The following drug interactions and / or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parenthesis where appropriate) - not necessarily inclusive: Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.
Acetaminophen: Risk of hepatotoxicity with single toxic dose or prolonged use of high doses of acetaminophen may be increased, and therapeutic effects of acetaminophen may be decreased in patients taking hepatic enzyme-inducing agents such as carbamazepine.
Adrenocorticoids, glucocorticoid, and mineralocorticoid: Concurrent use may decrease the adrenocorticoid effect because of increased adrenocorticoid metabolism resulting from induction of hepatic microsomal enzymes.
Aminophylline or Oxtriphylline or Theophylline: Concurrent use with carbamazepine may stimulate hepatic metabolism of the xanthines (except dyphylline), resulting in increased theophylline clearance.
Anticoagulants, coumarin or indandione-derivative: Anticoagulant effects may be decreased because of induction of hepatic microsomal enzyme activity, resulting in increased anticoagulant metabolism leading to decreased anticoagulant serum concentration and elimination half-life; dosage adjustments based on monitoring of prothrombin time may be necessary during and after carbamazepine therapy.
Anticonvulsant, hydantoin or Anticonvulsant, succinimide or Barbiturate or Benzodiazepine metabolized via hepatic microsomal enzymes especially clonazepam or Primidone or Valproic acid: Concurrent use with carbamazepine may result in increased metabolism, leading to decreased serum concentrations and reduced elimination half-lives of these medications because of induction of hepatic microsomal enzyme activity; monitoring of blood concentrations as a guide to dosage is recommended, especially when any of these medications or carbamazepine is added to or withdrawn from existing regimen.
Valproic acid causes an increase in the active 10,11-epoxide metabolite of carbamazepine by inhibition of its breakdown product.
In addition, use of carbamazepine in combination with other anticonvulsant has been reported to be associated with an increased risk of congenital defects.
Antidepressants tricyclic or Haloperidol or Loxapine or Maprotiline or Molindone or Phenothiazide or Pimozide or Thioxanthenes: Concurrent use of these agents with carbamazepine may enhance the CNS depressant effects of Carbamazepine, lower the seizure threshold and decrease the anticonvulsant effect of carbamazepine; dosage adjustment may be necessary to control seizures; anticholinergic effects may be potentiated, leading to confusion and delirium.
Also, concurrent use of haloperidol, and possibly other neuroleptics with carbamazepine may decrease plasma concentration of the neuroleptic by about 60% with or without adverse clinical effects; close observation of patient for clinical signs of ineffectiveness of the neuroleptic is recommended; dosage adjustment may be necessary.
Carbonic anhydrase inhibitors: Concurrent use may increase the risk of carbamazepine-induced osteopenia; it is recommended that patients receiving concurrent therapy be monitored for early signs or osteopenia and that the carbonic anhydrase inhibitor be discontinued and appropriate treatment initiated is necessary.
Chlorpropamide or Clofibrate or Desmopressin or Lypressin or Posterior pituitary or Thiazide diuretics (when used for their paradoxical antidiuretic activity in the treatment of diabetes insipidus) or Vasopressin: Concurrent use with carbamazepine may potentiate the antidiuretic effect, leading to a lower sodium concentration and causing adverse effects that include increased seizure activity; a reduction in dosage of either or both medication may be necessary for optimal therapeutic effect in the treatment of diabetes insipidus.
Cimetidine: Concurrent use may result in increased plasma concentration of carbamazepine by delaying its clearance, leading to carbamazepine toxicity.
Contraceptive, estrogen-containing oral, or Cyclosporine, or Decarbazine, or Digitalis glycosides with the possible exception of digoxin, or Disopyramide, or Estrogen including estramustine, or Levothyroxine, or Maxiletine, or Quinitine: Concurrent use may decrease the effects of these medications because of increased metabolism resulting from induction of hepatic microsomal enzyme activity; dosage adjustment may be necessary.
Patients should be advised to use a non-hormonal method of birth control or an oral contraceptive containing only a progestin.
Danazol, or Diltiazem, or Verapamil: Concurrent use of these agents with carbamazepine may inhibit carbamazepine metabolism, resulting in increased plasma concentration and toxicity.
Carbamazepine toxicity may be delayed for several weeks after initiation of danazol therapy; carbamazepine dosage may need to be reduced.
It is recommended that nifedipine be used as an alternative to verapamil or diltiazem.
Doxycycline: Concurrent use may decrease plasma concentration and elimination half-life of doxycycline because of induction of hepatic microsomal enzyme activity; if concurrent use cannot be avoided, doxycycline plasma concentration or the therapeutic response to doxycycline should be closely monitored and dosage adjustments made as necessary.
Enflurane, or Malothane, or Methoxyflurane: Chronic use of a hepatic enzyme-inducing agent such as carbamazepine prior to anesthesia, leading to an increased risk of hepatotoxicity.
Formation of nephrotoxic metabolites of methoxyflurane may be increased by chronic use of a hepatic enzyme-inducing agent such as carbamazepine prior to anesthesia, leading to increased risk of nephrotoxicity.
Erythromycin or Troleandomycin: Concurrent use of these agents with carbamazepine may inhibit carbamazepine metabolism, resulting in increased plasma concentration and toxicity; it is recommended that an alternative antibiotic to erythromycin or troleandomycin be used.
Influenza virus vaccine: Concurrent use with carbamazepine may inhibit carbamazepine metabolism, resulting in increased plasma concentrations and toxicity; carbamazepine serum concentrations may be increased on days 7 to 14 after influenza virus vaccination; dosage adjustment of carbamazepine based on the patient’s clinical status and serum concentration may be necessary.
Isoniazid: Carbamazepine may induce microsomal metabolism of isoniazid, increasing formation of a reactive intermediate and leading to hepatotoxicity; also, isoniazid administration may result in elevated plasma concentration of carbamazepine and possible toxicity.
Lithium: Concurrent use may decrease the antidiuretic effect of carbamazepine and increase the neurotoxic side effects even at nontoxic blood concentration of both lithium and carbamazepine; however, the concurrent use of lithium with carbamazepine may be synergistic in the treatment of patients with manic-depressive illness who fail to respond to either drug alone.
Mebendazole: In patients receiving high oral doses of mebendazole for treatment of tissue-dwelling organisms such as Echinococcus mulyocularis or granulosus [Hydatid disease], carbamazepine has been shown to lower plasma mebendazole concentration by induction of hepatic microsomal enzymes and to impair the therapeutic response; if carbamazepine is being used for seizures, replacement with another anticonvulsant is recommended; treatment of intestinal helminthes such as whipworms or hookworms does not appear to be affected by the rate of hepatic metabolism of mebendazole
Monoamine oxidase (MAO) inhibitor, including furazolidone, pargyline and procarbazine: Concurrent use with carbamazepine has resulted hyperpyretic crises, hypertensive crises, severe convulsions, and death; a medication-free interval of at least 14 days is recommended between discontinuing MAO inhibitor therapy and initiating carbamazepine therapy, or vice versa.
MAO inhibitors may also cause a change in the pattern of epileptiform seizures in patients receiving carbamazepine as an anticonvulsant.
Propoxyphene: Concurrent use with carbamazepine may inhibit carbamazepine metabolism, resulting in increased plasma concentration and toxicity; it is recommended that an alternative analgesic to propoxyphene be used.