycitrateand/orurinarypHmeasurementsshould
beusedtodeterminetheadequacyoftheinitialdosageandtoevaluatethe
effectivenessofanydosagechange.DosesofUrocit®-K greater than 100 mEq/
dayhavenotbeenstudiedandshouldbeavoided.
• 5mEqtabletsareuncoated,tantoyellowishincolor,modifiedball shaped,withMPC600debossedononesideandblankontheother
• 10mEqtabletsareuncoated,tantoyellowishincolor,ellipticalshaped,
with610debossedononesideandMISSIONontheother
• 15mEqtabletsareuncoated,tantoyellowishincolor,modifiedrectangle
shaped,withM15debossedononesideandblankontheother
4 CONTRAINDICATIONS
Urocit®-K is contraindicated:
• Inpatientswithhyperkalemia(orwhohaveconditionspre-disposingthem
tohyperkalemia),asafurtherriseinserumpotassiumconcentrationmay
produce cardiac arrest. Such conditions include: chronic renal failure,
uncontrolleddiabetesmellitus,acutedehydration,strenuousphysical exerciseinunconditionedindividuals,adrenalinsufficiency,extensive tissuebreakdownortheadministrationofapotassium-sparingagent (such as triamterene, spironolactone or amiloride).
• Inpatientsinwhomthereiscauseforarrestordelayintabletpassage
through the gastrointestinaltract,suchasthosesufferingfromdelayed
gastricemptying,esophagealcompression,intestinalobstructionor stricture,orthosetakinganticholinergic medication.
• Inpatientswithpepticulcerdiseasebecauseofitsulcerogenicpotential.
• Inpatientswithactiveurinarytractinfection(witheitherurea-splittingor
otherorganisms,inassociationwitheithercalciumorstruvitestones).
TheabilityofUrocit®-Ktoincreaseurinarycitratemaybeattenuatedby
bacterialenzymaticdegradationofcitrate.Moreover,theriseinurinary
pH resulting from Urocit®-Ktherapymightpromotefurtherbacterial growth.
• Inpatientswithrenalinsufficiency(glomerularfiltrationrateofless than0.7ml/kg/min),becauseofthedangerofsofttissuecalcification
andincreasedriskforthedevelopmentofhyperkalemia.
5.1 Hyperkalemia
Inpatientswithimpairedmechanismsforexcretingpotassium,Urocit®-K
administrationcanproducehyperkalemiaandcardiacarrest.Potentiallyfatal
hyperkalemiacandeveloprapidlyandbeasymptomatic.TheuseofUrocit®-K
inpatientswithchronicrenalfailure,oranyotherconditionwhichimpairs
potassiumexcretionsuchasseveremyocardialdamageorheartfailure,
shouldbeavoided.Closelymonitorforsignsofhyperkalemiawithperiodic
bloodtestsandECGs.
5.2 Gastrointestinal Lesions
Because of reports of upper gastrointestinal mucosal lesions following
administrationofpotassiumchloride(wax-matrix),anendoscopicexamination
oftheuppergastrointestinalmucosawasperformedin30normalvolunteers
aftertheyhadtakenglycopyrrolate2mgp.o.t.i.d.,Urocit®-K95mEq/day,
wax-matrixpotassiumchloride96mEq/dayorwax-matrixplacebo,inthrice
dailyscheduleinthefastingstateforoneweek.Urocit®-Kandthewax-matrix
formulationofpotassiumchloridewereindistinguishablebutbothwere
significantlymoreirritatingthanthewax-matrixplacebo.Inasubsequent,
similarstudy,lesionswerelessseverewhenglycopyrrolatewasomitted.
Soliddosageformsofpotassiumchlorideshaveproducedstenoticand/
orulcerativelesionsofthesmallbowelanddeaths.Theselesionsarecaused
byahighlocalconcentrationofpotassiumionsintheregionofthedissolving
tablets,whichinjuredthebowel.Inaddition,perhapsbecausewax-matrix
preparations are not enteric-coated and release some of their potassium
contentinthestomach,therehavebeenreportsofuppergastrointestinal
bleedingassociatedwiththeseproducts.Thefrequencyofgastrointestinal
lesionswithwax-matrixpotassiumchlorideproductsisestimatedatoneper
100,000patient-years.ExperiencewithUrocit®-Kislimited,butasimilar
frequencyofgastrointestinallesionsshouldbeanticipated.
Ifthereisseverevomiting,abdominalpainorgastrointestinalbleeding,
Urocit®-Kshouldbediscontinuedimmediatelyandthepossibilityofbowel
perforationorobstructioninvestigated.
6 ADVERSE REACTIONS
6.1 Postmarketing Experience
Somepatientsmaydevelopminorgastrointestinalcomplaintsduring
Urocit®-Ktherapy,suchasabdominaldiscomfort,vomiting,diarrhea,loose
bowelmovementsornausea.Thesesymptomsareduetotheirritationofthe
gastrointestinaltract,andmaybealleviatedbytakingthedosewithmealsor
snacks,orbyreducingthedosage.Patientsmayfindintactmatricesintheir
feces.
7 DRUG INTERACTIONS
7.1 Potential Effects of Potassium citrate on Other Drugs
Potassium-sparing Diuretics: Concomitant administration of Urocit®-K
and a potassium-sparing diuretic (such as triamterene, spironolactone or
amiloride)shouldbeavoidedsincethesimultaneousadministrationofthese
agentscanproduceseverehyperkalemia.
7.2 Potential Effects of Other Drugs on Potassium citrate
Drugs that slow gastrointestinal transit time:Theseagents(suchasanticholinergics)canbeexpectedtoincreasethegastrointestinalirritationproduced
bypotassiumsalts.
8.1 Pregnancy
Pregnancy Category C
Animalreproductionstudieshavenotbeenconducted.Itisalsonot
knownwhetherUrocit®-K can cause fetal harm when administered to a
pregnantwomanorcanaffectreproductioncapacity.Urocit®-Kshouldbe
giventoapregnantwomanonlyifclearlyneeded.
8.3 Nursing Mothers
Thenormalpotassiumioncontentofhumanmilkisabout13mEq/L.Itis
notknownifUrocit®-K has an effect on this content. Urocit®-Kshouldbe
giventoawomanwhoisbreastfeedingonlyifclearlyneeded.
8.4 Pediatric Use
Safetyandeffectivenessinchildrenhavenotbeenestablished.
10 OVERDOSAGE
Treatment of Overdosage:Theadministrationofpotassiumsaltsto
personswithoutpredisposingconditionsforhyperkalemiararelycauses
serioushyperkalemiaatrecommendeddosages.Itisimportanttorecognize
thathyperkalemiaisusuallyasymptomaticandmaybemanifestedonlyby
an increased serum potassium concentration and characteristic electrocardiographicchanges(peakingofT-wave,lossofP-wave,depressionofS-T
segmentandprolongationoftheQTinterval).Latemanifestationsinclude
muscleparalysisandcardiovascularcollapsefromcardiacarrest.
Treatmentmeasuresforhyperkalemiaincludethefollowing:
1.Patientsshouldbecloselymonitoredforarrhythmiasandelectrolyte
changes. 2. Elimination of medications containing potassium and of agents
with potassium-sparing properties such as potassium-sparing diuretics,
ARBs,ACEinhibitors,NSAIDs,certainnutritionalsupplementsandmany
others.3.Eliminationoffoodscontaininghighlevelsofpotassiumsuchas
almonds, apricots, bananas,beans(lima,pinto,white),cantaloupe,carrot
juice(canned),figs,grapefruitjuice,halibut,milk,oatbran,potato(withskin),
salmon,spinach,tunaandmanyothers.4.Intravenouscalciumgluconateif
thepatientisatnoriskorlowriskofdevelopingdigitalistoxicity.5.Intravenousadministrationof300-500mL/hrof10%dextrosesolutioncontaining
10-20unitsofcrystallineinsulinper1,000mL.6.Correctionofacidosis,if
present,withintravenoussodiumbicarbonate.7.Hemodialysisorperitoneal
dialysis.8.Exchangeresinsmaybeused.However,thismeasurealoneisnot
sufficientfortheacutetreatmentofhyperkalemia.
Loweringpotassiumlevelstoorapidlyinpatientstakingdigitaliscan
producedigitalistoxicity.
11 DESCRIPTION
Urocit®-Kisacitratesaltofpotassium.Itsempiricalformulais
K3C6H507 • H20, and it has the following chemical structure:
CH2
HO
COOK
C
COOK
CH2
COOK
•
H2O
Urocit®-Kyellowishtotan,oralwax-matrixtablets,contain5mEq
(540mg)potassiumcitrate,10mEq(1080mg)potassiumcitrateand
15mEq(1620mg)potassiumcitrateeach.Inactiveingredientsinclude
carnaubawaxandmagnesiumstearate.
12.1 Mechanism of Action
When Urocit®-Kisgivenorally,themetabolismofabsorbedcitrate
producesanalkalineload.Theinducedalkalineloadinturnincreases
urinarypHandraisesurinarycitratebyaugmentingcitrateclearancewithout
measurablyalteringultrafilterableserumcitrate.Thus,Urocit®-Ktherapy
appearstoincreaseurinarycitrateprincipallybymodifyingtherenalhandling
ofcitrate,ratherthanbyincreasingthefilteredloadofcitrate.Theincreased
filteredloadofcitratemayplaysomerole,however,asinsmallcomparisons
oforalcitrateandoralbicarbonate,citratehadagreatereffectonurinary
citrate.
InadditiontoraisingurinarypHandcitrate,Urocit®-Kincreasesurinary
potassiumbyapproximatelytheamountcontainedinthemedication.In
some patients, Urocit®-Kcausesatransientreductioninurinarycalcium.
ThechangesinducedbyUrocit®-Kproduceurinethatislessconducive
tothecrystallizationofstone-formingsalts(calciumoxalate,calcium
phosphateanduricacid).Increasedcitrateintheurine,bycomplexingwith
calcium,decreasescalciumionactivityandthusthesaturationofcalcium
oxalate.Citratealsoinhibitsthespontaneousnucleationofcalciumoxalate
andcalciumphosphate(brushite).
TheincreaseinurinarypHalsodecreasescalciumionactivityby
increasingcalciumcomplexationtodissociatedanions.TheriseinurinarypH
alsoincreasestheionizationofuricacidtothemoresolubleurateion.
Urocit®-Ktherapydoesnotaltertheurinarysaturationofcalcium
phosphate,sincetheeffectofincreasedcitratecomplexationofcalciumis
opposedbytheriseinpH-dependentdissociationofphosphate.Calcium
phosphatestonesaremorestableinalkalineurine.
Inthesettingofnormalrenalfunction,theriseinurinarycitratefollowingasingledosebeginsbythefirsthourandlastsfor12hours.With
multipledosestheriseincitrateexcretionreachesitspeakbythethirdday
andavertsthenormallywidecircadianfluctuationinurinarycitrate,thus
maintainingurinarycitrateatahigher,moreconstantlevelthroughoutthe
day.Whenthetreatmentiswithdrawn,urinarycitratebeginstodecline
towardthepre-treatmentlevelonthefirstday.
TheriseincitrateexcretionisdirectlydependentontheUrocit®-K dosage. Following long-term treatment, Urocit®-Katadosageof60mEq/day
raisesurinarycitratebyapproximately400mg/dayandincreasesurinarypH
byapproximately0.7units.
Inpatientswithsevererenaltubularacidosisorchronicdiarrhealsyndromewhereurinarycitratemaybeverylow(<100mg/day),Urocit®-Kmay
berelativelyineffectiveinraisingurinarycitrate.AhigherdoseofUrocit®-K
maythereforeberequiredtoproduceasatisfactorycitraturicresponse.
InpatientswithrenaltubularacidosisinwhomurinarypHmaybehigh,
Urocit®-KproducesarelativelysmallriseinurinarypH.
14 CLINICAL STUDIES
ThepivotalUrocit®-Ktrialswerenon-randomizedandnon-placebo
controlledwheredietarymanagementmayhavechangedcoincidentally
withpharmacologicaltreatment.Therefore,theresultsaspresentedinthe
followingsectionsmayoverstatetheeffectivenessoftheproduct.
14.1 Renal tubular acidosis (RTA) with calcium stones
Theeffectoforalpotassiumcitratetherapyinanon-randomized,nonplacebocontrolledclinicalstudyoffivemenandfourwomenwithcalcium
oxalate/calciumphosphatenephrolithiasisanddocumentedincompletedistal
renaltubularacidosiswasexamined.Themaininclusioncriterionwasahistoryofstonepassageorsurgicalremovalofstonesduringthe3yearsprior
toinitiationofpotassiumcitratetherapy.Allpatientsbeganalkalitreatment
with60-80mEqpotassiumcitratedailyin3or4divideddoses.Throughout
treatment,patientswereinstructedtostayonasodiumrestricteddiet(100
mEq/day)andtoreduceoxalateintake(limitedintakeofnuts,darkroughage,
chocolateandtea).Amoderatecalciumrestriction(400-800mg/day)was
imposedonpatientswithhypercalciuria.
X-raysoftheurinarytract,availableinallpatients,werereviewedto
determinepresenceofpre-existingstones,appearanceofnewstones,or
changeinthenumberofstones.
Potassiumcitratetherapywasassociatedwithinhibitionofnewstone
formationinpatientswithdistaltubularacidosis.Threeoftheninepatients
continuedtopassstonesduringtheon-treatmentphase.Whileitislikely
thatthesepatientspassedpre-existingstonesduringtherapy,themost
conservativeassumptionisthatthepassedstoneswerenewlyformed.Using
thisassumption,thestone-passageremissionratewas67%.Allpatients
hadareducedstoneformationrate.Overthefirst2yearsoftreatment,the
on-treatmentstoneformationratewasreducedfrom13±27to1±2per
year.
14.2 Hypocitraturic calcium oxalate nephrolithiasis of
any etiology
Eighty-ninepatientswithhypocitraturiccalciumnephrolithiasisoruric
acid lithiasis with or without calcium nephrolithiasis participated in this nonrandomized,non-placebocontrolledclinicalstudy.Fourgroupsofpatients
weretreatedwithpotassiumcitrate:Group1wascomprisedof19patients,
10withrenaltubularacidosisand9withchronicdiarrhealsyndrome,Group
2wascomprisedof37patients,5withuricacidstonesalone,6withuric
acidlithiasisandcalciumstones,3withtype1absorptivehypercalciuria,9
withtype2absorptivehypercalciuriaand14withhypocitraturia.Group3
wascomprisedof15patientswithhistoryofrelapseonothertherapyand
Group4wascomprisedof18patients,9withtype1absorptivehypercalciuriaandcalciumstones,1withtype2absorptivehypercalciuriaandcalcium
stones,2withhyperuricosuriccalciumoxalatenephrolithiasis,4withuric
acidlithiasisaccompaniedbycalciumstonesand2withhypocitraturiaand
hyperuricemiaaccompaniedbycalciumstones.Thedoseofpotassium
citraterangedfrom30to100mEqperday,andusuallywas20mEq
administeredorally3timesdaily.Patientswerefollowedinanoutpatient
settingevery4monthsduringtreatmentandwerestudiedoveraperiod
from1to4.33years.Athree-yearretrospectivepre-studyhistoryforstone
passageorremovalwasobtainedandcorroboratedbymedicalrecords.
Concomitanttherapy(withthiazideorallopurinol)wasallowedifpatientshad
hypercalciuria,hyperuricosuriaorhyperuricemia.Group2wastreatedwith
potassium citrate alone.
Inallgroups,treatmentthatincludedpotassiumcitratewasassociated
withasustainedincreaseinurinarycitrateexcretionfromsubnormalvalues
tonormalvalues(400to700mg/day),andasustainedincreaseinurinary
pHfrom5.6-6.0toapproximately6.5.Thestoneformationratewasreduced
in all groups as shown in Table 1.
Table 1. Effect of Urocit®-K In Patients With Calcium Oxalate
Nephrolithiasis.
Stones Formed Per Year
Group
Baseline On Treatment Remission* Any Decrease
I(n=19) 12±30
0.9±1.3
58%
95%
II(n=37) 1.2±2
0.4±1.5
89%
97%
III(n=15) 4.2±7
0.7±2 67%
100%
IV(n=18) 3.4±8
0.5±2 94%
100%
Total(n=89) 4.3±15
0.6±2 80%
98%
*Remissiondefinedas“thepercentageofpatientsremainingfreeofnewly
formed stones during treatment”.
Along-termnon-randomized,non-placebocontrolledclinicaltrialwith
eighteenadultpatientswithuricacidlithiasisparticipatedinthestudy.Six
patientsformedonlyuricacidstones,andtheremaining12patientsformed
mixedstonescontainingbothuricacidandcalciumsaltsorformedbothuric
acid stones (without calcium salts) and calcium stones (without uric acid) on
separate occasions.
Elevenofthe18patientsreceivedpotassiumcitratealone.Sixofthe7
otherpatientsalsoreceivedallopurinolforhyperuricemiawithgoutyarthritis,
symptomatichyperuricemia,orhyperuricosuria.Onepatientalsoreceived
hydrochlorothiazidebecauseofunclassifiedhypercalciuria.Themaininclusioncriterionwasahistoryofstonepassageorsurgicalremovalofstones
duringthe3yearspriortoinitiationofpotassiumcitratetherapy.Allpatients
receivedpotassiumcitrateatadosageof30-80mEq/dayinthree-to-four
divideddosesandwerefollowedeveryfourmonthsforupto5years.
Whileonpotassiumcitratetreatment,urinarypHrosesignificantlyfrom
alowvalueof5.3±0.3towithinnormallimits(6.2to6.5).Urinarycitrate
whichwaslowbeforetreatmentrosetothehighnormalrangeandonlyone
stonewasformedintheentiregroupof18patients.
15 REFERENCES
1.Pak,C.(1987).CitrateandRenalCalculi.Mineral and Electrolyte
Metabolism13,257-266.
2.Pak,C.(1985).Long-TermTreatmentofCalciumNephrolithiasiswith
PotassiumCitrate.The Journal of Urology 134, 11-19.
3.Preminger,G.M.,K.Sakhaee,C.SkurlaandC.Y.C.Pak.(1985).
PreventionofRecurrentCalciumStoneFormationwithPotassiumCitrate
TherapyinPatientswithDistalRenalTubularAcidosis.The Journal of Urology 134, 20-23.
4.Pak,C.Y.C.,K.SakhaeeandC.Fuller.(1986).SuccessfulManagement
ofUricAcidNephrolithiasiswithPotassiumCitrate.Kidney International 30,
422-428.
5.Hollander-Rodriguez,Jetal.(2006).Hyperkalemia,American Family
Physician,Vol.73/No.2.
6.Greenberg,Aetal.(1998).Hyperkalemia:treatmentoptions.Semen
Nephrol.Jan;18(1):46-57.
Urocit®-K5mEqtabletsareuncoated,tantoyellowishincolor,modified
ballshaped,withMPC600debossedononesideandblankontheother,
suppliedinbottlesas:
NDC0178-0600-01
Bottleof100
Urocit®-K10mEqtabletsareuncoated,tantoyellowishincolor,elliptical
shaped,with610debossedononesideandMISSIONontheother,supplied
inbottlesas:
NDC0178-0610-01
Bottleof100
Urocit®-K15mEqtabletsareuncoated,tantoyellowishincolor,modified
rectangleshaped,withM15debossedononesideandblankontheother,
suppliedinbottlesas:
NDC0178-0615-01
Bottleof100
Storage: Store in a tight container.
17.1 Administration of Drug
Tellpatientstotakeeachdosewithoutcrushing,chewingorsucking
thetablet.
Tellpatientstotakethismedicineonlyasdirected.Thisisespecially
importantifthepatientisalsotakingbothdiureticsanddigitalispreparations.
Tellpatientstocheckwiththedoctorifthereistroubleswallowing
tabletsorifthetabletseemstostickinthethroat.
Tellpatientstocheckwiththedoctoratonceiftarrystoolsorother
evidenceofgastrointestinalbleedingisnoticed.
Tellpatientsthattheirdoctorwillperformregularbloodtestsandelectrocardiogramstoensuresafety.
KP-503C02Rev004100
MISSIONPHARMACALCOMPANY,SANANTONIO,TXUSA782301355
Uribel® Visual Highlights
Product Logo
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Product
Put relief back in the picture with
Uribe
#40
l
TM
capsul
es
Sig
: 1qid
D.A
.W.*
Restore re
5 elements of comfort
Provide analgesic, antispasmodic, and antiseptic therapy.
■ Analgesic—phenyl salicylate for relief of pain and burning
lief with Ur
n Provid
ibel™
es analge
sic, antisp
■ Antispasmodic—hyoscyamine sulfate to help relax
s the pai
n, burning,
the discom
fort caused
n), B.M.N
. (brand
uribelinfo.
com • 1-8
medically
necessary),
or D.N.S.
333
Uribel helps relieve local
discomfort caused by
■ Lower urinary tract
infections (UTIs) and
■ Painful bladder
syndrome (PBS)
■ Prediagnostic and
postdiagnostic procedures
Uribel capsules are indicated for the treatment of symptoms of irritative voiding. Indicated for the
tract infections. Indicated for the relief of urinary tract symptoms caused by diagnostic procedures.
pany. All
rights reser
ved. Print
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in USA
UBL-2 Rev
me. Urol Nurs.
0610
Symptom
relief
Antiseptic
Methenamine
Methylene blue
Sodium phosphate monobasic
■ Antiseptic—methenamine with antibacterial/antifungal activity
■ Mild antiseptic—methylene blue with antibacterial activity
■
—sodium phosphate monobasic to facilitate methenamine action
A safe way to complement recovery1
Symptom relief can begin within 30 minutes.
Pa in . B u
r n in g . SP
a Sm S.
■ Analgesic therapies are commonly prescribed in conjunction with antibiotic
therapies in the treatment of urinary tract disorders1,2
■ Generally well tolerated
■ No restriction on length of therapy
■ Convenient, easy-dosing capsule form — 4 times per day
When urinary
tract sympto
ms
have your pa
tients
on edge…
of breath, or trouble breathing.
Please see full Prescribing Information on back page.
carefully considered when certain medical conditions exist, including cardiac disease, gastrointestinal tract
obstructive disease, glaucoma, urinary bladder neck obstruction, or myasthenia gravis.
TOPIN &
205 N. MichiASSOCIATES,
INC.
gan Ave.–
Chicago, Illinoi
Suite 2315
Tel: 312.645.01 s 60601-5923
Gothic, Leslin
00 Fax: 312.6
e, Myriad Pro,
45.01
Symbol, Zapf 20
D
■ Interstitial cystitis (IC)
macal Com
Hyoscyamine sulfate
itute).
Rx Only
100 Capsu
les
PHENYL SALICY
DESCRIPTION
LATE release
SODIUM PHOSP
s salicylate,
Each capsul : Uribel ™ capsu
les for oral
a mild analge
HATE
the urine
Methenaminee contains:
administration
sic for pain.
necessary MONOBASIC an acidifie
for the degrad
Sodium Phosph
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INDICATIONS
ation of methen
maintain
urine to becom
Phenyl Salicyl ate Monobasic
an acid pH
amine.
Uribel ™ capsuAND USAGE:
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Indicated
118 mg
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1 hour apart to formaldehyde g effectiveness of
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Hyoscyamine
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methenamine
and pain,
40.8 mg
Sulfate
hyoscyamine from doses of hyoscyDoses of these medica
which accomof local symptoms, ent of symptoms of
by inhibiti
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such as inflamm irritative voiding
ng
amine;
may further
tions
HYOSCYAMIN
36 mg
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tract sympto pany lower urinary
reduce intestin antimyasthenics should be spaced
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benzeneacetic
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Risk benefit ATIONS: Hypers
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may intensi
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heart failure, cardiac diseas considered when theingredients is possib
with
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in the urine,
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METHENAMIN
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light, it is crystalline
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DRUG
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WARNINGS:
capsules
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DENCE: A
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hexamethylen etetramine; HMT;
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PRECAUTION
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OVERDOSAGE
C6 H N ; mol
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Its solutio
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al motility
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tion of other
to
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well absorb
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ation form
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References
ethylen
its
in the urine.
tions
UBL-1 Rev
may intensi conversion to formal g the effectiveness e diuretics (may
75% is excretee blue which is
0410
cause
fy antimu
dehyde); antimu
of methen
1. McPhe
d unchan
antimuscarini
scarinic effects
amine
e JS, Papad
ged.
of hyoscy scarinics (concurrent by
Treatment.
akis MA,
reduce absorpc activities of these
amine becaus
eds.
use
New York,
medica
tion of hyoscy
e
2. Panzera
NY: McGra Current Medical Diagno
amine, concurtions); antacids/antid of secondary
AK.
w
Copyright
sis and
iarrheals
rent use with
2007;27(1): Interstitial cystitis Hill Medical; 2009:
© 2010
(may
/painfu
828,8
13-19
antacid
Mission
37-838.
.
l bladder
s may cause
syndro
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Antispasmodic
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Multiple conditions,
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00-531-3
Phenyl salicylate
DOC INFO
FINAL TRIM : CREATED with
INDESIGN
FINAL SIZE: SIZE: 17"w x 11"h
CS4
@ crops with
ALL LIVE 8.5”w x 11”h
.125" bleed
GRAP
FONTS: Helve HICS INCLUDED
IN x_AR
tica LT Std,
Helvetica Neue TWORK FOLDER.
LT Std, ITC
Avant Garde
asmodic,
and antise
ptic therap
y
and spasm
s associate
d with UT
Is, IC, and
by diagno
age requi
PBS
red by state:
stic proced
D.A.W. (dispe
ures
nse as writte
n Target
n Treats
*Use langu
smooth muscle tissue
Analgesic
RX ONLY
Rx Only
100 Capsules
DESCRIPTION: Uribel™ capsules for oral administration
Each capsule contains:
Methenamine
Sodium Phosphate Monobasic
Phenyl Salicylate
Methylene Blue
Hyoscyamine Sulfate
administered to a pregnant woman or can affect reproduction capacity. Uribel™ capsules
should be given to a pregnant woman only if clearly needed.
118 mg
40.8 mg
36 mg
10 mg
0.12 mg
HYOSCYAMINE SULFATE. [620-61-1] [3(S)-endo]-a-(Hydroxymethyl)-benzeneacetic
acid 8-methyl-8-azabicyclo[3.2.1]oct-3-yl ester sulfate(2:1)(salt); 1aH,5aH-tropan3a-ol(-)-tropate (ester) sulfate(2:1)(salt); 3a-tropanyl S-(-)-tropate; I-tropic acid ester
with tropine; I-tropine tropate. C34H48N2O10S. Hyoscyamine Sulfate is an alkaloid of
belladonna. Exists as a white crystalline powder. Its solutions are alkaline to litmus.
Affected by light, it is slightly soluble in water; freely soluble in alcohol; sparingly soluble
in ether.
METHENAMINE. [100-97-0] 1,3,5,7-Tetraazatricyclo [3.3.1.-1 3,7] decane;
hexamethylenetetramine; HMT; HMTA; hexamine; 1,3,5,7-tetraazaadamantane
hexamethylenemine; Uritone; Urotropin. C6H12N4; mol wt 140.19; C 51.40%,
H 8.63%, N 39.96%. Methenamine (hexamethylenetetramine) exists as colorless,
lustrous crystals or white crystalline powder. Its solutions are alkaline to litmus.
Freely soluble in water, soluble in alcohol and in chloroform.
METHYLENE BLUE. [61-73-4] 3,7-Bis(dimethylamino) phenothiazin-5-ium
chloride; C.I. Basic Blue 9; methylthioninium chloride; tetramethylthionine chloride;
3,7-bis(dimethylamino) phenazathionium chloride. C16H18ClN3S; mol wt 319.85,
C 60.08%, H 5.67%, Cl 11.08%, N 13.14%, S 10.03%. Methylene Blue
(Methylthionine chloride) exists as dark green crystals. It is soluble in water and in
chloroform; sparingly soluble in alcohol.
PHENYL SALICYLATE. [118-55-8] 2-Hydroxybenzoic acid phenyl ester; Salol.
C13H10O3; mol wt 214.22, C 72.89%, H 4.71%, O 22.41%. Made by the action of
phosphorus oxy-chloride on a mixture of phenol and salicylic acid. Phenyl
Salicylate exists as white crystals with a melting point of 41°-43° C. It is very
slightly soluble in water and freely soluble in alcohol.
SODIUM PHOSPHATE MONOBASIC. [7558-80-7] Phosphoric acid sodium salt
(1:1); Sodium biphosphate; sodium dihydrogen phosphate; acid sodium
phosphate; monosodium orthophosphate; primary sodium phosphate; H2NaO4P;
mol wt 119.98, H 1.68%, Na 19.16%, O 53.34%, P 25.82%. Monohydrate, white,
odorless slightly deliquesce crystals or granules. At 100° C loses all its water;
when ignited it converts to metaphosphate. It is freely soluble in water and
practically insoluble in alcohol. The aqueous solution is acid. pH of 0.1 molar
aqueous solution at 25° C: 4.5.
Uribel™ capsules contain inactive ingredients: Dicalcium Phosphate,
FD&C Blue #1, FD&C Red #3, Gelatin, Magnesium Stearate, Microcrystalline
Cellulose, Povidone, Propylene Glycol, Shellac, Silicon Dioxide, Sodium
Hydroxide, Stearic Acid, and Titanium Dioxide.
CLINICAL PHARMACOLOGY:
HYOSCYAMINE SULFATE is a parasympatholytic which relaxes smooth muscles
and thus produces an antispasmodic effect. It is well absorbed from the
gastrointestinal tract and is rapidly distributed throughout the body tissues.
Most is excreted in the urine within 12 hours, 13% to 50% being unchanged.
Its biotransformation is hepatic. Its protein binding is moderate.
METHENAMINE degrades in an acidic urine environment releasing formaldehyde
which provides bactericidal or bacteriostatic action. It is well absorbed from the
gastrointestinal tract. 70%-90% reaches the urine unchanged at which point it is
hydrolyzed if the urine is acidic. Within 24 hours it is almost completely (90%)
excreted; of this at a pH of 5, approximately 20% is formaldehyde. Protein
binding – some formaldehyde is bound to substances in the urine and
surrounding tissues. Methenamine is freely distributed to body tissue and fluids
but is not clinically significant as it does not hydrolyze at pH greater than 6.8.
METHYLENE BLUE possesses weak antiseptic properties. It is well absorbed by
the gastrointestinal tract and rapidly reduced to leukomethylene blue which is
stabilized in some combination form in the urine. 75% is excreted unchanged.
PHENYL SALICYLATE releases salicylate, a mild analgesic for pain.
SODIUM PHOSPHATE MONOBASIC an acidifier, helps to maintain an acid pH in
the urine necessary for the degradation of methenamine.
INDICATIONS AND USAGE:
Uribel™ capsules indicated for the treatment of symptoms of irritative voiding.
Indicated for the relief of local symptoms, such as inflammation, hypermotility, and
pain, which accompany lower urinary tract infections. Indicated for the relief of
urinary tract symptoms caused by diagnostic procedures.
CONTRAINDICATIONS: Hypersensitivity to any of the ingredients is possible. Risk
benefits should be carefully considered when the following medical problems exist:
cardiac disease (especially cardiac arrhythmias, congestive heart failure, coronary heart
disease, and mitral stenosis); gastrointestinal tract obstructive disease; glaucoma;
myasthenia gravis, acute urinary retention may be precipitated in obstructive uropathy
(such as bladder neck obstruction due to prostatic hypertrophy).
WARNINGS: Do not exceed recommended dosage. If rapid pulse, dizziness or
blurring of vision occurs discontinue use immediately.
PRECAUTIONS:
Cross sensitivity and/or related problems - patients intolerant of belladonna alkaloids
or salicylates may be intolerant of this medication also. Delay in gastric emptying could
complicate the management of gastric ulcers.
Pregnancy/Reproduction (FDA Pregnancy Category C) - hyoscyamine and
methenamine cross the placenta. Studies concerning the effect of hyoscyamine
and methenamine on pregnancy and reproduction have not been done in animals
or humans. Thus it is not known whether Uribel™ capsules cause fetal harm when
Breast feeding - problems in humans have not been documented; however, methenamine
and traces of hyoscyamine are excreted in breast milk. Accordingly, Uribel™ capsules should
be given to a nursing mother with caution and only if clearly needed.
Prolonged use - there have been no studies to establish the safety of prolonged use in
humans. No known long-term animal studies have been performed to evaluate carcinogenic
potential.
Pediatric - infants and young children are especially susceptible to the toxic effect of the
belladonna alkaloids.
Geriatric Use - use with caution in elderly patients as they may respond to usual doses of
hyoscyamine with excitement, agitation, drowsiness or confusion.
ADVERSE REACTIONS:
Cardiovascular: rapid heartbeat, flushing
Central Nervous System: blurred vision, dizziness, drowsiness
Genitourinary: difficulty micturition, acute urinary retention
Gastrointestinal: dry mouth, nausea and vomiting
Respiratory: shortness of breath or trouble breathing
Serious allergic reactions to this drug are rare. Seek immediate medical attention
if you notice symptoms of a serious allergic reaction, including itching, rash,
severe dizziness, swelling or trouble breathing.
This medication can cause urine and sometimes stools to turn blue to blue-green.
This effect is harmless and will subside after medication is stopped.
Call your doctor or physician for medical advice about side effects. To report
SUSPECTED ADVERSE REACTIONS, contact Star Pharmaceuticals, LLC at
1-800-845-7827 or FDA at 1-800-FDA-1088, www.fda.gov/medwatch.
Drug interactions - because of this product’s effect on gastrointestinal motility and gastric
emptying, it may decrease the absorption of other oral medications during concurrent
use such as: urinary alkalizers; thiazide diuretics (may cause the urine to become alkaline
reducing the effectiveness of methenamine by inhibiting its conversion to formaldehyde);
antimuscarinics (concurrent use may intensify antimuscarinic effects of hyoscyamine
because of secondary antimuscarinic activities of these medications); antacids/antidiarrheals
(may reduce absorption of hyoscyamine, concurrent use with antacids may cause urine
to become alkaline, reducing effectiveness of methenamine by inhibiting its conversion
to formaldehyde). Doses of these medications should be spaced 1 hour apart from doses
of hyoscyamine; antimyasthenics (concurrent use with hyoscyamine may further reduce
intestinal motility); ketoconazole (patients should be advised to take this combination at
least 2 hours after ketoconazole); monoamine oxidase (MAO) inhibitors (concurrent use may
intensify antimuscarinic side effects), opioid (narcotic analgesics may result in increased risk
of severe constipation); sulfonamides (these drugs may precipitate with formaldehyde in the
urine, increasing the danger of crystalluria). Patients should be advised that the urine may
become blue to blue-green and the feces may be discolored as a result of the excretion of the
Methylene blue.
DRUG ABUSE AND DEPENDENCE: A dependence on the use of Uribel™ capsules has
not been reported and due to the nature of its ingredients, abuse of Uribel™ capsules is not
expected.
OVERDOSAGE: Emesis or gastric lavage. Slow intravenous administration of physostigmine
in doses of 1 to 4 mg (0.5 to 1 mg in children), repeated as needed in one to two hours to
reverse severe antimuscarinic symptoms.
Administration of small doses of diazepam to control excitement and seizures. Artificial
respiration with oxygen if needed for respiratory depression. Adequate hydration.
Symptomatic treatment as necessary.
If overdose is suspected, contact your local poison center or emergency room immediately.
US residents can contact the US National Poison Hotline at 1-800-222-1222.
DOSAGE AND ADMINISTRATION:
Adults - one capsule orally 4 times per day followed by liberal fluid intake.
Older Children - Dosage must be individualized by physician. Not recommended
for use in children six years of age or younger.
HOW SUPPLIED: Uribel™ capsules are purple/purple capsules imprinted “S 111”.
NDC 0076-0111-01, Bottle of 100 Capsules and NDC 0076-0111-02, Carton of 20 individually
pouched capsules.
STORAGE:
Dispense in a tight, light-resistant container as defined in the USP/NF with a child resistant
closure.
Store at controlled room temperature 15° - 30°C (59° - 86°F).
Keep in a cool, dry place.
Keep container tightly closed.
WARNING: Keep this and all drugs out of reach of children.
Rx Only
Uribel™ is a trademark of Star Pharmaceuticals, LLC
Manufactured for:
STAR PHARMACEUTICALS, LLC
New Brunswick, NJ 08901
Distributed by
Distributed by:
San Antonio, TX 78230
Rev. 11101-20 04/10
mission pharmacal.com
Available by prescription only.
UBL-1 Rev 0410
Dr. Smith’s® Visual Highlights
Product Logo
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Other Info
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Ingr
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Calcet® Creamy Bites
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Eletone Visual Highlights
®
Eletone
®
Cream
Product Logo
Product Packaging
atitis
Atopic Derm
Item #6935I
Rev. 11/09
Nonsteroidal
Eletone ® —ForNonsteroidal SkinBarrierRepair
Cream
py
Dermatitis Thera
with hydrolipid
atological use
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How Supplied
in a 100 gram
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Eletone Crea
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TheSafetyandEfficacyYouDemand…
theEleganceYourPatientsWant
• Eletone ® provides
emollient properties for an elegant feel
and spreadability while it restores the skin barrier
• Eletone ® Cream has a high lipid content—
delivered by Hydrolipid Technology™, a unique
reverse-phase formulation of 70% lipids
dispersed in 30% outer phase of water
Eletone ® can be used between and during flares
30%
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70% lipids
• Eletone ® has a nonirritating base and is odorless,
which may enhance patient compliance
• Eletone ® offers nonsteroidal skin barrier repair without
restrictions on age, treatment duration, or body area
Skin Barrier Repair and Protection for Long-term Daily Use
Eletone®
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Eletone
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Allrig
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©2009
Reproduction
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Restores and Repairs Atopic Skin
prohibited
5,635,497
U.S. Patent No.
Protected under
ed to 4.25” x
4.25” x 9” fold
, black ink
0.75”, 1-sided
For topical dermatological use only
Product Description
Eletone® Cream is a nonsteroidal,
lipid-rich, fragrance free emulsion formulated with Hydrolipid™ Technology for
the management and relief of burning,
itching, and redness associated with
various types of dermatoses. There are
no restrictions on age or duration of use
and the product has a low potential for
irritation.
Indications for Use
Eletone® Cream is indicated for the
management and relief of burning,
itching, and redness associated with
various types of dermatoses, including
atopic dermatitis, allergic contact
dermatitis, and radiation dermatitis (postradiation treatment).
Contraindications
THIS PRODUCT SHOULD NOT BE USED
DURING THE PERIOD OF TIME WHEN
RADIATION TREATMENT IS OCCURRING
BECAUSE OF THE INCREASED RISK
OF SKIN TOXICITY WHEN RADIATING
THROUGH PETROLATUM AND OIL.
Eletone® Cream is contraindicated in
patients with a known hypersensitivity to
any of the components of the formulation.
Precautions
Eletone® Cream is for external use only.
Eletone® Cream does not contain a
sunscreen and should always be used
in conjunction with a sunscreen in sun
exposed areas.
Instructions for Use
Apply liberally to the affected areas three
times daily or as needed. If skin is broken,
cover Eletone® Cream with a dressing of
choice.
Ingredients
Eletone® Cream contains petrolatum,
purified water, mineral oil, cetostearyl
alcohol, ceteth-20, citric acid,
sodium citrate, propylparaben, and
butyl-paraben.
How Supplied
Eletone® Cream is available in a 100 gram
tube, HRIC 0496-0598-01.
Store at 25°C (77°F); excursions permitted
to 15-30°C (59-86°F)
[see USP Controlled Room Temperature].
Caution
Rx only. Federal law restricts this device to
sale by or on the order of a physician.
Texacort Visual Highlights
®
Product Logo
Product Packaging
dermatitis
Tough ontle relief for patients
gen
Information for the Patient: Patients using topical corticosteroids should receive the following
information and instructions:
1. This medication is to be used as directed by the physician. It is for external use only. Avoid contact
with the eyes.
2. Patients should be advised not to use this medication for any disorder other than for which it was
prescribed.
3. The treated skin area should not be bandaged or otherwise covered or wrapped as to be occlusive
unless directed by the physician.
4. Patients should report any signs of local adverse reactions especially under occlusive dressing.
5. Parents of pediatric patients should be advised not to use tight-fitting diapers or plastic pants on a
child being treated in the diaper area, as these garments may constitute occlusive dressings.
HYDROCORTISONE TOPICAL SOLUTION
Paraben and Lipid-Free
FOR EXTERNAL USE ONLY
DESCRIPTION: Topical corticosteroids constitute a class of primarily synthetic steroids used as antiinflammatory and antipruritic agents. Texacort® Topical Solution contains hydrocortisone as the active
corticosteroid, having the chemical formula of Pregn-4-ene-3, 20-dione, 11,17,21 -trihydroxy-,
(11 ß)-. The molecular weight is 362.47. Its empirical formula is C21H30O5 and the structural formula is:
Laboratory Tests: The following tests may be helpful in evaluating the HPA axis suppression:
Urinary free cortisol test
ACTH stimulation test
Carcinogenesis, Mutagenesis, and Impairment of Fertility: Long-term animal studies have
not been performed to evaluate the carcinogenic potential or the effect on fertility of topical
corticosteroids.
Studies to determine mutagenicity with prednisolone and hydrocortisone have revealed
negative results.
Each milliliter contains 25 mg of hydrocortisone (2.5% W/V) in a specially formulated vehicle containing S.D. Alcohol (48.8% W/W), purified water, polysorbate 20, and isoceteth-20.
CLINICAL PHARMACOLOGY: Topical corticosteroids share anti-inflammatory, antipruritic and vasoconstrictive actions.
Steroid
HCcorticosteroids
The mechanisms of anti-inflammatory activity
of the topical
is unclear. Various labora%
Only 2.5
tory methods,
including
assays, are used to compare and predict potencies and/or
Thevasoconstrictor
q
clinical efficacies of the topical corticosteroids.
There is le
some evidence to suggest that a recognizable
n Availab
utio
ctive Option
correlation existsSol
between
vasoconstrictor potency and therapeutic efficacy in man.
qSafe & Effe
Pharmacokinetics: The extent of percutaneous absorption of topical corticosteroids is
for Managing
determined
by
many
factors
including
the
vehicle,
the
integrity
of
the
epidermal
barrier, and the
in
matitis
Will Not Sta
use of occlusive
dressings.
q
– Atopic Der
DermatitisTopical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease
– Seborrheic
e Occlusive dressings substantially increase
processes in the skin increase percutaneous Fre
nce absorption.
Fragra
the percutaneous
absorption
of topical corticosteroids. Thus, occlusive dressings may be a valuable
q
– Cradle Cap
therapeutic adjunct for treatment of resistant dermatoses. (See DOSAGE AND ADMINISTRATION).
Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic
pathways similar to systemically administered corticosteroids. Corticosteroids are bound to plasma
proteins in varying degrees. Corticosteroids are metabolized primarily in the liver and are then
excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted
into the bile.
icated for the
relief of the
and
inflammatory
s
iliter contain
Each mill
ion is ind
l (48.8%),
dermatoses.
® Topical Solut
S.D. Alcoho
-responsive
Texacort
icle containing
corticosteroid
ulated veh
stations of
pruritic manife ortisone in a specially form
roc
eteth-20.
25 mg of hyd
te 20, and isoc
er, polysorba
purified wat
UPC
NDC
Wholesaler
ABC
Cardinal
McKesson
Morris Dickson
3
2
01780 45501
0178-0455-01
®
30cc
Texacort 2.5%
145-557
10101400
4538070
2191708
543942
INDICATIONS AND USAGE: Texacort® Topical Solution 2.5% is indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses.
CONTRAINDICATIONS: Topical corticosteroids are contraindicated in those patients with a history of
hypersensitivity to any of the components of the preparation.
PRECAUTIONS:
General: Systemic absorption of topical corticosteroids has produced reversible hypothalamicpituitary-adrenal (HPA) axis suppression, manifestations of Cushing’s syndrome, hyperglycemia, and
glucosuria in some patients.
Pregnancy Category C: Corticosteroids are generally teratogenic in laboratory animals when
administered systemically at relatively low dosage levels. The more potent corticosteroids have been
shown to be teratogenic after dermal application in laboratory animals. There are no adequate and
well-controlled studies in pregnant women on teratogenic effects from topically applied corticosteroids. Therefore, topical corticosteroids should be used during pregnancy only if the potential benefit
justifies the potential risk to the fetus. Drugs of this class should not be used extensively on pregnant
patients, in large amounts, or for prolonged periods of time.
Nursing Mothers: It is not known whether topical administration of corticosteroids could result in
sufficient systemic absorption to produce detectable quantities in breast milk. Systemically administered corticosteroids are secreted into breast milk in quantities not likely to have a deleterious effect
on the infant. Nevertheless, caution should be exercised when topical corticosteroids are administered
to a nursing woman.
Pediatric Use: Pediatric patients may demonstrate greater susceptibility to topical corticosteroidinduced HPA axis suppression and Cushing’s syndrome than mature patients because of a larger skin
surface area to body weight ratio.
Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing’s syndrome, and intracranial hypertension have been reported in children receiving topical corticosteroids. Manifestations of adrenal
suppression in children include linear growth retardation, delayed weight gain, low plasma cortisol
levels, and absence of response to ACTH stimulation. Manifestations of intracranial hypertension
include bulging fontanelles, headaches, and bilateral papilledema.
Administration of topical corticosteroids to children should be limited to the least amount compatible
with an effective therapeutic regimen. Chronic corticosteroid therapy may interfere with the growth
and development of children.
ADVERSE REACTIONS: The following local adverse reactions are reported infrequently with topical
corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions
are listed in an approximate decreasing order of occurrence: burning, itching, irritation, dryness,
folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact
dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, miliaria.
OVERDOSAGE: Topically applied corticosteroids can be absorbed in sufficient amount to produce
systemic effects (See PRECAUTIONS).
DOSAGE AND ADMINISTRATION: Topical corticosteroids are generally applied to the affected area as
a thin film for three or four times daily depending on the severity of the condition.
Occlusive dressings may be used for the management of psoriasis or recalcitrant conditions.
Conditions which augment systemic absorption include the application of the more potent steroids,
use over large surface areas, prolonged use, and the addition of occlusive dressings.
Savings Card
s
Patient save
up to
Available
Therefore, patients receiving a large dose of a potent topical steroid applied to a large surface area or
under an occlusive dressing should be evaluated periodically for evidence of HPA axis suppression by
using the urinary free cortisol and ACTH stimulation tests. If HPA axis suppression is noted, an attempt
should be made to withdraw the drug, to reduce the frequency of application, or to substitute a less
potent steroid.
$
50
Recovery of HPA axis function is generally prompt and complete upon discontinuation of the drug.
Infrequently, signs and symptoms of steroid withdrawal may occur, requiring supplemental systemic
corticosteroids.
Children may absorb proportionally larger amounts of topical corticosteroids and thus be more
susceptible to systemic toxicity. (See PRECAUTIONS - Pediatric Use.)
If an infection develops, the use of occlusive dressings should be discontinued and appropriate
antimicrobial therapy instituted.
HOW SUPPLIED:
Texacort® Topical Solution 2.5% is available in a 1 fl. oz. plastic bottle with an applicator tip,
NDC 0178-0455-01, and in a 3 mL sample packet, NDC 0178-0455-03.
Rx Only
Distributed by:
Mission Pharmacal Company
San Antonio, TX 78230-1355
If irritation develops, topical corticosteroids should be discontinued and appropriate therapy instituted.
In the presence of dermatological infections, the use of an appropriate antifungal or antibacterial
agent should be instituted. If a favorable response does not occur promptly, the corticosteroid should
be discontinued until the infection has been adequately controlled.
TEX_T2312 Rev 0212
HYDROCORTISONE TOPICAL SOLUTION
Paraben and Lipid-Free
FOR EXTERNAL USE ONLY
DESCRIPTION: Topical corticosteroids constitute a class of primarily synthetic steroids used as antiinflammatory and antipruritic agents. Texacort® Topical Solution contains hydrocortisone as the active
corticosteroid, having the chemical formula of Pregn-4-ene-3, 20-dione, 11,17,21 -trihydroxy-,
(11 ß)-. The molecular weight is 362.47. Its empirical formula is C21H30O5 and the structural formula is:
Information for the Patient: Patients using topical corticosteroids should receive the following
information and instructions:
1. This medication is to be used as directed by the physician. It is for external use only. Avoid contact
with the eyes.
2. Patients should be advised not to use this medication for any disorder other than for which it was
prescribed.
3. The treated skin area should not be bandaged or otherwise covered or wrapped as to be occlusive
unless directed by the physician.
4. Patients should report any signs of local adverse reactions especially under occlusive dressing.
5. Parents of pediatric patients should be advised not to use tight-fitting diapers or plastic pants on a
child being treated in the diaper area, as these garments may constitute occlusive dressings.
Laboratory Tests: The following tests may be helpful in evaluating the HPA axis suppression:
Urinary free cortisol test
ACTH stimulation test
Carcinogenesis, Mutagenesis, and Impairment of Fertility: Long-term animal studies have
not been performed to evaluate the carcinogenic potential or the effect on fertility of topical
corticosteroids.
Studies to determine mutagenicity with prednisolone and hydrocortisone have revealed
negative results.
Each milliliter contains 25 mg of hydrocortisone (2.5% W/V) in a specially formulated vehicle containing S.D. Alcohol (48.8% W/W), purified water, polysorbate 20, and isoceteth-20.
CLINICAL PHARMACOLOGY: Topical corticosteroids share anti-inflammatory, antipruritic and vasoconstrictive actions.
The mechanisms of anti-inflammatory activity of the topical corticosteroids is unclear. Various laboratory methods, including vasoconstrictor assays, are used to compare and predict potencies and/or
clinical efficacies of the topical corticosteroids. There is some evidence to suggest that a recognizable
correlation exists between vasoconstrictor potency and therapeutic efficacy in man.
Pharmacokinetics: The extent of percutaneous absorption of topical corticosteroids is
determined by many factors including the vehicle, the integrity of the epidermal barrier, and the
use of occlusive dressings.
Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease
processes in the skin increase percutaneous absorption. Occlusive dressings substantially increase
the percutaneous absorption of topical corticosteroids. Thus, occlusive dressings may be a valuable
therapeutic adjunct for treatment of resistant dermatoses. (See DOSAGE AND ADMINISTRATION).
Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic
pathways similar to systemically administered corticosteroids. Corticosteroids are bound to plasma
proteins in varying degrees. Corticosteroids are metabolized primarily in the liver and are then
excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted
into the bile.
INDICATIONS AND USAGE: Texacort® Topical Solution 2.5% is indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses.
CONTRAINDICATIONS: Topical corticosteroids are contraindicated in those patients with a history of
hypersensitivity to any of the components of the preparation.
PRECAUTIONS:
General: Systemic absorption of topical corticosteroids has produced reversible hypothalamicpituitary-adrenal (HPA) axis suppression, manifestations of Cushing’s syndrome, hyperglycemia, and
glucosuria in some patients.
Pregnancy Category C: Corticosteroids are generally teratogenic in laboratory animals when
administered systemically at relatively low dosage levels. The more potent corticosteroids have been
shown to be teratogenic after dermal application in laboratory animals. There are no adequate and
well-controlled studies in pregnant women on teratogenic effects from topically applied corticosteroids. Therefore, topical corticosteroids should be used during pregnancy only if the potential benefit
justifies the potential risk to the fetus. Drugs of this class should not be used extensively on pregnant
patients, in large amounts, or for prolonged periods of time.
Nursing Mothers: It is not known whether topical administration of corticosteroids could result in
sufficient systemic absorption to produce detectable quantities in breast milk. Systemically administered corticosteroids are secreted into breast milk in quantities not likely to have a deleterious effect
on the infant. Nevertheless, caution should be exercised when topical corticosteroids are administered
to a nursing woman.
Pediatric Use: Pediatric patients may demonstrate greater susceptibility to topical corticosteroidinduced HPA axis suppression and Cushing’s syndrome than mature patients because of a larger skin
surface area to body weight ratio.
Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing’s syndrome, and intracranial hypertension have been reported in children receiving topical corticosteroids. Manifestations of adrenal
suppression in children include linear growth retardation, delayed weight gain, low plasma cortisol
levels, and absence of response to ACTH stimulation. Manifestations of intracranial hypertension
include bulging fontanelles, headaches, and bilateral papilledema.
Administration of topical corticosteroids to children should be limited to the least amount compatible
with an effective therapeutic regimen. Chronic corticosteroid therapy may interfere with the growth
and development of children.
ADVERSE REACTIONS: The following local adverse reactions are reported infrequently with topical
corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions
are listed in an approximate decreasing order of occurrence: burning, itching, irritation, dryness,
folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact
dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, miliaria.
OVERDOSAGE: Topically applied corticosteroids can be absorbed in sufficient amount to produce
systemic effects (See PRECAUTIONS).
DOSAGE AND ADMINISTRATION: Topical corticosteroids are generally applied to the affected area as
a thin film for three or four times daily depending on the severity of the condition.
Occlusive dressings may be used for the management of psoriasis or recalcitrant conditions.
Conditions which augment systemic absorption include the application of the more potent steroids,
use over large surface areas, prolonged use, and the addition of occlusive dressings.
Therefore, patients receiving a large dose of a potent topical steroid applied to a large surface area or
under an occlusive dressing should be evaluated periodically for evidence of HPA axis suppression by
using the urinary free cortisol and ACTH stimulation tests. If HPA axis suppression is noted, an attempt
should be made to withdraw the drug, to reduce the frequency of application, or to substitute a less
potent steroid.
If an infection develops, the use of occlusive dressings should be discontinued and appropriate
antimicrobial therapy instituted.
HOW SUPPLIED:
Texacort® Topical Solution 2.5% is available in a 1 fl. oz. plastic bottle with an applicator tip,
NDC 0178-0455-01, and in a 3 mL sample packet, NDC 0178-0455-03.
Recovery of HPA axis function is generally prompt and complete upon discontinuation of the drug.
Infrequently, signs and symptoms of steroid withdrawal may occur, requiring supplemental systemic
corticosteroids.
Children may absorb proportionally larger amounts of topical corticosteroids and thus be more
susceptible to systemic toxicity. (See PRECAUTIONS - Pediatric Use.)
Rx Only
Distributed by:
Mission Pharmacal Company
San Antonio, TX 78230-1355
If irritation develops, topical corticosteroids should be discontinued and appropriate therapy instituted.
In the presence of dermatological infections, the use of an appropriate antifungal or antibacterial
agent should be instituted. If a favorable response does not occur promptly, the corticosteroid should
be discontinued until the infection has been adequately controlled.
TEX_T2312 Rev 0212
Ferralet Visual Highlights
®
Product Logo
Product Packaging
Product
ains:
ration cont
administ
t for oral
coated table . . . . 90 mg
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3. Ferralet® 90 provides both the initial bolus
of ferrous iron and the more prolonged
absorption of carbonyl iron
Gentle and effective treatment
1 Even when dosed at 10 times the standard dose of ferrous sulfate, carbonyl iron
shows no significant difference in GI side effects3
1 50 mg docusate sodium for patients who are sensitive to iron therapy
1 Small pill, dosed once a day, to help improve iron convenience and compliance
Comfort your patients will love
Affordability to improve the patient’s experience
1 Valuable coupon can save your patients up to $15 on each of their next
12 prescriptions—making Ferralet 90 comparable to some generics
1 Multi-ingredient Ferralet 90 can cost little more than some iron supplements
with no additional ingredients
1 With Ferralet 90, your patients also benefit from a stool softener,
iron-enhancing vitamin C4, and more
This product contains FD&C Yellow No. 5 (tartrazine) which may cause
allergic-type reactions (including bronchial asthma) in certain susceptible
persons. Although the overall incidence of FD&C Yellow No. 5 (tartrazine)
sensitivity in the general population is low, it is frequently seen in patients
who also have aspirin hypersensitivity.
DESCRIPTION: Each green film-coated tablet for oral
administration contains:
Iron (Carbonyl iron, ferrous gluconate)......................................... 90 mg
Folic Acid...................................................................................... 1mg
Vitamin B12 (Cyanocobalamin)...................................................... 12mcg
Vitamin C (Ascorbic acid).............................................................120mg
Docusate sodium......................................................................... 50mg
Inactive Ingredients: Povidone, croscarmellose sodium, acrylic resin,
color added, magnesium stearate, FD&C Yellow No. 5, magnesium silicate,
FD&C Blue No. 1, polyethylene glycol, vitamin A palmitate, ethyl vanillin.
Folic Acid: Folic acid in doses above 0.1 mg daily may obscure
neurological manifestations remain progressive. Pernicious anemia
should be excluded before using these products since folic acid may
mask the symptoms of pernicious anemia.
Pediatric Use: Safety and effectiveness in pediatric patients have not
been established.
Geriatric Use: Dosing for elderly patients should be cautious. Due to the
greater frequency of decreased hepatic, renal, or cardiac function, and
of concomitant disease or other drug therapy, dosing should start at the
lower end of the dosing range.
CLINICAL PHARMACOLOGY: Oral iron is absorbed most efficiently
when administered between meals. Iron is critical for normal hemoglobin
synthesis to maintain oxygen transport for energy production and proper
function of cells. Adequate amounts of iron are necessary for effective
erythropoiesis. Iron also serves as a cofactor of several essential enzymes,
including cytochromes, which are involved in electron transport. Folic acid
is required for nucleoprotein synthesis and the maintenance of normal
erythropoiesis. Folic acid is the precursor of tetrahydrofolic acid, which is
involved as a cofactor for transformylation reactions in the biosynthesis
of purines and thymidylates of nucleic acids. Deficiency of folic acid may
account for the defective deoxyribonucleic acid (DNA) synthesis that
leads to megaloblast formation and megaloblastic macrocytic anemias.
Vitamin B12 is essential to growth, cell reproduction, hematopoiesis, nucleic
acid, and myelin synthesis. Deficiency may result in megaloblastic anemia
or pernicious anemia.
ADVERSE REACTIONS: Adverse reactions with iron therapy may
include GI irritation, constipation, diarrhea, nausea, vomiting, and dark
stools. Adverse reactions with iron therapy are usually transient. Allergic
sensitization has been reported following both oral and parenteral
administration of folic acid.
INDICATIONS AND USAGE: Ferralet® 90 is indicated for the treatment
of all anemias that are responsive to oral iron therapy. These include:
hypochromic anemia associated with pregnancy, chronic and/or
acute blood loss, metabolic disease, postsurgical convalescence, and
dietary needs.
DOSAGE AND ADMINISTRATION: One tablet daily or as directed by a
physician. Do not chew tablet.
CONTRAINDICATIONS: Hypersensitivity to any of the ingredients.
Hemolytic anemia, hemochromatosis, and hemosiderosis are
contraindications to iron therapy.
pernicious anemia and other megaloblastic anemias where vitamin B12
is deficient.
PRECAUTIONS:
General: Take 2 hours after meals. Do not exceed recommended dose.
Discontinue use if symptoms of intolerance appear. The type of anemia
and underlying cause or causes should be determined before starting
therapy with Ferralet® 90 tablets. Ensure Hgb, Hct, and reticulocyte counts
are determined before starting therapy and periodically thereafter during
prolonged treatment. Periodically review therapy to determine if it needs to
be continued without change or if a dose change is indicated.
DRUG INTERACTIONS: Prescriber should be aware of a number of iron/
drug interactions, including antacids, tetracyclines, or fluoroquinolones.
OVERDOSAGE: Symptoms: abdominal pain, metabolic acidosis,
anuria, CNS damage, coma, convulsions, death, dehydration, diffuse
vascular congestion, hepatic cirrhosis, hypotension, hypothermia,
lethargy, nausea, vomiting, diarrhea, tarry stools, melena, hematemesis,
tachycardia, hyperglycemia, drowsiness, pallor, cyanosis, lassitude,
seizures, and shock.
STORAGE: Store at 25°C (77°F). Excursions permitted to 15°- 30°C
(59°- 86°F). (See USP Controlled Room Temperature.)
HOW SUPPLIED: Ferralet® 90 (NDC 0178-0089-90) is a green, modified
rectangle shaped, film-coated tablet, debossed with “F6” on one side
and blank on the other, and packaged in bottles of 90.
To report a serious adverse event or obtain product information,
call (210) 696-8400.
ferralet90.com
Trademark of Mission Pharmacal Company
FEP-19 C01 Rev 001120
Tindamax Visual Highlights
®
Product Logo
Product
Product Packaging
of
able treatment
For short, afford
sis (BV)…
bacterial vagino
s
Give your patient s
rld
o
w
the best of both
TINDAMAX takes the stress out of BV therapy with
®
2-day convenience
convenience
2-day
$10 co-pay*
about BV
n TINDAMAX is the only first-line oral therapy1,2 that can give patients relief from BV symptoms in just
2 days (a 5-day dosing option is also available)
n The new TINDAMAX co-pay card reduces out-of-pocket
costs for most patients to a single, $10 co-pay*
n Short, convenient dosing regimens significantly reduce total treatment time vs 7-day oral metronidazole
n Coupon is good for any prescriptions and has no
expiration date
with
n TINDAMAX has a reduced risk of secondary candidiasis (4.7%) vs other BV therapies4,5
n TINDAMAX is well tolerated with high compliance and minimal risk of GI side effects3
n Lower cost makes TINDAMAX an easy, affordable option
to generic metronidazole for almost all patients
*For eligible patients only and limited to a maximum savings of $40 per prescription.
start your patients with TInDAMAX…
The July 2010 issue of Treatment Guidelines from The Medical Letter®
recommends tinidazole as a “drug of choice” for BV and trichomoniasis2
The 2010 Sanford Guide to Antimicrobial Therapy
lists tinidazole as a primary BV regimen1
*For Eligible Patients only and limited to a
maximum savings of $40 per prescription.
TINDAMAX offers 2 streamlined dosing options for bacterial vaginosis and trichomoniasis
2 convenient oral dosing options
for bacterial vaginosis (BV)
2 g/2-day dosing
4 x 500 mg tablets
once daily for 2 days, taken with food
Day 1
Day 2
2g
2g
1 simple oral dosing
regimen for trichomoniasis (TV)
1 g/5-day dosing
2 x 500 mg tablets
once daily for 5 days, taken with food
Day 1
1g
Day 2
1g
Day 3
1g
Day 4
1g
Day 5
1g
1,2
First-line efficacy. Patient-friendly convenience.
Day 1
2g
WARnInG: POTenTIAL RIsK fOR cARcInOGenIcITY
Carcinogenicity has been seen in mice and rats treated chronically with metronidazole, another nitroimidazole agent.
Although such data have not been reported for tinidazole, the two drugs are structurally related and have similar biologic
effects. Its use should be reserved for the conditions described in InDIcATIOns AnD UsAGe.
WARNING: POTENTIAL RISK FOR CARCINOGENICITY
Carcinogenicity has been seen in mice and rats treated chronically with metronidazole,
another nitroimidazole agent. Although such data have not been reported for tinidazole,
the two drugs are structurally related and have similar biologic effects. Its use should be
reserved for the conditions described in INDICATIONS AND USAGE.
RxPCN: CN
ID#: LYC195842976
Other Coverage Code Indication Required.
2 g/1-day dosing
4 x 500 mg tablets at
one time taken with food
Please see attached full Prescribing Information, including Boxed Warning.
Submit this claim/information to Therapy First Plus:
Bin: 004682
Group ID: LCLYC374
DIDYOU
YOUKNOW?
KNOW?
DID
TINDAMAXeffectively
effectivelytreats
treatsBV
BVwhile
whilesparing
sparingthe
thelactobacilli
lactobacilliessential
essentialfor
forestablishment
establishmentofofnormal
normalvaginal
vaginalfloral
floralpatterns
patterns6 6
TINDAMAX
PATIenT cOUnseLInG InfORMATIOn
• Administration of Drug—Patients should be told to take TINDAMAX® with food to minimize the incidence of epigastric discomfort
and other gastrointestinal side effects. Food does not affect the oral bioavailability of tinidazole.
• Alcohol Avoidance—Patients should be told to avoid alcoholic beverages and preparations containing ethanol or propylene glycol
during TINDAMAX therapy and for 3 days afterward because abdominal cramps, nausea, vomiting, headaches, and flushing may occur.
• Drug Resistance—Patients should be counseled that antibacterial drugs including TINDAMAX should only be used to treat bacterial infections.
They do not treat viral infections (eg, the common cold). When TINDAMAX is prescribed to treat a bacterial infection, patients should be told
that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses
or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that
bacteria will develop resistance and will not be treatable by TINDAMAX or other antibacterial drugs in the future.
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use Tindamax® safely
and effectively. See full prescribing information for Tindamax®.
Tindamax (tinidazole) tablets for oral use
Initial U.S. Approval: 2004
To reduce the development of drug-resistant bacteria and maintain the effectiveness of
Tindamax and other antibacterial drugs, Tindamax should be used only to treat or prevent
infections that are proven or strongly suspected to be caused by bacteria.
®
See full prescribing information for complete
boxed warning.
Carcinogenicity has been seen in mice and rats treated chronically with
metronidazole, another nitroimidazole agent (13.1). Although such data have not
been reported for tinidazole, the two drugs are structurally related and have
similar biologic effects. Use should be limited to approved indications only.
——————————————RECENT MAJOR CHANGES——————————————Indications and Usage, Bacterial Vaginosis (1.4)
5/2007
Dosage and Administration, Bacterial Vaginosis (2.6)
5/2007
——————————————INDICATIONS AND USAGE———————————————
Tindamax is a nitroimidazole antimicrobial indicated for:
• Trichomoniasis (1.1)
• Giardiasis: in patients age 3 and older (1.2)
• Amebiasis: in patients age 3 and older (1.3)
• Bacterial Vaginosis: in non-pregnant, adult women (1.4, 8.1)
————————————DOSAGE AND ADMINISTRATION——————————————
• Trichomoniasis: a single 2 g oral dose taken with food. Treat sexual partners with the same
dose and at the same time (2.3)
• Giardiasis: Adults: a single 2 g dose taken with food. Pediatric patients older than three
years of age: a single dose of 50 mg/kg (up to 2 g) with food (2.4)
• Amebiasis, Intestinal: Adults: 2 g per day for 3 days with food. Pediatric patients older than
three years of age: 50 mg/kg/day (up to 2 g per day) for 3 days with food (2.5). Amebic liver
abscess: Adults: 2 g per day for 3-5 days with food. Pediatric patients older than three
years of age: 50 mg/kg/day (up to 2 g per day) for 3-5 days with food (2.5)
• Bacterial vaginosis: Non-pregnant, adult women: 2 g once daily for 2 days taken with food, or
1 g once daily for 5 days taken with food (2.6)
———-———-———-—DOSAGE FORMS AND STRENGTHS——————-———-———Tablets: 250 mg and 500 mg (3)
————————-———-—-CONTRAINDICATIONS—————-———-———-—————
• Prior history of hypersensitivity to tinidazole or other nitroimidazole derivatives (4, 6.1, 6.2)
• First trimester of pregnancy (4, 8.1)
• Nursing mothers, unless breast-feeding is interrupted during tinidazole therapy and for 3
days following the last dose (4, 8.3)
———-———-————-WARNINGS AND PRECAUTIONS—————-———-———-——
• Seizures and neuropathy have been reported. Discontinue Tindamax if abnormal neurologic
signs develop (5.1)
• Vaginal candidiasis may develop with Tindamax and require treatment with an antifungal
agent (5.2)
• Use Tindamax with caution in patients with blood dyscrasias. Tindamax may produce
transient leukopenia and neutropenia (5.3, 7.3)
———————-———-————ADVERSE REACTIONS———-———-———-—————Most common adverse reactions for a single 2 g dose of tinidazole (incidence >1%) are
metallic/bitter taste, nausea, weakness/fatigue/malaise, dyspepsia/cramps/epigastric
discomfort, vomiting, anorexia, headache, dizziness and constipation (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Mission Pharmacal Company
at 1-800-298-1087 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
——————-———-—————DRUG INTERACTIONS———-———-———-——————
The following drug interactions were reported for metronidazole, a chemically-related
nitroimidazole and may therefore occur with tinidazole:
• Warfarin and other oral coumarin anticoagulants: Anticoagulant dosage may need
adjustment during and up to 8 days after tinidazole therapy (7.1)
• Alcohol-containing beverages/preparations: Avoid during and up to 3 days after tinidazole therapy
(7.1)
• Lithium: Monitor serum lithium concentrations (7.1)
• Cyclosporine, tacrolimus: Monitor for toxicities of these immunosuppressive drugs (7.1)
• Fluorouracil: Monitor for fluorouracil-associated toxicities (7.1)
• Phenytoin, fosphenytoin: Adjustment of anticonvulsant and/or tinidazole dose(s) may be
needed (7.1, 7.2)
• CYP3A4 inducers/inhibitors: Monitor for decreased tinidazole effect or increased adverse
reactions (7.2)
———-———-———-——USE IN SPECIFIC POPULATIONS———-———-———————
• Pediatric Use: Data on tinidazole use in children is limited to treatment of giardiasis and
amebiasis in patients age 3 and older (8.4)
• Hemodialysis patients: If tinidazole is administered the same day and prior to hemodialysis,
administer an additional 1/2 dose after end of hemodialysis (8.6, 12.3)
See 17 for PATIENT COUNSELING INFORMATION
Revised: 8/2007
FULL PRESCRIBING INFORMATION: CONTENTS*
1.1 Trichomoniasis
1.2 Giardiasis
1.3 Amebiasis
1.4 Bacterial Vaginosis
2.2 Compounding of the Oral Suspension
2.3 Trichomoniasis
2.4 Giardiasis
2.5 Amebiasis
4 CONTRAINDICATIONS
5.1 Neurological Adverse Reactions
5.2 Vaginal Candidiasis
5.3 Blood Dyscrasia
5.4 Drug Resistance
6 ADVERSE REACTIONS
6.1 Clinical Studies Experience
7 DRUG INTERACTIONS
7.1 Potential Effects of Tinidazole on Other Drugs
7.2 Potential Effects of Other Drugs on Tinidazole
7.3 Laboratory Test Interactions
8.1 Pregnancy
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Renal Impairment
8.7 Hepatic Impairment
10 OVERDOSAGE
11 DESCRIPTION
12.3 Pharmacokinetics
12.4 Microbiology
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
13.2 Animal Toxicology and/or Pharmacology
14 CLINICAL STUDIES
14.1 Trichomoniasis
14.2 Giardiasis
14.3 Intestinal Amebiasis
14.4 Amebic Liver Abscess
17.2 Alcohol Avoidance
17.3 Drug Resistance
*Sections or subsections omitted from the full prescribing information are not listed
FULL PRESCRIBING INFORMATION
Carcinogenicity has been seen in mice and rats treated chronically with metronidazole, another
nitroimidazole agent (13.1). Although such data have not been reported for tinidazole, the two
drugs are structurally related and have similar biologic effects. Its use should be reserved
for the conditions described in INDICATIONS AND USAGE (1).
1.1 Trichomoniasis
Tinidazole is indicated for the treatment of trichomoniasis caused by Trichomonas
vaginalis. The organism should be identified by appropriate diagnostic procedures. Because
trichomoniasis is a sexually transmitted disease with potentially serious sequelae, partners of
infected patients should be treated simultaneously in order to prevent re-infection [see
Clinical Studies (14.1)].
1.2 Giardiasis
Tinidazole is indicated for the treatment of giardiasis caused by Giardia duodenalis (also
termed G. lamblia) in both adults and pediatric patients older than three years of age [see
Clinical Studies (14.2)].
1.3 Amebiasis
Tinidazole is indicated for the treatment of intestinal amebiasis and amebic liver abscess
caused by Entamoeba histolytica in both adults and pediatric patients older than three years of
age. It is not indicated in the treatment of asymptomatic cyst passage [see Clinical Studies
(14.3, 14.4)].
Tinidazole is indicated for the treatment of bacterial vaginosis (formerly referred to as
Haemophilus vaginitis, Gardnerella vaginitis, nonspecific vaginitis, or anaerobic vaginosis) in
non-pregnant women [see Use in Specific Populations (8.1) and Clinical Studies (14.5)].
Other pathogens commonly associated with vulvovaginitis such as Trichomonas vaginalis,
Chlamydia trachomatis, Neisseria gonorrhoeae, Candida albicans and Herpes simplex virus
should be ruled out.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of
Tindamax and other antibacterial drugs, Tindamax should be used only to treat or prevent
infections that are proven or strongly suspected to be caused by susceptible bacteria. When
culture and susceptibility information are available, they should be considered in selecting or
modifying antibacterial therapy. In the absence of such data, local epidemiology and
susceptibility patterns may contribute to the empiric selection of therapy.
↕
It is advisable to take tinidazole with food to minimize the incidence of epigastric
discomfort and other gastrointestinal side-effects. Food does not affect the oral
bioavailability of tinidazole [see Clinical Pharmacology (12.3)].
Alcoholic beverages should be avoided when taking tinidazole and for 3 days afterwards
[see Drug Interactions (7.1)].
2.2 Compounding of the Oral Suspension
For those unable to swallow tablets, tinidazole tablets may be crushed in artificial cherry
syrup to be taken with food.
Procedure for Extemporaneous Pharmacy Compounding of the Oral Suspension: Pulverize
four 500 mg oral tablets with a mortar and pestle. Add approximately 10 mL of cherry syrup
to the powder and mix until smooth. Transfer the suspension to a graduated amber
container. Use several small rinses of cherry syrup to transfer any remaining drug in the
mortar to the final suspension for a final volume of 30 mL. The suspension of crushed tablets
in artificial cherry syrup is stable for 7 days at room temperature. When this suspension is
used, it should be shaken well before each administration.
2.3 Trichomoniasis
The recommended dose in both females and males is a single 2 g oral dose taken with
food. Since trichomoniasis is a sexually transmitted disease, sexual partners should be
treated with the same dose and at the same time.
2.4 Giardiasis
The recommended dose in adults is a single 2 g dose taken with food. In pediatric patients
older than three years of age, the recommended dose is a single dose of 50 mg/kg (up to 2 g)
with food.
2.5 Amebiasis
Intestinal: The recommended dose in adults is a 2 g dose per day for 3 days taken with
food. In pediatric patients older than three years of age, the recommended dose is
50 mg/kg/day (up to 2 g per day) for 3 days with food.
Amebic Liver Abscess: The recommended dose in adults is a 2 g dose per day for 3-5 days
taken with food. In pediatric patients older than three years of age, the recommended dose is
50 mg/kg/day (up to 2 g per day) for 3-5 days with food. There are limited pediatric data on
durations of therapy exceeding 3 days, although a small number of children were treated for
5 days without additional reported adverse reactions. Children should be closely monitored
when treatment durations exceed 3 days.
The recommended dose in non-pregnant females is a 2 g oral dose once daily for 2 days
taken with food or a 1 g oral dose once daily for 5 days taken with food. The use of
tinidazole in pregnant patients has not been studied for bacterial vaginosis.
• 250 mg tablets are pink, round, scored tablets, with TM debossed on one side and 250 on
the other
• 500 mg tablets are pink, oval, scored tablets, with TM debossed on one side and 500 on
the other
4 CONTRAINDICATIONS
The use of tinidazole is contraindicated:
• In patients with a previous history of hypersensitivity to tinidazole or other nitroimidazole
derivatives. Reported reactions have ranged in severity from urticaria to Stevens-Johnson
syndrome [see Adverse Reactions (6.1, 6.2)].
• During first trimester of pregnancy [see Use in Specific Populations (8.1)].
• In nursing mothers: Interruption of breast-feeding is recommended during tinidazole
therapy and for 3 days following the last dose [see Use in Specific Populations (8.3)].
5.1 Neurological Adverse Reactions
Convulsive seizures and peripheral neuropathy, the latter characterized mainly by
numbness or paresthesia of an extremity, have been reported in patients treated with
tinidazole. The appearance of abnormal neurologic signs demands the prompt
discontinuation of tinidazole therapy.
5.2 Vaginal Candidiasis
The use of tinidazole may result in Candida vaginitis. In a clinical study of 235 women who
received tinidazole for bacterial vaginosis, a vaginal fungal infection developed in 11 (4.7%) of
all study subjects [see Clinical Studies (14.5)].
5.3 Blood Dyscrasia
Tinidazole should be used with caution in patients with evidence of or history of blood
dyscrasia [see Drug Interactions (7.3)].
5.4 Drug Resistance
Prescribing Tindamax in the absence of a proven or strongly suspected bacterial infection
or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk
of the development of drug-resistant bacteria.
6 ADVERSE REACTIONS
6.1 Clinical Studies Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction
rates observed in the clinical trials of a drug cannot be directly compared to rates in the
clinical trials of another drug and may not reflect the rates observed in practice.
Among 3669 patients treated with a single 2 g dose of tinidazole, in both controlled and
uncontrolled trichomoniasis and giardiasis clinical studies, adverse reactions were reported by
11.0% of patients. For multi-day dosing in controlled and uncontrolled amebiasis studies,
adverse reactions were reported by 13.8% of 1765 patients. Common (≥ 1% incidence)
adverse reactions reported by body system are as follows. (Note: Data described in Table 1
below are pooled from studies with variable designs and safety evaluations.)
Other adverse reactions reported with tinidazole include:
Central Nervous System: Two serious adverse reactions reported include convulsions and
transient peripheral neuropathy including numbness and paresthesia [see Warnings and
Precautions (5.1)]. Other CNS reports include vertigo, ataxia, giddiness, insomnia,
drowsiness.
Gastrointestinal: tongue discoloration, stomatitis, diarrhea
Hypersensitivity: urticaria, pruritis, rash, flushing, sweating, dryness of mouth, fever,
burning sensation, thirst, salivation, angioedema
Renal: darkened urine
Cardiovascular: palpitations
Hematopoietic: transient neutropenia, transient leukopenia
Other: Candida overgrowth, increased vaginal discharge, oral candidiasis, hepatic
abnormalities including raised transaminase level, arthralgias, myalgias, and arthritis.
Table 1. Adverse Reactions Summary of Published Reports
GI: Metallic/bitter taste
Nausea
Anorexia
Dyspepsia/cramps/
epigastric discomfort
Vomiting
Constipation
CNS: Weakness/fatigue/malaise
Dizziness
Other: Headache
Total patients with adverse reactions
2 g single
dose
3.7%
3.2%
1.5%
Multi-day
dose
6.3%
4.5%
2.5%
1.8%
1.4%
1.5%
0.4%
2.1%
1.1%
1.3%
11.0%
(403/3669)
0.9%
1.4%
1.1%
0.5%
0.7%
13.8%
(244/1765)
Rare reported adverse reactions include bronchospasm, dyspnea, coma, confusion, depression,
furry tongue, pharyngitis and reversible thrombocytopenia.
Adverse Reactions in Pediatric Patients: In pooled pediatric studies, adverse reactions
reported in pediatric patients taking tinidazole were similar in nature and frequency to adult
findings including nausea, vomiting, diarrhea, taste change, anorexia, and abdominal pain.
Bacterial vaginosis: The most common adverse reactions in treated patients (incidence
>2%), which were not identified in the trichomoniasis, giardiasis and amebiasis studies, are
gastrointestinal: decreased appetite, and flatulence; renal: urinary tract infection, painful
urination, and urine abnormality; and other reactions including pelvic pain, vulvo-vaginal
discomfort, vaginal odor, menorrhagia, and upper respiratory tract infection [See Clinical
Studies (14.5)].
The following adverse reactions have been identified and reported during post-approval use
of Tindamax. Because the reports of these reactions are voluntary and the population is of
uncertain size, it is not always possible to reliably estimate the frequency of the reaction or
establish a causal relationship to drug exposure.
Severe acute hypersensitivity reactions have been reported on initial or subsequent
exposure to tinidazole. Hypersensitivity reactions may include urticaria, pruritis, angioedema,
Stevens-Johnson syndrome and erythema multiforme.
7 DRUG INTERACTIONS
Although not specifically identified in studies with tinidazole, the following drug
interactions were reported for metronidazole, a chemically-related nitroimidazole. Therefore,
these drug interactions may occur with tinidazole.
7.1 Potential Effects of Tinidazole on Other Drugs
Warfarin and Other Oral Coumarin Anticoagulants: As with metronidazole, tinidazole may
enhance the effect of warfarin and other coumarin anticoagulants, resulting in a prolongation
of prothrombin time. The dosage of oral anticoagulants may need to be adjusted during
tinidazole co-administration and up to 8 days after discontinuation.
Alcohols, Disulfiram: Alcoholic beverages and preparations containing ethanol or propylene
glycol should be avoided during tinidazole therapy and for 3 days afterward because
abdominal cramps, nausea, vomiting, headaches, and flushing may occur. Psychotic
reactions have been reported in alcoholic patients using metronidazole and disulfiram
concurrently. Though no similar reactions have been reported with tinidazole, tinidazole
should not be given to patients who have taken disulfiram within the last two weeks.
Lithium: Metronidazole has been reported to elevate serum lithium levels. It is not known if
tinidazole shares this property with metronidazole, but consideration should be given to
measuring serum lithium and creatinine levels after several days of simultaneous lithium and
tinidazole treatment to detect potential lithium intoxication.
Phenytoin, Fosphenytoin: Concomitant administration of oral metronidazole and
intravenous phenytoin was reported to result in prolongation of the half-life and reduction in
the clearance of phenytoin. Metronidazole did not significantly affect the pharmacokinetics of
orally-administered phenytoin.
Cyclosporine, Tacrolimus: There are several case reports suggesting that metronidazole has
the potential to increase the levels of cyclosporine and tacrolimus. During tinidazole coadministration with either of these drugs, the patient should be monitored for signs of
calcineurin-inhibitor associated toxicities.
Fluorouracil: Metronidazole was shown to decrease the clearance of fluorouracil, resulting
in an increase in side-effects without an increase in therapeutic benefits. If the concomitant
use of tinidazole and fluorouracil cannot be avoided, the patient should be monitored for
fluorouracil-associated toxicities.
7.2 Potential Effects of Other Drugs on Tinidazole
CYP3A4 Inducers and Inhibitors: Simultaneous administration of tinidazole with drugs that
induce liver microsomal enzymes, i.e., CYP3A4 inducers such as phenobarbital, rifampin,
phenytoin, and fosphenytoin (a pro-drug of phenytoin), may accelerate the elimination of
tinidazole, decreasing the plasma level of tinidazole. Simultaneous administration of drugs
that inhibit the activity of liver microsomal enzymes, i.e., CYP3A4 inhibitors such as cimetidine
and ketoconazole, may prolong the half-life and decrease the plasma clearance of tinidazole,
increasing the plasma concentrations of tinidazole.
↕
Cholestyramine: Cholestyramine was shown to decrease the oral bioavailability of
metronidazole by 21%. Thus, it is advisable to separate dosing of cholestyramine and
tinidazole to minimize any potential effect on the oral bioavailability of tinidazole.
Oxytetracycline: Oxytetracycline was reported to antagonize the therapeutic effect of
metronidazole.
7.3 Laboratory Test Interactions
Tinidazole, like metronidazole, may interfere with certain types of determinations of serum
chemistry values, such as aspartate aminotransferase (AST, SGOT), alanine aminotransferase
(ALT, SGPT), lactate dehydrogenase (LDH), triglycerides, and hexokinase glucose. Values of
zero may be observed. All of the assays in which interference has been reported involve
enzymatic coupling of the assay to oxidation-reduction of nicotinamide adenine dinucleotide
(NAD + NADH). Potential interference is due to the similarity of absorbance peaks of NADH
and tinidazole.
Tinidazole, like metronidazole, may produce transient leukopenia and neutropenia;
however, no persistent hematological abnormalities attributable to tinidazole have been
observed in clinical studies. Total and differential leukocyte counts are recommended if retreatment is necessary.
8.1 Pregnancy
Teratogenic effects: Pregnancy Category C
The use of tinidazole in pregnant patients has not been studied. Since tinidazole crosses
the placental barrier and enters fetal circulation it should not be administered to pregnant
patients in the first trimester.
Embryo-fetal developmental toxicity studies in pregnant mice indicated no embryo-fetal
toxicity or malformations at the highest dose level of 2,500 mg/kg (approximately 6.3-fold the
highest human therapeutic dose based upon body surface area conversions). In a study with
pregnant rats a slightly higher incidence of fetal mortality was observed at a maternal dose of
500 mg/kg (2.5-fold the highest human therapeutic dose based upon body surface area
conversions). No biologically relevant neonatal developmental effects were observed in rat
neonates following maternal doses as high as 600 mg/kg (3-fold the highest human
therapeutic dose based upon body surface area conversions). Although there is some
evidence of mutagenic potential and animal reproduction studies are not always predictive of
human response, the use of tinidazole after the first trimester of pregnancy requires that the
potential benefits of the drug be weighed against the possible risks to both the mother and
the fetus.
8.3 Nursing Mothers
Tinidazole is excreted in breast milk in concentrations similar to those seen in serum.
Tinidazole can be detected in breast milk for up to 72 hours following administration.
Interruption of breast-feeding is recommended during tinidazole therapy and for 3 days
following the last dose.
8.4 Pediatric Use
Other than for use in the treatment of giardiasis and amebiasis in pediatric patients older
than three years of age, safety and effectiveness of tinidazole in pediatric patients have not
been established.
Pediatric Administration: For those unable to swallow tablets, tinidazole tablets may be
crushed in artificial cherry syrup, to be taken with food [see Dosage and Administration (2.2)].
8.5 Geriatric Use
Clinical studies of tinidazole did not include sufficient numbers of subjects aged 65 and
over to determine whether they respond differently from younger subjects. In general, dose
selection for an elderly patient should be cautious, reflecting the greater frequency of
decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug
therapy.
8.6 Renal Impairment
Because the pharmacokinetics of tinidazole in patients with severe renal impairment
(CrCL < 22 mL/min) are not significantly different from those in healthy subjects, no
dose adjustments are necessary in these patients.
Patients undergoing hemodialysis: If tinidazole is administered on the same day as and prior
to hemodialysis, it is recommended that an additional dose of tinidazole equivalent to onehalf of the recommended dose be administered after the end of the hemodialysis [see Clinical
Pharmacology (12.3)].
8.7 Hepatic Impairment
There are no data on tinidazole pharmacokinetics in patients with impaired hepatic
function. Reduced elimination of metronidazole, a chemically-related nitroimidazole, has been
reported in this population. Usual recommended doses of tinidazole should be administered
cautiously in patients with hepatic dysfunction [see Clinical Pharmacology (12.3)].
10 OVERDOSAGE
There are no reported overdoses with tinidazole in humans.
Treatment of Overdosage: There is no specific antidote for the treatment of overdosage
with tinidazole; therefore, treatment should be symptomatic and supportive. Gastric lavage
may be helpful. Hemodialysis can be considered because approximately 43% of the amount
present in the body is eliminated during a 6-hour hemodialysis session.
11 DESCRIPTION
Tinidazole is a synthetic antiprotozoal and antibacterial agent. It is 1-[2-ethylsulfonyl)ethyl]2-methyl-5-nitroimidazole, a second-generation 2-methyl-5-nitroimidazole, which has the
following chemical structure:
N
O2N
N
CH3
CH2–CH2–SO2–CH2–CH3
Tindamax pink oral tablets contain 250 mg or 500 mg of tinidazole. Inactive ingredients
include croscarmellose sodium, FD&C Red 40 lake, FD&C Yellow 6 lake, hypromellose,
magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol,
pregelatinized corn starch, titanium dioxide, and triacetin.
Tinidazole is an antiprotozoal, antibacterial agent. [See Clinical Pharmacology (12.4)].
12.3 Pharmacokinetics
Absorption: After oral administration, tinidazole is rapidly and completely absorbed. A
bioavailability study of Tindamax tablets was conducted in adult healthy volunteers. All
subjects received a single oral dose of 2 g (four 500 mg tablets) of Tindamax following an
overnight fast. Oral administration of four 500 mg tablets of Tindamax under fasted conditions
produced a mean peak plasma concentration (Cmax) of 47.7 (±7.5) µg/mL with a mean time to
peak concentration (Tmax) of 1.6 (±0.7) hours, and a mean area under the plasma
concentration-time curve (AUC, 0-∞) of 901.6 (± 126.5) µg.hr/mL at 72 hours. The elimination
half-life (T1/2) was 13.2 (±1.4) hours. Mean plasma levels decreased to 14.3 µg/mL at
24 hours, 3.8 µg/mL at 48 hours and 0.8 µg/mL at 72 hours following administration. Steadystate conditions are reached in 21/2 - 3 days of multi-day dosing.
Administration of Tindamax tablets with food resulted in a delay in Tmax of approximately
2 hours and a decline in Cmax of approximately 10%, compared to fasted conditions.
However, administration of Tindamax with food did not affect AUC or T1/2 in this study.
In healthy volunteers, administration of crushed Tindamax tablets in artificial cherry syrup,
[prepared as described in Dosage and Administration (2.2)] after an overnight fast had no
effect on any pharmacokinetic parameter as compared to tablets swallowed whole under
fasted conditions.
Distribution: Tinidazole is distributed into virtually all tissues and body fluids and also
crosses the blood-brain barrier. The apparent volume of distribution is about 50 liters. Plasma
protein binding of tinidazole is 12%. Tinidazole crosses the placental barrier and is secreted
in breast milk.
Metabolism: Tinidazole is significantly metabolized in humans prior to excretion. Tinidazole
is partly metabolized by oxidation, hydroxylation, and conjugation. Tinidazole is the major
drug-related constituent in plasma after human treatment, along with a small amount of the
2-hydroxymethyl metabolite.
Tinidazole is biotransformed mainly by CYP3A4. In an in vitro metabolic drug interaction
study, tinidazole concentrations of up to 75 µg/mL did not inhibit the enzyme activities of
CYP1A2, CYP2B6, CYP2C9, CYP2D6, CYP2E1, and CYP3A4.
The potential of tinidazole to induce the metabolism of other drugs has not been evaluated.
Elimination: The plasma half-life of tinidazole is approximately 12-14 hours. Tinidazole is
excreted by the liver and the kidneys. Tinidazole is excreted in the urine mainly as
unchanged drug (approximately 20-25% of the administered dose). Approximately 12% of the
drug is excreted in the feces.
Patients with impaired renal function: The pharmacokinetics of tinidazole in patients with
severe renal impairment (CrCL < 22 mL/min) are not significantly different from the
pharmacokinetics seen in healthy subjects. However, during hemodialysis, clearance of
tinidazole is significantly increased; the half-life is reduced from 12.0 hours to 4.9 hours.
Approximately 43% of the amount present in the body is eliminated during a 6-hour
hemodialysis session [See Use in Specific Populations (8.6)]. The pharmacokinetics of
tinidazole in patients undergoing routine continuous peritoneal dialysis have not been
investigated.
Patients with impaired hepatic function: There are no data on tinidazole pharmacokinetics
in patients with impaired hepatic function. Reduction of metabolic elimination of
metronidazole, a chemically-related nitroimidazole, in patients with hepatic dysfunction has
been reported in several studies [See Use in Specific Populations (8.7)].
12.4 Microbiology
Mechanism of Action: Tinidazole is an antiprotozoal,antibacterial agent. The nitro-group of
tinidazole is reduced by cell extracts of Trichomonas. The free nitro- radical generated as a
result of this reduction may be responsible for the antiprotozoal activity. Chemically reduced
tinidazole was shown to release nitrites and cause damage to purified bacterial DNA in vitro.
Additionally, the drug caused DNA base changes in bacterial cells and DNA strand breakage
in mammalian cells. The mechanism by which tinidazole exhibits activity against Giardia and
Entamoeba species is not known.
Antibacterial: Culture and sensitivity testing of bacteria are not routinely performed to
establish the diagnosis of bacterial vaginosis [see Indications and Usage (1.4)]; standard
methodology for the susceptibility testing of potential bacterial pathogens, Gardnerella
vaginalis, Mobiluncus spp. or Mycoplasma hominis, has not been defined. The following in
vitro data are available, but their clinical significance is unknown. Tinidazole is active in vitro
against most strains of the following organisms that have been reported to be associated with
bacterial vaginosis:
Bacteroides spp.
Gardnerella vaginalis
Prevotella spp.
Tinidazole does not appear to have activity against most strains of vaginal lactobacilli.
Antiprotozoal: Tinidazole demonstrates activity both in vitro and in clinical infections against
the following protozoa: Trichomonas vaginalis; Giardia duodenalis (also termed G. lamblia);
and Entamoeba histolytica.
For protozoal parasites, standardized susceptibility tests do not exist for use in clinical
microbiology laboratories.
Drug Resistance: The development of resistance to tinidazole by G. duodenalis, E.
histolytica, or bacteria associated with bacterial vaginosis has not been examined.
Cross-resistance: Approximately 38% of T. vaginalis isolates exhibiting reduced susceptibility
to metronidazole also show reduced susceptibility to tinidazole in vitro. The clinical significance
of such an effect is not known.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Metronidazole, a chemically-related nitroimidazole, has been reported to be carcinogenic
in mice and rats but not hamsters. In several studies metronidazole showed evidence of
pulmonary, hepatic, and lymphatic tumorigenesis in mice and mammary and hepatic tumors
in female rats. Tinidazole carcinogenicity studies in rats, mice or hamsters have not been
reported.
Tinidazole was mutagenic in the TA 100, S. typhimurium tester strain both with and without
the metabolic activation system and was negative for mutagenicity in the TA 98 strain.
Mutagenicity results were mixed (positive and negative) in the TA 1535, 1537, and 1538
strains. Tinidazole was also mutagenic in a tester strain of Klebsiella pneumonia. Tinidazole
was negative for mutagenicity in a mammalian cell culture system utilizing Chinese hamster
lung V79 cells (HGPRT test system) and negative for genotoxicity in the Chinese hamster
ovary (CHO) sister chromatid exchange assay. Tinidazole was positive for in vivo genotoxicity
in the mouse micronucleus assay.
In a 60-day fertility study, tinidazole reduced fertility and produced testicular
histopathology in male rats at a 600 mg/kg/day dose level (approximately 3-fold the highest
human therapeutic dose based upon body surface area conversions). Spermatogenic effects
resulted from 300 and 600 mg/kg/day dose levels. The no observed adverse reaction level for
testicular and spermatogenic effects was 100 mg/kg/day (approximately 0.5-fold the highest
human therapeutic dose based upon body surface area conversions). This effect is
characteristic of agents in the 5-nitroimidazole class.
13.2 Animal Toxicology and/or Pharmacology
In acute studies with mice and rats, the LD50 for mice was generally > 3,600 mg/kg for oral
administration and was > 2,300 mg/kg for intraperitoneal administration. In rats, the LD50
was > 2,000 mg/kg for both oral and intraperitoneal administration.
A repeated-dose toxicology study has been performed in beagle dogs using oral dosing of
tinidazole at 100 mg/kg/day, 300 mg/kg/day, and 1000 mg/kg/day for 28-days. On Day 18 of
the study, the highest dose was lowered to 600 mg/kg/day due to severe clinical symptoms.
The two compound-related effects observed in the dogs treated with tinidazole were
increased atrophy of the thymus in both sexes at the middle and high doses, and atrophy of
the prostate at all doses in the males. A no-adverse-effect level (NOAEL) of
100 mg/kg/day for females was determined. There was no NOAEL identified for males
because of minimal atrophy of the prostate at 100 mg/kg/day (approximately 0.9-fold
the highest human dose based upon plasma AUC comparisons).
14 CLINICAL STUDIES
14.1 Trichomoniasis
Tinidazole (2 g single oral dose) use in trichomoniasis has been well documented in 34
published reports from the world literature involving over 2,800 patients treated with
tinidazole. In four published, blinded, randomized, comparative studies of the 2 g tinidazole
single oral dose where efficacy was assessed by culture at time points post-treatment ranging
from one week to one month, reported cure rates ranged from 92% (37/40) to 100% (65/65)
(n=172 total subjects). In four published, blinded, randomized, comparative studies where
efficacy was assessed by wet mount between 7-14 days post-treatment, reported cure rates
ranged from 80% (8/10) to 100% (16/16) (n=116 total subjects). In these studies, tinidazole
was superior to placebo and comparable to other anti-trichomonal drugs. The single oral 2 g
tinidazole dose was also assessed in four open-label trials in men (one comparative to
metronidazole and 3 single-arm studies). Parasitological evaluation of the urine was
performed both pre- and post-treatment and reported cure rates ranged from 83% (25/30) to
100% (80/80) (n=142 total subjects).
14.2 Giardiasis
Tinidazole (2 g single dose) use in giardiasis has been documented in 19 published reports
from the world literature involving over 1,600 patients (adults and pediatric patients). In eight
controlled studies involving a total of 619 subjects of whom 299 were given the 2 g x 1 day
(50 mg/kg x 1 day in pediatric patients) oral dose of tinidazole, reported cure rates ranged
from 80% (40/50) to 100% (15/15). In three of these trials where the comparator was 2 to 3
days of various doses of metronidazole, reported cure rates for metronidazole were 76%
(19/25) to 93% (14/15). Data comparing a single 2 g dose of tinidazole to usually
recommended 5-7 days of metronidazole are limited.
14.3 Intestinal Amebiasis
Tinidazole use in intestinal amebiasis has been documented in 26 published reports from
the world literature involving over 1,400 patients. Most reports utilized tinidazole 2 g/day x 3 days.
In four published, randomized, controlled studies (1 investigator single-blind, 3 open-label) of the
2 g/day x 3 days oral dose of tinidazole, reported cure rates after 3 days of therapy among a
total of 220 subjects ranged from 86% (25/29) to 93% (25/27).
14.4 Amebic Liver Abscess
Tinidazole use in amebic liver abscess has been documented in 18 published reports from
the world literature involving over 470 patients. Most reports utilized tinidazole 2 g/day x 2-5 days.
In seven published, randomized, controlled studies (1 double-blind, 1 single-blind, 5 openlabel) of the 2 g/day x 2-5 days oral dose of tinidazole accompanied by aspiration of the liver
abscess when clinically necessary, reported cure rates among 133 subjects ranged from
81% (17/21) to 100% (16/16). Four of these studies utilized at least 3 days of tinidazole.
A randomized, double-blind, placebo-controlled clinical trial in 235 non-pregnant women
was conducted to evaluate the efficacy of tinidazole for the treatment of bacterial vaginosis. A
clinical diagnosis of bacterial vaginosis was based on Amsel’s criteria and defined by the
presence of an abnormal homogeneous vaginal discharge that (a) has a pH of greater than
4.5, (b) emits a “fishy” amine odor when mixed with a 10% KOH solution, and (c) contains
≥20% clue cells on microscopic examination. Clinical cure required a return to normal vaginal
discharge and resolution of all Amsel’s criteria. A microbiologic diagnosis of bacterial vaginosis
was based on Gram stain of the vaginal smear demonstrating (a) markedly reduced or absent
Lactobacillus morphology, (b) predominance of Gardnerella morphotype, and (c) absent or few
white blood cells, with quantification of these bacterial morphotypes to determine the Nugent
score, where a score ≥4 was required for study inclusion and a score of 0-3 considered a
microbiologic cure. Therapeutic cure was a composite endpoint, consisting of both a clinical
cure and microbiologic cure. In patients with all four Amsel’s criteria and with a baseline
Nugent score ≥4, tinidazole oral tablets given as either 2 g once daily for 2 days or 1 g once
daily for 5 days demonstrated superior efficacy over placebo tablets as measured by
therapeutic cure, clinical cure, and a microbiologic cure.
Table 2. Efficacy of Tindamax in the Treatment of Bacterial Vaginosis in a
Randomized, Double-Blind, Double-Dummy, Placebo-Controlled Trial:
Modified Intent-to-Treat Population1 (n=227)
Outcome
Tindamax
Tindamax
Placebo
1 g x 5 days
2 g x 2 days
(n=76)
(n=73)
(n=78)
% Cure
% Cure
% Cure
Therapeutic Cure
36.8
27.4
5.1
Difference2
31.7
22.3
3
97.5% CI
(16.8, 46.6)
(8.0, 36.6)
Clinical Cure
51.3
35.6
11.5
Difference2
39.8
24.1
3
97.5% CI
(23.3, 56.3)
(7.8, 40.3)
Nugent Score Cure
38.2
27.4
5.1
Difference2
33.1
22.3
(18.1, 48.0)
(8.0, 36.6)
97.5% CI3
1
Modified Intent-to-Treat defined as all patients randomized with a baseline Nugent score of at
least 4
Difference in cure rates (Tindamax-placebo)
3
CI: confidence interval
p-values for both Tindamax regimens vs. placebo for therapeutic, clinical and Nugent score
cure rates for both 2 and 5 days <0.001
2
The therapeutic cure rates reported in this clinical study conducted with Tindamax were
based on resolution of 4 out of 4 Amsel’s criteria and a Nugent score of <4. The cure rates for
previous clinical studies with other products approved for bacterial vaginosis were based on
resolution of either 2 or 3 out of 4 Amsel’s criteria. At the time of approval for other products
for bacterial vaginosis, there was no requirement for a Nugent score on Gram stain, resulting
in higher reported rates of cure for bacterial vaginosis for those products than for those
reported here for tinidazole.
Tindamax 250 mg tablets are pink, round, scored tablets, with TM debossed on one side
and 250 on the other, supplied in bottles with child-resistant caps as:
NDC 0178-8250-40
Bottle of 40
Tindamax 500 mg tablets are pink, oval, scored tablets, with TM debossed on one side and
500 on the other, supplied in bottles with child-resistant caps as:
NDC 0178-8500-60
Bottle of 60
NDC 0178-8500-20
Bottle of 20
Professional Samples:
NDC 0178-8500-02
Bottle of 2
Storage: Store at controlled room temperature 20-25º C (68-77º F); excursions permitted to
15-30º C (59-86º F) [see USP]. Protect contents from light.
Patients should be told to take Tindamax with food to minimize the incidence of epigastric
discomfort and other gastrointestinal side-effects. Food does not affect the oral bioavailability
of tinidazole.
17.2 Alcohol Avoidance
Patients should be told to avoid alcoholic beverages and preparations containing ethanol
or propylene glycol during Tindamax therapy and for 3 days afterward because abdominal
cramps, nausea, vomiting, headaches, and flushing may occur.
17.3 Drug Resistance
Patients should be counseled that antibacterial drugs including Tindamax should only be
used to treat bacterial infections. They do not treat viral infections (e.g., the common cold).
When Tindamax is prescribed to treat a bacterial infection, patients should be told that
although it is common to feel better early in the course of therapy, the medication should be
taken exactly as directed. Skipping doses or not completing the full course of therapy may
(1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that
bacteria will develop resistance and will not be treatable by Tindamax or other antibacterial
drugs in the future.
TM-81 C02 Rev 008070

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