TEGretol-XR

• It is used to treat seizures.
• It is used to treat pain caused by a problem with a nerve in the face.
• It may be given to you for other reasons. Talk with the doctor.

• If you have an allergy to carbamazepine or any other part of Tegretol XR.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have had any of these health problems: Bone marrow disease or porphyria.
• If you are taking any of these drugs: Boceprevir, delavirdine, efavirenz, etravirine, nefazodone, nevirapine, rilpivirine, or another drug that has carbamazepine in it.
• If you have taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for Parkinson's disease like selegiline or rasagiline in the last 14 days. Taking this medicine within 14 days of those drugs can cause very bad high blood pressure.
• If you are breast-feeding or plan to breast-feed.

This is not a list of all drugs or health problems that interact with Tegretol XR.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Dizziness.
• Feeling sleepy.
• Upset stomach or throwing up.
• Dry mouth.
• Hard stools (constipation).
• Feeling very tired or weak.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• Store at room temperature.
• Protect from light.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time this medicine is refilled. If you have any questions about Tegretol XR, please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Tegretol XR. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Tegretol XR.

Review Date: October 4, 2017

Carbamazepine is used to treat certain types of seizures (epilepsy). It is also used to relieve pain due to trigeminal neuralgia (tic douloureux) and in the treatment of bipolar disorder (manic-depressive illness). Carbamazepine works in the brain and nervous system to control seizures, pain, and bipolar disorder. This medicine is an anticonvulsant.

This medicine is available only with your doctor's prescription.

This section provides information on the proper use of a number of products that contain carbamazepine. It may not be specific to Tegretol-XR. Please read with care.

Take this medicine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects.

This medicine comes with a Medication Guide Read and follow the instructions carefully. Ask your doctor if you have any questions.

Carbamazepine should be taken with meals to lessen the chance of stomach upset (nausea and vomiting).

Carbamazepine extended-release capsules do not need to be taken with meals unless they upset your stomach. The contents of the extended-release capsules may be sprinkled over a teaspoon of applesauce or other similar food. The capsule or its contents should not be crushed or chewed.

The extended-release tablets must be swallowed whole and should not be crushed or chewed. Do not take extended-release tablets that are damaged or have chips or cracks.

Grapefruit and grapefruit juice may increase the effects of this medicine by increasing the amount in the body. You should not eat grapefruit or drink grapefruit juice while you are taking this medicine.

If you are taking this medicine for pain relief:

• Carbamazepine is not an ordinary pain reliever. It should be used only when a doctor prescribes it for certain kinds of pain. Do not take carbamazepine for any other aches or pains.

If you are taking Tegretol® oral suspension:

• Shake the oral suspension well before each use. Measure your dose with a marked measuring spoon, oral syringe, or medicine cup. The average household teaspoon may not hold the right amount of liquid.
• Do not take any other liquid medicines at the same time that you take your dose of Tegretol® without first checking with your doctor.

Tegretol® tablets works differently than Tegretol® oral suspension, even at the same dose (number of milligrams). Do not switch from the tablets to the oral suspension unless your doctor tells you to.

Tegretol® may be used alone or together with other seizure medicines. Ask your doctor first before taking any other seizure medicine together with Tegretol®.

Do not take Equetro® capsules if you are also using Tegretol® suspension or tablets. These medicines should not be taken together because both medicines contains carbamazepine. Ask your doctor if you have any questions.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (extended-release capsules):
  • For bipolar disorder:
    • Adults—At first, 200 milligrams (mg) two times a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 1600 mg per day.
    • Children—Use and dose must be determined by your doctor.
  • For epilepsy:
    • Adults and children 12 years of age and older—At first, 200 milligrams (mg) two times a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 500 to 800 mg two times a day.
    • Children younger than 12 years of age—Dose is based on body weight and must be determined by your doctor. However, the dose is usually not more than 1000 mg per day.
  • For trigeminal neuralgia:
    • Adults—At first, 200 milligrams (mg) once a day. Your doctor may increase your dose as needed and tolerated. However, the dose is usually not more than 1200 mg per day.
    • Children—Use and dose must be determined by your doctor.
• For oral dosage form (extended-release tablets):
  • For epilepsy:
    • Adults—At first, 200 mg two times a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 1000 to 1600 mg per day.
    • Children 6 to 12 years of age—At first, 100 mg two times a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 1000 mg per day.
    • Children younger than 6 years of age—Use and dose must be determined by your doctor.
  • For trigeminal neuralgia:
    • Adults—At first, 100 milligrams (mg) two times a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 1200 mg per day.
    • Children—Use and dose must be determined by your doctor.
• For oral dosage form (suspension):
  • For epilepsy:
    • Adults—100 milligrams (mg) or 1 teaspoon four times a day (400 mg per day). Your doctor may adjust your dose if needed. However, the dose is usually not more than 1000 to 1600 mg per day.
    • Children 6 to 12 years of age—At first, 50 milligrams (mg) or one-half teaspoon four times a day (200 mg per day). Your doctor may adjust your dose if needed. However, the dose is usually not more than 1000 mg per day.
    • Children younger than 6 years of age—Dose is based on body weight and will be determined by your doctor. The dose is 10 to 20 milligrams (mg) per kilogram (kg) of body weight per day, taken four times a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 35 mg per kg of body weight per day.
  • For trigeminal neuralgia:
    • Adults—At first, 50 milligrams (mg) or one-half teaspoon four times a day (200 mg per day). Your doctor may adjust your dose if needed. However, the dose is usually not more than 1200 mg per day.
    • Children—Use and dose must be determined by your doctor.
• For oral dosage forms (tablets or chewable tablets):
  • For epilepsy:
    • Adults—At first, 200 milligrams (mg) two times a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 1000 to 1600 mg per day.
    • Children 6 to 12 years of age—At first, 100 mg two times a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 1000 mg per day.
    • Children younger than 6 years of age—Dose is based on body weight and will be determined by your doctor. The dose is 10 to 20 milligrams (mg) per kilogram (kg) of body weight per day, taken two or three times a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 35 mg per kg of body weight per day.
  • For trigeminal neuralgia:
    • Adults and teenagers—At first, 100 milligrams (mg) two times a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 1200 mg per day.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Applies to carbamazepine: oral capsule extended release, oral suspension, oral tablet, oral tablet chewable, oral tablet extended release

Other dosage forms:

• intravenous solution

Along with its needed effects, carbamazepine (the active ingredient contained in Tegretol XR) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking carbamazepine:

• Blurred vision or double vision
• continuous back-and-forth eye movements

• Actions that are out of control
• behavioral changes (especially in children)
• confusion, agitation, or hostility (especially in the elderly)
• diarrhea (severe)
• discouragement
• drooling
• fear
• feeling of unreality
• feeling sad or empty
• headache (continuing)
• increase in seizures
• irritability
• lack of appetite
• loss of balance control
• loss of interest or pleasure
• muscle trembling, jerking, or stiffness
• nausea and vomiting (severe)
• other problems with muscle control or coordination
• sense of detachment from self or body
• shakiness and unsteady walk
• shuffling walk
• stiffness of the limb
• sudden, wide mood swings
• talking, feeling, and acting with excitement
• thoughts or attempts of killing oneself
• tiredness
• trouble concentrating
• trouble sleeping
• twisting movements of the body
• uncontrolled movements, especially of the face, neck, and back
• unusual drowsiness

• Black, tarry stools
• blood in the urine or stools
• bone or joint pain
• chest pain
• cough or hoarseness
• darkening of the urine
• difficulty with speaking or slurred speech
• fainting
• frequent urination
• irregular, pounding, or unusually slow heartbeat
• lower back or side pain
• mental depression with restlessness and nervousness or other mood or mental changes
• muscle or stomach cramps
• nosebleeds or other unusual bleeding or bruising
• numbness, tingling, pain, or weakness in the hands and feet
• pain, tenderness, swelling, or bluish color in the leg or foot
• painful or difficult urination
• pale stools
• pinpoint red spots on the skin
• rapid weight gain
• rigidity
• ringing, buzzing, or other unexplained sounds in the ears
• skin rash, hives, or itching
• sore throat, chills, and fever
• sores, ulcers, or white spots on the lips or in the mouth
• swelling of the face, hands, feet, or lower legs
• swollen or painful glands
• sudden decrease in the amount of urine
• tightness in the chest
• trembling
• troubled breathing
• uncontrolled body movements
• unusual tiredness or weakness
• visual hallucinations (seeing things that are not there)
• yellow eyes or skin

Some side effects of carbamazepine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Dizziness (mild)
• drowsiness (mild)
• lightheadedness
• nausea or vomiting (mild)

• Accidental injury
• aching joints or muscles
• acid or sour stomach
• back pain
• belching
• constipation
• diarrhea
• dryness of the mouth
• headache
• heartburn
• increased sensitivity of the skin to sunlight (skin rash, itching, redness or other discoloration of the skin, or severe sunburn)
• increased sweating
• indigestion
• irritation or soreness of the tongue or mouth
• lack or loss of strength
• loss of hair
• loss of memory
• problems with memory
• sexual problems in males
• sleepiness
• stomach pain, upset, or discomfort

Applies to carbamazepine: compounding powder, intravenous solution, oral capsule extended release, oral suspension, oral tablet, oral tablet chewable, oral tablet extended release

Gastrointestinal

Very common (10% or more): Nausea (29%), vomiting (18%), constipation (10%)
Very rare (less than 0.01%): Colitis, glossitis, stomatitis, pancreatitis
Frequency not reported: Dryness of the mouth, with suppositories occasional rectal irritation may occur, diarrhea, oral ulceration
Postmarketing reports: Gastric distress, abdominal pain, anorexia[Ref]

A single case of chemical pancreatitis has been reported in association with carbamazepine intoxication.[Ref]

Endocrine

Carbamazepine increases the rate of T4 and T3 metabolism and may lead to hypothyroidism in patients with hypothyroidism who are being treated with T4. Carbamazepine may also cause a 20% to 40% decrease in serum total and free T4 concentrations and a smaller decrease in serum total and free T3 concentrations in patients who have no thyroid disease.

Chronic administration of carbamazepine (the active ingredient contained in Tegretol XR) may increase total cholesterol and HDL cholesterol levels. Carbamazepine may also transiently increase serum triglyceride and LDL cholesterol levels. One study has suggested that demeclocycline may be useful in prophylaxis of carbamazepine-induced hyponatremia.[Ref]

Very rare (less than 0.01%): Increase in prolactin (with or without symptoms such as gynecomastia or galactorrhea), impaired male fertility and/or abnormal spermatogenesis, abnormal thyroid function tests (e.g., decreased L-thyroxine [FT4, T4, T3] and increased TSH)
Frequency not reported: Hyponatremia, pancreatitis, lower serum testosterone, lower free androgen indexes, increased cerebrospinal fluid thyrotropin-releasing hormone levels[Ref]

Hematologic

Very common (10% or more): Leucopenia
Common (1% to 10%): Eosinophilia, thrombocytopenia, neutropenia
Rare (0.01% to 0.1%): Leukocytosis, lymphadenopathy, folic acid deficiency
Very rare (less than 0.01%): Agranulocytosis, aplastic anemia, pure red cell aplasia, megaloblastic anemia, acute intermittent porphyria, reticulocytosis, hemolytic anemia
Frequency not reported: Aplastic anemia, pancytopenia, bone marrow depression, leukopenia, thrombophlebitis, thromboembolism, adenopathy[Ref]

Thrombocytopenia is the most common hematologic effect of carbamazepine and may be either mild and transient or severe. Significant decreases in white blood cell counts may occur although the values may still be within the normal range. Often counts will return to baseline during continued therapy, and therefore, discontinuation of carbamazepine may not be necessary. Dose reductions may also result in normalization of white blood cell counts. Aplastic anemia has been reported (although many of the reported cases had confounding exposures to other medications). The manufacturer reports an incidence of 2 per 1,000,000 patients for aplastic anemia and 6 per 1,000,000 patients for agranulocytosis. Cases of reticulocytosis have been reported rarely in association with carbamazepine therapy as well. In addition, cases of hemolytic anemia and erythroid arrest have been reported.

Both humoral and nonimmune mechanisms have been implicated in the etiology of carbamazepine-induced bone marrow suppression.[Ref]

Cardiovascular

Rare (0.01% to 0.1%): Disturbances of cardiac conduction
Very rare (less than 0.01%): Bradycardia, arrhythmias, AV-block with syncope, collapse, congestive heart failure, hypertension or hypotension, aggravation of coronary artery disease, thrombophlebitis, thromboembolism[Ref]

Most of the cases of cardiovascular effects reported have occurred in patients receiving carbamazepine for trigeminal neuralgia. The reported effects included congestive heart failure, edema, hypotension, syncope and arrhythmias. In general, the doses were titrated quickly because of severe pain. Many of the doses were higher than those used to treat epilepsy. Many of the reported cardiovascular effects resolved after discontinuation of carbamazepine.

Increased sympathetic activity in the setting of seizure-induced hypoxia could predispose a patient to sudden unexpected death in epilepsy (SUDEP).[Ref]

Nervous system

Very common (10% or more): Dizziness (44%), somnolence (32%), ataxia (15%) Common (1% to 10%): Headache, tremor, vertigo
Uncommon (0.1% to 1%): Abnormal involuntary movements (tremor, asterixis, dystonia, tics)
Rare (less than 0.1%): Choreoathetotic disorders, orofacial dyskinesia, oculomotor disturbances, speech disorders (e.g., dysarthria or slurred speech), peripheral neuritis, paresthesia, paretic symptoms, neuroleptic malignant syndrome
Frequency not reported: Drowsiness, fatigue, fever and chills[Ref]

Rigidity and oculogyric crises have been reported. Euphoria has also been reported and has led to abuse of carbamazepine in some patients. Impairment of psychomotor function has been noted in association with use of the liquid suspension of carbamazepine. Additionally, impaired cognition, exacerbations of focal seizures and asterixis have been reported in association with carbamazepine treatment. One case of a lingual-facial-buccal extrapyramidal reaction has also been described.

One study has suggested that gradual withdrawal of carbamazepine over ten days results in significantly fewer generalized tonic-clonic seizures compared to rapid withdrawal over four days.

One study has suggested that the epoxide metabolite of carbamazepine may be responsible for the occasional occurrence of seizure exacerbations in patients receiving carbamazepine.[Ref]

Hypersensitivity

Rare (0.01% to 0.1%): A delayed multi-organ hypersensitivity disorder (of serum sickness type) with fever, skin rashes, vasculitis, lymphadenopathy, disorders mimicking lymphoma, arthralgia, leucopenia, eosinophilia, hepato-splenomegaly and abnormal liver function tests, occurring in various combinations, other organs may also be affected (e.g., lungs, kidneys, pancreas, myocardium, colon)
Very rare (less than 0.01%): Aseptic meningitis (with myoclonus and peripheral eosinophilia), anaphylactic reaction, angioedema
Frequency not reported: Multiorgan hypersensitivity reactions occurring days, weeks, or months after initiating treatment[Ref]

Rash and pruritus often resolve after discontinuation of carbamazepine therapy. Both cases of lupus-like syndrome resolved after discontinuation of carbamazepine. Stevens-Johnson syndrome, erythema multiforme, and a mononucleosis-like syndrome have also been reported.[Ref]

Hepatic

Very common (10% or more): Elevated gamma-GT (due to hepatic enzyme induction) usually not clinically relevant
Common (1% to 10%): Elevated alkaline phosphatase
Uncommon (0.1% to 1%): Elevated transaminases
Rare (0.01% to 0.1%): Cholestatic and hepatocellular jaundice, hepatitis of cholestatic, parenchymal (hepatocellular), or mixed type
Very rare (less than 0.01%): Granulomatous hepatitis, hepatic failure
Frequency not reported: Liver function test abnormalities, variegate porphyria, porphyria cutanea tarda[Ref]

Alterations in liver function tests may progress to hepatotoxicity including cholangitis, granuloma formation, fever and hepatocellular necrosis. Discontinuation of carbamazepine often results in improvement in laboratory abnormalities and liver injury.[Ref]

Renal

Very rare (less than 0.01%): Interstitial nephritis, renal failure, renal dysfunction (including albuminuria, hematuria, oliguria, and elevated BUN/azotemia)[Ref]

Respiratory

Very rare (less than 0.01%): Pulmonary hypersensitivity (characterized by fever, dyspnea, pneumonitis or pneumonia), pulmonary embolism[Ref]

Dermatologic

Very common (10% or more): Allergic skin reactions, urticaria
Common (1% to 10%): Pruritus, rash, paresthesia
Uncommon (0.1% to 1%): Exfoliative dermatitis, erythroderma
Rare (0.01% to 0.1%): Systemic lupus erythematosus-like syndrome
Very rare (less than 0.01%): Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), photosensitivity, erythema multiforme, erythema nodosum, alterations in skin pigmentation, purpura, acne, sweating, alopecia, hirsutism, unusual bruising, pruritic and erythematous rashes, diaphoresis, onychomycosis, dermatitis
Frequency not reported: Psoriasiform eruption[Ref]

Dangerous, sometimes fatal skin reactions (Stevens Johnson syndrome and toxic epidermal necrolysis), that can be caused by carbamazepine therapy are significantly more common in patients with the human leukocyte antigen (HLA) allele, HLA-B 1502. This allele occurs almost exclusively in patients with ancestry across broad areas of Asia, including South Asian Indians. Patients with ancestry from areas in which HLA-B 1502 is present should be screened for the HLA-B 1502 allele before starting treatment with carbamazepine. If these individuals test positive, carbamazepine should not be started unless the expected benefit clearly outweighs the increased risk of serious skin reactions. Patients who have been taking carbamazepine for more than a few months without developing skin reactions are at low risk of these events ever developing from carbamazepine. This is true for patients of any ethnicity or genotype, including patients who test positive for HLA-B 1502.[Ref]

Ocular

Common (1% to 10%): Diplopia, accommodation disorders (blurred vision)
Very rare (less than 0.01%): Lens opacities, conjunctivitis
Postmarketing reports: Diplopia, oculomotor disturbances, nystagmus, photosensitivity, visual hallucinations, scattered punctate cortical lens opacities, overall impairment of the chromatic and achromatic systems, increased intraocular pressure[Ref]

Oncologic

Frequency not reported: Disorders mimicking lymphoma[Ref]

Immunologic

Frequency not reported: Antibody deficiency
Postmarketing reports: Aseptic meningitis (with myoclonus and peripheral eosinophilia)[Ref]

Psychiatric

Common (1% to 10%): Abnormal thinking
Rare (0.01% to 0.1%): Hallucinations (visual or acoustic), depression, loss of appetite, restlessness, aggressive behavior, agitation, confusion, talkativeness
Very rare (less than 0.01%): Activation of psychosis, rebound mania following discontinuation of therapy[Ref]

Genitourinary

Very rare (less than 0.01%): Sexual disturbances/impotence, abnormal spermatogenesis (with decreased sperm count and/or motility)
Frequency not reported: Urinary frequency, acute urinary retention, oliguria with elevated blood pressure, azotemia, albuminuria, glycosuria, elevated BUN, microscopic deposits in the urine[Ref]

Metabolic

Common (1% to 10%): Hyponatremia, fluid retention, edema, weight gain, reduced plasma osmolarity due to an antidiuretic hormone (ADH)-like effect (leading in rare cases to water intoxication accompanied by lethargy)
Very rare (less than 0.01%): Disturbances of bone metabolism (decrease in plasma calcium and 25-OH-cholecalciferol) leading to osteomalacia, elevated cholesterol (including HDL cholesterol), elevated triglycerides[Ref]

Musculoskeletal

Rare (0.01% to 0.1%): Muscle weakness
Very rare (less than 0.01%): Arthralgia
Postmarketing reports: Leg cramps[Ref]

Other

Very rare (less than 0.01%): Taste disturbances, tinnitus, hyperacusis, hypoacusis, changes in pitch perception[Ref]

Some side effects of Tegretol XR may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.