Anticonvulsant drug interactions

Loiseau P. Treatment of concomitant illnesses in patients receiving anticonvulsants drug interactions of clinical significance. Drug Safety 1998 19 495-510. 

Perucca E and Richens A Anticonvulsant drug interactic is In Tyrer J (ed) The treatment of epilep MTP Lancaster (1980) p 95-128. 

Popli AP, Tanquary J, LampareUa V, MasandPS. Bupropion and anticonvulsant drug interactions. Ann Clin Psychiatry (1995) 7, 99-101. 

I with seizures and require anticonvulsant therapy. Phenytoin is the most frequently used agent, with a loading dose of 15 mg/kg followed by 300 mg by mouth daily (titrated to therapeutic levels between 10 and 20 mcg/mL). Diazepam 5 mg intravenously may be used for rapid control of persistent seizures. Prophylactic anticonvulsants have been used frequently, but a recent meta-analysis did not support their use.23 Thus, because adverse effects and drug interactions are common, the routine use of prophylactic anticonvulsants is not recommended. 

The following drug classes may have a potential drug interaction with nevirapine Antiarrhythmics, anticonvulsants, antifungals, calcium channel blockers, cancer chemotherapy (cyclophosphamide), ergot alkaloids, immunosuppressants, motility agents, opiate agonists. 

Recent drug development studies have centered on the capacity of known antiepileptic drugs (AEDs) to interact with ion channels, and it is now established that several agents appear to be exerting their effects primarily by inhibiting ion channels. Modulation of neuronal sodium channels decreases cellular excitability and the propagation of nerve impulses. Inhibition of sodium channels appears to be a major component of the mechanism of action of several anticonvulsant drugs. 

Carbamazepine also can induce the enzymes that metabolize other anticonvulsant drugs, including phenytoin, primidone, phenobarbital, valproic acid, clonazepam, and ethosuximide, and metabolism of other drugs the patient may be taking. Similarly, other drugs may induce metabolism of carbamazepine the end result is the same as for autoinduction, and the dose of carbamazepine must be readjusted. A common drug-drug interaction is between carbamazepine and the macrolide antibiotics erythromycin and trolean-domycin. After a few days of antibiotic therapy, symptoms of carbamazepine toxicity develop this is readily reversible if either the antibiotic or carbamazepine is discontinued. 

Significant drug-drug interactions are those that potentiate the effects of other agents and require dosage modification. These include certain anticoagulants, hypoglycemic sulfonylureas, and hydantoin anticonvulsants. 

Carbamazepine (CBZ) and divalproex sodium (DVP) are the most common anticonvulsant agents prescribed for adult BD (Bowden et ah, 1994) Post et ah, 1998b) and pediatric epileptic disorders (Trimble, 1990 Dunn et al., 1998). As a consequence of their documented efficacy in these populations, their use has been extended to pediatric behavioral and mood disorders (Biederman et ah, 1998). We review here their mechanisms of action, pharmacokinetics, side effects, and pediatric uses. The multiple cytochrome P450 (CYB)-mediated potential drug interactions of CBZ and DVP are not covered in detail in this chapter. For a comprehensive review of this subjects the reader is referred to a recent publication by Flockhart and Oesterheld (2000). 

As with any other medication prescribing there must be awareness of drug interactions, with important ones for methadone relating to antivirals, psychotropics, anticonvulsants and antibiotics. 

An excellent brief article on buprenorphine treatment has been provided by Taikato et al. (2005), which notes the common possible side-effects (headaches, nausea and vomiting, sweating, constipation, etc.) and drug interactions. The limited central depressant effect of buprenorphine may be compounded by alcohol and antidepressants, while the metabolism of buprenorphine can be enhanced by anticonvulsants, with therefore possibly reduced efficacy. There have been some case reports of liver toxicity from buprenorphine that is reversible if the medication is stopped (Herve et al. 2004), and often clinical guidelines will recommend that liver function tests are included in buprenorphine treatment, as they definitely should be with naltrexone. 

Because most antidepressants require oxidative metabolism as a necessary step in their elimination, they can be the target of a pharmacokinetic drug-drug interaction, as well as the cause. The CYP enzymes mediating the biotransformation of the various antidepressants are also shown in Table 7-30. CYP 1A2 and 3A3/4 are induced by anticonvulsants such as barbiturates and carbamazepine. As expected, coadministration of these anticonvulsants has been shown to lower plasma levels of TCAs and would be predicted to have the same effect on nefazodone, sertraline, and venlafaxine. 

Wilbur K, Ensom MH. Pharmacokinetic drug interactions between oral contraceptives and second-generation anticonvulsants. Clin Pharmacokinet 2000 38(4) 355-65. 

Phenobarbital is the oldest antiepileptic drug in common use and has a solid efficiency record for the control of seizure. However, due to some side effects (hypertension, depression, dizziness, rash, memory lapses) and drug interactions (primarily other anticonvulsants), phenobarbital is now generally used as a second-line treatment. 

Data JL, Wilkinson GR, Nies AS. Interaction of quinidine with anticonvulsant drugs. N Engl J Med 1976 294 699-702. 

Mather GG, Levy RH. Anticonvulsants. In Levy RH, Thummel KE, Trager WF, et al., eds. Metabolic Drug Interactions. Philadelphia Lippincott Williams and Wilkins, 2000 217-232. 

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