indication

For the treatment of epilepsy and pain associated with true trigeminal neuralgia.

pharmacology

Carbamazepine, an anticonvulsant structurally similar to tricyclic antidepressants, is used to treat partial seizures, tonic-clonic seizures, pain of neurologic origin such as trigeminal neuralgia, and psychiatric disorders including manic-depressive illness and aggression due to dementia.

mechanism of action

Carbamazepine inhibits sustained repetitive firing by blocking use-dependent sodium channels. Pain relief is believed to be associated with blockade of synaptic transmission in the trigeminal nucleus and seizure control with reduction of post-tetanic potentiation of synaptic transmission in the spinal cord. Carbamazepine also possesses anticholinergic, central antidiuretic, antiarrhythmic, muscle relaxant, antidepressant (possibly through blockade of norepinephrine release), sedative, and neuromuscular-blocking properties.

toxicity

Mild ingestions cause vomiting, drowsiness, ataxia, slurred speech, nystagmus, dystonic reactions, and hallucinations. Severe intoxications may produce coma, seizures, respiratory depression, and hypotension

biotransformation

Hepatic

half life

25-65 hours

drug interactions

Acenocoumarol: Carbamazepine may decrease the anticoagulant effect of acenocoumarol by decreasing its serum concentration.

Alprazolam: Carbamazepine may decrease the effect of the benzodiazepine, alprazolam.

Aminophylline: Carbamazepine may decrease the serum concentration of aminophylline. Aminophylline may decrease the serum concentration of carbamazepine. Monitor for changes in the therapeutic effect of both agents if concomitant therapy is initiated, discontinued or dose changed.

Amitriptyline: Carbamazepine may decrease the serum concentration of the tricyclic antidepressant, amitriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if carbamazepine is initiated, discontinued or dose changed.

Anisindione: Carbamazepine may decrease the anticoagulant effect of anisindione by decreasing its serum concentration.

Aprepitant: The CYP3A4 inducer, carbamazepine, may decrease the effect of aprepitant.

Aripiprazole: Carbamazepine, a strong CYP3A4 inducer, may decrease the serum concentration of aripiprazole by increasing its metabolism.

Atorvastatin: Carbamazepine, a p-glycoprotein inducer and strong CYP3A4 inducer, may decrease the effect of atorvastatin by increasing its efflux and metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if carbamazepine is initiated, discontinued or dose changed.

Atracurium: Decreases the effect of muscle relaxant

Bupropion: Carbamazepine, a strong CYP2B6 inducer, may increase the metabolism of bupropion. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of bupropion if carbamazepine is initiated, discontinued or dose changed.

Cimetidine: Cimetidine may increase the serum concentration of carbamazepine during the first few days of concomitant therapy. Monitor for changes in the therapeutic and adverse effects of carbamazepine if cimetidine is initiated, discontinued or dose changed.

Clarithromycin: Clarithromycin may decrease the metabolism of carbamazepine. Monitor for changes in the therapeutic or adverse effects of carbamazepine if clarithromycin is initiated, discontinued or dose changed.

Clozapine: Carbamazepine may decrease the serum concentration of clozapine by increasing its metabolism. Concomitant therapy should also be avoided due to increased risk of bone marrow suppression. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of clozapine if carbamazepine is initiated, discontinued or dose changed.

Cyclosporine: Carbamazepine may decrease the therapeutic effect of cyclosporine.

Dabigatran etexilate: P-Glycoprotein inducers such as carbamazepine may decrease the serum concentration of dabigatran etexilate. This combination should be avoided.

Danazol: Danazol may decrease the metabolism of carbamazepine. Monitor for changes in the therapeutic and adverse effects of carbamazepine if danazol is initiated, discontinued or dose changed.

Delavirdine: The anticonvulsant, carbamazepine, decreases the effect of delavirdine.

Desipramine: Carbamazepine may decrease the serum concentration of the tricyclic antidepressant, desipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of desipramine if carbamazepine is initiated, discontinued or dose changed.

Dicumarol: Carbamazepine may decrease the anticoagulant effect of dicumarol by decreasing its serum concentration.

Diltiazem: Carbamazepine may decrease the serum concentration of diltiazem by increasing its metabolism. Diltiazem may increase the serum concentration of carbamazepine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or if dosages are changed.

Doxacurium chloride: Decreases the effect of muscle relaxant

Doxepin: Carbamazepine may decrease the serum concentration of the tricyclic antidepressant, doxepin, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxepin if carbamazepine is initiated, discontinued or dose changed.

Doxycycline: The anticonvulsant, carbamazepine, may decrease the therapeutic effect of doxycycline.

Dyphylline: Carbamazepine may decrease the serum concentration of diphylline. Diphylline may decrease the serum concentration of carbamazepine. Monitor for changes in the therapeutic effect of both agents if concomitant therapy is initiated, discontinued or dose changed.

Erythromycin: The macrolide, erythromycin, may increase the effect of carbamazepine.

Ethinyl Estradiol: Carbamazepine may decrease the contraceptive effect of ethinyl estradiol. Hormonal contraception should not be relied on alone during concomitant therapy with carbamazepine.

Felbamate: Decreased effect of both products

Felodipine: Carbamazepine may increase the metabolism of felodipine. Monitor for changes in the therapeutic and adverse effects of felodipine if carbamazepine is initiated, discontinued or dose changed.

Fluconazole: Fluconazole may increase the therapeutic and adverse effects of carbamazepine.

Fluoxetine: Carbamazepine may decrease the serum concentration of fluoxetine by increasing its metabolism. Fluoxetine may increase the serum concentration of carbamazepine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or doses are changed.

Fluvoxamine: Fluvoxamine increases the effect of carbamazepine

Gefitinib: The CYP3A4 inducer, carbamazepine, may decrease the serum concentration and therapeutic effects of gefitinib.

Haloperidol: Carbamazepine may decrease the serum concentration of haloperidol by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of haloperidol if carbamazepine is initiated, discontinued or dose changed.

Imatinib: Carbamazepine, a strong CYP3A4 inducer, may increase the metabolism of imatinib. Imatinib, a strong CYP3A4 inhibitor, may increase the metabolism of carbamazepine. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or dose changed.

Imipramine: Carbamazepine may decrease the serum concentration of the tricyclic antidepressant, imipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if carbamazepine is initiated, discontinued or dose changed.

Indinavir: Indinavir increases the effect and toxicity of carbamazepine

Isoniazid: Carbamazepine effect is increased as is isoniazid toxicity

Isotretinoin: Isotretinoine decreases the effect of carbamazepine

Itraconazole: Itraconazole may increase the effect of carbamazepine.

Josamycin: The macrolide, josamycin, may increase the effect of carbamazepine.

Ketoconazole: Ketoconazole may increase the effect of carbamazepine.

Lamotrigine: Lamotrigine may increase the adverse effects of carbamazepine by increasing the concentration of its active metabolite, carbamazepine-epoxide. Carbamazepine may decrease the therapeutic effect of lamotrigine by increasing its metabolism. Lamotrigine doses should be adjusted accordingly. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinue or doses are changed.

Levetiracetam: Concomitant therapy may results in additive adverse CNS effects.

Levonorgestrel: Carbamazepine may decrease the contraceptive effect of levonorgestrel.

Lovastatin: Carbamazepine, a p-glycoprotein inducer and strong CYP3A4 inducer, may decrease the effect of lovastatin by increasing its efflux and metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if carbamazepine is initiated, discontinued or dose changed.

Mestranol: This product may cause a slight decrease of contraceptive effect

Methadone: Carbamazepine may decrease the serum level of methadone. Monitor for changes in the therapeutic and adverse effects of methadone if carbamazepine is initiated, discontinued or dose changed.

Methylphenidate: Carbamazepine may decrease the effect of methylphendiate.

Metocurine: Decreases the effect of muscle relaxant

Metronidazole: Metronidazole increases the effect of carbamazepine

Midazolam: Carbamazepine may decrease the effect of the benzodiazepine, midazolam.

Mivacurium: Decrease the effect of muscle relaxant

Nefazodone: Nefazodone increases the effect of carbamazepine

Norethindrone: This product may cause a slight decrease of contraceptive effect

Nortriptyline: Carbamazepine may decrease the serum concentration of the tricyclic antidepressant, nortriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if carbamazepine is initiated, discontinued or dose changed.

Oxtriphylline: Carbamazepine may decrease the serum concentration of oxtriphylline. Oxtriphylline may decrease the serum concentration of carbamazepine. Monitor for changes in the therapeutic effect of both agents if concomitant therapy is initiated, discontinued or dose changed.

Oxybutynin: Oxybutynin may cause carbamazepine toxicity

Pancuronium: Decreases the effect of muscle relaxant

Praziquantel: Markedly lower praziquantel levels

Propoxyphene: Propoxyphene increases the effect of carbamazepine

Quinupristin: This combination presents an increased risk of toxicity

Risperidone: Decreases the effect of risperidone

Ritonavir: Ritonavir increases the effect of carbamazepine

Sertraline: Sertraline increases the effect of carbamazepine

Simvastatin: Carbamazepine, a p-glycoprotein inducer, may decrease the effect of simvastatin by increasing its efflux. Monitor for changes in the therapeutic and adverse effects of simvastatin if carbamazepine is initiated, discontinued or dose changed.

Sunitinib: Possible decrease in sunitinib levels

Tacrolimus: Carbamazepine may decrease the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Carbamazepine therapy is initiated, discontinued or altered.

Telithromycin: Co-administration may cause decreased Telithromycin and increased Carbemazepine plasma concentrations. Consider alternate therapy.

Temsirolimus: Carbamazepine may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.

Theophylline: Carbamazepine may decrease the serum concentration of theophylline. Theophylline may decrease the serum concentration of carbamazepine. Monitor for changes in the therapeutic effect of both agents if concomitant therapy is initiated, discontinued or dose changed.

Ticlopidine: Ticlopidine increases the effect of carbamazepine

Tipranavir: Concomitant use may result in decreased Tipranavir and increased Carbamazepine concentrations.

Topiramate: Carbamazepine may decrease the effectiveness of Topiramate by increase its clearance. Monitor for changes in the therapeutic and adverse effects of Topiramate if Carbamazepine is initiated, discontinued or dose changed. Adverse effects related to CNS depression have also been observed during concomitant therapy.

Tramadol: Carbamazepine may decrease the effect of tramadol by increasing Tramadol metabolism and clearance.

Trazodone: The CYP3A4 inducer, Carbamazepine, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Carbamazepine is initiated, discontinued or dose changed.

Tretinoin: The strong CYP2C8 inducer, Carbamazepine, may increase the metabolism and clearance of oral Tretinoin. Consider alternate therapy to avoid failure of Tretinoin therapy or monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Carbamazepine is initiated, discontinued or dose changed.

Triprolidine: The CNS depressants, Triprolidine and Carbamazepine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.

Troleandomycin: The macrolide, troleandomycin, may increase the effect of carbamazepine.

Tubocurarine: Decreases the effect of muscle relaxant

Valproic Acid: Decreases the effect of valproic acid

Vecuronium: Decreases the effect of muscle relaxant

Verapamil: Verapamil may increase the serum concentration of Carbamazepine by decreasing its metabolism. Monitor for changes in the therapeutic/adverse effects of Carbamazepine if Verapamil is initiated, discontinued or dose changed.

Vilazodone: Carbamazepine may increase the metabolism of Selective Serotonin Reuptake Inhibitors (SSRI). Specifically those agents metabolized via CYP1A2, 2C, and/or 3A4 isoenzymes. Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Carbamazepine. Specifically those SSRIs that inhibit CYP3A4 isoenzymes.

Voriconazole: Carbamazepine may reduce serum concentrations and efficacy of voriconazole likely by increasing its metabolism. Concomitant voriconazole and carbamazepine therapy is contraindicated.

Warfarin: Carbamazepine may decrease the anticoagulant effect of warfarin. Monitor for changes in prothrombin time and therapeutic and adverse effects of warfarin if carbamazepine is initiated, discontinued or dose changed.

Ziprasidone: Increases the effect and toxicity of ziprasidone