Adalat GITS 30 Drug Interactions

The blood pressure-lowering effect of nifedipine may be potentiated upon co-administration of other antihypertensive drugs.
When nifedipine is administered simultaneously with β-receptor blockers, the patient should be carefully monitored since fairly severe hypotension can occur. Deterioration of heart failure is also known to develop in isolated cases.
Nifedipine is metabolized via the cytochrome P-450 3A4 system, located both in the intestinal mucosa and in liver. Drugs that are known to either inhibit or induce this enzyme system may therefore alter the first-pass (after oral administration) or the clearance of nifedipine.
Digoxin: The simultaneous administration of nifedipine and digoxin may lead to reduced digoxin clearance and hence, an increase in plasma concentrations of digoxin. The patient should therefore be checked for symptoms of digoxin overdosage as a precaution and, if necessary, the glycoside dose should be reduced, taking account of the plasma concentration of digoxin.
Cytochrome P-450 3A4 System-Inducing Antiepileptic Drugs, eg Phenytoin, Carbamazepine and Phenobarbitone: Phenytoin induces the cytochrome P-450 3A4 system. Upon co-administration with phenytoin, the bioavailability of nifedipine is reduced and thus its efficacy weakened. When both drugs are concomitantly administered, the clinical response to nifedipine should be monitored and, if necessary, an increase of the nifedipine dose considered. If the dose of nifedipine is increased during co-administration of both drugs, a reduction of the nifedipine dose should be considered when the treatment with phenytoin is discontinued.
No formal studies have been performed to investigate the potential interaction between nifedipine and carbamazepine or phenobarbitone. As both drugs have been shown to reduce the plasma concentrations of the structurally similar calcium channel blocker nimodipine due to enzyme induction, a decrease in nifedipine plasma concentrations and hence a decrease in efficacy cannot be excluded.
Quinidine: When nifedipine and quinidine have been administered simultaneously, lowered quinidine levels or, after discontinuance of nifedipine, a distinct increase in plasma concentrations of quinidine have been observed in individual cases. For this reason, when nifedipine is either additionally administered or discontinued, monitoring of the quinidine plasma concentration and, if necessary, adjustment of the quinidine dose are recommended.
Some authors reported increased plasma concentrations of nifedipine upon co-administration of both drugs, while others did not observe an alteration in the pharmacokinetics of nifedipine. Therefore, the blood pressure should be carefully monitored if quinidine is added to an existing therapy with nifedipine. If necessary, the dose of nifedipine should be decreased.
Quinupristin/Dalfopristin: Simultaneous administration of quinupristin/dalfopristin and nifedipine may lead to increased plasma concentrations of nifedipine. Upon co-administration of both drugs, the blood pressure should be monitored and, if necessary, a reduction of the nifedipine dose is considered.
Cimetidine: Due to its inhibition of cytochrome P-450 3A4, cimetidine elevates the plasma concentrations of nifedipine and may potentiate the antihypertensive effect.
Rifampicin: Strongly induces the cytochrome P-450 3A4 system. Upon co-administration with rifampicin, the bioavailability of nifedipine is distinctly reduced and thus its efficacy is weakened. The use of nifedipine in combination with rifampicin is therefore contraindicated.
Diltiazem: Decreases the clearance of nifedipine. The combination of both drugs should be administered with caution and a reduction of the nifedipine dose may be considered.
Grapefruit Juice: Inhibits the cytochrome P-450 3A4 system. Administration of nifedipine together with grapefruit juice thus results in elevated plasma concentrations of nifedipine due to an increase in drug bioavailability. As a consequence, the blood pressure-lowering effect may be increased.
Cisapride: Simultaneous administration of cisapride and nifedipine may lead to increased plasma concentrations of nifedipine. Upon co-administration of both drugs, the blood pressure should be monitored and, if necessary, a reduction of the nifedipine dose is considered.
Anti-HIV Protease Inhibitors (eg, Ritonavir): A clinical study investigating the potential of a drug interaction between nifedipine and certain anti-HIV protease inhibitors has not yet been performed. Drugs of this class are known to inhibit the cytochrome P-450 3A4 system. In addition, drugs of this class have been shown to inhibit in vitro the cytochrome P-450 3A4 mediated metabolism of nifedipine. When administered together with nifedipine, a substantial increase in plasma concentrations of nifedipine due to a decreased first pass metabolism and a decreased elimination cannot be excluded.
Fluoxetine: A clinical study investigating the potential of a drug interaction between nifedipine and fluoxetine has not yet been performed. Fluoxetine has been shown to inhibit in vitro the cytochrome P-450 3A4 mediated metabolism of nifedipine. Therefore an increase of nifedipine plasma concentrations upon co-administration of both drugs cannot be excluded.
Nefazodone: A clinical study investigating the potential of a drug interaction between nifedipine and nefazodone has not yet been performed. Nefazodone is known to inhibit the cytochrome P-450 3A4 mediated metabolism of other drugs. Therefore an increase of nifedipine plasma concentrations upon co-administration of both drugs cannot be excluded.
Macrolide Antibiotics (eg, Erythromycin): No interaction studies have been carried out between nifedipine and macrolide antibiotics. Certain macrolide antibiotics are known to inhibit the cytochrome P-450 3A4 mediated metabolism of other drugs. Therefore the potential for an increase of nifedipine plasma concentrations upon co-administration of both drugs cannot be excluded.
Azithromycin, although structurally related to the class of macrolide antibiotics is void of CYP3A4 inhibition.
Azole Antimycotics (eg, Ketoconazole): A formal interaction study investigating the potential of a drug interaction between nifedipine and ketoconazole, itraconazole or fluconazole has not yet been performed. Drugs of this class are known to inhibit the cytochrome P-450 3A4 system. When administered orally together with nifedipine, a substantial increase in systemic bioavailability of nifedipine due to an increased absorption cannot be excluded. Upon co-administration, the blood pressure should be monitored and, if necessary, a reduction in the nifedipine dose is considered.
Tacrolimus: It has been shown to be metabolized via the cytochrome P-450 3A4 system. Data recently published indicate that the dose of nifedipine administered simultaneously with tacrolimus may be reduced in individual cases. Upon co-administration of both drugs, the tacrolimus plasma concentration should be monitored and, if necessary, a reduction in the tacrolimus dose is considered.
Valproic Acid: No formal studies have been performed to investigate the potential interaction between nifedipine and valproic acid. As valproic acid has been shown to increase the plasma concentrations of the structurally similar calcium-channel blocker nimodipine due to enzyme inhibition, an increase in nifedipine plasma concentrations and hence an increase in efficacy cannot be excluded.
Other Forms of Interaction: Nifedipine may cause falsely increased spectrophotometric values of urinary vanillyl-mandelic acid. However, measurement with HPLC is unaffected.
Incompatibilities: None.