CARBAMAZEPINE tablet
For Healthcare Providers >

1. Carbamazepine Tablets Are A Prescription Medicine Used To Treat:
2. Who Should Not Take Carbamazepine Tablets?do Not Take Carbamazepine Tablets If You:
3. What Should I Avoid While Taking Carbamazepine Tablets?
4. Carbamazepine Tablets May Cause Other Serious Side Effects. These Include:
5. The Most Common Side Effects Of Carbamazepine Tablets Include:
6. Patient Information
7. What Is The Most Important Information I Should Know About Carbamazepine Tablets?
8. Carbamazepine Tablets Can Cause Serious Side Effects, Including:
9. Do Not Take Carbamazepine Tablets If You:
10. Before You Take Carbamazepine Tablets, Tell Your Healthcare Provider If You:
11. How Should I Take Carbamazepine Tablets?
12. Carbamazepine Tablets May Cause Other Serious Side Effects. These Include:
13. How Should I Store Carbamazepine Tablets, Usp?
14. What Are The Ingredients In Carbamazepine Tablets?

Carbamazepine Tablets Are 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 Tablets?do Not Take Carbamazepine Tablets If You: ⮝

• have a history of bone marrow depression.
• are allergic to carbamazepine or any of the ingredients in carbamazepine tablets.
  • Do not stop taking carbamazepine tablets without first talking to your healthcare provider. Stopping carbamazepine tablets 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 tablets exactly as prescribed. Your healthcare provider will tell you how much carbamazepine tablets to take.
  • Your healthcare provider may change your dose. Do not change your dose of carbamazepine tablets without talking to your healthcare provider.
  • Take carbamazepine tablets with food.
  • If you take too much carbamazepine tablets, call your healthcare provider or local Poison Control Center right away.

What Should I Avoid While Taking Carbamazepine Tablets? ⮝

• 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 tablets 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 tablets affects you. Carbamazepine may slow your thinking and motor skills.

Carbamazepine Tablets 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 tablets .

The Most Common Side Effects Of Carbamazepine Tablets Include: ⮝

• dizziness
• drowsiness
• problems with walking and coordination (unsteadiness)
• nausea
• vomiting

These are not all the possible side effects of carbamazepine tablets. 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.

Patient Information ⮝

Patients should be advised to contact their physician if they experience any adverse reactions to carisoprodol.

17.1 Sedation

Patients should be advised that carisoprodol may cause drowsiness and/or dizziness, and has been associated with motor vehicle accidents. Patients should be advised to avoid taking carisoprodol before engaging in potentially hazardous activities such as driving a motor vehicle or operating machinery [seeWarnings and Precautions (5.1)].

17.2 Avoidance of Alcohol and Other CNS Depressants

Patients should be advised to avoid alcoholic beverages while taking carisoprodol and to check with their doctor before taking other CNS depressants such as benzodiazepines, opioids, tricyclic antidepressants, sedating antihistamines, or other sedatives [seeWarnings and Precautions (5.1)].

17.3 Carisoprodol Should Only Be Used for Short-Term Treatment

Patients should be advised that treatment with carisoprodol should be limited to acute use (up to two or three weeks) for the relief of acute, musculoskeletal discomfort. In the post-marketing experience with carisoprodol, cases of dependence, withdrawal, and abuse have been reported with prolonged use. If the musculoskeletal symptoms still persist, patients should contact their healthcare provider for further evaluation.

To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 orwww.fda.gov/medwatch.

Manufactured for:
Aurobindo Pharma USA, Inc.
2400 Route 130 North
Dayton, NJ 08810

Manufactured by:
Aurobindo Pharma Limited
Hyderabad 500 072, India

Revised: 02/2012

What Is The Most Important Information I Should Know About Carbamazepine Tablets? ⮝

Do not stop takingcarbamazepine tablets without first talking to your healthcare provider.

Stopping carbamazepine suddenly can cause serious problems.

Carbamazepine Tablets Can Cause Serious Side Effects, Including: ⮝

1.Carbamazepine tablets 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

• 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 stopcarbamazepine tablets without first talking to a healthcare provider.

Stopping carbamazepine tablets 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.

Do Not Take Carbamazepine Tablets If You: ⮝

• have a history of bone marrow depression.
• are allergic to carbamazepine or any of the ingredients in carbamazepine tablets.

Before You Take Carbamazepine Tablets, 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 tablets may make your birth control less effective. Tell your healthcare provider if your menstrual bleeding changes while you take birth control and carbamazepine tablets.
• are pregnant or plan to become pregnant. Carbamazepine tablets may harm your unborn baby. Tell your healthcare provider right away if you become pregnant while taking carbamazepine tablets. You and your healthcare provider should decide if you should take carbamazepine while you are pregnant.
  • If you become pregnant while taking carbamazepine tablets, USP, 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 tablets 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 Tablets? ⮝

• Do not stop taking carbamazepine tablets without first talking to your healthcare provider. Stopping carbamazepine tablets 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 tablets exactly as prescribed. Your healthcare provider will tell you how much carbamazepine tablets to take.
• Your healthcare provider may change your dose. Do not change your dose of carbamazepine tablets without talking to your healthcare provider.
• Take carbamazepine tablets with food.
• If you take too much carbamazepine tablets, call your healthcare provider or local Poison Control Center right away.

Carbamazepine Tablets 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 tablets".

The most common side effects of carbamazepinetabletsinclude:

• dizziness
• drowsiness
• problems with walking and coordination (unsteadiness)
• nausea
• vomiting

These are not all the possible side effects of carbamazepine tablets. 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 Tablets, Usp? ⮝

• Do not store above 30 C (86 F).

  • Keep carbamazepine tablets dry.

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

General Information about carbamazepine tablets

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use carbamazepine tablets for a condition for which it was not prescribed. Do not give carbamazepine tablets 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 tablets, USP. 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 tablets, USP that is written for health professionals.

For more information, contact Apotex Corp., Drug safety at 1-800-706-5575

What Are The Ingredients In Carbamazepine Tablets? ⮝

Active ingredient: carbamazepine USP

Inactive ingredients: croscarmellose sodium, magnesium stearate, and microcrystalline cellulose.

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

APOTEX INC.

CARBAMAZEPINE TABLETS, USP 200 mg

Manufactured by Manufactured for

Apotex Inc. Apotex Corp.

Toronto, Ontario Weston, Florida

Canada M9L 1T9 33326

March 2018

Rev. 5

1. No Title 1572548234
2. No Title 1572551231
3. No Title 1572551868
4. No Title 1572553657
5. No Title 1572553658
6. Carbamazepine
7. Boxed Warning
8. Description
9. Clinical Pharmacology
10. Indications & Usage
11. Contraindications
12. Warnings
13. Precautions
14. Adverse Reactions
15. Drug Abuse And Dependence
16. Overdosage
17. Dosage & Administration
18. Principal Display Panel
19. Warning
20. Indications And Usage
21. Dosage And Administration
22. How Supplied
23. Principal Display Panels
24. Principal Display Panel
25. Dosage And Administration(see Table Below)
26. Repackaging Information
27. Principal Display Panel - 200mg
28. Highlights Of Prescribing Information
29. Recent Major Changes
30. Dosage Forms And Strengths
31. Warnings And Precautions
32. Drug Interactions
33. 1 Indications And Usage
34. 2 Dosage And Administration
35. 3 Dosage Forms And Strengths
36. 4 Contraindications
37. 5 Warnings And Precautions
38. 6 Adverse Reactions
39. 7 Drug Interactions
40. 8 Use In Specific Populations
41. 9 Drug Abuse And Dependence
42. 10 Overdosage
43. 11 Description
44. 12 Clinical Pharmacology
45. 13 Nonclinical Toxicology
46. 14 Clinical Studies
47. 16 How Supplied/storage And Handling
48. Package Label-principal Display Panel - 350 Mg (100 Tablet Bottle)
49. No Title 1572452656
50. Dosage And Administration(see Table Below)
51. Carbamazepine Tablets, Usp
52. Packaging Information
53. Package/label Display Panel Carton 200 Mg
54. Package/label Display Panel Blister 200 Mg
55. No Title 1572454771
56. Dosage And Administration (see Table Below)
57. No Title 1572454772
58. 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
59. No Title 1572456270
60. No Title 1572456526
61. Label Image (apotex) 200mg
62. Carbamazepine Tablets Usp 200 Mgrx Only
63. Drug Interactions
64. Package Label Principal Display Panel

No Title 1572548234 ⮝

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.

No Title 1572551231 ⮝

CARBAMAZEPINE carbamazepine tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:64725-4005(NDC:51672-4005) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Carbamazepine (UNII: 33CM23913M) (Carbamazepine - UNII:33CM23913M) Carbamazepine 200 mg

Inactive Ingredients Ingredient Name Strength STARCH, CORN (UNII: O8232NY3SJ) CROSCARMELLOSE SODIUM (UNII: M28OL1HH48) DIETHYL PHTHALATE (UNII: UF064M00AF) MAGNESIUM STEARATE (UNII: 70097M6I30) CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)

Product Characteristics Color WHITE Score 2 pieces Shape ROUND Size 9mm Flavor Imprint Code TARO;11 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:64725-4005-1 100 in 1 BOTTLE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA074649 10/03/1996

Labeler - TYA Pharmaceuticals (938389038)

Registrant - TYA Pharmaceuticals (938389038)

Establishment
Name	Address	ID/FEI	Business Operations
TYA Pharmaceuticals		938389038	RELABEL(64725-4005) , REPACK(64725-4005)

Revised: 4/2013 Document Id: bd525ac0-d234-4a1d-936a-7c485882b41f 34391-3 Set id: 19fa8a00-51a0-4f8f-8060-45f7053ceb29 Version: 2 Effective Time: 20130423 TYA Pharmaceuticals

No Title 1572551868 ⮝

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.

No Title 1572553657 ⮝

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.

No Title 1572553658 ⮝

Manufactured by:

TORRENT PHARMACEUTICALS LTD., Indrad-382 721, Dist. Mehsana, INDIA.

For:

TORRENT PHARMA INC., 5380 Holiday Terrace, Suite 40, Kalamazoo, Michigan 49009.

8018789 Revised October 2009

Carbamazepine ⮝

CARBAMAZEPINE carbamazepine tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:50090-2161(NDC:60505-0183) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBAMAZEPINE (UNII: 33CM23913M) (CARBAMAZEPINE - UNII:33CM23913M) CARBAMAZEPINE 200 mg

Inactive Ingredients Ingredient Name Strength CROSCARMELLOSE SODIUM (UNII: M28OL1HH48) MAGNESIUM STEARATE (UNII: 70097M6I30) MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U)

Product Characteristics Color WHITE Score 2 pieces Shape ROUND Size 10mm Flavor Imprint Code APO;200 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:50090-2161-0 100 in 1 BOTTLE; Type 0: Not a Combination Product 10/21/2015 2 NDC:50090-2161-1 60 in 1 BOTTLE; Type 0: Not a Combination Product 10/21/2015 07/31/2018 3 NDC:50090-2161-3 28 in 1 BOTTLE; Type 0: Not a Combination Product 10/21/2015

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA075948 09/01/2002

Labeler - A-S Medication Solutions (830016429)

Establishment
Name	Address	ID/FEI	Business Operations
A-S Medication Solutions		830016429	RELABEL(50090-2161) , REPACK(50090-2161)

Revised: 11/2018 Document Id: f0604087-fd69-40a4-92c7-6d7dbf963ac0 34391-3 Set id: 3554a0b6-ea96-4516-81d7-cc2d27b4fc33 Version: 6 Effective Time: 20181105 A-S Medication Solutions

Boxed Warning ⮝

WARNING

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 5-8 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.

Description ⮝

Carbamazepine USP is an anticonvulsant and specific analgesic for trigeminal neuralgia, available for oral administration as tablets of 200 mg. Its chemical name is 5H-dibenz[b,f]azepine-5-carboxamide, and its structural formula is:

C15H12N2O

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:200 mg tablets- ammonio methacrylate copolymer, diethyl phthalate, microcrystalline cellulose, corn starch, croscarmellose sodium, and magnesium stearate.

The 200 mg tablet meets USP Dissolution Test 2.

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 b.i.d. 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 t.i.d. dosage regimen, carbamazepine suspension affords steady-state plasma levels comparable to carbamazepine tablets given b.i.d. when administered at the same total mg daily dose. Following a b.i.d. dosage regimen, carbamazepine extended-release tablets afford steady-state plasma levels comparable to conventional carbamazepine tablets given q.i.d., 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 g /mL, with no apparent relationship to the daily intake of the drug. Usual adult therapeutic levels are between 4 and 12 g/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. After oral administration of 14C-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 & Usage ⮝

Epilepsy

Carbamazepine tablets, USP are 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).

Trigeminal Neuralgia

Carbamazepine tablets, USP are 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 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.

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 <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 WARNINGS 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 anticonvulsant hypersensitivity syndrome or nonserious rash (maculopapular eruption [MPE]).

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 anti-epileptic drugs associated with SJS/TEN. 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.

Application of HLA-B*1502 genotyping as a screening tool has important limitations and must never substitute for appropriate clinical vigilance and patient management. Many HLA-B*1502-positive Asian patients treated with Carbamazepine will not develop SJS/TEN, and these reactions can still occur infrequently in HLA-B*1502-negative patients of any ethnicity. The role of other possible factors in the development of, and morbidity from, SJS/TEN, such as antiepileptic drug (AED) dose, compliance, concomitant medications, co-morbidities, and the level of dermatologic monitoring have not been studied.

Aplastic Anemia and Agranulocytosis

Patients with a history of adverse hematologic reaction to any drug may be particularly at risk of bone marrow depression.

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 (5-100 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	1.0	3.4	3.5	2.4
Psychiatric	5.7	8.5	1.5	2.9
Other	1.0	1.8	1.9	0.9
Total	2.4	4.3	1.8	1.9

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.

Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and 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.

General

Carbamazepine has shown mild anticholinergic activity; 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 resumed 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.

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, hypospadias and anomalies involving various body systems). Developmental delays based on neurobehavioral assessments have been reported. In 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/m2 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 underling 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.

Multiorgan hypersensitivity reactions occurring days to weeks or months after initiating treatment have been reported in rare cases (see ADVERSE REACTIONS, Other and PRECAUTIONS, Information for Patients).

Discontinuation of carbamazepine should be considered if any evidence of hypersensitivity develops.

Hypersensitivity reactions to carbamazepine have been reported in patients who previously experienced this reaction to anticonvulsants including phenytoin and phenobarbital. A history of hypersensitivity reactions should be obtained for a patient and the immediate family members. If positive, caution should be used in prescribing carbamazepine.

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).

Information for Patients

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, 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 non-prescription 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.

Hyponatremia has been reported in association with carbamazepine use, either alone or in combination with other drugs.

Interference with some pregnancy tests has been reported.

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 (see BOXEDWARNING), 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 low 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.

Skin: Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) (see BOXEDWARNING), pruritic and erythematous rashes, urticaria, photosensitivity reactions, alterations in skin pigmentation, exfoliative dermatitis, erythema multiforme and nodosum, purpura, aggravation of disseminated lupus erythematosus, alopecia, and diaphoresis. In certain cases, discontinuation of therapy may be necessary. Isolated cases of hirsutism have been reported, but a causal relationship is not clear.

Cardiovascular System: Congestive heart failure, edema, aggravation of hypertension, hypotension, syncope and collapse, aggravation of coronary artery disease, arrhythmias and AV block, thrombophlebitis, thromboembolism, 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.

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, and hyperacusis.

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 with 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, 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. Inappropriate antidiuretic hormone (ADH) secretion syndrome has been reported. Cases of frank water intoxication, with decreased serum sodium (hyponatremia) and confusion, have been reported in association with carbamazepine use (see PRECAUTIONS, Laboratory Tests). Decreased levels of plasma calcium have been reported.

Other: Multi-organ hypersensitivity reactions occurring days to weeks or months after initiating treatment have been reported in rare cases. Signs or symptoms may include, but are not limited to fever, skin rashes, vasculitis, lymphadenopathy, disorders mimicking lymphoma, arthralgia, leukopenia, eosinophilia, hepato-splenomegaly and abnormal liver function tests. These signs and symptoms may occur in various combinations and not necessarily concurrently. Signs and symptoms may initially be mild. Various organs, including but not limited to, liver, skin, immune system, lungs, kidneys, pancreas, myocardium, and colon may be affected (see PRECAUTIONS, General and PRECAUTIONS, Information for Patients).

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 LD50 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 (>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 one 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) 59Fe-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 A2 and F hemoglobin, and (7) serum folic acid and B12 levels.

A fully developed aplastic anemia will require appropriate, intensive monitoring and therapy, for which specialized consultation should be sought.

Dosage & Administration ⮝

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.

Epilepsy (see INDICATIONS AND USAGE)

Adults and children over 12 years of age - Initial: 200 mg b.i.d. for tablets (400 mg/day). Increase at weekly intervals by adding up to 200 mg/day using a t.i.d. or q.i.d. regimen of carbamazepine tablets until the optimal response is obtained. Dosage generally should not exceed 1,000 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: 100 mg b.i.d. for tablets (200 mg/day). Increase at weekly intervals by adding up to 100 mg/day using a t.i.d. or q.i.d. regimen of carbamazepine tablets until the optimal response is obtained. Dosage generally should not exceed 1,000 mg daily. Maintenance: Adjust dosage to the minimum effective level, usually 400 to 800 mg daily.

Children under 6 years of age - Initial: 10 to 20 mg/kg/day b.i.d. or t.i.d. for tablets. Increase weekly to achieve optimal clinical response administered t.i.d. or q.i.d. 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 Category D).

Trigeminal Neuralgia (see INDICATIONS AND USAGE)

Initial: On the first day, 100 mg b.i.d. for tablets 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, 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 TABLE CAN BE FOUND AT THE MANUFACTURER'S LABEL SITE HERE:

http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bf0d012f-da14-8ce3-d74f-56172cddebc5

Principal Display Panel ⮝

Carbamazepine Tablets ,

USP (Chewable) 100mg

CARBAMAZEPINE carbamazepine tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0615-4515(NDC:13668-271) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBAMAZEPINE (UNII: 33CM23913M) (CARBAMAZEPINE - UNII:33CM23913M) CARBAMAZEPINE 100 mg

Inactive Ingredients Ingredient Name Strength SILICON DIOXIDE (UNII: ETJ7Z6XBU4) FD&C RED NO. 40 (UNII: WZB9127XOA) HYPROMELLOSES (UNII: 3NXW29V3WO) MAGNESIUM STEARATE (UNII: 70097M6I30) STARCH, CORN (UNII: O8232NY3SJ) STARCH, CORN (UNII: O8232NY3SJ) SODIUM STARCH GLYCOLATE TYPE A POTATO (UNII: 5856J3G2A2)

Product Characteristics Color PINK Score no score Shape CAPSULE Size 10mm Flavor Imprint Code 271 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0615-4515-39 30 in 1 BLISTER PACK

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA077272 12/07/2005

Labeler - NCS HealthCare of KY, Inc dba Vangard Labs (050052943)

Establishment
Name	Address	ID/FEI	Business Operations
NCS HealthCare of KY, Inc dba Vangard Labs		050052943	RELABEL(0615-4515) , REPACK(0615-4515)

Revised: 3/2013 Document Id: 05a19461-16b8-443f-ab47-ff5c96e3694a 34391-3 Set id: fd97d064-4c55-481d-b7ef-cfb948fc75b4 Version: 6 Effective Time: 20130315 NCS HealthCare of KY, Inc dba Vangard Labs

Warning ⮝

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.

Indications And Usage ⮝

Epilepsy

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).

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.

Dosage And Administration ⮝

(see table)

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.

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., b.i.d. tablets to t.i.d. 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.

Epilepsy:

(See INDICATIONS AND USAGE)

Adults and Children over 12 Years of Age

Initial: 200 mg b.i.d. for tablets. Increase at weekly intervals by adding up to 200 mg/day using a t.i.d. or q.i.d. regimen 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: 100 mg b.i.d. Increase at weekly intervals by adding up to 100 mg/day using a t.i.d. or q.i.d. regimen 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 to 20 mg/kg/day b.i.d. or t.i.d. Increase weekly to achieve optimal clinical response administered t.i.d. or q.i.d. 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, DrugInteractions and Pregnancy Category D).

Trigeminal Neuralgia:

(See INDICATIONS AND USAGE)

Initial: On the first day, 100 mg b.i.d. 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 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

Indication	Initial Dose Tablet	Subsequent Dose Tablet	Maximum Daily Dose Tablet
Epilepsy
Under 6 yr	10 to 20 mg/kg/day b.i.d. or t.i.d.	Increase weekly to achieve optimal clinical response, t.i.d. or q.i.d.	35 mg/kg/24 hr (see Dosage and Administration section above)
6 to 12 yr	100 mg b.i.d. (200 mg/day)	Add up to 100 mg/day at weekly intervals, t.i.d. or q.i.d.	1000 mg/24 hr
Over 12 yr	200 mg b.i.d. (400 mg/day)	Add up to 200 mg/day at weekly intervals, t.i.d. or q.i.d.	1000 mg/24 hr (12 to 15 yr) 1200 mg/24 hr (>15 yr) 1600 mg/24 hr (adults, in rare instances)
Trigeminal Neuralgia	100 mg b.i.d. (200 mg/day)	Add up to 200 mg/day in increments of 100 mg every 12 hr	1200 mg/24 hr

How Supplied ⮝

CARBAMAZEPINE Tablets USP are supplied as 200 mg white, round, flat beveled-edge, one side scored and engraved TARO above the score and 11 below the score, the other side plain.

CARBAMAZEPINE Tablets USP are packaged in Bottles of 30 and 60.

Store at 20 to 25 C (68 to 77 F) [See USP Controlled Room Temperature]. Protect from moisture.

Manufactured In Israel by:

Taro Pharmaceutical Industries Ltd.

Haifa Bay, Israel 26110

Distributed by:

TEVA PHARMACEUTICALS USA

Sellersville, PA 18960

Iss. 5/2009

Repackaged by:

REBEL DISTRIBUTORS CORP

Thousand Oaks, CA 91320

Principal Display Panels  ⮝

Blister of 30

NDC 67046-086-30

CARBAMAZEPINE

Tablets USP

200 mg

Each tablet contains:

carbamazepine, USP 200 mg

Carbamazepine 200 mg tablets

meet USP Dissolution Test 3.

Rx only

30 TABLETS

TEVA

Principal Display Panel ⮝

Blister of 60

NDC 67046-086-60

CARBAMAZEPINE

Tablets USP

200 mg

Each tablet contains:

carbamazepine, USP 200 mg

Carbamazepine 200 mg tablets

meet USP Dissolution Test 3.

Rx only

60 TABLETS

TEVA

CARBAMAZEPINE carbamazepine tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:67046-086(NDC:0093-0109) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBAMAZEPINE (UNII: 33CM23913M) (CARBAMAZEPINE - UNII:33CM23913M) CARBAMAZEPINE 200 mg

Inactive Ingredients Ingredient Name Strength COLLOIDAL SILICON DIOXIDE (UNII: ETJ7Z6XBU4) CROSCARMELLOSE SODIUM (UNII: M28OL1HH48) ETHYLCELLULOSE (UNII: 7Z8S9VYZ4B) GLYCERIN (UNII: PDC6A3C0OX) LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X) MAGNESIUM STEARATE (UNII: 70097M6I30)

Product Characteristics Color WHITE Score 2 pieces Shape ROUND Size 10mm Flavor Imprint Code T;109 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:67046-086-30 30 in 1 BLISTER PACK 2 NDC:67046-086-60 60 in 1 BLISTER PACK

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA070541 02/24/2010

Labeler - Contract Pharmacy Services-PA (945429777)

Revised: 2/2010 Document Id: 8e06995c-26c9-4ef3-9421-16a2360db628 34391-3 Set id: 8e06995c-26c9-4ef3-9421-16a2360db628 Version: 1 Effective Time: 20100224 Contract Pharmacy Services-PA

Dosage And Administration(see Table Below)  ⮝

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.

Epilepsy (see INDICATIONS AND USAGE)

Adults and children over 12 years of age-Initial: 200 mg b.i.d. for tablets (400 mg/day). Increase at weekly intervals by adding up to 200 mg/day using a t.i.d. or q.i.d. regimen of carbamazepine tablets until the optimal response is obtained. Dosage generally should not exceed 1,000 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: 100 mg b.i.d. for tablets (200 mg/day). Increase at weekly intervals by adding up to 100 mg/day using a t.i.d. or q.i.d. regimen of carbamazepine tablets until the optimal response is obtained. Dosage generally should not exceed 1,000 mg daily. Maintenance: Adjust dosage to the minimum effective level, usually 400 to 800 mg daily.

Children under 6 years of age-Initial: 10 to 20 mg/kg/day b.i.d. or t.i.d. for tablets. Increase weekly to achieve optimal clinical response administered t.i.d. or q.i.d. 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 Category D).

Trigeminal Neuralgia (see INDICATIONS AND USAGE)

Initial: On the first day, 100 mg b.i.d. for tablets 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, 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 for Tablets

Indication	Initial Dose	Subsequent Dose	Maximum Daily Dose
Epilepsy Under 6 yr	10 to 20 mg/kg/day b.i.d. or t.i.d.	Increase weekly to achieve optimal clinical response, t.i.d. or q.i.d.	35 mg/kg/24 hr (see Dosage and Administration section above)
6 to 12 yr	100 mg b.i.d. (200 mg/day)	Add up to 100 mg/day at weekly intervals, t.i.d. or q.i.d.	1000 mg/24 hr
Over 12 yr	200 mg b.i.d. (400 mg/day)	Add up to 200 mg/day at weekly intervals, t.i.d. or q.i.d.	1000 mg/24 hr (12 to 15 yr) 1200 mg/24 hr (>15 yr) 1600 mg /24 hr (adults, in rare instances)
Trigeminal Neuralgia	100 mg b.i.d. (200 mg/day)	Add up to 200 mg/day in increments of 100 mg every 12 hr	1200 mg/24 hr

Repackaging Information ⮝

Please reference the How Supplied section listed above for a description of individual tablets. This drug product has been received by Aphena Pharma - TN in a manufacturer or distributor packaged configuration and repackaged in full compliance with all applicable cGMP regulations. The package configurations available from Aphena are listed below:

Count	500mg
60	43353-953-53
90	43353-953-60
180	43353-953-80

Store between 20 -25 C (68 -77 F). See USP Controlled Room Temperature. Dispense in a tight light-resistant container as defined by USP. Keep this and all drugs out of the reach of children.

Repackaged by:

Cookeville, TN 38506

20160602JH

Principal Display Panel - 200mg ⮝

NDC 43353-953 - Carbamazepine 200mg - Rx Only

CARBAMAZEPINE carbamazepine tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:43353-953(NDC:60429-032) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBAMAZEPINE (UNII: 33CM23913M) (CARBAMAZEPINE - UNII:33CM23913M) CARBAMAZEPINE 200 mg

Inactive Ingredients Ingredient Name Strength CROSCARMELLOSE SODIUM (UNII: M28OL1HH48) MAGNESIUM STEARATE (UNII: 70097M6I30) CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)

Product Characteristics Color WHITE Score 2 pieces Shape ROUND Size 10mm Flavor Imprint Code APO;200 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:43353-953-53 60 in 1 BOTTLE; Type 0: Not a Combination Product 07/03/2014 2 NDC:43353-953-60 90 in 1 BOTTLE; Type 0: Not a Combination Product 07/03/2014 3 NDC:43353-953-80 180 in 1 BOTTLE; Type 0: Not a Combination Product 07/25/2014

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA075948 03/07/2014

Labeler - Aphena Pharma Solutions - Tennessee, LLC (128385585)

Establishment
Name	Address	ID/FEI	Business Operations
Aphena Pharma Solutions - Tennessee, LLC		128385585	REPACK(43353-953)

Revised: 6/2016 Document Id: 7c7b8491-2291-48de-8b76-bf2eca6c9d9c 34391-3 Set id: c1fc31ef-6b2e-4de4-a185-ec44e94e7b40 Version: 1 Effective Time: 20160602 Aphena Pharma Solutions - Tennessee, LLC

Highlights Of Prescribing Information ⮝

These highlights do not include all the information needed to use carisoprodol safely and effectively. See full prescribing information for carisoprodol tablets, USP.

Carisoprodol Tablets, USP for Oral use CIV
Initial U.S. Approval: 1959

Recent Major Changes ⮝

Warnings and Precautions, Sedation (5.1) 10/2009
Warnings and Precautions, Drug Dependence, Withdrawal, and Abuse (5.2) 10/2009

Dosage Forms And Strengths ⮝

Tablets: 350 mg (3)

Warnings And Precautions ⮝

• Due to sedative properties, may impair ability to perform hazardous tasks such as driving or operating machinery (5.1)
• Additive sedative effects when used with other CNS depressants including alcohol (5.1)
• Cases of Drug Dependence, Withdrawal, and Abuse (5.2)
• Seizures (5.3)

Drug Interactions ⮝

• CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) - additive sedative effects (5.1 and 7.1)

See 17 for PATIENT COUNSELING INFORMATION.

Revised: 9/2012

1 Indications And Usage ⮝

Carisoprodol tablets, USP are indicated for the relief of discomfort associated with acute, painful musculoskeletal conditions in adults.

Carisoprodol tablets, USP should only be used for short periods (up to two or three weeks) because adequate evidence of effectiveness for more prolonged use has not been established and because acute, painful musculoskeletal conditions are generally of short duration [see Dosage and Administration (2)].

2 Dosage And Administration ⮝

The recommended dose of carisoprodol tablets is 350 mg three times a day and at bedtime. The recommended maximum duration of carisoprodol tablets use is up to two or three weeks.

3 Dosage Forms And Strengths ⮝

Carisoprodol tablets USP, 350 mg are white colored, round shaped, biconvex, uncoated tablets, identified with D debossed on one side and 31 on the other side.

4 Contraindications ⮝

Carisoprodol tablets are contraindicated in patients with a history of acute intermittent porphyria or a hypersensitivity reaction to a carbamate such as meprobamate.

5 Warnings And Precautions ⮝

5.1 Sedation

Carisoprodol has sedative properties (in the low back pain trials, 13% to 17% of patients who received carisoprodol experienced sedation compared to 6% of patients who received placebo) [see ADVERSE REACTIONS (6.1)] and may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a motor vehicle or operating machinery. There have been post-marketing reports of motor vehicle accidents associated with the use of carisoprodol.

Since the sedative effects of carisoprodol and other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) may be additive, appropriate caution should be exercised with patients who take more than one of these CNS depressants simultaneously.

5.2 Drug Dependence, Withdrawal, and Abuse

In the postmarketing experience with carisoprodol, cases of dependence, withdrawal, and abuse have been reported with prolonged use. Most cases of dependence, withdrawal, and abuse occurred in patients who have had a history of addiction or who used carisoprodol in combination with other drugs with abuse potential. However, there have been post-marketing adverse event reports of carisoprodol-associated abuse when used without other drugs with abuse potential. Withdrawal symptoms have been reported following abrupt cessation after prolonged use. To reduce the chance of carisoprodol dependence, withdrawal, or abuse, carisoprodol should be used with caution in addiction-prone patients and in patients taking other CNS depressants including alcohol, and carisoprodol should not be used more than two to three weeks for the relief of acute musculoskeletal discomfort.

Carisoprodol, and one of its metabolites, meprobamate (a controlled substance), may cause dependence [see Clinical Pharmacology (12.3)].

5.3 Seizures

There have been postmarketing reports of seizures in patients who received carisoprodol. Most of these cases have occurred in the setting of multiple drug overdoses (including drugs of abuse, illegal drugs, and alcohol) [see Overdosage (10)].

6 Adverse Reactions ⮝

6.1 Clinical Studies Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect rates observed in practice.

The data described below are based on 910 patients pooled from two double blind, randomized, multicenter, placebo controlled, one-week trials in adult patients with acute, mechanical, lower back pain [see Clinical Studies (14)]. In these studies, patients were treated with 350 mg of carisoprodol, or placebo three times a day and at bedtime for seven days. The mean age was about 41 years old with 54% females and 46% males and 74% Caucasian, 16% Black, 9% Asian, and 2% other.

There were no deaths and there were no serious adverse reactions in these two trials. In these two studies, 2.7% and 5.4%, of patients treated with placebo and 350 mg of carisoprodol, respectively, discontinued due to adverse events; and 0.5% and 1.8% of patients treated with placebo and 350 mg of carisoprodol, respectively, discontinued due to central nervous system adverse reactions.

Table 1 displays adverse reactions reported with frequencies greater than 2% and more frequently than placebo in patients treated with carisoprodol in the two trials described above.

Table 1. Patients with Adverse Reactions in Controlled Studies

Adverse Reaction	Placebo (n=560) n (%)	Carisoprodol 350 mg (n=279) n (%)
Drowsiness	31 (6)	47 (17)
Dizziness	11 (2)	19 (7)
Headache	11 (2)	9 (3)

6.2 Postmarketing Experience

The following events have been reported during postapproval use of carisoprodol. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiovascular: Tachycardia, postural hypotension, and facial flushing [see Overdosage (10)].

Central Nervous System: Drowsiness, dizziness, vertigo, ataxia, tremor, agitation, irritability, headache, depressive reactions, syncope, insomnia, and seizures [see Overdosage (10)].

Gastrointestinal: Nausea, vomiting, and epigastric discomfort.

Hematologic: Leukopenia, pancytopenia.

7 Drug Interactions ⮝

7.1 CNS Depressants

The sedative effects of carisoprodol and other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) may be additive. Therefore, caution should be exercised with patients who take more than one of these CNS depressants simultaneously. Concomitant use of carisoprodol and meprobamate, a metabolite of carisoprodol, is not recommended [see Warnings and Precautions (5.1)].

7.2 CYP2C19 Inhibitors and Inducers

Carisoprodol is metabolized in the liver by CYP2C19 to form meprobamate [see Clinical Pharmacology (12.3)]. Co-administration of CYP2C19 inhibitors, such as omeprazole or fluvoxamine, with carisoprodol could result in increased exposure of carisoprodol and decreased exposure of meprobamate. Co-administration of CYP2C19 inducers, such as rifampin or St. John s Wort, with carisoprodol could result in decreased exposure of carisoprodol and increased exposure of meprobamate. Low dose aspirin also showed an induction effect on CYP2C19. The full pharmacological impact of these potential alterations of exposures in terms of either efficacy or safety of carisoprodol is unknown.

8 Use In Specific Populations ⮝

8.1 Pregnancy: Pregnancy Category C.

There are no data on the use of carisoprodol during human pregnancy. Animal studies indicate that carisoprodol crosses the placenta and results in adverse effects on fetal growth and postnatal survival. The primary metabolite of carisoprodol, meprobamate, is an approved anxiolytic. Retrospective, post-marketing studies do not show a consistent association between maternal use of meprobamate and an increased risk for particular congenital malformations.

Teratogenic effects: Animal studies have not adequately evaluated the teratogenic effects of carisoprodol. There was no increase in the incidence of congenital malformations noted in reproductive studies in rats, rabbits, and mice treated with meprobamate. Retrospective, post-marketing studies of meprobamate during human pregnancy were equivocal for demonstrating an increased risk of congenital malformations following first trimester exposure. Across studies that indicated an increased risk, the types of malformations were inconsistent.

Nonteratogenic effects: In animal studies, carisoprodol reduced fetal weights, postnatal weight gain, and postnatal survival at maternal doses equivalent to 1 to 1.5 times the human dose (based on a body surface area comparison). Rats exposed to meprobamate in-utero showed behavioral alterations that persisted into adulthood. For children exposed to meprobamate in-utero, one study found no adverse effects on mental or motor development or IQ scores. Carisoprodol should be used during pregnancy only if the potential benefit justifies the risk to the fetus.

8.2 Labor and Delivery

There is no information about the effects of carisoprodol on the mother and the fetus during labor and delivery.

8.3 Nursing Mothers

Very limited data in humans show that carisoprodol is present in breast milk and may reach concentrations two to four times the maternal plasma concentrations. In one case report, a breast-fed infant received about 4 to 6% of the maternal daily dose through breast milk and experienced no adverse effects. However, milk production was inadequate and the baby was supplemented with formula. In lactation studies in mice, female pup survival and pup weight at weaning were decreased. This information suggests that maternal use of carisoprodol may lead to reduced or less effective infant feeding (due to sedation) and/or decreased milk production. Caution should be exercised when carisoprodol is administered to a nursing woman.

8.4 Pediatric Use

The efficacy, safety, and pharmacokinetics of carisoprodol in pediatric patients less than 16 years of age have not been established.

8.5 Geriatric Use

The efficacy, safety, and pharmacokinetics of carisoprodol in patients over 65 years old have not been established.

8.6 Renal Impairment

The safety and pharmacokinetics of carisoprodol in patients with renal impairment have not been evaluated. Since carisoprodol is excreted by the kidney, caution should be exercised if carisoprodol is administered to patients with impaired renal function. Carisoprodol is dialyzable by hemodialysis and peritoneal dialysis.

8.7 Hepatic Impairment

The safety and pharmacokinetics of carisoprodol in patients with hepatic impairment have not been evaluated. Since carisoprodol is metabolized in the liver, caution should be exercised if carisoprodol is administered to patients with impaired hepatic function.

8.8 Patients with Reduced CYP2C19 Activity

Patients with reduced CYP2C19 activity have higher exposure to carisoprodol. Therefore, caution should be exercised in administration of carisoprodol to these patients [see Clinical Pharmacology (12.3)].

9 Drug Abuse And Dependence ⮝

Carisoprodol is a controlled substance [see Warnings and Precautions (5.2)]. Discontinuation of carisoprodol in animals or in humans after chronic administration can produce withdrawal signs, and there are published case reports of human carisoprodol dependence.

In vitro studies demonstrate that carisoprodol elicits barbiturate-like effects. Animal behavioral studies indicate that carisoprodol produces rewarding effects. Monkeys self administer carisoprodol. Drug discrimination studies using rats indicate that carisoprodol has positive reinforcing and discriminative effects similar to barbital, meprobamate, and chlordiazepoxide.

10 Overdosage ⮝

Overdosage of carisoprodol commonly produces CNS depression. Death, coma, respiratory depression, hypotension, seizures, delirium, hallucinations, dystonic reactions, nystagmus, blurred vision, mydriasis, euphoria, muscular incoordination, rigidity, and/or headache have been reported with carisoprodol overdosage. Many of the carisoprodol overdoses have occurred in the setting of multiple drug overdoses (including drugs of abuse, illegal drugs, and alcohol). The effects of an overdose of carisoprodol and other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) can be additive even when one of the drugs has been taken in the recommended dosage. Fatal accidental and non-accidental overdoses of carisoprodol have been reported alone or in combination with CNS depressants.

Treatment of Overdosage: Basic life support measures should be instituted as dictated by the clinical presentation of the carisoprodol overdose. Induced emesis is not recommended due to the risk of CNS and respiratory depression, which may increase the risk of aspiration pneumonia. Gastric lavage should be considered soon after ingestion (within one hour). Circulatory support should be administered with volume infusion and vasopressor agents if needed. Seizures should be treated with intravenous benzodiazepines and the reoccurrence of seizures may be treated with phenobarbital. In cases of severe CNS depression, airway protective reflexes may be compromised and tracheal intubation should be considered for airway protection and respiratory support.

The following types of treatment have been used successfully with an overdose of meprobamate, a metabolite of carisoprodol: activated charcoal (oral or via nasogastric tube), forced diuresis, peritoneal dialysis, and hemodialysis (carisoprodol is also dialyzable). Careful monitoring of urinary output is necessary and overhydration should be avoided. Observe for possible relapse due to incomplete gastric emptying and delayed absorption. For more information on the management of an overdose of carisoprodol, contact a Poison Control Center.

11 Description ⮝

Carisoprodol tablets are available as 350 mg round, white tablets. Carisoprodol USP is a white, crystalline powder, having a mild, characteristic odor and a bitter taste. It is slightly soluble in water; freely soluble in alcohol, in chloroform, and in acetone; and its solubility is practically independent of pH. Carisoprodol is present as a racemic mixture. Chemically, carisoprodol is N-isopropyl-2-methyl-2-propyl-1,3-propanediol dicarbamate and the molecular formula is C12H24N2O4, with a molecular weight of 260.33. The structural formula is:

Other ingredients in the carisoprodol tablets include pregelatinized starch, crospovidone, povidone, microcrystalline cellulose, colloidal silicon dioxide, and magnesium stearate.

12 Clinical Pharmacology ⮝

12.1 Mechanism of Action

The mechanism of action of carisoprodol in relieving discomfort associated with acute painful musculoskeletal conditions has not been clearly identified.

In animal studies, muscle relaxation induced by carisoprodol is associated with altered interneuronal activity in the spinal cord and in the descending reticular formation of the brain.

12.2 Pharmacodynamics

Carisoprodol is a centrally acting skeletal muscle relaxant that does not directly relax skeletal muscles.

A metabolite of carisoprodol, meprobamate, has anxiolytic and sedative properties. The degree to which these properties of meprobamate contribute to the safety and efficacy of carisoprodol is unknown.

12.3 Pharmacokinetics

The pharmacokinetics of carisoprodol and its metabolite meprobamate were studied in a crossover study of 24 healthy subjects (12 male and 12 female) who received single doses of 350 mg carisoprodol (see Table 2). The Cmax of meprobamate was 2.5 0.5 mcg/mL (mean SD) after administration of a single 350 mg dose of carisoprodol, which is approximately 30% of the Cmax of meprobamate (approximately 8 mcg/mL) after administration of a single 400 mg dose of meprobamate.

Table 2. Pharmacokinetic Parameters of Carisoprodol and Meprobamate (Mean SD, n=24)

	350 mg Carisoprodol
Carisoprodol
Cmax (mcg/mL)	1.8 1
AUCinf (mcg*hr/mL)	7 5
Tmax (hr)	1.7 0.8
T1/2 (hr)	2 0.5
Meprobamate
Cmax (mcg/mL)	2.5 0.5
AUCinf (mcg*hr/mL)	46 9
Tmax (hr)	4.5 1.9
T1/2 (hr)	9.6 1.5

Absorption: Absolute bioavailability of carisoprodol has not been determined. The mean time to peak plasma concentrations (Tmax) of carisoprodol was approximately 1.5 to 2 hours. Co-administration of a high-fat meal with carisoprodol (350 mg tablet) had no effect on the pharmacokinetics of carisoprodol. Therefore, carisoprodol may be administered with or without food.

Metabolism: The major pathway of carisoprodol metabolism is via the liver by cytochrome enzyme CYP2C19 to form meprobamate. This enzyme exhibits genetic polymorphism (see Patients with Reduced CYP2C19 Activity below).

Elimination: Carisoprodol is eliminated by both renal and non-renal routes with a terminal elimination half-life of approximately 2 hours. The half-life of meprobamate is approximately 10 hours.

Gender: Exposure of carisoprodol is higher in female than in male subjects (approximately 30 to 50% on a weight adjusted basis). Overall exposure of meprobamate is comparable between female and male subjects.

Patients with Reduced CYP2C19 Activity: Carisoprodol should be used with caution in patients with reduced CYP2C19 activity. Published studies indicate that patients who are poor CYP2C19 metabolizers have a 4-fold increase in exposure to carisoprodol, and concomitant 50% reduced exposure to meprobamate compared to normal CYP2C19 metabolizers. The prevalence of poor metabolizers in Caucasians and African Americans is approximately 3 to 5% and in Asians is approximately 15 to 20%.

13 Nonclinical Toxicology ⮝

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Long term studies in animals have not been performed to evaluate the carcinogenic potential of carisoprodol.

Carisoprodol was not formally evaluated for genotoxicity. In published studies, carisoprodol was mutagenic in the in vitro mouse lymphoma cell assay in the absence of metabolizing enzymes, but was not mutagenic in the presence of metabolizing enzymes. Carisoprodol was clastogenic in the in vitro chromosomal aberration assay using Chinese hamster ovary cells with or without the presence of metabolizing enzymes. Other types of genotoxic tests resulted in negative findings. Carisoprodol was not mutagenic in the Ames reverse mutation assay using S. typhimurium strains with or without metabolizing enzymes, and was not clastogenic in an in vivo mouse micronucleus assay of circulating blood cells.

Carisoprodol was not formally evaluated for effects on fertility. Published reproductive studies of carisoprodol in mice found no alteration in fertility although an alteration in reproductive cycles characterized by a greater time spent in estrus was observed at a carisoprodol dose of 1200 mg/kg/day. In a 13-week toxicology study that did not determine fertility, mouse testes weight and sperm motility were reduced at a dose of 1200 mg/kg/day. In both studies, the no effect level was 750 mg/kg/day, corresponding to approximately 2.6 times the human equivalent dosage of 350 mg four times a day, based on a body surface area comparison.

The significance of these findings for human fertility is not known.

14 Clinical Studies ⮝

The safety and efficacy of carisoprodol for the relief of acute, idiopathic mechanical low back pain was evaluated in two, 7-day, double blind, randomized, multicenter, placebo controlled, U.S. trials (Studies 1 and 2). Patients had to be 18 to 65 years old and had to have acute back pain ( 3 days of duration) to be included in the trials. Patients with chronic back pain; at increased risk for vertebral fracture (e.g., history of osteoporosis); with a history of spinal pathology (e.g., herniated nucleus pulposis, spondylolisthesis or spinal stenosis); with inflammatory back pain, or with evidence of a neurologic deficit were excluded from participation. Concomitant use of analgesics (e.g., acetaminophen, NSAIDs, tramadol, opioid agonists), other muscle relaxants, botulinum toxin, sedatives (e.g., barbiturates, benzodiazepines, promethazine hydrochloride), and anti-epileptic drugs was prohibited.

In Study 1, patients were randomized to one of two treatment groups (i.e., carisoprodol 350 mg or placebo). In the study, patients received study medication three times a day and at bedtime for seven days.

The primary endpoints were the relief from starting backache and the global impression of change, as reported by patients, on Study Day 3. Both endpoints were scored on a 5-point rating scale from 0 (worst outcome) to 4 (best outcome) in both studies. The primary statistical comparison was between the carisoprodol 250 mg and placebo groups in both studies.

The proportion of patients who used concomitant acetaminophen, NSAIDs, tramadol, opioid agonists, other muscle relaxants, and benzodiazepines was similar in the treatment groups.

The results for the primary efficacy evaluations in the acute, low back pain studies are presented in Table 3.

Table 3. Results of the Primary Efficacy Endpointsa in Study 1

Study	Parameter	Placebo	Carisoprodol 350 mg
a The primary efficacy endpoints (Relief from Starting Backache and Global Impression of Change) were assessed by the patients on Study Day 3. These endpoints were scored on a 5-point rating scale from 0 (worst outcome) to 4 (best outcome). b Mean is the least squared mean and SE is the standard error of the mean.
1	Number of Patients	n=269	n=273
	Relief from Starting Backache, Mean (SE)b	1.4 (0.1)	1.8 (0.1)
	Difference between Carisoprodol and Placebo, Mean (SE)b (95% CI)		0.4 (0.2, 0.6)
	Global Impression of Change, Mean (SE)b	1.9 (0.1)	2.2 (0.1)
	Difference between Carisoprodol and Placebo, Mean (SE)b (95% CI)		0.3 (0.1, 0.4)

Patients treated with carisoprodol experienced improvement in function as measured by the Roland-Morris Disability Questionnaire (RMDQ) score on Days 3 and 7.

16 How Supplied/storage And Handling ⮝

Carisoprodol Tablets USP, 350 mg are white colored, round shaped, biconvex, uncoated tablets, identified with D debossed on one side and 31 on the other side.

Bottles of 60 NDC 33261-676-60

Store at controlled room temperature 20 to 25 C (68 to 77 F).

Dispense in tight container.

Package Label-principal Display Panel - 350 Mg (100 Tablet Bottle) ⮝

CARBAMAZEPINE carbamazepine tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:33261-676(NDC:51672-4005) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBAMAZEPINE (UNII: 33CM23913M) (CARBAMAZEPINE - UNII:33CM23913M) CARBAMAZEPINE 200 mg

Inactive Ingredients Ingredient Name Strength STARCH, CORN (UNII: O8232NY3SJ) CROSCARMELLOSE SODIUM (UNII: M28OL1HH48) DIETHYL PHTHALATE (UNII: UF064M00AF) MAGNESIUM STEARATE (UNII: 70097M6I30) CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)

Product Characteristics Color WHITE Score 2 pieces Shape ROUND Size 9mm Flavor Imprint Code TARO;11 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:33261-676-60 60 in 1 BOTTLE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA074649 10/03/1996

Labeler - Aidarex Pharmaceuticals LLC (801503249)

Revised: 9/2012 Document Id: 2b8c4ae6-ba9f-43d3-93d1-e731b10a0a4d 34391-3 Set id: 80be25d9-2e4c-4e7c-b924-9cffbcf87b9e Version: 1 Effective Time: 20120912 Aidarex Pharmaceuticals LLC

No Title 1572452656 ⮝

Rx only

Prescribing Information

Dosage And Administration(see Table Below)  ⮝

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.

Epilepsy (see INDICATIONS AND USAGE)

Adults and children over 12 years of age-Initial: 200 mg twice a day for tablets (400 mg/day). Increase at weekly intervals by adding up to 200 mg/day using a three times a day or four times a day regimen of carbamazepine tablets until the optimal response is obtained. Dosage generally should not exceed 1,000 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: 100 mg twice a day for tablets (200 mg/day). Increase at weekly intervals by adding up to 100 mg/day using a three times a day or four times a day regimen of carbamazepine tablets until the optimal response is obtained. Dosage generally should not exceed 1,000 mg daily. Maintenance: Adjust dosage to the minimum effective level, usually 400 to 800 mg daily.

Children under 6 years of age-Initial: 10 to 20 mg/kg/day twice a day or three times a day as tablets. 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, 100 mg twice a day for tablets 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, 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 for Tablets

Indication	Initial Dose	Subsequent Dose	Maximum Daily Dose
Epilepsy Under 6 yr	10 to 20 mg/kg/day twice a day or 3 times a day	Increase weekly to achieve optimal clinical response, 3 times a day or 4 times a day	35 mg/kg/24 hr (see Dosage and Administration section above)
6 to 12 yr	100 mg twice a day (200 mg/day)	Add up to 100 mg/day at weekly intervals, 3 times a day or 4 times a day	1000 mg/24 hr
Over 12 yr	200 mg twice a day (400 mg/day)	Add up to 200 mg/day at weekly intervals, 3 times a day or 4 times a day	1000 mg/24 hr (12 to 15 yr) 1200 mg/24 hr (>15 yr) 1600 mg /24 hr (adults, in rare instances)
Trigeminal Neuralgia	100 mg twice a day (200 mg/day)	Add up to 200 mg/day in increments of 100 mg every 12 hr	1200 mg/24 hr

Carbamazepine Tablets, Usp ⮝

8244401/1118
Rx only
Prescribing Information

Packaging Information ⮝

American Health Packaging unit dose blisters (see How Supplied section) contain drug product from Apotex Corp. as follows:
(200 mg / 100 UD) NDC 68084-444-01 packaged from NDC 60505-0183

Distributed by:
American Health Packaging
Columbus, OH 43217

8244401/1118

Package/label Display Panel Carton 200 Mg ⮝

NDC 68084- 444-01

Carbamazepine
Tablets, USP

200 mg

100 Tablets (10 x 10) Rx Only

PHARMACIST: Dispense with the accompanying Medication
Guide to each patient.

Each Tablet Contains:
Carbamazepine .......................................................................200 mg

Usual Dosage: See package insert for full prescribing information.

Do not store above 30 C (86 F). Store in a dry place. Protect from
moisture.

Keep this and all drugs out of reach of children.

FOR YOUR PROTECTION: Do not use if blister is torn or broken.

The drug product contained in this package is from
NDC # 60505-0183, Apotex Corp.

Distributed by:
American Health Packaging
Columbus, Ohio 43217

044401
0244401/1118

Package/label Display Panel Blister 200 Mg ⮝

Carbamazepine
Tablet, USP

200 mg

CARBAMAZEPINE carbamazepine tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:68084-444(NDC:60505-0183) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBAMAZEPINE (UNII: 33CM23913M) (CARBAMAZEPINE - UNII:33CM23913M) CARBAMAZEPINE 200 mg

Inactive Ingredients Ingredient Name Strength CROSCARMELLOSE SODIUM (UNII: M28OL1HH48) MAGNESIUM STEARATE (UNII: 70097M6I30) MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U)

Product Characteristics Color white Score 2 pieces Shape ROUND Size 10mm Flavor Imprint Code APO;200 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:68084-444-01 100 in 1 BOX, UNIT-DOSE 04/03/2014 1 NDC:68084-444-11 1 in 1 BLISTER PACK; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA075948 04/03/2014

Labeler - American Health Packaging (929561009)

Establishment
Name	Address	ID/FEI	Business Operations
American Health Packaging		929561009	repack(68084-444)

Revised: 2/2019 Document Id: 81b2dbfc-6b42-5969-e053-2a91aa0ae849 34391-3 Set id: 1dd3d934-efee-4fdb-ae6f-f47b61831a2e Version: 4 Effective Time: 20190212 American Health Packaging

No Title 1572454771 ⮝

Rx Only

Dosage And Administration (see Table Below) ⮝

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.

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., b.i.d. tablets to t.i.d. suspension).

Epilepsy (SEE INDICATIONS AND USAGE)

Adults and children over 12 years of age -Initial: 200 mg b.i.d. Increase at weekly intervals by adding up to 200 mg/day using a t.i.d. or q.i.d. regimen until the optimal response is obtained. Dosage generally should not exceed 1000 mg daily in children 12-15 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 800-1200 mg daily.

Children 6-12 years of age -Initial: 100 mg b.i.d. Increase at weekly intervals by adding up to 100 mg/day using a t.i.d. or q.i.d. regimen until the optimal response is obtained. Dosage generally should not exceed 1000 mg daily. Maintenance: Adjust dosage to the minimum effective level, usually 400-800 mg daily.

Children under 6 years of age -Initial: 10-20 mg/kg/day b.i.d. or t.i.d. Increase weekly to achieve optimal clinical response administered t.i.d. or q.i.d. 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 Category D).

Trigeminal Neuralgia (SEE INDICATIONS AND USAGE)

Initial: On the first day, 100 mg b.i.d. 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 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 400-800 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

* Tablet = Chewable or conventional tablets
	Initial Dose	Subsequent Dose	Maximum Daily Dose
Indication	Tablet*	Tablet*	Tablet*
Epilepsy Under 6 yr	10-20 mg/kg/day b.i.d. or t.i.d.	Increase weekly to achieve optimal clinical response, t.i.d. or q.i.d.	35 mg/kg/24 hr. (See Dosage and Administration section above)
6-12 yr	100 mg b.i.d. (200 mg/day)	Add up to 100 mg/day at weekly intervals, t.i.d. or q.i.d.	1000 mg/24 hr.
Over 12 yr	200 mg b.i.d. (400 mg/day)	Add up to 200 mg/day at weekly intervals, t.i.d. or q.i.d.	1000 mg/24 hr. (12-15 yr) 1200 mg/24 hr. (>15 yr) 1600 mg/24 hr. (adults, in rare instances)
Trigeminal Neuralgia	100 mg b.i.d. (200 mg/day)	Add up to 200 mg/day in increments of 100 mg every 12 hr.	1200 mg/24 hr.

No Title 1572454772 ⮝

Manufactured by:

TORRENT PHARMACEUTICALS LTD., Indrad-382 721, Dist. Mehsana, INDIA.

For:

TORRENT PHARMA INC., 5380 Holiday Terrace, Suite 40, Kalamazoo, Michigan 49009.

8018789 Revised October 2009

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

No Title 1572456270 ⮝

CARBAMAZEPINE carbamazepine tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:64725-4005(NDC:51672-4005) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Carbamazepine (UNII: 33CM23913M) (Carbamazepine - UNII:33CM23913M) Carbamazepine 200 mg

Inactive Ingredients Ingredient Name Strength STARCH, CORN (UNII: O8232NY3SJ) CROSCARMELLOSE SODIUM (UNII: M28OL1HH48) DIETHYL PHTHALATE (UNII: UF064M00AF) MAGNESIUM STEARATE (UNII: 70097M6I30) CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)

Product Characteristics Color WHITE Score 2 pieces Shape ROUND Size 9mm Flavor Imprint Code TARO;11 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:64725-4005-1 100 in 1 BOTTLE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA074649 10/03/1996

Labeler - TYA Pharmaceuticals (938389038)

Registrant - TYA Pharmaceuticals (938389038)

Establishment
Name	Address	ID/FEI	Business Operations
TYA Pharmaceuticals		938389038	RELABEL(64725-4005) , REPACK(64725-4005)

Revised: 4/2013 Document Id: bd525ac0-d234-4a1d-936a-7c485882b41f 34391-3 Set id: 19fa8a00-51a0-4f8f-8060-45f7053ceb29 Version: 2 Effective Time: 20130423 TYA Pharmaceuticals

No Title 1572456526 ⮝

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.

Label Image (apotex) 200mg ⮝

CARBAMAZEPINE carbamazepine tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:53808-0913(NDC:51672-4041) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBAMAZEPINE (UNII: 33CM23913M) (CARBAMAZEPINE - UNII:33CM23913M) CARBAMAZEPINE 100 mg

Inactive Ingredients Ingredient Name Strength LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X) CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U) HYPROMELLOSE (UNII: 3NXW29V3WO) ETHYLCELLULOSE (UNII: 7Z8S9VYZ4B) CROSCARMELLOSE SODIUM (UNII: M28OL1HH48) MAGNESIUM STEARATE (UNII: 70097M6I30)

Product Characteristics Color WHITE Score 2 pieces Shape ROUND Size 10mm Flavor Imprint Code TARO;16 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:53808-0913-1 30 in 1 BLISTER PACK

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA074649 07/01/2009

CARBAMAZEPINE carbamazepine tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:53808-0916(NDC:51672-4005) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBAMAZEPINE (UNII: 33CM23913M) (CARBAMAZEPINE - UNII:33CM23913M) CARBAMAZEPINE 200 mg

Inactive Ingredients Ingredient Name Strength LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X) CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U) HYPROMELLOSE (UNII: 3NXW29V3WO) ETHYLCELLULOSE (UNII: 7Z8S9VYZ4B) CROSCARMELLOSE SODIUM (UNII: M28OL1HH48) MAGNESIUM STEARATE (UNII: 70097M6I30)

Product Characteristics Color WHITE Score 2 pieces Shape ROUND Size 10mm Flavor Imprint Code TARO;11 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:53808-0916-1 30 in 1 BLISTER PACK

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA074649 07/01/2009

CARBAMAZEPINE carbamazepine tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:53808-0915(NDC:60505-0183) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBAMAZEPINE (UNII: 33CM23913M) (CARBAMAZEPINE - UNII:33CM23913M) CARBAMAZEPINE 200 mg

Inactive Ingredients Ingredient Name Strength LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X) CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U) HYPROMELLOSE (UNII: 3NXW29V3WO) ETHYLCELLULOSE (UNII: 7Z8S9VYZ4B) CROSCARMELLOSE SODIUM (UNII: M28OL1HH48) MAGNESIUM STEARATE (UNII: 70097M6I30)

Product Characteristics Color WHITE Score 2 pieces Shape ROUND Size 10mm Flavor Imprint Code APO;200 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:53808-0915-1 30 in 1 BLISTER PACK

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA075948 07/01/2009

Labeler - State of Florida DOH Central Pharmacy (829348114)

Establishment
Name	Address	ID/FEI	Business Operations
State of Florida DOH Central Pharmacy		829348114	repack

Revised: 5/2010 Document Id: 18def499-cbff-49a0-bdf7-dd5d38fc6f01 34391-3 Set id: 6903e7ef-8b5c-4b64-a87d-62f1f102bc75 Version: 1 Effective Time: 20100520 State of Florida DOH Central Pharmacy

Carbamazepine Tablets Usp 200 Mgrx Only ⮝

1233

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 TABLETS USP, 200 MG. 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.

Drug Interactions ⮝

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

CYP 3A4 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: cimetidine, danazol, diltiazem, macrolides, erythromycin, troleandomycin, clarithromycin, fluoxetine, fluvoxamine, nefazodone, loratadine, terfenadine, isoniazid, niacinamide, nicotinamide, propoxyphene, azoles (e.g., ketoconazole, itraconazole, fluconazole), acetazolamide, verapamil, grapefruit juice, protease inhibitors, valproate.*

CYP 3A4 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, rifampin, phenobarbital, phenytoin, primidone, methsuximide, theophylline.

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.

* increased levels of the active 10,11-epoxide

decreased levels of carbamazepine and increased levels of the 10,11-epoxide

Effect of Carbamazepine on Plasma Levels of Concomitant Agents

Increased levels: clomipramine HCl, phenytoin, primidone.

Carbamazepine induces hepatic CYP activity. Carbamazepine causes, or would be expected to cause, decreased levels of the following:

acetaminophen, alprazolam, dihydropyridine calcium channel blockers (e.g., felodipine), cyclosporine, corticosteroids (e.g., prednisolone, dexamethasone), clonazepam, clozapine, dicumarol, doxycycline, ethosuximide, haloperidol, itraconazole, lamotrigine, levothyroxine, methadone, methsuximide, midazolam, olanzapine, oral and other hormonal contraceptives, oxcarbazepine, phensuximide, phenytoin, praziquantel, protease inhibitors, risperidone, theophylline, tiagabine, topiramate, tramadol, tricyclic antidepressants (e.g., imipramine, amitriptyline, nortriptyline), valproate, warfarin,ziprasidone, zonisamide.

In concomitant use with Carbamazepine, dosage adjustment of the above agents may be necessary.

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

Co-administration of carbamazepine with nefazodone results in insufficient plasma concentrations of nefazodone and its active metabolite to achieve a therapeutic effect. Co-administration of carbamazepine with nefazodone is contraindicated. (See CONTRAINDICATIONS).

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.

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

Pregnancy Category D (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 breast feeding 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.

Package Label Principal Display Panel ⮝

CARBAMAZEPINE carbamazepine tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:21695-724(NDC:0093-0109) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBAMAZEPINE (UNII: 33CM23913M) (CARBAMAZEPINE - UNII:33CM23913M) CARBAMAZEPINE 200 mg

Inactive Ingredients Ingredient Name Strength DIETHYL PHTHALATE (UNII: UF064M00AF) CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U) STARCH, CORN (UNII: O8232NY3SJ) CROSCARMELLOSE SODIUM (UNII: M28OL1HH48) MAGNESIUM STEARATE (UNII: 70097M6I30)

Product Characteristics Color WHITE Score 2 pieces Shape ROUND Size 9mm Flavor Imprint Code TARO;11 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:21695-724-30 30 in 1 BOTTLE 2 NDC:21695-724-60 60 in 1 BOTTLE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA074649 07/01/2009

Labeler - Rebel Distributors Corp (118802834)

Establishment
Name	Address	ID/FEI	Business Operations
Rebel Distributors Corp		118802834	RELABEL, REPACK

Revised: 1/2011 Document Id: fc51bad7-8a77-4c0e-9ff8-fa3474796d35 34391-3 Set id: 25cca2b1-9020-4d8a-bc22-b8063e57f9e1 Version: 2 Effective Time: 20110104 Rebel Distributors Corp