Nitrendipine

Nitrendipine is metabolized via the CYP3A4 system. Therefore, drugs known to inhibit or induce the cytochrome P450 3A4 system may alter the initial passage or clearance of nitrendipine.

Drugs that are inhibitors of the CYP3A4 system and therefore may lead to increased plasma concentrations of nitrendipine are e.g.:

• Antibiotic macrolides (eg erythomycin)
• Anti-HIV protease inhibitors (eg ritonavir)
• Azole antifungals (eg ketoconazole)
• The antidepressants nefazodone and fluoxetine
• Quinupristin/dalfopristin
• Valproic acid
• Cimetidine and ranitidine

In co-administration with these drugs, blood pressure should be controlled and if necessary, a reduction in the dose of nitrendipine should be considered.

Nitrendipine is metabolized in the liver. It is therefore recommended that patients with hepatic dysfunction start treatment with the lowest available dose (10 mg nitrendipine/day), after careful monitoring of clinical response, as the effects of the drug may be intensified and prolonged.

The duration and intensity of the action of muscle relaxants such as pancuronium may be increased by treatment with nitrendipine.

Fertilization

In isolated cases of in-vitro fertilization, calcium antagonists have been associated with reversible biochemical changes in the spermatozoa that may lead to impaired sperm function. In those men who repeatedly fail to have a child by in-vitro fertilization and no other explanation can be found, calcium antagonists should be considered as possible causes.

Increased digoxin plasma levels should be expected when digoxin is taken concomitantly. Therefore, patients should be monitored for symptoms of digoxin overdose, if necessary by determination of digoxin plasma levels, and the glycoside dose may need to be reduced.

Nitrendipine may increase the blood pressure lowering effect with the simultaneous administration of antihypertensives such as:

• Diuretics
• β-blockers
• MAO inhibitors
• A-1 competitors
• Other calcium antagonists
• α-adrenergic blockers
• PDE 5 inhibitors
• α-methyldopa

Antiepileptic drugs that can induce CYP3A4, such as phenytoin, phenobarbitone, carbamazepine

No formal interaction study has been conducted. Phenytoin, phenobarbitone and carbamazepine are known to be potential inducers of the CYP3A4 system. Concomitant administration of these anticonvulsants may lead to a clinically relevant decrease in the bioavailability of nitrendipine and therefore a decrease in efficacy may be expected. If the dose of nitrendipine is increased during coadministration with phenytoin, phenobarbitone, or carbamazepine, consideration should be given to reducing the nitrendipine dose when anticonvulsant therapy is discontinued.