What medications interact with nifedipine?

Drug Interactions with Nifedipine

Nifedipine has numerous clinically significant drug interactions primarily through CYP3A4 metabolism, with the most critical being strong CYP3A4 inducers like rifampin (which are contraindicated), CYP3A4 inhibitors that increase nifedipine levels requiring dose reduction, and concurrent use with other cardiovascular agents that may require clinical monitoring or alternative therapy. 1

Critical Contraindicated Interactions

• Strong CYP3A4 inducers (rifampin, rifapentin, rifabutin) are contraindicated with nifedipine as they reduce nifedipine bioavailability by 95-97%, rendering it ineffective 1
• Rifamycins should not be used with nifedipine; clinical monitoring is recommended and may require change to an alternate cardiovascular agent 2

CYP3A4 Inhibitors (Increase Nifedipine Levels - Require Monitoring and Dose Reduction)

Antifungal Agents

• Ketoconazole, itraconazole, and fluconazole inhibit nifedipine metabolism and increase exposure; blood pressure should be monitored and nifedipine dose reduced 1

Antibiotics

• Erythromycin inhibits CYP3A4 and increases nifedipine exposure; monitor blood pressure and consider dose reduction 1
• Clarithromycin can cause life-threatening interactions including vasodilatory shock and heart block when combined with nifedipine 3
• Quinupristin/dalfopristin increases nifedipine AUC by 1.44-fold and Cmax by 1.18-fold; monitor blood pressure and reduce nifedipine dose 1

Antisecretory Drugs

• Cimetidine increases nifedipine AUC by 1.52-2.01 fold and Cmax by 1.60-2.02 fold, causing clinically relevant blood pressure changes; monitor blood pressure and reduce nifedipine dose 1
• Ranitidine does not significantly affect nifedipine pharmacokinetics or blood pressure 1
• Omeprazole has minimal clinical impact on nifedipine 1

Antiviral Drugs

• Protease inhibitors (amprenavir, atazanavir, delavirdine, fosamprenavir, indinavir, nelfinavir, ritonavir) inhibit CYP3A4 and increase nifedipine exposure; caution warranted with clinical monitoring 1

CNS Drugs

• Nefazodone inhibits CYP3A4 and increases nifedipine exposure; monitor blood pressure and reduce dose 1
• Fluoxetine inhibits CYP3A4 and increases nifedipine exposure; monitor blood pressure and reduce dose 1
• Valproic acid may increase nifedipine exposure; monitor blood pressure and consider dose reduction 1

CYP3A4 Inducers (Decrease Nifedipine Levels - Consider Alternative Therapy)

• Phenytoin lowers nifedipine AUC and Cmax by approximately 70%; alternative antihypertensive therapy should be considered 1
• Phenobarbital and carbamazepine are CYP3A4 inducers; alternative antihypertensive therapy should be considered 1
• St. John's Wort induces CYP3A4 and decreases nifedipine exposure; alternative antihypertensive therapy should be considered 1

Cardiovascular Drug Interactions

Calcium Channel Blocker Combinations

• Concurrent nifedipine with ciclosporin may result in increased risk of gingival hyperplasia 2
• Calcium channel blockers with aminoglycosides can produce complete neuromuscular blockade and should be avoided in patients with botulism 2

Beta-Blockers

• Beta-blockers can be safely combined with nifedipine and may actually be protective, as immediate-release nifedipine without beta-blocker therapy increases adverse cardiovascular events 2, 4
• Immediate-release nifedipine must be avoided without concomitant beta blockade due to increased adverse potential 2

Cardiac Glycosides

• Digoxin levels increase by approximately 15-45% when combined with nifedipine, though this is usually not clinically significant; therapeutic drug monitoring recommended in patients with renal insufficiency 2, 1, 5
• Nifedipine may reduce digoxin clearance and cause digoxin toxicity 2

Other Antihypertensives

• Diuretics, PDE5 inhibitors, and alpha-methyldopa: nifedipine may increase blood pressure lowering effects 1
• ACE inhibitors and clonidine can be usefully combined with nifedipine with additive antihypertensive effects 6

Anticoagulants

• Warfarin: rare reports of increased prothrombin time; monitor prothrombin time and may require 2-3 fold warfarin dose increase 2, 1

Immunosuppressive Agents

• Tacrolimus metabolism is inhibited by nifedipine; transplant patients required 26-38% smaller tacrolimus doses; monitor tacrolimus blood concentrations and reduce dose 1
• Cyclosporine: monitoring of serum concentrations may assist with dosing 2

Other Significant Interactions

Dietary

• Grapefruit juice increases nifedipine AUC by 2-fold and Cmax by 1.35-fold; grapefruit juice should be avoided completely and stopped at least 3 days prior to initiating nifedipine 1

Glucose-Lowering Drugs

• Metformin: nifedipine increases metformin Cmax by 20% and AUC by 9% 1
• Acarbose: nifedipine tends to produce hyperglycemia; monitor blood glucose carefully and consider dose adjustment 1

Narcotics

• Methadone: rifamycins (not nifedipine directly) may require methadone dose increase 2

Corticosteroids

• May require 2-3 fold increase in corticosteroid dose when combined with rifamycins 2

Clinical Monitoring Recommendations

• Always check for drug interactions whenever the patient is taking other medications 2
• Monitor blood pressure closely when initiating or adjusting doses of interacting medications 1
• Use extended-release formulations only; immediate-release nifedipine carries higher risk of adverse events 2
• Avoid short-acting oral nifedipine as it can induce uncontrolled hypotension, particularly when combined with magnesium sulfate 2