Mezacar Drug Interactions

Cytochrome P450 3A4 (CYP 3A4) is the main enzyme catalysing formation of the active metabolite carbamazepine 10, 11-epoxide. Co-administration of inhibitors of CYP 3A4 may result in increased carbamazepine plasma concentrations which could induce adverse reactions. Co-administration of CYP 3A4 inducers might increase the rate of carbamazepine metabolism, thus leading to potential decreases in the carbamazepine serum level and therapeutic effect. Similarly, discontinuation of a CYP3A4 inducer may decrease the rate of metabolism of carbamazepine, leading to an increase in carbamazepine plasma levels.
Carbamazepine is a potent inducer of CYP3A4 and other phase I and phase II enzyme systems in the liver, and may therefore reduce plasma concentrations of comedications mainly metabolized by CYP3A4 by induction of their metabolism.
Human microsomal epoxide hydrolase has been identified as the enzyme responsible for the formation of the 10,11-transdiol derivative from carbamazepine-10,11 epoxide. Co-administration of inhibitors of human microsomal epoxide hydrolase may result in increased carbamazepine-10,11 epoxide plasma concentrations.
Interactions resulting in a contraindication: The use of Mezacar is contraindicated in combination with monoamine-oxidase inhibitors (MAOIs); before administering Mezacar MAOIs should be discontinued for a minimum of 2 weeks, or longer if the clinical situation permits (see Contraindications).
Agents that may raise carbamazepine plasma levels: Since raised plasma carbamazepine levels may result in adverse reactions (e.g. dizziness, drowsiness, ataxia, diplopia), the dosage of Mezacar should be adjusted accordingly and/or the plasma levels monitored when used concomitantly with the substances described as follows: Analgesics, anti-inflammatory drugs: Dextropropoxyphene.
Androgens: Danazol.
Antibiotics: Macrolide antibiotics (e.g. erythromycin, clarithromycin), ciprofloxacin.
Antidepressants: Fluoxetine, fluvoxamine, paroxetine, trazodone.
Antiepileptics: Vigabatrin.
Antifungals: Azoles (e.g. itraconazole, ketoconazole, fluconazole, voriconazole). Alternative anti-convulsants may be recommended in patients treated with voriconazole or itraconazole.
Antihistamines: Loratadine.
Antipsychotics: Olanzapine.
Antituberculosis: Isoniazid.
Antivirals: Protease inhibitors for HIV treatment (e.g. ritonavir).
Carbonic anhydrase inhibitors: Acetazolamide.
Cardiovascular drugs: Diltiazem, verapamil.
Gastrointestinal drugs: Possibly cimetidine, omeprazole.
Other interactions: Grapefruit juice, nicotinamide (only in high dosage).
Agents that may raise the active metabolite carbamazepine-10, 11-epoxide plasma levels: Since raised plasma carbamazepine-10, 11-epoxide levels may result in adverse reactions (e.g. dizziness, drowsiness, ataxia, diplopia), the dosage of Mezacar should be adjusted accordingly and/or the plasma levels monitored when used concomitantly with the substances described as follows: Quetiapine, primidone, progabide, valproic acid, valnoctamide and valpromide.
Agents that may decrease carbamazepine plasma levels: The dose of Mezacar may have to be adjusted when used concomitantly with the substances described as follows: Antiepileptics: Oxcarbazepine, phenobarbital, phenytoin (to avoid phenytoin intoxication and subtherapeutic concentrations of carbamazepine it is recommended to adjust the plasma concentration of phenytoin to 13 micrograms /mL before adding carbamazepine to the treatment) and fosphenytoin, primidone, and, although the data are partly contradictory, possibly also clonazepam.
Antineoplastics: Cisplatin or doxorubicin.
Antituberculosis: Rifampicin.
Bronchodilatators or anti-asthma drugs: Theophylline, aminophylline.
Dermatological drugs: Isotretinoin.
Other interactions: Herbal preparations containing St John's wort (Hypericum perforatum).
Effect of Carbamazepine on plasma levels of concomitant agents: Carbamazepine may lower the plasma level, diminish or even abolish the activity of certain drugs. The dosage of the following drugs may have to be adjusted to clinical requirement: Analgesics, anti-inflammatory agents: Buprenorphine, methadone, paracetamol (long term administration of carbamazepine and paracetamol (acetaminophen) may be associated with hepatotoxicity), tramadol.
Antibiotics: Doxycycline, rifabutin.
Anticoagulants: Oral anticoagulants (e.g. warfarin and acenocoumarol).
Antidepressants: Bupropion, citalopram, mianserin, sertraline, trazodone, tricyclic antidepressants (e.g. imipramine, amitriptyline, nortriptyline, clomipramine).
Antiemetics: Aprepitant.
Antiepileptics: Clobazam, eslicarbazepine, clonazepam, ethosuximide, lamotrigine, oxcarbazepine, primidone, tiagabine, topiramate, valproic acid, zonisamide. To avoid phenytoin intoxication and subtherapeutic concentrations of carbamazepine it is recommended to adjust the plasma concentration of phenytoin to 13 micrograms /mL before adding carbamazepine to the treatment. There have been rare reports of an increase in plasma mephenytoin levels.
Antifungals: Itraconazole, voriconazole. Alternative anti-convulsants may be recommended in patients treated with voriconazole or itraconazole.
Anthelmintics: Albendazole.
Antineoplastics: Imatinib, cyclophosphamide, lapatinib, temsirolimus.
Antipsychotics: Clozapine, haloperidol and bromperidol, olanzapine, quetiapine, risperidone, aripiprazole, paliperidone.
Antivirals: Protease inhibitors for HIV treatment (e.g. indinavir, ritonavir, saquinavir).
Anxiolytics: Alprazolam.
Bronchodilatators or anti-asthma drugs: Theophylline.
Contraceptives: Hormonal contraceptives (alternative contraceptive methods should be considered).
Cardiovascular drugs: Calcium channel blockers (dihydropyridine group) e.g. felodipine, digoxin, simvastatin, atorvastatin, lovastatin, cerivastatin, ivabradine.
Corticosteroids: Corticosteroids (e.g. prednisolone, dexamethasone).
Drugs used in erectile dysfunction: Tadalafil.
Immunosuppressants: Ciclosporin, everolimus, tacrolimus, sirolimus.
Thyroid agents: Levothyroxine.
Other drug interactions: Products containing oestrogens and/or progesterones.
Combinations that require specific consideration: Concomitant use of carbamazepine and levetiracetam has been reported to increase carbamazepine-induced toxicity.
Concomitant use of carbamazepine and isoniazid has been reported to increase isoniazid-induced hepatotoxicity.
The combination of lithium and carbamazepine may cause enhanced neurotoxicity in spite of lithium plasma concentrations being within the therapeutic range. Combined use of carbamazepine with metoclopramide or major tranquillisers, e.g. haloperidol, thioridazine, may also result in an increase in neurological side-effects.
Concomitant medication with Carbamazepine and some diuretics (hydrochlorothiazide, furosemide) may lead to symptomatic hyponatraemia.
Carbamazepine may antagonise the effects of non-depolarising muscle relaxants (e.g. pancuronium). Their dosage should be raised and patients monitored closely for a more rapid recovery from neuromuscular blockade than expected.
Carbamazepine, like other psychoactive drugs, may reduce alcohol tolerance. It is therefore advisable for the patient to abstain from alcohol.
Interference with serological testing: Carbamazepine may result in false positive perphenazine concentrations in HPLC analysis due to interference.
Carbamazepine and the 10,11-epoxide metabolite may result in false positive tricyclic antidepressant concentration in fluorescence polarized immunoassay method.