Note: This document contains side effect information about carbamazepine. Some dosage forms listed on this page may not apply to the brand name Tegretol XR.

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

Serious side effects of Tegretol XR

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:

More common

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

Less common

• 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 (severe)
• other problems with muscle control or coordination
• sense of detachment from self or body
• shakiness and unsteady walk
• shuffling walk
• stiffness of the arm or leg
• 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
• vomiting (severe)

Rare

• Black, tarry stools
• blood in the urine or stools
• bone or joint pain
• chest pain or tightness
• cough
• darkening of the urine
• difficulty with speaking or slurred speech
• fainting
• frequent urination
• hoarseness
• 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
• 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
• trembling
• trouble breathing
• uncontrolled body movements
• unusual tiredness or weakness
• visual hallucinations (seeing things that are not there)
• yellow eyes or skin

Incidence not known

• Blistering, peeling, or loosening of the skin
• chills
• decreased urine output
• dilated neck veins
• extreme tiredness or weakness
• general feeling of discomfort or illness
• irregular breathing
• irregular heartbeat
• joint or muscle pain
• red skin lesions, often with a purple center
• red, irritated eyes
• sore throat
• swelling of the face, fingers, feet, or lower legs
• thickening of bronchial secretions
• unusual bleeding or bruising
• weight gain

Other side effects of Tegretol XR

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:

More common

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

Incidence not known

• Accidental injury
• aching joints or muscles
• back pain
• belching
• constipation
• 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

For Healthcare Professionals

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]

Endocrine

Carbamazepine (the active ingredient contained in Tegretol XR) 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.^[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: 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

Frequency not reported: Edema^[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.^[Ref]

Nervous system

Rigidity and oculogyric crises have been reported. Impairment of psychomotor function has been noted in association with use of the liquid suspension of carbamazepine (the active ingredient contained in Tegretol XR) 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]

Very common (10% or more): Dizziness (44%), somnolence (32%), ataxia (15%)

Common (1% to 10%): Headache, tremor

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, taste disturbances^[Ref]

Hypersensitivity

Rash and pruritus often resolve after discontinuation of carbamazepine (the active ingredient contained in Tegretol XR) 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]

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]

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, hypogammaglobulinemia

Postmarketing reports: Aseptic meningitis (with myoclonus and peripheral eosinophilia)^[Ref]

Psychiatric

Euphoria has also been reported and has led to abuse of carbamazepine (the active ingredient contained in Tegretol XR) in some patients^[Ref]

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

Frequency not reported: Euphoria, abuse^[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%): Elevated cholesterol (including HDL cholesterol), elevated triglycerides^[Ref]

Musculoskeletal

Rare (0.01% to 0.1%): Muscle weakness

Very rare (less than 0.01%): Arthralgia

Frequency not reported: Osteoporosis, disturbances of bone metabolism (decrease in plasma calcium and 25-OH-cholecalciferol) leading to osteomalacia, decreased levels of plasma calcium^[Ref]

Other

Common (1% to 10%): Vertigo

Very rare (less than 0.01%): Tinnitus, hyperacusis, hypoacusis, changes in pitch perception

Frequency not reported: Fever and chills^[Ref]