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Tegretol-XR (Carbamazepine) - Drug Interactions, Contraindications, Overdosage, etc

 
 



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. (see DOSAGE AND ADMINISTRATION).

Clinically meaningful drug interactions have occurred with concomitant medications and include, but are not limited to, the following:

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, 1100-3750; rats, 3850-4025; rabbits, 1500-2680; guinea pigs, 920.

SIGNS AND SYMPTOMS

The first signs and symptoms appear after 1-3 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 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.

Measures to Reduce Absorption: Activated charcoal, laxatives.

Measures to Accelerate Elimination: Forced diuresis.

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

Respiratory Depression: Keep the airways free; resort, if necessary, to endotracheal intubation, artificial respiration, and administration of oxygen.

Hypotension, Shock: Keep the patient's legs raised and administer a plasma expander. If blood pressure fails to rise despite measures taken to increase plasma volume, use of vasoactive substances should be considered.

Convulsions: Diazepam or barbiturates.

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

Surveillance: Respiration, cardiac function (ECG monitoring), blood pressure, body temperature, pupillary reflexes, and kidney and bladder function should be monitored for several days.

Treatment of Blood Count Abnormalities: If evidence of significant bone marrow depression develops, the following recommendations are suggested: (1) stop the drug, (2) perform daily CBC, platelet, and reticulocyte counts, (3) do a bone marrow aspiration and trephine biopsy immediately and repeat with sufficient frequency to monitor recovery.

Special periodic studies might be helpful as follows: (1) white cell and platelet antibodies, (2)59 Fe-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 AND ADMINISTRATION (see table below)

Tegretol suspension in combination with liquid chlorpromazine or thioridazine results in precipitate formation, and, in the case of chlorpromazine, there has been a report of a patient passing an orange rubbery precipitate in the stool following coadministration of the two drugs. (see PRECAUTIONS, Drug Interactions). Because the extent to which this occurs with other liquid medications is not known, Tegretol suspension should not be administered simultaneously with other liquid medications or diluents.

Monitoring of blood levels has increased the efficacy and safety of anticonvulsants (see PRECAUTIONS, Laboratory Tests). Dosage should be adjusted to the needs of the individual patient. A low initial daily dosage with a gradual increase is advised. As soon as adequate control is achieved, the dosage may be reduced very gradually to the minimum effective level. Medication should be taken with meals.

Since a given dose of Tegretol suspension will produce higher peak levels than the same dose given as the tablet, it is recommended to start with low doses (children 6-12 years: 1/2 teaspoon q.i.d.) and to increase slowly to avoid unwanted side effects.

Conversion of patients from oral Tegretol tablets to Tegretol 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).

Tegretol-XR is an extended-release formulation for twice-a-day administration. When converting patients from Tegretol conventional tablets to Tegretol-XR, the same total daily mg dose of Tegretol-XR should be administered. Tegretol-XR tablets must be swallowed whole and never crushed or chewed. Tegretol-XR tablets should be inspected for chips or cracks. Damaged tablets, or tablets without a release portal, should not be consumed. Tegretol-XR tablet coating is not absorbed and is excreted in the feces; these coatings may be noticeable in the stool.

Epilepsy (see INDICATIONS AND USAGE)

Adults and children over 12 years of age - Initial: Either 200 mg b.i.d. for tablets and XR tablets, or 1 teaspoon q.i.d. for suspension (400 mg/day). Increase at weekly intervals by adding up to 200 mg/day using a b.i.d. regimen of Tegretol-XR or a t.i.d. or q.i.d. regimen of the other formulations 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: Either 100 mg b.i.d. for tablets or XR tablets, or 1/2 teaspoon q.i.d. for suspension (200 mg/day). Increase at weekly intervals by adding up to 100 mg/day using a b.i.d. regimen of Tegretol-XR or a t.i.d. or q.i.d. regimen of the other formulations until the optimal response is obtained. Dosage generally should not exceed 1000 mg daily. Maintenance: Adjust dosage to the minimum effective level, usually 400-800 mg daily.

Children under 6 years of age - Initial: 10-20 mg/kg/day b.i.d. or t.i.d. as tablets, or q.i.d. as suspension. 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: Tegretol 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, either 100 mg b.i.d. for tablets or XR tablets, or 1/2 teaspoon q.i.d. for suspension, for a total daily dose of 200 mg. This daily dose may be increased by up to 200 mg/day using increments of 100 mg every 12 hours for tablets or XR tablets, or 50 mg (1/2 teaspoon) q.i.d. for suspension, only as needed to achieve freedom from pain. Do not exceed 1200 mg daily. Maintenance: Control of pain can be maintained in most patients with 400-800 mg daily. However, some patients may be maintained on as little as 200 mg daily, while others may require as much as 1200 mg daily. At least once every 3 months throughout the treatment period, attempts should be made to reduce the dose to the minimum effective level or even to discontinue the drug.

Dosage Information
Initial Dose Subsequent Dose Maximum Daily Dose
Indication Tablet * XR **/* Suspension Tablet * XR **/* Suspension Tablet * XR **/* Suspension
Epilepsy
Under 6 yr 10-20 mg/kg/day
b.i.d. or t.i.d.
10-20 mg/kg/day
q.i.d.
Increase weekly
to achieve
optimal clinical
response, t.i.d.
or q.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)
35 mg/kg/24 hr
(see DOSAGE
AND ADMINISTRATION
section above)
6-12 yr 100 mg b.i.d.
(200 mg/day)
100 mg b.i.d.
(200 mg/day)
1/2 tsp q.i.d.
(200 mg/day)
Add up to
100 mg/day
at weekly
intervals,
t.i.d. or q.i.d.
Add
100 mg/day
at weekly
intervals,
b.i.d.
Add up to 1 tsp
(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)
200 mg b.i.d.
(400 mg/day)
1 tsp q.i.d.
(400 mg/day)
Add up to
200 mg/day
at weekly
intervals, t.i.d.
or q.i.d.
Add up to
200 mg/day
at weekly
intervals, b.i.d.
Add up to
2 tsp
(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)
100 mg b.i.d. (200 mg/day) 1/2 tsp q.i.d.
(200 mg/day)
Add up to
200 mg/day in increments
of 100 mg
every 12 hr
Add up to
200 mg/day in increments
of 100 mg
every 12 hr
Add up to 2 tsp (200 mg)/day in increments of
50 mg
(1/2 tsp) q.i.d.
1200 mg/24 hr
*Tablet = Chewable or conventional tablets
**/* XR = Tegretol®-XR extended-release tablets

CONTRAINDICATIONS

Tegretol should not be used in patients with a history of previous bone marrow depression, acute intermittent porphyria, hypersensitivity to the drug, or known sensitivity to any of the tricyclic compounds, such as amitriptyline, desip-ramine, imipramine, protriptyline, nortriptyline, etc. Likewise, on theoretical grounds its use with monoamine oxidase 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.

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