What are the potential interactions with nimodipine (calcium channel blocker) and other medications?

Nimodipine Drug Interactions

Nimodipine has critical interactions with CYP3A4 inhibitors and inducers, other antihypertensive medications, and should never be combined with strong CYP3A4 inhibitors or inducers due to risk of severe hypotension or loss of efficacy. 1

Critical Contraindicated Interactions

Strong CYP3A4 Inhibitors (Absolute Contraindication)

Do not coadminister nimodipine with strong CYP3A4 inhibitors, as this significantly increases nimodipine plasma concentrations and risk of severe hypotension. 1

Strong inhibitors to avoid include:

• Macrolide antibiotics: clarithromycin, telithromycin 1
• HIV protease inhibitors: delavirdine, indinavir, nelfinavir, ritonavir, saquinavir 1
• Azole antifungals: ketoconazole, itraconazole, voriconazole 1
• Antidepressants: nefazodone 1
• Grapefruit juice: blood pressure lowering effects persist for at least 4 days after last ingestion 1

Strong CYP3A4 Inducers (Should Not Be Used)

Strong CYP3A4 inducers should generally not be administered with nimodipine as they significantly reduce plasma concentrations and efficacy. 1

Strong inducers include:

• Anticonvulsants: carbamazepine, phenobarbital, phenytoin (cause 7-fold decrease in AUC and 8-10 fold decrease in maximum plasma concentration) 2
• Other inducers: rifampin, St. John's Wort 1

Significant Interactions Requiring Monitoring

Moderate/Weak CYP3A4 Inhibitors

When nimodipine is combined with moderate or weak CYP3A4 inhibitors, blood pressure must be monitored closely and nimodipine dose reduction may be necessary. 1

These include:

• Cimetidine: doubles nimodipine bioavailability, though dose adjustment may not be clinically necessary 2
• Other moderate inhibitors: amprenavir, aprepitant, atazanavir, amiodarone, cyclosporine, erythromycin, fluconazole, fluoxetine, isoniazid, oral contraceptives, quinupristin/dalfopristin, valproic acid 1
• Valproic acid: increases nimodipine AUC by 50% and maximum concentrations by 30% 2

Moderate/Weak CYP3A4 Inducers

Patients on moderate or weak CYP3A4 inducers should be closely monitored for lack of nimodipine effectiveness, and dosage increase may be required. 1

These include: amprenavir, aprepitant, armodafinil, bosentan, efavirenz, etravirine, Echinacea, modafinil, nafcillin, pioglitazone, prednisone, rufinamide 1

Additive Antihypertensive Effects

Blood Pressure Lowering Drugs

Nimodipine may increase the blood pressure lowering effect of concomitantly administered antihypertensives, requiring careful blood pressure monitoring and possible dose adjustment. 1

Drugs with additive hypotensive effects:

• Diuretics 1
• Beta-blockers 1
• ACE inhibitors 1
• A1-antagonists 1
• Other calcium channel blockers: combining multiple calcium channel blockers is not recommended by ACC/AHA due to risk of excessive hypotension, severe bradycardia, and worsening heart failure 3
• Alpha-adrenergic blocking agents 1
• PDE5 inhibitors 1
• Alpha-methyldopa 1

Specific Calcium Channel Blocker Combinations

The American College of Cardiology/American Heart Association does not recommend combining multiple calcium channel blockers. 3

Risks of combining nimodipine with other calcium channel blockers:

• Excessive hypotension, particularly concerning in patients with pre-existing cardiovascular conditions 3
• Additive effects on heart rate, especially when combined with beta blockers 3
• Worsening heart failure in susceptible patients 3

If additional blood pressure control is needed, consider alternative drug classes such as ACE inhibitors, ARBs, or thiazide diuretics rather than adding a second calcium channel blocker. 3

Interactions Without Clinically Relevant Effects

The following drugs showed no clinically relevant interactions with nimodipine in studies:

• Antiarrhythmics: mexiletine, propafenone, disopyramide, quinidine 2
• Digoxin 2
• Beta-blockers: propranolol, atenolol 2
• Nifedipine 2
• Warfarin 2
• Diazepam 2
• Indomethacin 2
• Ranitidine 2
• Glibenclamide 2

Critical Monitoring Parameters

When nimodipine is used with interacting medications:

• Monitor blood pressure closely during treatment, as approximately 5% of patients experience blood pressure lowering and 1% discontinue due to hypotension 1
• Monitor for symptoms of hypotension: dizziness, lightheadedness 3
• Monitor heart rate when combining with other cardiovascular medications 3
• Monitor for peripheral edema 3

Special Population Considerations

In patients with hepatic impairment, nimodipine metabolism is decreased, requiring close monitoring of blood pressure and pulse rate with lower dosing. 1