Nimotop Drug Interactions

Tab: Nimodipine is metabolized via the cytochrome P450 3A4 system, located both in the intestinal mucosa and in the liver. Drugs that are known to either inhibit or to induce this enzyme system may therefore alter the first pass or the clearance of nimodipine.
The extent as well the duration of interactions should be taken into account when administering nimodipine together with the following drugs: Rifampicin: From the experience with other calcium antagonists it has to be expected that rifampicin accelerates the metabolism of nimodipine due to enzyme induction. Thus, efficacy of nimodipine could be significantly reduced when concomitantly administered with rifampicin. The use of nimodipine in combination with rifampicin is therefore contraindicated (see Contraindications).
Cytochrome P450 3A4 system-inducing anti-epileptic drugs, such as phenobarbital, phenytoin or carbamazepine: Previous chronic administration of the antiepileptic drugs phenobarbital, phenytoin or carbamazepine markedly reduces the bioavailability of orally administered nimodipine. Therefore, the concomitant use of oral nimodipine and these antiepileptic drugs is contraindicated. (see Contraindications).
Upon co-administration with the following inhibitors of the cytochrome P450 3A4 system the blood pressure should be monitored and, if necessary, an adaptation in the nimodipine dose should be considered (see Dosage & Administration).
Macrolide antibiotics (e.g., erythromycin): No interaction studies have been carried out between nimodipine and macrolide antibiotics. Certain macrolide antibiotics are known to inhibit the cytochrome P450 3A4 system and the potential for drug interaction cannot be ruled out at this stage. Therefore, macrolide antibiotics should not be used in combination with nimodipine (see Precautions).
Azithromycin, although structurally related to the class of macrolide antibiotic is void of CYP3A4 inhibition.
Anti-HIV protease inhibitors (e.g., ritonavir): No formal studies have been performed to investigate the potential interaction between nimodipine and anti-HIV protease inhibitors. Drugs of this class have been reported to be potent inhibitors of the cytochrome P450 3A4 system. Therefore, the potential for a marked and clinically relevant increase in nimodipine plasma concentrations upon coadministration with these protease inhibitors cannot be excluded (see Precautions).
Azole anti-mycotics (e.g., ketoconazole): A formal interaction study investigating the potential of drug interaction between nimodipine and ketoconazole has not been performed. Azole anti-mycotics are known to inhibit the cytochrome P450 3A4 system, and various interactions have been reported for other dihydropyridine calcium antagonists. Therefore, when administered together with oral nimodipine, a substantial increase in systemic bioavailability of nimodipine due to a decreased first-pass metabolism cannot be excluded (see Precautions).
Nefazodone: No formal studies have been performed to investigate the potential interaction between nimodipine and nefazodone. This antidepressant drug has been reported to be a potent inhibitor of the cytochrome P450 3A4. Therefore, the potential for an increase in nimodipine plasma concentrations upon co-administration with nefazodone cannot be excluded (see Precautions).
Fluoxetine: The steady-state concomitant administration of nimodipine with the antidepressant fluoxetine led to about 50% higher nimodipine plasma concentrations. Fluoxetine exposure was markedly decreased, while its active metabolite norfluoxetine was not affected.
Quinupristin/dalfopristin: Based on experience with the calcium-antagonist nifedipine, co-administration of quinupristin/dalfopristin may lead to increased plasma concentrations of nimodipine (see Precautions).
Cimetidine: The simultaneous administration of the H2-antagonist cimetidine can lead to an increase in the plasma nimodipine concentration (see Precautions).
Valproic acid: The simultaneous administration of the anticonvulsant valproic acid can lead to an increase in the plasma nimodipine concentration (see Precautions).
Further drug interaction: Nortryptyline: The steady-state concomitant administration of nimodipine and nortryptyline led to a slight decrease in nimodipine exposure with unaffected nortryptyline plasma concentrations.
Effects of nimodipine on other drugs: Blood pressure lowering drugs: Nimodipine may increase the blood pressure lowering effect of concomitantly applied antihypertensives, such as: diuretics, β-blockers, ACE inhibitors, A1-antagonists, other calcium antagonists, α-adrenergic blocking agents, PDE5 inhibitors, α-methyldopa.
However, if a combination of this type proves unavoidable particularly careful monitoring of the patient is necessary.
Zidovudine: In a monkey study simultaneous administration of anti-HIV drug zidovudine i.v. and nimodipine bolus i.v. resulted for zidovudine in significantly higher AUC, whereas the distribution volume and clearance were significantly reduced.
Drug-food interactions: Grapefruit juice: Grapefruit juice inhibits the cytochrome P450 3A4 system. Administration of dyhydropyridine calcium antagonists together with grapefruit juice thus results in elevated plasma concentrations and prolonged action of nimodipine due to a decreased first pass metabolism or reduced clearance.
As a consequence, the blood pressure lowering effect may be increased. After intake of grapefruit juice this effect may last for at least 4 days after the last ingestion of grapefruit juice.
Ingestion of grapefruit/grapefruit juice is therefore to be avoided while taking nimodipine (see Dosage & Administration).
Soln for IV infusion: Drugs that affect nimodipine: Fluoxetine: The steady-state concomitant administration of nimodipine with the antidepressant fluoxetine led to about 50% higher nimodipine plasma concentrations. Fluoxetine exposure was markedly decreased, while its active metabolite norfluoxetine was not affected.
Nortryptyline: The steady-state concomitant administrationof nimodipine and nortryptyline led to a slight decrease in nimodipine exposure with unaffected nortryptyilne plasma concentrations. Effects of nimodipine on other drugs: Blood pressure lowering drugs: Nimodipine may increase the blood pressure lowering effect of concomitant applied anti-hypertensives, such as: diuretics, β-blockers, ACE inhibitors, A1-antagonists, other calcium antagonists, α-adrenergic blocking agents, PDE5 inhibitors, α-methyldopa.
However, if a combination of this type proves unavoidable particularly careful monitoring of the patient is necessary.
Simultaneous intravenous administration of β-blockers may lead to mutual potentiation of negative ionotropic action going as far as decompensated heart failure.
Renal function can deteriorate if potentially nephrotoxic drugs (e.g. aminoglycosides, cephalosporins, furosemide) are given simultaneously, and also in patients whose renal function is already impaired. Renal function must be monitored carefully in such cases, and if a deterioration is found discontinuation of the treatment should be considered.
Zidovudine: In a monkey study simultaneous administration of anti-HIV drug zidovudine i.v. and nimodipine bolus i.v. resulted for zidovudine in significantly higher AUC, whereas the distribution volume and clearance were significantly reduced.
Other forms of interaction: Since nimodipine (Nimotop) solution for infusion contain 23.7% vol-% of alcohol, interactions with alcohol-incompatible drugs should be taken into consideration (see Precautions).