Carbamazepine, drug interactions

Pippenger CE. Clinically significant carbamazepine drug interactions an overview. Epilepsia 1987 28 571-576. 

BaciewiczAM. Carbamazepine drug interactions. Ther Drug Monitor 1986 8 305-317. 

Topiramate Topamax Suspension 300 mg/5 mL Tablet 25, 100, 200 mg Doses should be slowly adjusted up and down according to response and adverse effects (e.g., 150-300 mg twice daily and increase by 300-600 mg/day at weekly intervals) 50-200 mg/day in divided doses drug-drug interactions than carbamazepine, but causes more gastrointestinal side effects and hyponatremia Evidence is limited regarding efficacy Not recommended for the... 

Drug Interactions Carbamazepine induces the hepatic metabolism of many drugs, including other antiepileptic drugs, antipsychotics, some antidepressants, oral contraceptives, and... 

Carbamazepine may interact with other drugs by inducing their metabolism. Valproic acid increases concentrations ofthe 10,11-epoxide metabolite without affecting the concentration of carbamazepine. The interaction of erythromycin and clarithromycin (CYP3A4 inhibition) with carbamazepine is particularly significant. 

Oxcarbazepine has mood-stabilizing effects similar to those of carbamaz-epine, but with milder side effects, no autoinduction of metabolizing enzymes, and potentially fewer drug interactions. There are fewer data supporting its efficacy than there are for carbamazepine s efficacy. 

Caution is needed to avoid potential drug interactions. Tamsulosin decreases metabolism of cimetidine and diltiazem. Carbamazepine and phenytoin increase catabolism of a-adrenergic antagonists. 

Egnell, A.-C., Houston, B. and Boyer, S. (2003) in vivo CYP3A4 heteroactivation is a possible mechanism for the drug interaction between felbamate and carbamazepine. The Journal of Pharmacology and Experimental Therapeutics, 305, 1251-1262. 

Drug-drug interactions are often more problematic with carbamazepine than other mood stabilizers. Carbamazepine increases the activity of certain liver enzymes. Because these enzymes metabolize and eliminate medications and other substances introduced to the body, carbamazepine therapy can decrease the blood level and thereby reduce the effectiveness of itself (a phenomenon called autoinduction) and other medications that are metabolized by these enzymes. It is not unusual to find that the dose of carbamazepine must be increased after several weeks, because it has increased its own elimination. Other medications may likewise be less effective. Of particular concern are the oral contraceptives, Depo-Provera, and protease inhibitors used for the treatment of HI V+ patients. Oral contraceptives often require an increase in dose. 

Carbamazepine is also most beneficial for patients with mixed episodes and rapid cycling. However, many patients find the side effects of carbamazepine more troublesome than those of valproate, and becanse carbamazepine has a penchant for nntoward drug-drug interactions, we reserve the use of carbamazepine for those patients who are unable to tolerate valproate, lithium, and the atypical antipsychotic... 

Unlike carbamazepine, valproic acid has few drug interactions, an added benefit for elderly patients. One interaction worthy of mention, however, is that aspirin can increase levels of valproic acid. For this reason, vascular dementia patients taking an aspirin a day may need a lower dose of valproic acid or at least more careful monitoring of blood levels when starting valproic acid. 

Tegretol consists of carbamazepine, which is an anti-epileptic drug. There is a clinically significant drug interaction between carbamazepine and clarithromycin (macrolide antibacterial agent) resulting in higher plasma concentrations of carbamazepine. 

Coadministration with cisapride, pimozide, or carbamazepine (see Warnings and Drug Interactions) patients who were withdrawn from nefazodone because of evidence of liver injury (see Warning box. Warnings) hypersensitivity to nefazodone or other phenylpiperazine antidepressants. 

Oxcarbazepine is a derivative of carbamazepine and although its precise mechanism of action is unknown it has similar properties as carbamazepine and is also used for the treatment of primary generalized tonic-clonic seizures and partial seizures. Also the adverse effects are similar to those of carbamazepine. However the drug interaction profile is different as oxcarbazepine has hardly any enzyme-inducing capacity. 

No satisfactory randomised controlled trials have been published demonstrating the efficacy of carbamazepine in anxiety disorders, although it has a history of use as an anxiolytic in panic disorder and PTSD. It has an unfavourable side-effect profile (nausea, dizziness, ataxia) and multiple drug interactions due to induction of liver enzymes. 

As with carbamazepine, the historical use of valproate for anxiety is not supported by robust clinical trials. A randomised study showed efficacy in panic disorder (Lum et al. 1991) and benefit has been reported in open studies in OCD and PTSD. The major side-effects are tremor, nausea, ataxia and weight gain and there is the potential for drug interactions via inhibition of hepatic enzymes. 

Most of the drug interactions with carbamazepine are related to its effects on microsomal drug metabolism. Carbamazepine can induce its own metabolism (autoinduction) after prolonged administration, decreasing its clearance rate, half-life, and serum concentrations. The possibility of autoinduction requires the clinician to reevaluate the patient s blood levels after a month of carbamazepine therapy. The autoinduction phenomenon is over in about a month. 

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. 

Oxcarbazepine is chemically and pharmacologically closely related to carbamazepine, but it has much less capacity to induce drug-metabolizing enzymes. This property decreases the problems associated with drug interactions when oxcarbazepine is used in combination with other drugs. The clinical uses and adverse effect profile of oxcarbazepine appear to be similar to those of carbamazepine. 

Geriatric Considerations - Summary Well-tolerated in older adults. Adjust dose based on creatinine clearance. Autoinduction of metabolism does not occur as seen with carbamazepine, but drug interactions are still an issue. Many of the CNS effects occur early in treatment and are transitory. One-third of patients with hypersensitivity reactions to carbamazepine will experience cross-sensitivity to oxcarbazepine. 

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). 

The use of two or more agents concurrently has the potential for possibly deleterious drug interactions. Thus, as noted in subsequent chapters, the addition or elimination of an agent may significantly alter the activity of the concurrent drug treatment (e.g., carbamazepine lowering haloperidol plasma levels nefazodone increasing the levels of triazolam). 

Spina E, Pisani F, Perucca E. Clinically significant pharmacokinetic drug interactions with carbamazepine. An update. Clin Pharmacokinei 1996 31 198-214. 

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