TEGRETOL®

PATIENT INFORMATION
TEGRETOL® and TEGRETOL® -XR
(Teg-ret-ol)
(Carbamazepine)

What is Tegretol and how is it used?

Tegretol is a prescription medicine used to treat the symptoms of epilepsy,
trigeminal neuralgia and bipolar mania. Tegretol may be used alone or with other
medications.
Tegretol belongs to a class of drugs called anticonvulsants.

What are the possible side effects of Tegretol?

Tegretol may cause serious side effects including:

Skin rash,
Loss of appetite,
Right-sided upper stomach pain,
Dark urine,
Slow, fast or pounding heartbeats,
Fever,
Chills,
Sore throat,
Mouth sores,
Bleeding gums,
Nosebleeds,
Pale skin,
Easy bruising,
Unusual tiredness,
Lightheadedness,
Shortness of breath,
Headache,
Confusion,
Severe weakness,
Feeling unsteady, and
Increased seizures
Get medical help right away, if you have any of the symptoms listed above.

The most common side effects of Tegretol include:

Dizziness,
Loss of coordination,
Problems with walking,
Nausea,
Vomiting, and
Drowsiness
Tell the doctor if you have any side effect that bothers you or that does not go
away.
DESCRIPTION
Tegretol, carbamazepine USP, is an anticonvulsant and specific analgesic for
trigeminal neuralgia, available for oral administration as chewable tablets of 100
mg, tablets of 200 mg, XR tablets of 100, 200, and 400 mg, and as a suspension of
100 mg/5 mL (teaspoon).

INDICATIONS
Epilepsy
Tegretol is indicated for use as an anticonvulsant drug. Evidence supporting
efficacy of Tegretol 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 Tegretol.
Trigeminal Neuralgia
Tegretol is indicated in the treatment of the pain associated with true trigeminal
neuralgia.
 Dosage Information
Initial Dose Subsequent Dose Maximum Daily Dose

Indicati Suspensi Suspensi

Tablet* XR† Tablet* XR† Tablet* XR† Suspension
on on on

Increase
Increase
weekly
weekly to
to
10-20 achieve 35 mg/kg/24 hr 35 mg/kg/24 hr
Epilepsy 10-20 achieve
mg/kg/d optimal (see DOSAGE AND (see DOSAGE AND
Under 6 mg/kg/da optimal
ay b.i.d. clinical ADMINISTRATION se ADMINISTRATION se
yr y q.i.d. clinical
or t.i.d. response, ction above) ction above)
response
t.i.d. or
, t.i.d. or
q.i.d.
q.i.d.

Add up
Add up to
100 to 100 Add 100
1 tsp (100
100 mg mg % tsp mg/day mg/day
mg)/day
b.i.d. b.i.d. q.i.d. at at
6-12 yr at weekly 1000 mg/24 hr
(200 (200 (200 weekly weekly
intervals,
mg/day) mg/da mg/day) intervals intervals
t.i.d. or
y) , t.i.d. or , b.i.d.
q.i.d.
q.i.d.

Add up
Add up Add up to
200 to 200
to 200 2 tsp (200
200 mg mg 1 tsp mg/day
mg/day mg)/day
Over 12 b.i.d. b.i.d. q.i.d. at 1000 mg/24 hr (12-15 yr) 1200 mg/24 hr ( > 15 yr)
at at weekly
yr (400 (400 (400 weekly 1600 mg/24 hr (adults, in rare instances)
weekly intervals,
mg/day) mg/da mg/day) intervals
intervals t.i.d. or
y) , t.i.d. or
, b.i.d. q.i.d.
q.i.d.

Add up Add up
Add up to
to 200 to 200
100 2 tsp (200
mg/day mg/day
Trigemi 100 mg mg % tsp mg)/day
in in
nal b.i.d. b.i.d. q.i.d. in
increme increme 1200 mg/24 hr
Neuralgi (200 (200 (200 increment
nts of nts of
a mg/day) mg/da mg/day) s of 50
100 mg 100 mg
y) mg (%
every 12 every 12
tsp) q.i.d.
hr hr

*Tablet = Chewable or conventional tablets

†XR = Tegretol-XR extended-release tablets
SIDE EFFECTS
The most frequently observed adverse reactions, particularly during the initial
phases of therapy, are dizziness, drowsiness, unsteadiness, nausea, and vomiting.
To minimize the possibility of such reactions, therapy should be initiated at the
lowest dosage recommended.

The following additional adverse reactions have been reported:

Hemopoietic System
Aplastic anemia, agranulocytosis, pancytopenia, bone marrow depression,
thrombocytopenia, leukopenia, leukocytosis, eosinophilia.

Skin
Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), Acute
Generalized Exanthematous Pustulosis (AGEP), pruritic and erythematous rashes,
urticaria, photosensitivity reactions, alterations in skin pigmentation, exfoliative
dermatitis, erythema multiforme and nodosum, purpura.

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

Liver
Abnormalities in liver function tests, cholestatic and hepatocellular jaundice,
hepatitis, very rare cases of hepatic failure.
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.

Nervous System
Dizziness, drowsiness, disturbances of coordination, confusion, headache, fatigue,
blurred vision, visual hallucinations, transient diplopia, oculomotor disturbances,
nystagmus, speech disturbances, abnormal involuntary movements, peripheral
neuritis and paresthesias, depression with agitation, talkativeness, tinnitus,
hyperacusis, neuroleptic malignant syndrome.

Digestive System
Nausea, vomiting, gastric distress and abdominal pain, diarrhea, constipation,
anorexia, and dryness of the mouth and pharynx, including glossitis and stomatitis.

Musculoskeletal System
Aching joints and muscles, and leg cramps.

Metabolism
Fever and chills. Hyponatremia .Decreased levels of plasma calcium have been
reported. Osteoporosis has been reported.

DRUG INTERACTIONS
There has been a report of a patient who passed an orange rubbery precipitate in
his stool the day after ingesting Tegretol suspension immediately followed by
Thorazine® * solution. Subsequent testing has shown that mixing Tegretol
suspension and chlorpromazine solution (both generic and brand name) as well as
Tegretol suspension and liquid Mellaril® , resulted in the occurrence of this
precipitate. Because the extent to which this occurs with other liquid medications is
not known, Tegretol suspension should not be administered simultaneously with
other liquid medicinal agents or diluents.

PRECAUTIONS
General
Before initiating therapy, a detailed history and physical examination should be
made.
Tegretol should be used with caution in patients with a mixed seizure disorder that
includes atypical absence seizures, since in these patients Tegretol has been
associated with increased frequency of generalized convulsions.
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 Tegretol.
AV heart block, including second-and third-degree block, have been reported
following Tegretol treatment. This occurred generally, but not solely, in patients
with underlying EKG abnormalities or risk factors for conduction disturbances.
Hepatic effects, ranging from slight elevations in liver enzymes to rare cases of
hepatic failure have been reported (see ADVERSE REACTIONS and
PRECAUTIONS, Laboratory Tests). In some cases, hepatic effects may progress
despite discontinuation of the drug. In addition rare instances of vanishing bile duct
syndrome have been reported. This syndrome consists of a cholestatic process with
a variable clinical course ranging from fulminant to indolent, involving the
destruction and disappearance of the intrahepatic bile ducts. Some, but not all,
cases are associated with features that overlap with other immunoallergenic
syndromes such as multiorgan hypersensitivity (DRESS syndrome) and serious
dermatologic reactions. As an example there has been a report of vanishing bile
duct syndrome associated with Stevens-Johnson syndrome and in another case an
association with fever and eosinophilia.

Laboratory Tests
For genetically at-risk patients, 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 Tegretol
administered alone.

OVERDOSE
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).

Signs and Symptoms

The first signs and symptoms appear after 1 to 3 hours. Neuromuscular
disturbances are the most prominent. Cardiovascular disorders are generally
milder, and severe cardiac complications occur only when very high doses (greater
than 60 g) have been ingested.

Respiration: Irregular breathing, respiratory depression.

Cardiovascular System: Tachycardia, hypotension or hypertension, shock,

conduction disorders.

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

deep coma. Convulsions, especially in small children. Motor restlessness, muscular
twitching, tremor, athetoid movements, opisthotonos, ataxia, drowsiness, dizziness,
mydriasis, nystagmus, adiadochokinesia, ballism, psychomotor disturbances,
dysmetria. Initial hyperreflexia, followed by hyporeflexia.

Gastrointestinal Tract: Nausea, vomiting.

Kidneys and Bladder: Anuria or oliguria, urinary retention.
Laboratory Findings: Isolated instances of overdosage have included leukocytosis,
reduced leukocyte count, glycosuria, and acetonuria. EEG may show
dysrhythmias.

Combined Poisoning: When alcohol, tricyclic antidepressants, barbiturates, or

hydantoins are taken at the same time, the signs and symptoms of acute poisoning
with Tegretol 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.

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.

Warning
Diazepam or barbiturates may aggravate respiratory depression (especially in
children), hypotension, and coma. However, barbiturates should not be used if
drugs that inhibit monoamine oxidase have also been taken by the patient either in
overdosage or in recent therapy (within 1 week).

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.

CONTRAINDICATIONS
Tegretol should not be used in patients with a history of previous bone marrow
depression, hypersensitivity to the drug, or known sensitivity to any of the tricyclic
compounds, such as amitriptyline, desipramine, imipramine, protriptyline,
nortriptyline, etc. Likewise, on theoretical grounds its use with monoamine oxidase
(MAO) inhibitors is not recommended. Before administration of Tegretol, MAO
inhibitors should be discontinued for a minimum of 14 days, or longer if the
clinical situation permits.

Coadministration of carbamazepine and nefazodone may result in insufficient

plasma concentrations of nefazodone and its active metabolite to achieve a
therapeutic effect. Coadministration of carbamazepine with nefazodone is
contraindicated.