Cimetidine with carbamazepine

When carbamazepine is administered with primidone, decreased primidone levels and higher carbamazepine serum levels may result. Cimetidine administered with carbamazepine may result in an increase in plasma levels of carbamazepine that can lead to toxicity. Blood levels of lamotrigine increase when the agent is administered with valproic acid, requiring a lower dosage of lamotrigine... 

The effects of buspirone are decreased when the drug is administered with fluoxetine Increased serum levels of buspirone occur if the drug is taken with erythromycin or itraconazole Should any of these combinations be required, the dosage of buspirone is decreased to 2.5 mg BID, and the patient is monitored closely. Venlafaxine blood levels increase with a risk of toxicity when administered witii MAOIs or cimetidine There is an increased risk of toxicity when trazodone is administered with the phenothiazines and decreased effectiveness of trazodone when it is administered with carbamazepine Increased serum digoxin levels have occurred when digoxin is administered with trazodone There is a risk for increased phenytoin levels when phenytoin is administered witii trazodone... 

The serum levels of those taking long-term carbamazepine may transiently increase, possibly accompanied by an increase in adverse effects, for the first few days after starting to take cimeti-dine, but these adverse effects rapidly disappear. Cimetidine does not appear to have this effect on oxcarbazepine levels. Ranitidine appears not to interact with carbamazepine. 

The interaction between carbamazepine and cimetidine is established but of minimal importance. Patients receiving long-term treatment with carbamazepine should be warned that for the first few days after starting to take cimetidine they may possibly experience some increase in carbamazepine adverse effects (nausea, headache, dizziness, fatigue, drowsiness, ataxia, an inability to concentrate, a bitter taste). However, because the serum levels are only transiently increased, these effects should subside and disappear by the end of a week. Ranitidine appears to be a noninteracting alternative to cimetidine. 

Telerman-TopetN, Duret ME, Co C. Cimetidine interaction with carbamazepine. Arm In-temMed( 9 ) 94,544. 

Theophylline is a narrow therapeutic index drug with significant difference in bioavailability following oral administration. The half-life of the drug is increased by heart failure, cirrhosis and viral infections, in elderly patients, and by certain drugs, such as cimetidine, ciprofloxacin, oral contraceptives and fluvoxamine. The half-life is decreased in smokers, chronic alcoholism, and by certain drugs, such as phenytoin, rifampicin and carbamazepine. 

Only a few well-documented drug combinations with phenytoin may necessitate dosage adjustment. Coadministration of the following drugs can result in elevations of plasma phenytoin levels in most patients cimetidine, chloramphenicol, disulfiram, sulthiame, and isoniazid (in slow acetylators). Phenytoin often causes a decline in plasma carbamazepine levels if these two drugs are given concomitantly. 

Praziquantel is readily absorbed (80% in 24 hours) after oral administration, with serum concentrations being maximal in 1 to 3 hours the drug has a half-life of 0.8 to 1.5 hours. Its bioavailability is reduced by pheny-toin or carbamazepine and increased by cimetidine. Dexamethasone decreases plasma praziquantel levels by 50%. Praziquantel is excreted by the kidneys. 

Because bupropion is metabolized in the liver, medications that alter hepatic enzyme metabolism, such as carbamazepine or cimetidine, may effect blood concentrations. Bupropion should not be administered in combination with the MAOIs because of risk of hypertensive crisis. Levo-dopa use in conjunction with bupropion has been associated with confusion, hallucinations, and dyskinesia. Although generally well tolerated, there are case reports documenting that the... 

Beta-blockers interact with a large number of other medications. The combination of beta-blockers with calcium antagonists should be avoided, given the risk for hypotension and cardiac arrhythmias. Cimetidine, hydralazine, and alcohol all increase blood levels of beta-blockers, whereas rifampicin decreases their concentrations. Beta-blockers may increase blood levels of phenothiazines and other neuroleptics, clonidine, phen-ytoin, anesthetics, lidocaine, epinephrine, monoamine oxidase inhibitors and other antidepressants, benzodiazepines, and thyroxine. Beta-blockers decrease the effects of insulin and oral hypoglycemic agents. Smoking, oral contraceptives, carbamazepine, and nonsteroidal anti-inflammatory analgesics decrease the effects of beta-blockers (Coffey, 1990). 

Cardiac depressant effects may occur when verapamil or diltiazem is combined with a (p-adrenoceptor antagonoist or a cardiac glycoside. Nifedipine and verapamil are metabolised by cytochrome P-450 3A4. Inhibitors of this enzyme, e.g. HIV-protease inhibitors, cimetidine, fluoxetine, ketoconazole, erythromycin, will increase plasma levels and the dose should be carefully monitored. Conversely, enzyme inducers, e.g. carbamazepine, rifampicin, phenytoin, will decrease their plasma concentrations. 

Mebendazole is teratogenic in animals and therefore contraindicated in pregnancy. It should be used with caution in children younger than 2 years of age because of limited experience and rare reports of convulsions in this age group. Plasma levels may be decreased by concomitant use of carbamazepine or phenytoin and increased by cimetidine. Mebendazole should be used with caution in patients with cirrhosis. 

Praziquantel is a synthetic isoquinoline-pyrazine derivative. It is rapidly absorbed, with a bioavailability of about 80% after oral administration. Peak serum concentrations are reached 1-3 hours after a therapeutic dose. Cerebrospinal fluid concentrations of praziquantel reach 14-20% of the drug s plasma concentration. About 80% of the drug is bound to plasma proteins. Most of the drug is rapidly metabolized to inactive mono- and polyhydroxylated products after a first pass in the liver. The half-life is 0.8-1.5 hours. Excretion is mainly via the kidneys (60-80%) and bile (15-35%). Plasma concentrations of praziquantel increase when the drug is taken with a high-carbohydrate meal or with cimetidine bioavailability is markedly reduced with some antiepileptics (phenytoin, carbamazepine) or with corticosteroids. 

Mebendazole Accidental mebendazole poisoning in infants is associated with convulsions, respiratory arrest, and tachyarrhythmia.181 If administered concomitantly, mebendazole interacts with phenytoin, carbamazepine, and cimetidine. 

Pharmacokinetics. Carbamazepine is extensively metabolised one of the main products, an epoxide (a chemically reactive form), has anticonvulsant activity similar to that of the parent drug but may also cause some of its adverse effects. The t) of carbamazepine falls from 35 h to 20 h over the first few weeks of therapy due to induction of hepatic enzymes that metabolise it as well as other drugs, including corticosteroids (adrenal and contraceptive), theophylline and warfarin. Cimetidine and valproate inhibit its metabolism. There are complex interactions with other antiepilepsy drugs, which constitute a reason for monodrug therapy. 

Adverse effects include nausea, headache, diarrhoea, constipation and rash but are uncommon. Omeprazole inhibits the 2C family of the cytochrome P450 system, decreasing the metabolism of warfarin, diazepam, carbamazepine and phenytoin, and enhancing the action of these drugs (but inhibition is less than with cimetidine). 

Cimetidine Carbamazepine Clobazam Clonazepam Diazepam Phenytoin Valproate Risk of toxicity, particularly with phenytoin Inhibition of metabolism of the object drugs... 

Clinically important, potentially hazardous interactions with antihistamines, azole antifungals, benzodiazepines, carbamazepine, cimetidine, delavirdine, diazepam, erythromycin, HIV protease inhibitors, ketorolac, macrolide antibiotics, neuroleptics, phenobarbital, phenytoin, rifampin, ritonavir... 

Clinically important, potentially hazardous interactions with alcohol, carbamazepine, cimetidine, phenytoin, valproic acid... 

Clinically important, potentially hazardous interactions with amprenavir, aprepitant, atazanavir, carbamazepine, chlorpheniramine, cimetidine, clarithromycin, clorazepate, CNS depressants, darunavir, delavirdine, dexamethasone, efavirenz, erythromycin, esomeprazole, fluconazole, fluoxetine, fosamprenavir, grapefruit juice, griseofulvin, imatinib, indinavir, itraconazole, ivermectin, ketoconazole, lopinavir, nelfinavir, nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, ritonavir, roxithromycin, saquinavir, St John s wort, telithromycin, tipranavir... 

States. The two principal metabolites, thiothixene sulfoxide and N-desmethyl thiothixene, are formed by CYP 450 oxidations (435). The CTYP isozymes involved are not known with certainty. However, the hepatic clearance of thiothixene was increased by the CYP3A4 inducer carbamazepine and decreased by the CYP3A4 inhibitor cimetidine... 

After single-dose administration, the mean bioavailability of quetiapine is 9% with significant interindividual variation. If a CYP 3A4 inhibitor (e.g., cimetidine, ketoconazole, nefazodone, grapefruit juice, or erythromycin) is added to quetiapine, increased side effects (e.g., sedation or orthostasis) may occur. Fluoxetine may also decrease clearance of a medication such as quetiapine metabolized through CYP 3A4. However, with fluoxetine, it is the long-acting metabolite norfluoxetine, and not fluoxetine, that is the primary inhibitor of 3 A4 metabolism. If an enzyme inducer such as carbamazepine or St. lohn s wort is added to quetiapine, then decreased antipsychotic effects may occur. ... 

Based on current information, inhibitors of CYP 1A2 have the greatest potential for causing interactions with olanzapine. Examples include cimetidine, fluvoxamine, and fluoroquinolone antibiotics (e.g., ciprofloxacin) to varying degrees. To date, however, no serious inhibition interactions have been reported with olanzapine, which may be a result of olanzapine s wide therapeutic index. Carbamazepine has been reported to increase olanzapine elimination by as much as 50%. Cigarette smoking is a potent inducer of CYP 1A2, and one would expect lower mean olanzapine serum concentrations in smokers compared to nonsmokers. 

Carbamazepine is metabolized to an active 10,11-epoxide metabolite, thus medications that inhibit 3A4 isoenzymes may result in carbamazepine toxicity (e.g., cimetidine, dUtiazem, erythromycin, fluoxetine, fluvoxamine, isoniazid, itraconazole, ketoconazole, nefa-zodone, propoxyphene, and verapamil). " When carbamazepine is combined with valproate, the carbamazepine dose should be reduced because valproate displaces carbamazepine from protein binding sites, thus increasing free levels." Combining clozapine and carbamazepine is not recommended because of the possibdity of bone marrow suppression with both agents. ... 

Caution is needed when cimetidine or diltiazem is used with tamsulosin or other a-adrenergic antagonists, as a drug-drug interaction leads to decreased metabolism of the latter agents. In contrast, carbamazepine and phenytoin may increase hepatic catabolism of... 

Transient elevation of carbamazepine plasma levels is evident with cimetidine (due to the latter s cytochrome P450 inhibition capacity). 

Conversely, the steady-state carbamazepine levels of 7 epileptic patients receiving long-term treatment remained unaltered when they were given cimetidine 1 g daily for a week. Another study also showed a lack of an interaction in 11 epileptic patients. However, an 89-year-old woman taking carbamazepine 600 mg daily developed symptoms of carbamazepine toxicity within 2 days of starting to take cimetidine 400 mg daily, and had a rise in serum carbamazepine levels, which fell when the cimetidine was withdrawn. The effects of cimetidine may be additive with those of iso-niazid, see Carbamazepine + Isoniazid or Rifampicin (Rifampin) , below. 

Not fully understood. It is thought that cimetidine can inhibit the activity of the liver enzymes concerned with the metabolism of carbamazepine (such as the cytochrome P450 isoenzyme CYP3A4), resulting in its reduced clearance from the body, but the effect is short-lived because the auto-inducing effects of the carbamazepine oppose it. This would possibly explain why the single-dose and short-term studies in healthy subjects... 

Carbamazepine toxicity, associated with marked rises in serum carbamazepine levels, has been described in other reports. " Some of the patients were also taking sodium valproate, which does not seem to be implicated in the interaction, and in one case cimetidine, which was thought to have potentiated the interaction. See also Carbamazepine or Oxcarbazepine + H2-receptor antagonists , p.529. 

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