CARBAMAZEPINE tablet

United States - English - NLM (National Library of Medicine)

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Active ingredient:
CARBAMAZEPINE (UNII: 33CM23913M) (CARBAMAZEPINE - UNII:33CM23913M)
Available from:
REMEDYREPACK INC.
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Carbamazepine is indicated for use as an anticonvulsant drug. Evidence supporting efficacy of carbamazepine as an anticonvulsant was derived from active drug-controlled studies that enrolled patients with the following seizure types: - Partial seizures with complex symptomatology (psychomotor, temporal lobe). Patients with these seizures appear to show greater improvement than those with other types. - Generalized tonic-clonic seizures (grand mal). - Mixed seizure patterns which include the above, or other partial or generalized seizures. Absence seizures (petit mal) do not appear to be controlled by carbamazepine (see PRECAUTIONS, General). Carbamazepine is indicated in the treatment of the pain associated with true trigeminal neuralgia. Beneficial results have also been reported in glossopharyngeal neuralgia. This drug is not a simple analgesic and should not be used for the relief of trivial aches or pains. Carbamazepine should not be used in patients with a history of previous bone marro
Product summary:
Carbamazepine Tablets USP, (Chewable), 100 mg: White, flat, round tablet with pink specks, and cherry fragrance. One side scored and engraved with "TARO" above the score and "16" under the score. Other side plain. Carbamazepine Tablets USP, (Chewable), 200 mg: White, flat, oval beveled tablet, with pink specks, and cherry fragrance. One side scored and engraved with "T" above the score and "27" under the score. Other side scored. Store Carbamazepine Tablets USP, (Chewable) at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from light and moisture. Dispense in tight, light-resistant container (USP). Meets USP Dissolution Test 1. Carbamazepine Tablets USP, 200 mg: White, round, flat beveled-edge, one side scored and engraved "TARO" above and "11" below the score, the other side plain. Store Carbamazepine Tablets USP at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from moisture. Dispense in tight container (USP). Meets USP Dissolution Test 2. Carbamazepine Extended-Release Tablets USP, 100 mg: White to off-white, round bi-convexed tablets engraved with "T91" on one side and plain on the other side. Carbamazepine Extended-Release Tablets USP, 200 mg: White to off-white, round bi-convexed tablets engraved with "T26" on one side and plain on the other side. Carbamazepine Extended-Release Tablets USP, 400 mg: White to off-white, capsule-shaped bi-convexed tablets engraved with "T29" on one side and plain on the other side. Store Carbamazepine Extended-Release Tablets USP at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from moisture. Dispense in tight container (USP). Carbamazepine Oral Suspension USP, 100 mg/5 mL (teaspoonful): Orange colored and orange flavored suspension. Shake well before using. Store Carbamazepine Oral Suspension USP at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from freezing and from excessive heat. Dispense in tight, light-resistant container (USP).
Authorization status:
Abbreviated New Drug Application
Authorization number:
70518-2242-0, 70518-2242-1, 70518-2242-2

CARBAMAZEPINE- carbamazepine tablet

REMEDYREPACK INC.

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MEDICATION GUIDE

Carbamazepine (kar" ba maz' e peen) Tablets,

Carbamazepine (kar" ba maz' e peen) Oral Suspension,

Carbamazepine (kar" ba maz' e peen) Tablets (Chewable),

and Carbamazepine (kar" ba maz' e peen) Extended-Release Tablets

Read this Medication Guide before you start taking Carbamazepine Tablets, Carbamazepine Oral

Suspension, Carbamazepine Tablets (Chewable), or Carbamazepine Extended-Release Tablets and each time

you get a refill. There may be new information. This information does not take the place of talking to your

healthcare provider about your medical condition or treatment.

What is the most important information I should know about carbamazepine?

Do not stop taking carbamazepine without first talking to your healthcare provider.

Stopping carbamazepine suddenly can cause serious problems.

Carbamazepine can cause serious side effects, including:

Carbamazepine may cause rare but serious skin rashes that may lead to death. These serious skin

reactions are more likely to happen when you begin taking carbamazepine within the first four months

of treatment but may occur at later times. These reactions can happen in anyone, but are more likely

in people of Asian descent. If you are of Asian descent, you may need a genetic blood test before you

take carbamazepine to see if you are at a higher risk for serious skin reactions with this medicine.

Symptoms may include:

skin rash

hives

sores in your mouth

blistering or peeling of the skin

Carbamazepine may cause rare but serious blood problems. Symptoms may include:

fever, sore throat, or other infections that come and go or do not go away

easy bruising

red or purple spots on your body

bleeding gums or nose bleeds

severe fatigue or weakness

Carbamazepine may cause allergic reactions or serious problems, which may affect organs and other

parts of your body like the liver or blood cells. You may or may not have a rash with these types of

reactions.

Call your healthcare provider right away if you have any of the following:

swelling of your face, eyes, lips, or tongue

a skin rash

painful sores in the mouth or around your eyes

unusual bruising or bleeding

frequent infections or infections that do not go away

fever, swollen glands, or sore throat that do not go away or come and go

trouble swallowing or breathing

hives

yellowing of your skin or eyes

severe fatigue or weakness

severe muscle pain

Like other antiepileptic drugs, carbamazepine may cause suicidal thoughts or actions in a very small

number of people, about 1 in 500.

Call your healthcare provider right away if you have any of these symptoms, especially if they are

new, worse, or worry you:

thoughts about suicide or dying

attempts to commit suicide

new or worse depression

new or worse anxiety

feeling agitated or restless

panic attacks

trouble sleeping (insomnia)

new or worse irritability

acting aggressive, being angry, or violent

acting on dangerous impulses

an extreme increase in activity and talking (mania)

other unusual changes in behavior or mood

How can I watch for early symptoms of suicidal thoughts and actions?

Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.

Keep all follow-up visits with your healthcare provider as scheduled.

Call your healthcare provider between visits as needed, especially if you are worried about symptoms.

Do not stop carbamazepine without first talking to a healthcare provider.

Stopping carbamazepine suddenly can cause serious problems. You should talk to your healthcare provider

before stopping.

Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts or

actions, your healthcare provider may check for other causes.

What is carbamazepine?

Carbamazepine is a prescription medicine used to treat:

certain types of seizures (partial, tonic-clonic, mixed)

certain types of nerve pain (trigeminal and glossopharyngeal neuralgia)

Carbamazepine is not a regular pain medicine and should not be used for aches or pains.

Who should not take carbamazepine?

Do not take carbamazepine if you:

have a history of bone marrow depression.

are allergic to carbamazepine or any of the ingredients in Carbamazepine Tablets, Carbamazepine

Oral Suspension, Carbamazepine Tablets (Chewable), or Carbamazepine Extended-Release Tablets.

See the end of this Medication Guide for a complete list of ingredients in Carbamazepine Tablets,

Carbamazepine Oral Suspension, Carbamazepine Tablets (Chewable), or Carbamazepine Extended-

Release Tablets.

take nefazodone.

are allergic to medicines called tricyclic antidepressants (TCAs). Ask your healthcare provider or

pharmacist for a list of these medicines if you are not sure.

have taken a medicine called a Monoamine Oxidase Inhibitor (MAOI) in the last 14 days. Ask your

healthcare provider or pharmacist for a list of these medicines if you are not sure.

What should I tell my healthcare provider before taking carbamazepine?

Before you take carbamazepine, tell your healthcare provider if you:

have or have had suicidal thoughts or actions, depression, or mood problems

have or ever had heart problems

have or ever had blood problems

have or ever had liver problems

have or ever had kidney problems

have or ever had allergic reactions to medicines

have or ever had increased pressure in your eye

have any other medical conditions

drink grapefruit juice or eat grapefruit

use birth control. Carbamazepine may make your birth control less effective. Tell your healthcare

provider if your menstrual bleeding changes while you take birth control and carbamazepine.

are pregnant or plan to become pregnant. Carbamazepine may harm your unborn baby. Tell your

healthcare provider right away if you become pregnant while taking carbamazepine. You and your

healthcare provider should decide if you should take carbamazepine while you are pregnant.

If you become pregnant while taking carbamazepine, talk to your healthcare provider about

registering with the North American Antiepileptic Drug (NAAED) Pregnancy Registry. The

purpose of this registry is to collect information about the safety of antiepileptic medicine

during pregnancy. You can enroll in this registry by calling 1-888-233-2334.

are breastfeeding or plan to breastfeed. Carbamazepine passes into breast milk. You and your

healthcare provider should discuss whether you should take carbamazepine or breastfeed; you should

not do both.

Tell your healthcare provider about all the medicines you take , including prescription and non-prescription

medicines, vitamins, and herbal supplements.

Taking carbamazepine with certain other medicines may cause side effects or affect how well they work. Do

not start or stop other medicines without talking to your healthcare provider.

Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist

when you get a new medicine.

How should I take carbamazepine?

Do not stop taking carbamazepine without first talking to your healthcare provider. Stopping

carbamazepine suddenly can cause serious problems. Stopping seizure medicine suddenly in a patient

who has epilepsy may cause seizures that will not stop (status epilepticus).

Take carbamazepine exactly as prescribed. Your healthcare provider will tell you how much

carbamazepine to take.

Your healthcare provider may change your dose. Do not change your dose of carbamazepine without

talking to your healthcare provider.

Take carbamazepine with food.

Carbamazepine extended-release tablets:

Do not crush, chew, or break carbamazepine extended-release tablets.

Tell your healthcare provider if you can not swallow carbamazepine extended-release tablets

whole.

Carbamazepine oral suspension:

Shake the bottle well each time before use.

Do not take carbamazepine oral suspension at the same time you take other liquid medicines.

If you take too much carbamazepine, call your healthcare provider or local Poison Control Center

right away.

What should I avoid while taking carbamazepine?

Do not drink alcohol or take other drugs that make you sleepy or dizzy while taking carbamazepine

until you talk to your healthcare provider. Carbamazepine taken with alcohol or drugs that cause

sleepiness or dizziness may make your sleepiness or dizziness worse.

Do not drive, operate heavy machinery, or do other dangerous activities until you know how

carbamazepine affects you. Carbamazepine may slow your thinking and motor skills.

What are the possible side effects of carbamazepine?

See " What is the most important information I should know about carbamazepine? "

Carbamazepine may cause other serious side effects. These include:

Irregular heartbeat - symptoms include:

Fast, slow, or pounding heartbeat

Shortness of breath

Feeling lightheaded

Fainting

Liver problems - symptoms include:

yellowing of your skin or the whites of your eyes

dark urine

pain on the right side of your stomach area (abdominal pain)

easy bruising

loss of appetite

nausea or vomiting

Get medical help right away if you have any of the symptoms listed above or listed in "What is the most

important information I should know about carbamazepine?"

The most common side effects of carbamazepine include:

dizziness

drowsiness

problems with walking and coordination (unsteadiness)

nausea

vomiting

These are not all the possible side effects of carbamazepine. For more information, ask your healthcare

provider or pharmacist.

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-

1088.

How should I store carbamazepine?

Store Carbamazepine Tablets at 20° to 25°C (68° to 77°F).

Keep Carbamazepine Tablets dry.

Store Carbamazepine Tablets (Chewable) at 20° to 25°C (68° to 77°F).

Keep Carbamazepine Tablets (Chewable) out of the light.

Keep Carbamazepine Tablets (Chewable) dry.

Store Carbamazepine Extended-Release Tablets at 20° to 25°C (68° to 77°F).

Keep Carbamazepine Extended-Release Tablets dry.

Store Carbamazepine Oral Suspension at 20° to 25°C (68° to 77°F).

Shake well before using.

Keep Carbamazepine Oral Suspension in a tight, light-resistant container.

Keep carbamazepine and all medicines out of the reach of children.

General Information about carbamazepine

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use

carbamazepine for a condition for which it was not prescribed. Do not give carbamazepine to other people,

even if they have the same symptoms that you have. It may harm them.

This Medication Guide summarizes the most important information about carbamazepine. If you would like

more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for

the full prescribing information about carbamazepine that is written for health professionals .

For more information call 1-866-923-4914.

What are the ingredients in carbamazepine?

Active ingredient: carbamazepine

Inactive ingredients:

Carbamazepine Tablets, (Chewable), 100 mg and 200 mg – ammonio methacrylate copolymer,

croscarmellose sodium, diethyl phthalate, FD&C red no. 40 lake, magnesium stearate,

microcrystalline cellulose, natural cherry flavor, pregelatinized maize starch and sorbitol.

Carbamazepine Tablets, 200 mg – ammonio methacrylate copolymer, corn starch, croscarmellose

sodium, diethyl phthalate, magnesium stearate and microcrystalline cellulose.

Carbamazepine Extended-Release Tablets, 100 mg, 200 mg, and 400 mg – ammonio methacrylate

copolymer, corn starch, diethyl phthalate, lactose monohydrate, magnesium stearate, microcrystalline

cellulose and sodium starch glycolate.

Carbamazepine Oral Suspension, 100 mg/5 mL – citric acid monohydrate, FD&C yellow no. 6,

orange flavor, poloxamer 188, potassium sorbate, propylene glycol, purified water, sorbitol solution,

sucrose and xanthan gum.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Distributed by: Taro Pharmaceuticals U.S.A., Inc.

Hawthorne, NY 10532

Made in Israel

Revised: May 2018

70725-0518-11

Revised: 10/2019

Document Id: 95878758-f37b-f0c3-e053-2a95a90a4888

34391-3

Set id: 40bf2923-24b1-4af1-8d20-03cf06b455a5

Version: 2

Effective Time: 20191022

REMEDYREPACK INC.

CARBAMAZEPINE- carbamazepine tablet

REMEDYREPACK INC.

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Carbamazepine Tablets USP, (Chewable), 100 mg and 200 mg

Carbamazepine Tablets USP, 200 mg

Carbamazepine Extended-Release Tablets USP, 100 mg, 200 mg, and 400 mg

Carbamazepine Oral Suspension USP, 100 mg/5 mL

Rx only

Prescribing Information

WARNINGS

SERIOUS DERMATOLOGIC REACTIONS AND HLA-B*1502 ALLELE

SERIOUS AND SOMETIMES FATAL DERMATOLOGIC REACTIONS, INCLUDING TOXIC

EPIDERMAL NECROLYSIS (TEN) AND STEVENS-JOHNSON SYNDROME (SJS), HAVE

BEEN REPORTED DURING TREATMENT WITH CARBAMAZEPINE. THESE

REACTIONS ARE ESTIMATED TO OCCUR IN 1 TO 6 PER 10,000 NEW USERS IN

COUNTRIES WITH MAINLY CAUCASIAN POPULATIONS, BUT THE RISK IN SOME

ASIAN COUNTRIES IS ESTIMATED TO BE ABOUT 10 TIMES HIGHER. STUDIES IN

PATIENTS OF CHINESE ANCESTRY HAVE FOUND A STRONG ASSOCIATION

BETWEEN THE RISK OF DEVELOPING SJS/TEN AND THE PRESENCE OF HLA-B*1502,

AN INHERITED ALLELIC VARIANT OF THE HLA-B GENE. HLA-B*1502 IS FOUND

ALMOST EXCLUSIVELY IN PATIENTS WITH ANCESTRY ACROSS BROAD AREAS OF

ASIA. PATIENTS WITH ANCESTRY IN GENETICALLY AT-RISK POPULATIONS

SHOULD BE SCREENED FOR THE PRESENCE OF HLA-B*1502 PRIOR TO INITIATING

TREATMENT WITH CARBAMAZEPINE. PATIENTS TESTING POSITIVE FOR THE

ALLELE SHOULD NOT BE TREATED WITH CARBAMAZEPINE UNLESS THE BENEFIT

CLEARLY OUTWEIGHS THE RISK (SEE WARNINGS AND PRECAUTIONS,

LABORATORY TESTS).

APLASTIC ANEMIA AND AGRANULOCYTOSIS

APLASTIC ANEMIA AND AGRANULOCYTOSIS HAVE BEEN REPORTED IN

ASSOCIATION WITH THE USE OF CARBAMAZEPINE. DATA FROM A POPULATION-

BASED CASE CONTROL STUDY DEMONSTRATE THAT THE RISK OF DEVELOPING

THESE REACTIONS IS 5 TO 8 TIMES GREATER THAN IN THE GENERAL

POPULATION. HOWEVER, THE OVERALL RISK OF THESE REACTIONS IN THE

UNTREATED GENERAL POPULATION IS LOW, APPROXIMATELY SIX PATIENTS PER

ONE MILLION POPULATION PER YEAR FOR AGRANULOCYTOSIS AND TWO

PATIENTS PER ONE MILLION POPULATION PER YEAR FOR APLASTIC ANEMIA.

ALTHOUGH REPORTS OF TRANSIENT OR PERSISTENT DECREASED PLATELET OR

WHITE BLOOD CELL COUNTS ARE NOT UNCOMMON IN ASSOCIATION WITH THE

USE OF CARBAMAZEPINE, DATA ARE NOT AVAILABLE TO ESTIMATE

ACCURATELY THEIR INCIDENCE OR OUTCOME. HOWEVER, THE VAST MAJORITY

OF THE CASES OF LEUKOPENIA HAVE NOT PROGRESSED TO THE MORE SERIOUS

CONDITIONS OF APLASTIC ANEMIA OR AGRANULOCYTOSIS.

BECAUSE OF THE VERY LOW INCIDENCE OF AGRANULOCYTOSIS AND APLASTIC

ANEMIA, THE VAST MAJORITY OF MINOR HEMATOLOGIC CHANGES OBSERVED IN

MONITORING OF PATIENTS ON CARBAMAZEPINE ARE UNLIKELY TO SIGNAL THE

OCCURRENCE OF EITHER ABNORMALITY. NONETHELESS, COMPLETE

PRETREATMENT HEMATOLOGICAL TESTING SHOULD BE OBTAINED AS A

BASELINE. IF A PATIENT IN THE COURSE OF TREATMENT EXHIBITS LOW OR

DECREASED WHITE BLOOD CELL OR PLATELET COUNTS, THE PATIENT SHOULD

BE MONITORED CLOSELY. DISCONTINUATION OF THE DRUG SHOULD BE

CONSIDERED IF ANY EVIDENCE OF SIGNIFICANT BONE MARROW DEPRESSION

DEVELOPS.

Before prescribing carbamazepine, the physician should be thoroughly familiar with the details of

this prescribing information, particularly regarding use with other drugs, especially those which

accentuate toxicity potential.

DESCRIPTION

Carbamazepine USP, is an anticonvulsant and specific analgesic for trigeminal neuralgia, available for

oral administration as chewable tablets of 100 and 200 mg, tablets of 200 mg, extended-release tablets

of 100 mg, 200 mg, and 400 mg, and as a suspension of 100 mg/5 mL (teaspoon). Its chemical name is 5

H-dibenz[ b,f]azepine-5-carboxamide, and its structural formula is:

Carbamazepine USP is a white to off-white powder, practically insoluble in water and soluble in

alcohol and in acetone. Its molecular weight is 236.27.

Inactive Ingredients: Carbamazepine Tablets USP, (Chewable), 100 mg and 200 mg – ammonio

methacrylate copolymer, croscarmellose sodium, diethyl phthalate, FD&C red no. 40 lake, magnesium

stearate, microcrystalline cellulose, natural cherry flavor, pregelatinized maize starch and sorbitol.

Carbamazepine Tablets USP, 200 mg – ammonio methacrylate copolymer, corn starch,

croscarmellose sodium, diethyl phthalate, magnesium stearate and microcrystalline cellulose.

Carbamazepine Extended-Release Tablets USP, 100 mg, 200 mg, and 400 mg – ammonio

methacrylate copolymer, corn starch, diethyl phthalate, lactose monohydrate, magnesium stearate,

microcrystalline cellulose and sodium starch glycolate.

Carbamazepine Oral Suspension USP, 100 mg/5 mL – citric acid monohydrate, FD&C yellow no. 6,

orange flavor, poloxamer 188, potassium sorbate, propylene glycol, purified water, sorbitol solution,

sucrose and xanthan gum.

CLINICAL PHARMACOLOGY

In controlled clinical trials, carbamazepine has been shown to be effective in the treatment of

psychomotor and grand mal seizures, as well as trigeminal neuralgia.

Mechanism of Action

Carbamazepine has demonstrated anticonvulsant properties in rats and mice with electrically and

chemically induced seizures. It appears to act by reducing polysynaptic responses and blocking the

post-tetanic potentiation. Carbamazepine greatly reduces or abolishes pain induced by stimulation of the

infraorbital nerve in cats and rats. It depresses thalamic potential and bulbar and polysynaptic reflexes,

including the linguomandibular reflex in cats. Carbamazepine is chemically unrelated to other

anticonvulsants or other drugs used to control the pain of trigeminal neuralgia. The mechanism of action

remains unknown. The principal metabolite of carbamazepine, carbamazepine-10,11-epoxide, has

anticonvulsant activity as demonstrated in several in vivo animal models of seizures. Though clinical

activity for the epoxide has been postulated, the significance of its activity with respect to the safety

and efficacy of carbamazepine has not been established.

Pharmacokinetics

In clinical studies, carbamazepine suspension, conventional tablets, and extended-release tablets

delivered equivalent amounts of drug to the systemic circulation. However, the suspension was

absorbed somewhat faster, and the extended-release tablet slightly slower, than the conventional tablet.

The bioavailability of the extended-release tablet was 89% compared to suspension. Following a twice

a day dosage regimen, the suspension provides higher peak levels and lower trough levels than those

obtained from the conventional tablet for the same dosage regimen. On the other hand, following a three

times a day dosage regimen, carbamazepine suspension affords steady-state plasma levels comparable

to carbamazepine tablets given twice a day when administered at the same total mg daily dose.

Following a twice a day dosage regimen, carbamazepine extended-release tablets afford steady-state

plasma levels comparable to conventional carbamazepine tablets given twice a day, when administered at

the same total mg daily dose. Carbamazepine in blood is 76% bound to plasma proteins. Plasma levels of

carbamazepine are variable and may range from 0.5 to 25 mcg/mL, with no apparent relationship to the

daily intake of the drug. Usual adult therapeutic levels are between 4 and 12 mcg/mL. In polytherapy, the

concentration of carbamazepine and concomitant drugs may be increased or decreased during therapy,

and drug effects may be altered (see PRECAUTIONS, Drug Interactions). Following chronic oral

administration of suspension, plasma levels peak at approximately 1.5 hours compared to 4 to 5 hours

after administration of conventional carbamazepine tablets, and 3 to 12 hours after administration of

carbamazepine extended-release tablets. The CSF/serum ratio is 0.22, similar to the 24% unbound

carbamazepine in serum. Because carbamazepine induces its own metabolism, the half-life is also

variable. Autoinduction is completed after 3 to 5 weeks of a fixed dosing regimen. Initial half-life

values range from 25 to 65 hours, decreasing to 12 to 17 hours on repeated doses. Carbamazepine is

metabolized in the liver. Cytochrome P450 3A4 was identified as the major isoform responsible for the

formation of carbamazepine-10,11-epoxide from carbamazepine. Human microsomal epoxide hydrolase

has been identified as the enzyme responsible for the formation of the 10,11-transdiol derivative from

carbamazepine-10,11 epoxide. After oral administration of

C-carbamazepine, 72% of the administered

radioactivity was found in the urine and 28% in the feces. This urinary radioactivity was composed

largely of hydroxylated and conjugated metabolites, with only 3% of unchanged carbamazepine.

The pharmacokinetic parameters of carbamazepine disposition are similar in children and in adults.

However, there is a poor correlation between plasma concentrations of carbamazepine and

carbamazepine dose in children. Carbamazepine is more rapidly metabolized to carbamazepine-10,11-

epoxide (a metabolite shown to be equipotent to carbamazepine as an anticonvulsant in animal screens) in

the younger age groups than in adults. In children below the age of 15, there is an inverse relationship

between CBZ-E/CBZ ratio and increasing age (in one report from 0.44 in children below the age of 1

year to 0.18 in children between 10 to 15 years of age).

The effects of race and gender on carbamazepine pharmacokinetics have not been systematically

evaluated.

INDICATIONS AND USAGE

Epileps y

Carbamazepine is indicated for use as an anticonvulsant drug. Evidence supporting efficacy of

carbamazepine as an anticonvulsant was derived from active drug-controlled studies that enrolled

patients with the following seizure types:

1. Partial seizures with complex symptomatology (psychomotor, temporal lobe). Patients with these

seizures appear to show greater improvement than those with other types.

2. Generalized tonic-clonic seizures (grand mal).

3. Mixed seizure patterns which include the above, or other partial or generalized seizures. Absence

seizures (petit mal) do not appear to be controlled by carbamazepine (see PRECAUTIONS,

General).

Trigeminal Neuralgia

Carbamazepine is indicated in the treatment of the pain associated with true trigeminal neuralgia.

Beneficial results have also been reported in glossopharyngeal neuralgia.

This drug is not a simple analgesic and should not be used for the relief of trivial aches or pains.

CONTRAINDICATIONS

Carbamazepine should not be used in patients with a history of previous bone marrow depression,

hypersensitivity to the drug, or known sensitivity to any of the tricyclic compounds, such as

amitriptyline, desipramine, imipramine, protriptyline, nortriptyline, etc. Likewise, on theoretical grounds

its use with monoamine oxidase (MAO) inhibitors is not recommended. Before administration of

carbamazepine, MAO inhibitors should be discontinued for a minimum of 14 days, or longer if the

clinical situation permits.

Coadministration of carbamazepine and nefazodone may result in insufficient plasma concentrations of

nefazodone and its active metabolite to achieve a therapeutic effect. Coadministration of carbamazepine

with nefazodone is contraindicated.

WARNINGS

Serious Dermatologic Reactions

Serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN) and

Stevens-Johnson syndrome (SJS), have been reported with carbamazepine treatment. The risk of these

events is estimated to be about 1 to 6 per 10,000 new users in countries with mainly Caucasian

populations. However, the risk in some Asian countries is estimated to be about 10 times higher.

Carbamazepine should be discontinued at the first sign of a rash, unless the rash is clearly not drug-

related. If signs or symptoms suggest SJS/TEN, use of this drug should not be resumed and alternative

therapy should be considered.

SJS/TEN and HLA-B*1502 Allele

Retrospective case-control studies have found that in patients of Chinese ancestry there is a strong

association between the risk of developing SJS/TEN with carbamazepine treatment and the presence of

an inherited variant of the HLA-B gene, HLA-B*1502. The occurrence of higher rates of these

reactions in countries with higher frequencies of this allele suggests that the risk may be increased in

allele-positive individuals of any ethnicity.

Across Asian populations, notable variation exists in the prevalence of HLA-B*1502. Greater than 15%

of the population is reported positive in Hong Kong, Thailand, Malaysia, and parts of the Philippines,

compared to about 10% in Taiwan and 4% in North China. South Asians, including Indians, appear to

have intermediate prevalence of HLA-B*1502, averaging 2% to 4%, but higher in some groups. HLA-

B*1502 is present in less than 1% of the population in Japan and Korea.

HLA-B*1502 is largely absent in individuals not of Asian origin (e.g., Caucasians, African-Americans,

Hispanics, and Native Americans).

Prior to initiating carbamazepine therapy, testing for HLA-B*1502 should be performed in

patients with ancestry in populations in which HLA-B*1502 may be present. In deciding which

patients to screen, the rates provided above for the prevalence of HLA-B*1502 may offer a rough

guide, keeping in mind the limitations of these figures due to wide variability in rates even within ethnic

groups, the difficulty in ascertaining ethnic ancestry, and the likelihood of mixed ancestry.

Carbamazepine should not be used in patients positive for HLA-B*1502 unless the benefits clearly

outweigh the risks. Tested patients who are found to be negative for the allele are thought to have a low

risk of SJS/TEN (see BOXED WARNING and PRECAUTIONS, Laboratory Tests).

Over 90% of carbamazepine treated patients who will experience SJS/TEN have this reaction within the

first few months of treatment. This information may be taken into consideration in determining the need

for screening of genetically at-risk patients currently on carbamazepine.

The HLA-B*1502 allele has not been found to predict risk of less severe adverse cutaneous reactions

from carbamazepine such as maculopapular eruption (MPE) or to predict Drug Reaction with

Eosinophilia and Systemic Symptoms (DRESS).

Limited evidence suggests that HLA-B*1502 may be a risk factor for the development of SJS/TEN in

patients of Chinese ancestry taking other antiepileptic drugs associated with SJS/TEN, including

phenytoin. Consideration should be given to avoiding use of other drugs associated with SJS/TEN in

HLA-B*1502 positive patients, when alternative therapies are otherwise equally acceptable.

Hypersensitivity Reactions and HLA-A*3101 Allele

Retrospective case-control studies in patients of European, Korean, and Japanese ancestry have found a

moderate association between the risk of developing hypersensitivity reactions and the presence of

HLA-A*3101, an inherited allelic variant of the HLA-A gene, in patients using carbamazepine. These

hypersensitivity reactions include SJS/TEN, maculopapular eruptions, and Drug Reaction with

Eosinophilia and Systemic Symptoms (see DRESS/Multiorgan hypersensitivity below).

HLA-A*3101 is expected to be carried by more than 15% of patients of Japanese, Native American,

Southern Indian (for example, Tamil Nadu) and some Arabic ancestry; up to about 10% in patients of Han

Chinese, Korean, European, Latin American, and other Indian ancestry; and up to about 5% in African-

Americans and patients of Thai, Taiwanese, and Chinese (Hong Kong) ancestry.

The risks and benefits of carbamazepine therapy should be weighed before considering carbamazepine

in patients known to be positive for HLA-A*3101.

Application of HLA genotyping as a screening tool has important limitations and must never substitute

for appropriate clinical vigilance and patient management. Many HLA-B*1502-positive and HLA-

A*3101-positive patients treated with carbamazepine will not develop SJS/TEN or other

hypersensitivity reactions, and these reactions can still occur infrequently in HLA-B*1502-negative and

HLA-A*3101-negative patients of any ethnicity. The role of other possible factors in the development

of, and morbidity from, SJS/TEN and other hypersensitivity reactions, such as antiepileptic drug (AED)

dose, compliance, concomitant medications, comorbidities, and the level of dermatologic monitoring,

have not been studied.

Aplastic Anemia and Agranulocytosis

Aplastic anemia and agranulocytosis have been reported in association with the use of carbamazepine

(see BOXED WARNING). Patients with a history of adverse hematologic reaction to any drug may be

particularly at risk of bone marrow depression.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multiorgan

hypersensitivity, have occurred with carbamazepine. Some of these events have been fatal or life-

threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy,

and/or facial swelling, in association with other organ system involvement, such as hepatitis, nephritis,

hematologic abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection.

Eosinophilia is often present. This disorder is variable in its expression, and other organ systems not

noted here may be involved. It is important to note that early manifestations of hypersensitivity (e.g.,

fever, lymphadenopathy) may be present even though rash is not evident. If such signs or symptoms are

present, the patient should be evaluated immediately. Carbamazepine should be discontinued if an

alternative etiology for the signs or symptoms cannot be established.

Hypers ens itivity

Hypersensitivity reactions to carbamazepine have been reported in patients who previously experienced

this reaction to anticonvulsants including phenytoin, primidone, and phenobarbital. If such history is

present, benefits and risks should be carefully considered and, if carbamazepine is initiated, the signs

and symptoms of hypersensitivity should be carefully monitored.

Patients should be informed that about a third of patients who have had hypersensitivity reactions to

carbamazepine also experience hypersensitivity reactions with oxcarbazepine (Trileptal

Anaphylaxis and Angioedema

Rare cases of anaphylaxis and angioedema involving the larynx, glottis, lips, and eyelids have been

reported in patients after taking the first or subsequent doses of carbamazepine. Angioedema associated

with laryngeal edema can be fatal. If a patient develops any of these reactions after treatment with

carbamazepine, the drug should be discontinued and an alternative treatment started. These patients

should not be rechallenged with the drug.

Suicidal Behavior and Ideation

Antiepileptic drugs (AEDs), including carbamazepine, increase the risk of suicidal thoughts or behavior

in patients taking these drugs for any indication. Patients treated with any AED for any indication should

be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any

unusual changes in mood or behavior.

Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different

AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted

Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to

placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate

of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24%

among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal

thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in

the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about

drug effect on suicide.

The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week

after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because

most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or

behavior beyond 24 weeks could not be assessed.

The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed.

The finding of increased risk with AEDs of varying mechanisms of action and across a range of

indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary

substantially by age (5 to 100 years) in the clinical trials analyzed. Table 1 shows absolute and relative

risk by indication for all evaluated AEDs.

Table 1 Risk by Indication for Antiepileptic Drugs in the Pooled Analysis

Indication

Placebo Patients

with Events Per

1,000 Patients

Drug Patients

with Events Per

1,000 Patients

Relative Risk: Incidence

of Events in Drug

Patients/Incidence in

Placebo Patients

Risk Difference:

Additional Drug

Patients with

Events Per

1,000 Patients

Epilepsy

Psychiatric 5.7

Other

Total

The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in

clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the

epilepsy and psychiatric indications.

Anyone considering prescribing carbamazepine or any other AED must balance the risk of suicidal

thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which

AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of

suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the

prescriber needs to consider whether the emergence of these symptoms in any given patient may be

related to the illness being treated.

General

Carbamazepine has shown mild anticholinergic activity that may be associated with increased

intraocular pressure; therefore, patients with increased intraocular pressure should be closely observed

during therapy. Because of the relationship of the drug to other tricyclic compounds, the possibility of

activation of a latent psychosis and, in elderly patients, of confusion or agitation should be borne in

mind.

The use of carbamazepine should be avoided in patients with a history of hepatic porphyria (e.g., acute

intermittent porphyria, variegate porphyria, porphyria cutanea tarda). Acute attacks have been reported in

such patients receiving carbamazepine therapy. Carbamazepine administration has also been

demonstrated to increase porphyrin precursors in rodents, a presumed mechanism for the induction of

acute attacks of porphyria.

As with all antiepileptic drugs, carbamazepine should be withdrawn gradually to minimize the potential

of increased seizure frequency.

Hyponatremia can occur as a result of treatment with carbamazepine. In many cases, the hyponatremia

appears to be caused by the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The

risk of developing SIADH with carbamazepine treatment appears to be dose-related. Elderly patients

and patients treated with diuretics are at greater risk of developing hyponatremia. Signs and symptoms of

hyponatremia include headache, new or increased seizure frequency, difficulty concentrating, memory

impairment, confusion, weakness, and unsteadiness, which can lead to falls. Consider discontinuing

carbamazepine in patients with symptomatic hyponatremia.

Usage in Pregnancy

Carbamazepine can cause fetal harm when administered to a pregnant woman.

Epidemiological data suggest that there may be an association between the use of carbamazepine during

pregnancy and congenital malformations, including spina bifida. There have also been reports that

associate carbamazepine with developmental disorders and congenital anomalies (e.g., craniofacial

defects, cardiovascular malformations, and anomalies involving various body systems). Developmental

delays based on neurobehavioral assessments have been reported. When treating or counseling women

of childbearing potential, the prescribing physician will wish to weigh the benefits of therapy against

the risks. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this

drug, the patient should be apprised of the potential hazard to the fetus.

Retrospective case reviews suggest that, compared with monotherapy, there may be a higher

prevalence of teratogenic effects associated with the use of anticonvulsants in combination therapy.

Therefore, if therapy is to be continued, monotherapy may be preferable for pregnant women.

In humans, transplacental passage of carbamazepine is rapid (30 to 60 minutes), and the drug is

accumulated in the fetal tissues, with higher levels found in liver and kidney than in brain and lung.

Carbamazepine has been shown to have adverse effects in reproduction studies in rats when given

orally in dosages 10 to 25 times the maximum human daily dosage (MHDD) of 1200 mg on a mg/kg

basis or 1.5 to 4 times the MHDD on a mg/m

basis. In rat teratology studies, 2 of 135 offspring

showed kinked ribs at 250 mg/kg and 4 of 119 offspring at 650 mg/kg showed other anomalies (cleft

palate, 1; talipes, 1; anophthalmos, 2). In reproduction studies in rats, nursing offspring demonstrated a

lack of weight gain and an unkempt appearance at a maternal dosage level of 200 mg/kg.

Antiepileptic drugs should not be discontinued abruptly in patients in whom the drug is administered to

prevent major seizures because of the strong possibility of precipitating status epilepticus with attendant

hypoxia and threat to life. In individual cases where the severity and frequency of the seizure disorder

are such that removal of medication does not pose a serious threat to the patient, discontinuation of the

drug may be considered prior to and during pregnancy, although it cannot be said with any confidence

that even minor seizures do not pose some hazard to the developing embryo or fetus.

Tests to detect defects using currently accepted procedures should be considered a part of routine

prenatal care in childbearing women receiving carbamazepine.

There have been a few cases of neonatal seizures and/or respiratory depression associated with

maternal carbamazepine and other concomitant anticonvulsant drug use. A few cases of neonatal

vomiting, diarrhea, and/or decreased feeding have also been reported in association with maternal

carbamazepine use. These symptoms may represent a neonatal withdrawal syndrome.

To provide information regarding the effects of in utero exposure to carbamazepine, physicians are

advised to recommend that pregnant patients taking carbamazepine enroll in the North American

Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll free number 1-

888-233-2334, and must be done by patients themselves. Information on the registry can also be found at

the website http://www.aedpregnancyregistry.org/.

PRECAUTIONS

General

Before initiating therapy, a detailed history and physical examination should be made.

Carbamazepine should be used with caution in patients with a mixed seizure disorder that includes

atypical absence seizures, since in these patients carbamazepine has been associated with increased

frequency of generalized convulsions (see INDICATIONS AND USAGE).

Therapy should be prescribed only after critical benefit-to-risk appraisal in patients with a history of

cardiac conduction disturbance, including second- and third-degree AV heart block; cardiac, hepatic, or

renal damage; adverse hematologic or hypersensitivity reaction to other drugs, including reactions to

other anticonvulsants; or interrupted courses of therapy with carbamazepine.

AV heart block, including second- and third-degree block, have been reported following carbamazepine

treatment. This occurred generally, but not solely, in patients with underlying EKG abnormalities or risk

factors for conduction disturbances.

Hepatic effects, ranging from slight elevations in liver enzymes to rare cases of hepatic failure have

been reported (see ADVERSE REACTIONS and PRECAUTIONS, Laboratory Tests). In some cases,

hepatic effects may progress despite discontinuation of the drug. In addition rare instances of vanishing

bile duct syndrome have been reported. This syndrome consists of a cholestatic process with a variable

clinical course ranging from fulminant to indolent, involving the destruction and disappearance of the

intrahepatic bile ducts. Some, but not all, cases are associated with features that overlap with other

immunoallergenic syndromes such as multiorgan hypersensitivity (DRESS syndrome) and serious

dermatologic reactions. As an example there has been a report of vanishing bile duct syndrome

associated with Stevens-Johnson syndrome and in another case an association with fever and

eosinophilia.

Since a given dose of carbamazepine suspension will produce higher peak levels than the same dose

given as the tablet, it is recommended that patients given the suspension be started on lower doses and

increased slowly to avoid unwanted side effects (see DOSAGE AND ADMINISTRATION).

Carbamazepine chewable tablets and suspension contain sorbitol and, therefore, should not be

administered to patients with rare hereditary problems of fructose intolerance.

Information for Patients

Patients should be informed of the availability of a Medication Guide and they should be instructed to

read the Medication Guide before taking carbamazepine.

Patients should be made aware of the early toxic signs and symptoms of a potential hematologic

problem, as well as dermatologic, hypersensitivity or hepatic reactions. These symptoms may include,

but are not limited to, fever, sore throat, rash, ulcers in the mouth, easy bruising, lymphadenopathy and

petechial or purpuric hemorrhage, and in the case of liver reactions, anorexia, nausea/vomiting, or

jaundice. The patient should be advised that, because these signs and symptoms may signal a serious

reaction, that they must report any occurrence immediately to a physician. In addition, the patient should

be advised that these signs and symptoms should be reported even if mild or when occurring after

extended use.

Patients should be advised that serious skin reactions have been reported in association with

carbamazepine. In the event a skin reaction should occur while taking carbamazepine, patients should

consult with their physician immediately (see WARNINGS).

Patients should be advised that anaphylactic reactions and angioedema may occur during treatment with

carbamazepine (see WARNINGS). Advise patients to immediately report signs and symptoms

suggesting angioedema (swelling of the face, eyes, lips, or tongue, or difficulty in swallowing or

breathing) and to stop taking the drug until they have consulted with their healthcare provider.

Patients, their caregivers, and families should be counseled that AEDs, including carbamazepine, may

increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the

emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the

emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be

reported immediately to healthcare providers.

Carbamazepine may interact with some drugs. Therefore, patients should be advised to report to their

doctors the use of any other prescription or nonprescription medications or herbal products.

Caution should be exercised if alcohol is taken in combination with carbamazepine therapy, due to a

possible additive sedative effect.

Since dizziness and drowsiness may occur, patients should be cautioned about the hazards of operating

machinery or automobiles or engaging in other potentially dangerous tasks.

Patients should be encouraged to enroll in the NAAED Pregnancy Registry if they become pregnant.

This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To

enroll, patients can call the toll free number 1-888-233-2334 (see WARNINGS, Usage in Pregnancy

subsection).

Laboratory Tests

For genetically at-risk patients (see WARNINGS), high-resolution 'HLA-B*1502 typing' is

recommended. The test is positive if either one or two HLA-B*1502 alleles are detected and negative

if no HLA-B*1502 alleles are detected.

Complete pretreatment blood counts, including platelets and possibly reticulocytes and serum iron,

should be obtained as a baseline. If a patient in the course of treatment exhibits low or decreased white

blood cell or platelet counts, the patient should be monitored closely. Discontinuation of the drug

should be considered if any evidence of significant bone marrow depression develops.

Baseline and periodic evaluations of liver function, particularly in patients with a history of liver

disease, must be performed during treatment with this drug since liver damage may occur (see

PRECAUTIONS, General and ADVERSE REACTIONS). Carbamazepine should be discontinued,

based on clinical judgment, if indicated by newly occurring or worsening clinical or laboratory

evidence of liver dysfunction or hepatic damage, or in the case of active liver disease.

Baseline and periodic eye examinations, including slit-lamp, funduscopy, and tonometry, are

recommended since many phenothiazines and related drugs have been shown to cause eye changes.

Baseline and periodic complete urinalysis and BUN determinations are recommended for patients

treated with this agent because of observed renal dysfunction.

Monitoring of blood levels (see CLINICAL PHARMACOLOGY) has increased the efficacy and safety

of anticonvulsants. This monitoring may be particularly useful in cases of dramatic increase in seizure

frequency and for verification of compliance. In addition, measurement of drug serum levels may aid in

determining the cause of toxicity when more than one medication is being used.

Thyroid function tests have been reported to show decreased values with carbamazepine administered

alone. Interference with some pregnancy tests has been reported.

Drug Interactions

There has been a report of a patient who passed an orange rubbery precipitate in his stool the day after

ingesting carbamazepine suspension immediately followed by Thorazine

* solution. Subsequent

testing has shown that mixing carbamazepine suspension and chlorpromazine solution (both generic and

brand name) as well as carbamazepine suspension and liquid Mellaril

, resulted in the occurrence of

this precipitate. Because the extent to which this occurs with other liquid medications is not known,

carbamazepine suspension should not be administered simultaneously with other liquid medicinal agents

or diluents (See DOSAGE AND ADMINISTRATION).

Clinically meaningful drug interactions have occurred with concomitant medications and include (but are

not limited to) the following:

Agents That May Affect Carbamazepine Plasma Levels

When carbamazepine is given with drugs that can increase or decrease carbamazepine levels, close

monitoring of carbamazepine levels is indicated and dosage adjustment may be required.

Agents That Increase Carbamazepine Levels

CYP3A4 inhibitors inhibit carbamazepine metabolism and can thus increase plasma carbamazepine

levels. Drugs that have been shown, or would be expected, to increase plasma carbamazepine levels

include aprepitant, cimetidine, ciprofloxacin, danazol, diltiazem, macrolides, erythromycin,

troleandomycin, clarithromycin, fluoxetine, fluvoxamine, trazodone, olanzapine, loratadine, terfenadine,

omeprazole, oxybutynin, dantrolene, isoniazid, niacinamide, nicotinamide, ibuprofen, propoxyphene,

azoles (e.g., ketoconazole, itraconazole, fluconazole, voriconazole), acetazolamide, verapamil,

ticlopidine, grapefruit juice, and protease inhibitors. Human microsomal epoxide hydrolase has been

identified as the enzyme responsible for the formation of the 10,11-transdiol derivative from

carbamazepine-10,11 epoxide. Coadministration of inhibitors of human microsomal epoxide hydrolase

may result in increased carbamazepine-10,11 epoxide plasma concentrations. Accordingly, the dosage

of carbamazepine should be adjusted and/or the plasma levels monitored when used concomitantly with

loxapine, quetiapine, or valproic acid.

Agents That Decrease Carbamazepine Levels

CYP3A4 inducers can increase the rate of carbamazepine metabolism. Drugs that have been shown, or

that would be expected, to decrease plasma carbamazepine levels include cisplatin, doxorubicin HCl,

felbamate, fosphenytoin, rifampin, phenobarbital, phenytoin, primidone, methsuximide, theophylline,

aminophylline.

Effect of Carbamazepine on Plasma Levels of Concomitant Agents

Decreased Levels of Concomitant Medications

Carbamazepine is a potent inducer of hepatic 3A4 and is also known to be an inducer of CYP1A2, 2B6,

2C9/19 and may therefore reduce plasma concentrations of co-medications mainly metabolized by CYP

1A2, 2B6, 2C9/19 and 3A4, through induction of their metabolism. When used concomitantly with

carbamazepine, monitoring of concentrations or dosage adjustment of these agents may be necessary:

When carbamazepine is added to aripiprazole, the aripiprazole dose should be doubled. Additional

dose increases should be based on clinical evaluation. If carbamazepine is later withdrawn, the

aripiprazole dose should be reduced.

When carbamazepine is used with tacrolimus, monitoring of tacrolimus blood concentrations and

appropriate dosage adjustments are recommended.

The use of concomitant strong CYP3A4 inducers such as carbamazepine should be avoided with

temsirolimus. If patients must be coadministered carbamazepine with temsirolimus, an adjustment of

temsirolimus dosage should be considered.

The use of carbamazepine with lapatinib should generally be avoided. If carbamazepine is started in

a patient already taking lapatinib, the dose of lapatinib should be gradually titrated up. If

carbamazepine is discontinued, the lapatinib dose should be reduced.

Concomitant use of carbamazepine with nefazodone results in plasma concentrations of nefazodone

and its active metabolite insufficient to achieve a therapeutic effect. Coadministration of

carbamazepine with nefazodone is contraindicated (see CONTRAINDICATIONS).

Monitor concentrations of valproate when carbamazepine is introduced or withdrawn in patients

using valproic acid.

In addition, carbamazepine causes, or would be expected to cause, decreased levels of the following

drugs, for which monitoring of concentrations or dosage adjustment may be necessary: acetaminophen,

albendazole, alprazolam, aprepitant, buprenorphone, bupropion, citalopram, clonazepam, clozapine,

corticosteroids (e.g., prednisolone, dexamethasone), cyclosporine, dicumarol, dihydropyridine calcium

channel blockers (e.g., felodipine), doxycycline, eslicarbazepine, ethosuximide, everolimus,

haloperidol, imatinib, itraconazole, lamotrigine, levothyroxine, methadone, methsuximide, mianserin,

midazolam, olanzapine, oral and other hormonal contraceptives, oxcarbazepine, paliperidone,

phensuximide, phenytoin, praziquantel, protease inhibitors, risperidone, sertraline, sirolimus, tadalafil,

theophylline, tiagabine, topiramate, tramadol, trazodone, tricyclic antidepressants (e.g., imipramine,

amitriptyline, nortriptyline), valproate, warfarin, ziprasidone, zonisamide.

Other Drug Interactions

Cyclophosphamide is an inactive prodrug and is converted to its active metabolite in part by CYP3A.

The rate of metabolism and the leukopenic activity of cyclophosphamide are reportedly increased

by chronic coadministration of CYP3A4 inducers. There is a potential for increased

cyclophosphamide toxicity when coadministered with carbamazepine.

Concomitant administration of carbamazepine and lithium may increase the risk of neurotoxic side

effects.

Concomitant use of carbamazepine and isoniazid has been reported to increase isoniazid-induced

hepatotoxicity.

Alterations of thyroid function have been reported in combination therapy with other anticonvulsant

medications.

Concomitant use of carbamazepine with hormonal contraceptive products (e.g., oral, and

levonorgestrel subdermal implant contraceptives) may render the contraceptives less effective

because the plasma concentrations of the hormones may be decreased. Breakthrough bleeding and

unintended pregnancies have been reported. Alternative or back-up methods of contraception should

be considered.

Resistance to the neuromuscular blocking action of the nondepolarizing neuromuscular blocking

agents pancuronium, vecuronium, rocuronium and cisatracurium has occurred in patients chronically

administered carbamazepine. Whether or not carbamazepine has the same effect on other non-

depolarizing agents is unknown. Patients should be monitored closely for more rapid recovery from

neuromuscular blockade than expected, and infusion rate requirements may be higher.

Concomitant use of carbamazepine with rivaroxaban, apixaban, dabigatran, and edoxaban (direct

acting oral anticoagulants) is expected to result in decreased plasma concentrations of these

anticoagulants that may be insufficient to achieve the intended therapeutic effect. In general,

coadministration of carbamazepine with rivaroxaban, apixaban, dabigatran, and edoxaban should be

avoided.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carbamazepine, when administered to Sprague-Dawley rats for two years in the diet at doses of 25, 75,

and 250 mg/kg/day, resulted in a dose-related increase in the incidence of hepatocellular tumors in

females and of benign interstitial cell adenomas in the testes of males.

Carbamazepine must, therefore, be considered to be carcinogenic in Sprague-Dawley rats. Bacterial and

mammalian mutagenicity studies using carbamazepine produced negative results. The significance of

these findings relative to the use of carbamazepine in humans is, at present, unknown.

Usage in Pregnancy

(see WARNINGS).

Labor and Delivery

The effect of carbamazepine on human labor and delivery is unknown.

Nursing Mothers

Carbamazepine and its epoxide metabolite are transferred to breast milk. The ratio of the concentration

in breast milk to that in maternal plasma is about 0.4 for carbamazepine and about 0.5 for the epoxide.

The estimated doses given to the newborn during breastfeeding are in the range of 2 to 5 mg daily for

carbamazepine and 1 to 2 mg daily for the epoxide.

Because of the potential for serious adverse reactions in nursing infants from carbamazepine, a decision

should be made whether to discontinue nursing or to discontinue the drug, taking into account the

importance of the drug to the mother.

Pediatric Use

Substantial evidence of carbamazepine's effectiveness for use in the management of children with

epilepsy (see INDICATIONS AND USAGE for specific seizure types) is derived from clinical

investigations performed in adults and from studies in several in vitro systems which support the

conclusion that (1) the pathogenetic mechanisms underlying seizure propagation are essentially identical

in adults and children, and (2) the mechanism of action of carbamazepine in treating seizures is

essentially identical in adults and children. Taken as a whole, this information supports a conclusion that

the generally accepted therapeutic range of total carbamazepine in plasma (i.e., 4 to 12 mcg/mL) is the

same in children and adults.

The evidence assembled was primarily obtained from short-term use of carbamazepine. The safety of

carbamazepine in children has been systematically studied up to 6 months. No longer-term data from

clinical trials is available.

Geriatric Use

No systematic studies in geriatric patients have been conducted.

ADVERSE REACTIONS

If adverse reactions are of such severity that the drug must be discontinued, the physician must be aware

that abrupt discontinuation of any anticonvulsant drug in a responsive epileptic patient may lead to

seizures or even status epilepticus with its life-threatening hazards.

The most severe adverse reactions have been observed in the hemopoietic system and skin (see

BOXED WARNING), the liver, and the cardiovascular system.

The most frequently observed adverse reactions, particularly during the initial phases of therapy, are

dizziness, drowsiness, unsteadiness, nausea, and vomiting. To minimize the possibility of such

reactions, therapy should be initiated at the lowest dosage recommended.

The following additional adverse reactions have been reported:

Hemopoietic System: Aplastic anemia, agranulocytosis, pancytopenia, bone marrow depression,

thrombocytopenia, leukopenia, leukocytosis, eosinophilia, acute intermittent porphyria, variegate

porphyria, porphyria cutanea tarda.

Skin: Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) (see BOXED

WARNING), Acute Generalized Exanthematous Pustulosis (AGEP), pruritic and erythematous rashes,

urticaria, photosensitivity reactions, alterations in skin pigmentation, exfoliative dermatitis, erythema

multiforme and nodosum, purpura, aggravation of disseminated lupus erythematosus, alopecia,

diaphoresis, onychomadesis and hirsutism. In certain cases, discontinuation of therapy may be

necessary.

Cardiovascular System: Congestive heart failure, edema, aggravation of hypertension, hypotension,

syncope and collapse, aggravation of coronary artery disease, arrhythmias and AV block,

thrombophlebitis, thromboembolism (e.g., pulmonary embolism), and adenopathy or lymphadenopathy.

Some of these cardiovascular complications have resulted in fatalities. Myocardial infarction has been

associated with other tricyclic compounds.

Liver: Abnormalities in liver function tests, cholestatic and hepatocellular jaundice, hepatitis, very rare

cases of hepatic failure.

Pancreatic: Pancreatitis.

Respiratory System: Pulmonary hypersensitivity characterized by fever, dyspnea, pneumonitis or

pneumonia.

Genitourinary System: Urinary frequency, acute urinary retention, oliguria with elevated blood

pressure, azotemia, renal failure, and impotence. Albuminuria, glycosuria, elevated BUN, and

microscopic deposits in the urine have also been reported. There have been rare reports of impaired

male fertility and/or abnormal spermatogenesis.

Testicular atrophy occurred in rats receiving carbamazepine orally from 4 to 52 weeks at dosage levels

of 50 to 400 mg/kg/day. Additionally, rats receiving carbamazepine in the diet for 2 years at dosage

levels of 25, 75, and 250 mg/kg/day had a dose-related incidence of testicular atrophy and

aspermatogenesis. In dogs, it produced a brownish discoloration, presumably a metabolite, in the

urinary bladder at dosage levels of 50 mg/kg and higher. Relevance of these findings to humans is

unknown.

Nervous System: Dizziness, drowsiness, disturbances of coordination, confusion, headache, fatigue,

blurred vision, visual hallucinations, transient diplopia, oculomotor disturbances, nystagmus, speech

disturbances, abnormal involuntary movements, peripheral neuritis and paresthesias, depression with

agitation, talkativeness, tinnitus, hyperacusis, neuroleptic malignant syndrome.

There have been reports of associated paralysis and other symptoms of cerebral arterial insufficiency,

but the exact relationship of these reactions to the drug has not been established.

Isolated cases of neuroleptic malignant syndrome have been reported both with and without concomitant

use of psychotropic drugs.

Digestive System: Nausea, vomiting, gastric distress and abdominal pain, diarrhea, constipation, anorexia,

and dryness of the mouth and pharynx, including glossitis and stomatitis.

Eyes: Scattered punctate cortical lens opacities, increased intraocular pressure (see WARNINGS,

General) as well as conjunctivitis, have been reported. Although a direct causal relationship has not

been established, many phenothiazines and related drugs have been shown to cause eye changes.

Musculoskeletal System: Aching joints and muscles, and leg cramps.

Metabolism: Fever and chills. Hyponatremia (see WARNINGS, General). Decreased levels of plasma

calcium have been reported. Osteoporosis has been reported.

Isolated cases of a lupus erythematosus-like syndrome have been reported. There have been occasional

reports of elevated levels of cholesterol, HDL cholesterol, and triglycerides in patients taking

anticonvulsants. A case of aseptic meningitis, accompanied by myoclonus and peripheral eosinophilia,

has been reported in a patient taking carbamazepine in combination with other medications. The patient

was successfully dechallenged, and the meningitis reappeared upon rechallenge with carbamazepine.

DRUG ABUSE AND DEPENDENCE

No evidence of abuse potential has been associated with carbamazepine, nor is there evidence of

psychological or physical dependence in humans.

OVERDOSAGE

Acute Toxicity

Lowest known lethal dose: adults, 3.2 g (a 24-year-old woman died of a cardiac arrest and a 24-year-old

man died of pneumonia and hypoxic encephalopathy); children, 4 g (a 14-year-old girl died of a cardiac

arrest), 1.6 g (a 3-year-old girl died of aspiration pneumonia).

Oral LD

in animals (mg/kg): mice, 1100 to 3750; rats, 3850 to 4025; rabbits, 1500 to 2680; guinea

pigs, 920.

Signs and Symptoms

The first signs and symptoms appear after 1 to 3 hours. Neuromuscular disturbances are the most

prominent. Cardiovascular disorders are generally milder, and severe cardiac complications occur only

when very high doses (greater than 60 g) have been ingested.

Respiration: Irregular breathing, respiratory depression.

Cardiovascular System: Tachycardia, hypotension or hypertension, shock, conduction disorders.

Nervous System and Muscles: Impairment of consciousness ranging in severity to deep coma.

Convulsions, especially in small children. Motor restlessness, muscular twitching, tremor, athetoid

movements, opisthotonos, ataxia, drowsiness, dizziness, mydriasis, nystagmus, adiadochokinesia,

ballism, psychomotor disturbances, dysmetria. Initial hyperreflexia, followed by hyporeflexia.

Gastrointestinal Tract: Nausea, vomiting.

Kidneys and Bladder: Anuria or oliguria, urinary retention.

Laboratory Findings: Isolated instances of overdosage have included leukocytosis, reduced leukocyte

count, glycosuria, and acetonuria. EEG may show dysrhythmias.

Combined Poisoning: When alcohol, tricyclic antidepressants, barbiturates, or hydantoins are taken at

the same time, the signs and symptoms of acute poisoning with carbamazepine may be aggravated or

modified.

Treatment

The prognosis in cases of severe poisoning is critically dependent upon prompt elimination of the drug,

which may be achieved by inducing vomiting, irrigating the stomach, and by taking appropriate steps to

diminish absorption. If these measures cannot be implemented without risk on the spot, the patient should

be transferred at once to a hospital, while ensuring that vital functions are safeguarded. There is no

specific antidote.

Elimination of the Drug: Induction of vomiting.

Gastric lavage. Even when more than 4 hours have elapsed following ingestion of the drug, the stomach

should be repeatedly irrigated, especially if the patient has also consumed alcohol.

Measures to Reduce Absorption: Activated charcoal, laxatives.

Measures to Accelerate Elimination: Forced diuresis.

Dialysis is indicated only in severe poisoning associated with renal failure. Replacement transfusion is

indicated in severe poisoning in small children.

Respiratory Depression: Keep the airways free; resort, if necessary, to endotracheal intubation, artificial

respiration, and administration of oxygen.

Hypotension, Shock: Keep the patient's legs raised and administer a plasma expander. If blood pressure

fails to rise despite measures taken to increase plasma volume, use of vasoactive substances should be

considered.

Convulsions: Diazepam or barbiturates.

Warning: Diazepam or barbiturates may aggravate respiratory depression (especially in children),

hypotension, and coma. However, barbiturates should not be used if drugs that inhibit monoamine

oxidase have also been taken by the patient either in overdosage or in recent therapy (within 1 week).

Surveillance: Respiration, cardiac function (ECG monitoring), blood pressure, body temperature,

pupillary reflexes, and kidney and bladder function should be monitored for several days.

Treatment of Blood Count Abnormalities: If evidence of significant bone marrow depression develops,

the following recommendations are suggested: (1) stop the drug, (2) perform daily CBC, platelet, and

reticulocyte counts, (3) do a bone marrow aspiration and trephine biopsy immediately and repeat with

sufficient frequency to monitor recovery.

Special periodic studies might be helpful as follows: (1) white cell and platelet antibodies, (2)

ferrokinetic studies, (3) peripheral blood cell typing, (4) cytogenetic studies on marrow and peripheral

blood, (5) bone marrow culture studies for colony-forming units, (6) hemoglobin electrophoresis for A

and F hemoglobin, and (7) serum folic acid and B

levels.

A fully developed aplastic anemia will require appropriate, intensive monitoring and therapy, for which

specialized consultation should be sought.

DOSAGE AND ADMINISTRATION

(SEE TABLE BELOW)

Carbamazepine suspension in combination with liquid chlorpromazine or thioridazine results in

precipitate formation, and, in the case of chlorpromazine, there has been a report of a patient passing an

orange rubbery precipitate in the stool following coadministration of the two drugs (see

PRECAUTIONS, Drug Interactions). Because the extent to which this occurs with other liquid

medications is not known, carbamazepine suspension should not be administered simultaneously with

other liquid medications or diluents.

Monitoring of blood levels has increased the efficacy and safety of anticonvulsants (see

PRECAUTIONS, Laboratory Tests). Dosage should be adjusted to the needs of the individual patient.

A low initial daily dosage with a gradual increase is advised. As soon as adequate control is achieved,

the dosage may be reduced very gradually to the minimum effective level. Medication should be taken

with meals.

Since a given dose of carbamazepine suspension will produce higher peak levels than the same dose

given as the tablet, it is recommended to start with low doses (children 6 to 12 years: ½ teaspoon (four

times a day) and to increase slowly to avoid unwanted side effects.

Conversion of patients from oral carbamazepine tablets to carbamazepine suspension: Patients should be

converted by administering the same number of mg per day in smaller, more frequent doses (i.e., twice a

day tablets to three times a day suspension).

Carbamazepine extended-release tablets is an extended-release formulation for twice-a-day

administration. When converting patients from carbamazepine conventional tablets to carbamazepine

extended-release tablets, the same total daily mg dose of carbamazepine extended-release tablets should

be administered. Carbamazepine extended-release tablets must be swallowed whole and never

crushed or chewed. Carbamazepine extended-release tablets should be inspected for chips or cracks.

Damaged tablets should not be consumed.

Epileps y

(SEE INDICATIONS AND USAGE)

Adults and children over 12 years of age-Initial

Either 200 mg twice a day for tablets and extended-release tablets, or 1 teaspoon four times a day for

suspension (400 mg/day). Increase at weekly intervals by adding up to 200 mg/day using a twice a day

regimen of carbamazepine extended-release tablets or a three times a day or four times a day regimen of

the other formulations until the optimal response is obtained. Dosage generally should not exceed 1000

mg daily in children 12 to 15 years of age, and 1200 mg daily in patients above 15 years of age. Doses

up to 1600 mg daily have been used in adults in rare instances.

Maintenance

Adjust dosage to the minimum effective level, usually 800 to 1200 mg daily.

Children 6 to 12 years of age-Initial

Either 100 mg twice a day for tablets or extended-release tablets, or ½ teaspoon four times a day for

suspension (200 mg/day). Increase at weekly intervals by adding up to 100 mg/day using a twice a day

regimen of carbamazepine extended-release tablets or a three times a day or four times a day regimen of

the other formulations until the optimal response is obtained. Dosage generally should not exceed 1000

mg daily.

Maintenance

Adjust dosage to the minimum effective level, usually 400 to 800 mg daily.

Children under 6 years of age-Initial

10 mg/kg/day to 20 mg/kg/day twice a day or three times a day as tablets, or four times a day as

suspension. Increase weekly to achieve optimal clinical response administered three times a day or four

times a day

Maintenance

Ordinarily, optimal clinical response is achieved at daily doses below 35 mg/kg. If satisfactory clinical

response has not been achieved, plasma levels should be measured to determine whether or not they are

in the therapeutic range. No recommendation regarding the safety of carbamazepine for use at doses

above 35 mg/kg/24 hours can be made.

Combination Therapy

Carbamazepine may be used alone or with other anticonvulsants. When added to existing anticonvulsant

therapy, the drug should be added gradually while the other anticonvulsants are maintained or gradually

decreased, except phenytoin, which may have to be increased (see PRECAUTIONS, Drug Interactions,

and Pregnancy).

Trigeminal Neuralgia

(SEE INDICATIONS AND USAGE)

Initial

On the first day, either 100 mg twice a day for tablets or extended-release tablets, or ½ teaspoon four

times a day for suspension, for a total daily dose of 200 mg. This daily dose may be increased by up to

200 mg/day using increments of 100 mg every 12 hours for tablets or extended-release tablets, or 50

mg (½ teaspoon) four times a day for suspension, only as needed to achieve freedom from pain. Do not

exceed 1200 mg daily.

Maintenance

Control of pain can be maintained in most patients with 400 to 800 mg daily. However, some patients

may be maintained on as little as 200 mg daily, while others may require as much as 1200 mg daily. At

least once every 3 months throughout the treatment period, attempts should be made to reduce the dose

to the minimum effective level or even to discontinue the drug.

Dosage Information

Initial Dose

Subsequent Dose

Maximum Daily Dose

*

*

*

*

*

Indication Tablet

XR

Suspension Tablet

XR

Suspension Tablet

XR

Sus pens ion

Epilepsy

Under 6 yr

10 to 20

mg/kg/day

twice a

day or 3

times a

10 to 20

mg/kg/day 4

times a day

Increase

weekly to

achieve

optimal

clinical

response,

3 times a

day or 4

times a

Increase

weekly to

achieve

optimal

clinical

response, 3

times a day

or 4 times a

35 mg/kg/24

(see Dosage

Administration

section above)

35 mg/kg/24

(see Dosage

Administration

section above)

6 to 12 yr

100 mg

twice a

(200

mg/day)

100 mg

twice a

(200

mg/day)

½ tsp 4

times a day

(200

mg/day)

Add up to

mg/day at

weekly

intervals,

3 times a

day or 4

times a

Add 100

mg/day at

weekly

intervals,

twice a

Add up to 1

tsp (100

mg)/day at

weekly

intervals, 3

times a day

or 4 times a

1000

mg/24 hr

Over 12 yr

200 mg

twice a

(400

mg/day)

200 mg

twice a

(400

mg/day)

1 tsp 4

times a day

(400

mg/day)

Add up to

mg/day at

weekly

intervals,

3 times a

day or 4

times a

Add up to

mg/day at

weekly

intervals,

twice a

Add up to 2

tsp (200

mg)/day at

weekly

intervals, 3

times a day

or 4 times a

1000

mg/24 hr

(12 to 15

1200

mg/24 hr

(> 15 yr)

1600

mg/24 hr

(adults, in

rare

instances)

Trigeminal

Neuralgia

100 mg

twice a

(200

mg/day)

100 mg

twice a

(200

mg/day)

½ tsp 4

times a day

(200

mg/day)

Add up to

mg/day in

increments

of 100 mg

every 12

Add up to

mg/day in

increments

of 100 mg

every 12

Add up to 2

tsp (200

mg)/day in

increments

of 50 mg (½

tsp) 4 times

a day.

1200

mg/24 hr

HOW SUPPLIED

Carbamazepine Tablets USP, (Chewable), 100 mg: White, flat, round tablet with pink specks, and

cherry fragrance. One side scored and engraved with "TARO" above the score and "16" under the

score. Other side plain.

Bottles of 100

NDC 51672-4041-1

Bottles of 500

NDC 51672-4041-2

Unit Dose of 50

NDC 51672-4041-9

Unit Dose of 100

NDC 51672-4041-0

Carbamazepine Tablets USP, (Chewable), 200 mg: White, flat, oval beveled tablet, with pink specks,

and cherry fragrance. One side scored and engraved with "T" above the score and "27" under the score.

Other side scored.

*

*

*

*

*

Tablet = Chewable or conventional tablets

XR = Carbamazepine extended-release tablets

Bottles of 100

NDC 51672-4050-1

Bottles of 400

NDC 51672-4050-2

Store Carbamazepine Tablets USP, (Chewable) at 20° to 25°C (68° to 77°F) [see USP Controlled

Room Temperature]. Protect from light and moisture. Dispense in tight, light-resistant container (USP).

Meets USP Dissolution Test 1.

Carbamazepine Tablets USP, 200 mg: White, round, flat beveled-edge, one side scored and

engraved "TARO" above and "11" below the score, the other side plain.

Bottles of 100

NDC 51672-4005-1

Bottles of 500

NDC 51672-4005-2

Bottles of 1000

NDC 51672-4005-3

Store Carbamazepine Tablets USP at 20° to 25°C (68° to 77°F) [see USP Controlled Room

Temperature]. Protect from moisture. Dispense in tight container (USP). Meets USP Dissolution Test 2.

Carbamazepine Extended-Release Tablets USP, 100 mg: White to off-white, round bi-convexed

tablets engraved with "T91" on one side and plain on the other side.

Bottles of 30

NDC 51672-4123-6

Bottles of 100

NDC 51672-4123-1

Bottles of 1000

NDC 51672-4123-3

Carbamazepine Extended-Release Tablets USP, 200 mg: White to off-white, round bi-convexed

tablets engraved with "T26" on one side and plain on the other side.

Bottles of 30

NDC 51672-4124-6

Bottles of 100

NDC 51672-4124-1

Bottles of 1000

NDC 51672-4124-3

Carbamazepine Extended-Release Tablets USP, 400 mg: White to off-white, capsule-shaped bi-

convexed tablets engraved with "T29" on one side and plain on the other side.

Bottles of 30

NDC 51672-4125-6

Bottles of 100

NDC 51672-4125-1

Bottles of 1000

NDC 51672-4125-3

Store Carbamazepine Extended-Release Tablets USP at 20° to 25°C (68° to 77°F) [see USP

Controlled Room Temperature]. Protect from moisture. Dispense in tight container (USP).

Carbamazepine Oral Suspension USP, 100 mg/5 mL (teaspoonful): Orange colored and orange

flavored suspension.

Bottles of 450 mL

NDC 51672-4047-9

Shake well before using.

Store Carbamazepine Oral Suspension USP at 20° to 25°C (68° to 77°F) [see USP Controlled

Room Temperature]. Protect from freezing and from excessive heat. Dispense in tight, light-resistant

container (USP).

Trademarks are the property of their respective owners.

Manufactured by: Taro Pharmaceutical Industries Ltd., Haifa Bay, Israel 2624761

Distributed by: Taro Pharmaceuticals U.S.A., Inc., Hawthorne, NY 10532

Revised: May 2018

70725-0518-11

MEDICATION GUIDE

Carbamazepine (kar" ba maz' e peen) Tablets,

Carbamazepine (kar" ba maz' e peen) Oral Suspension,

Carbamazepine (kar" ba maz' e peen) Tablets (Chewable),

and Carbamazepine (kar" ba maz' e peen) Extended-Release Tablets

Read this Medication Guide before you start taking Carbamazepine Tablets, Carbamazepine Oral

Suspension, Carbamazepine Tablets (Chewable), or Carbamazepine Extended-Release Tablets and each

time you get a refill. There may be new information. This information does not take the place of talking

to your healthcare provider about your medical condition or treatment.

What is the most important information I should know about carbamazepine?

Do not stop taking carbamazepine without first talking to your healthcare provider.

Stopping carbamazepine suddenly can cause serious problems.

Carbamazepine can cause serious side effects, including:

Carbamazepine may cause rare but serious skin rashes that may lead to death. These serious

skin reactions are more likely to happen when you begin taking carbamazepine within the first

four months of treatment but may occur at later times. These reactions can happen in anyone,

but are more likely in people of Asian descent. If you are of Asian descent, you may need a

genetic blood test before you take carbamazepine to see if you are at a higher risk for serious

skin reactions with this medicine. Symptoms may include:

skin rash

hives

sores in your mouth

blistering or peeling of the skin

Carbamazepine may cause rare but serious blood problems. Symptoms may include:

fever, sore throat, or other infections that come and go or do not go away

easy bruising

red or purple spots on your body

bleeding gums or nose bleeds

severe fatigue or weakness

Carbamazepine may cause allergic reactions or serious problems, which may affect organs

and other parts of your body like the liver or blood cells. You may or may not have a rash with

these types of reactions.

Call your healthcare provider right away if you have any of the following:

swelling of your face, eyes, lips, or tongue

a skin rash

painful sores in the mouth or around your eyes

unusual bruising or bleeding

frequent infections or infections that do not go away

fever, swollen glands, or sore throat that do not go away or come and go

trouble swallowing or breathing

hives

yellowing of your skin or eyes

severe fatigue or weakness

severe muscle pain

Like other antiepileptic drugs, carbamazepine may cause suicidal thoughts or actions in a

very small number of people, about 1 in 500.

Call your healthcare provider right away if you have any of these symptoms, especially if they

are new, worse, or worry you:

thoughts about suicide or dying

attempts to commit suicide

new or worse depression

new or worse anxiety

feeling agitated or restless

panic attacks

trouble sleeping (insomnia)

new or worse irritability

acting aggressive, being angry, or violent

acting on dangerous impulses

an extreme increase in activity and talking (mania)

other unusual changes in behavior or mood

How can I watch for early symptoms of suicidal thoughts and actions?

Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.

Keep all follow-up visits with your healthcare provider as scheduled.

Call your healthcare provider between visits as needed, especially if you are worried about symptoms.

Do not stop carbamazepine without first talking to a healthcare provider.

Stopping carbamazepine suddenly can cause serious problems. You should talk to your healthcare

provider before stopping.

Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts

or actions, your healthcare provider may check for other causes.

What is carbamazepine?

Carbamazepine is a prescription medicine used to treat:

certain types of seizures (partial, tonic-clonic, mixed)

certain types of nerve pain (trigeminal and glossopharyngeal neuralgia)

Carbamazepine is not a regular pain medicine and should not be used for aches or pains.

Who should not take carbamazepine?

Do not take carbamazepine if you:

have a history of bone marrow depression.

are allergic to carbamazepine or any of the ingredients in Carbamazepine Tablets, Carbamazepine

Oral Suspension, Carbamazepine Tablets (Chewable), or Carbamazepine Extended-Release Tablets.

See the end of this Medication Guide for a complete list of ingredients in Carbamazepine Tablets,

Carbamazepine Oral Suspension, Carbamazepine Tablets (Chewable), or Carbamazepine Extended-

Release Tablets.

take nefazodone.

are allergic to medicines called tricyclic antidepressants (TCAs). Ask your healthcare provider or

pharmacist for a list of these medicines if you are not sure.

have taken a medicine called a Monoamine Oxidase Inhibitor (MAOI) in the last 14 days. Ask your

healthcare provider or pharmacist for a list of these medicines if you are not sure.

What should I tell my healthcare provider before taking carbamazepine?

Before you take carbamazepine, tell your healthcare provider if you:

have or have had suicidal thoughts or actions, depression, or mood problems

have or ever had heart problems

have or ever had blood problems

have or ever had liver problems

have or ever had kidney problems

have or ever had allergic reactions to medicines

have or ever had increased pressure in your eye

have any other medical conditions

drink grapefruit juice or eat grapefruit

use birth control. Carbamazepine may make your birth control less effective. Tell your healthcare

provider if your menstrual bleeding changes while you take birth control and carbamazepine.

are pregnant or plan to become pregnant. Carbamazepine may harm your unborn baby. Tell your

healthcare provider right away if you become pregnant while taking carbamazepine. You and your

healthcare provider should decide if you should take carbamazepine while you are pregnant.

If you become pregnant while taking carbamazepine, talk to your healthcare provider about

registering with the North American Antiepileptic Drug (NAAED) Pregnancy Registry. The

purpose of this registry is to collect information about the safety of antiepileptic medicine

during pregnancy. You can enroll in this registry by calling 1-888-233-2334.

are breastfeeding or plan to breastfeed. Carbamazepine passes into breast milk. You and your

healthcare provider should discuss whether you should take carbamazepine or breastfeed; you

should not do both.

Tell your healthcare provider about all the medicines you take, including prescription and non-

prescription medicines, vitamins, and herbal supplements.

Taking carbamazepine with certain other medicines may cause side effects or affect how well they

work. Do not start or stop other medicines without talking to your healthcare provider.

Know the medicines you take. Keep a list of them and show it to your healthcare provider and

pharmacist when you get a new medicine.

How should I take carbamazepine?

Do not stop taking carbamazepine without first talking to your healthcare provider. Stopping

carbamazepine suddenly can cause serious problems. Stopping seizure medicine suddenly in a

patient who has epilepsy may cause seizures that will not stop (status epilepticus).

Take carbamazepine exactly as prescribed. Your healthcare provider will tell you how much

carbamazepine to take.

Your healthcare provider may change your dose. Do not change your dose of carbamazepine

without talking to your healthcare provider.

Take carbamazepine with food.

Carbamazepine extended-release tablets:

Do not crush, chew, or break carbamazepine extended-release tablets.

Tell your healthcare provider if you can not swallow carbamazepine extended-release tablets

whole.

Carbamazepine oral suspension:

Shake the bottle well each time before use.

Do not take carbamazepine oral suspension at the same time you take other liquid medicines.

If you take too much carbamazepine, call your healthcare provider or local Poison Control Center

right away.

What should I avoid while taking carbamazepine?

Do not drink alcohol or take other drugs that make you sleepy or dizzy while taking carbamazepine

until you talk to your healthcare provider. Carbamazepine taken with alcohol or drugs that cause

sleepiness or dizziness may make your sleepiness or dizziness worse.

Do not drive, operate heavy machinery, or do other dangerous activities until you know how

carbamazepine affects you. Carbamazepine may slow your thinking and motor skills.

What are the possible side effects of carbamazepine?

See " What is the most important information I should know about carbamazepine?"

Carbamazepine may cause other serious side effects. These include:

Irregular heartbeat - symptoms include:

Fast, slow, or pounding heartbeat

Shortness of breath

Feeling lightheaded

Fainting

Liver problems - symptoms include:

yellowing of your skin or the whites of your eyes

dark urine

pain on the right side of your stomach area (abdominal pain)

easy bruising

loss of appetite

nausea or vomiting

Get medical help right away if you have any of the symptoms listed above or listed in "What is the

most important information I should know about carbamazepine?"

The most common side effects of carbamazepine include:

dizziness

drowsiness

problems with walking and coordination (unsteadiness)

nausea

vomiting

These are not all the possible side effects of carbamazepine. For more information, ask your healthcare

provider or pharmacist.

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-

800-FDA-1088.

How should I store carbamazepine?

Store Carbamazepine Tablets at 20° to 25°C (68° to 77°F).

Keep Carbamazepine Tablets dry.

Store Carbamazepine Tablets (Chewable) at 20° to 25°C (68° to 77°F).

Keep Carbamazepine Tablets (Chewable) out of the light.

Keep Carbamazepine Tablets (Chewable) dry.

Store Carbamazepine Extended-Release Tablets at 20° to 25°C (68° to 77°F).

Keep Carbamazepine Extended-Release Tablets dry.

Store Carbamazepine Oral Suspension at 20° to 25°C (68° to 77°F).

Shake well before using.

Keep Carbamazepine Oral Suspension in a tight, light-resistant container.

Keep carbamazepine and all medicines out of the reach of children.

General Information about carbamazepine

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not

use carbamazepine for a condition for which it was not prescribed. Do not give carbamazepine to other

people, even if they have the same symptoms that you have. It may harm them.

This Medication Guide summarizes the most important information about carbamazepine. If you would

like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare

provider for the full prescribing information about carbamazepine that is written for health

professionals .

For more information call 1-866-923-4914.

What are the ingredients in carbamazepine?

Active ingredient: carbamazepine

Inactive ingredients:

Carbamazepine Tablets, (Chewable), 100 mg and 200 mg – ammonio methacrylate copolymer,

croscarmellose sodium, diethyl phthalate, FD&C red no. 40 lake, magnesium stearate,

microcrystalline cellulose, natural cherry flavor, pregelatinized maize starch and sorbitol.

Carbamazepine Tablets, 200 mg – ammonio methacrylate copolymer, corn starch, croscarmellose

sodium, diethyl phthalate, magnesium stearate and microcrystalline cellulose.

Carbamazepine Extended-Release Tablets, 100 mg, 200 mg, and 400 mg – ammonio

methacrylate copolymer, corn starch, diethyl phthalate, lactose monohydrate, magnesium stearate,

microcrystalline cellulose and sodium starch glycolate.

Carbamazepine Oral Suspension, 100 mg/5 mL – citric acid monohydrate, FD&C yellow no. 6,

orange flavor, poloxamer 188, potassium sorbate, propylene glycol, purified water, sorbitol

solution, sucrose and xanthan gum.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Distributed by: Taro Pharmaceuticals U.S.A., Inc.

Hawthorne, NY 10532

Made in Israel

Revised: May 2018

70725-0518-11

PRINCIPAL DISPLAY PANEL

DRUG: Carbamazepine

GENERIC: Carbamazepine

DOSAGE: TABLET

ADMINSTRATION: ORAL

NDC: 70518-2242-0

NDC: 70518-2242-1

NDC:70518-2242-2

COLOR: white

SHAPE: ROUND

SCORE: Two even pieces

SIZE: 9 mm

IMPRINT: TARO;11

PACKAGING: 180 in 1 BOTTLE, PLASTIC

PACKAGING: 100 in 1 BOX, UNIT-DOSE

PACKAGING: 1 in 1 POUCH

ACTIVE INGREDIENT(S):

Carbamazepine 200mg in 1

INACTIVE INGREDIENT(S):

MICROCRYSTALLINE CELLULOSE

magnesium stearate

diethyl phthalate

croscarmellose sodium

starch, corn

CARBAMAZEPINE

carbamazepine tablet

Product Information

Product T ype

HUMAN PRESCRIPTION

DRUG

Ite m Code (Source )

NDC:70 518 -2242(NDC:516 72-40 0 5)

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

CARBAMAZEPINE (UNII: 33CM239 13M) (CARBAMAZEPINE - UNII:33CM239 13M)

CARBAMAZEPINE

20 0 mg

Inactive Ingredients

Ingredient Name

Stre ng th

STARCH, CO RN (UNII: O8 232NY3SJ)

CRO SCARMELLO SE SO DIUM (UNII: M28 OL1HH48 )

DIETHYL PHTHALATE (UNII: UF0 6 4M0 0 AF)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

MICRO CRYSTALLINE CELLULO SE (UNII: OP1R32D6 1U)

Product Characteristics

Color

white

S core

2 pieces

S hap e

ROUND

S iz e

9 mm

Flavor

Imprint Code

TARO;11

Contains

REMEDYREPACK INC.

Packag ing

#

Item Code

Package Description

Marketing Start

Date

Marketing End

Date

1

NDC:70 518 -2242-

18 0 in 1 BOTTLE, PLASTIC; Type 0 : No t a Co mbinatio n

Pro duc t

0 7/31/20 19

2

NDC:70 518 -2242-

1 in 1 BOX, UNIT-DOSE

10 /19 /20 19

2

NDC:70 518 -2242-

1 in 1 POUCH; Type 0 : No t a Co mbinatio n Pro duct

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 746 49

0 7/31/20 19

Labeler -

REMEDYREPACK INC. (829572556)

Revised: 10/2019

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