Cimetidine and Nifedipine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Cimetidine
Nifedipine
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased NIFEdipine exposure and an increased risk of NIFEdipine-related adverse reactions (headache, peripheral edema, hypotension, tachycardia)
Interaction Deep Dive
Concomitant use of NIFEdipine, a CYP3A4 substrate, with cimetidine, a CYP3A4 inhibitor may increase NIFEdipine exposure. Initiate NIFEdipine at the lowest dose available if given concomitantly with CYP3A4 inhibitors21. If NIFEdipine therapy is initiated in a patient currently receiving cimetidine, cautious titration is advised 2. The interaction between cimetidine and NIFEdipine is of clinical relevance and monitor blood pressure 1. Cimetidine in particular among H2 receptor antagonists can cause serum level elevations for most available calcium channel blockers, although clinically significant changes in hemodynamic response (heart rate, blood pressure) are most apparent only with NIFEdipine or dilTIAZem 89.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of NIFEdipine
Literature reports
6 reports — tap to read
a) Five studies in healthy volunteers investigated the impact of multiple cimetidine doses on the single or multiple dose pharmacokinetics of NIFEdipine. Two studies investigated the impact of coadministered cimetidine on blood pressure in hypertensive subjects on NIFEdipine. In normotensive subjects receiving single doses of 10 mg or multiple doses of up to 20 mg NIFEdipine three times day. alone or together with cimetidine up to 1000 mg/day, the AUC values of NIFEdipine in the presence of cimetidine were between 1.52 and 2.01 times those in the absence of cimetidine. The C values of NIFEdipine in the presence of cimetidine were increased by factors ranging between 1.60 and 2.02. The increase in exposure to NIFEdipine by cimetidine was accompanied by relevant changes in blood pressure or heart rate in normotensive subjects. Hypertensive subjects receiving 10 mg once a day NIFEdipine alone or in combination with cimetidine 1000 mg once a day. also experienced relevant changes in blood pressure when cimetidine was added to NIFEdipine 1.
b) Several studies comparing the effects of cimetidine and raNITIdine on NIFEdipine have consistently demonstrated a decrease in NIFEdipine's elimination and an increase in NIFEdipine's area under the plasma concentration-time curve when administered concurrently with cimetidine, but no alterations with raNITIdine. Patients previously stabilized on NIFEdipine have experienced elevated heart rates and blood pressures when cimetidine was introduced 3. Both alterations in hepatic metabolism of calcium channel blockers, and increased bioavailability secondary to reduced gastric acidity secondary to H2 blocker use are possible mechanisms 4.
c) Concomitant cimetidine (1000 mg daily) and NIFEdipine (40 mg daily) therapy resulted in an 80% increase in the peak plasma levels and a 74% increase in the area under the plasma concentration-time curve (AUC) for NIFEdipine in six healthy volunteers over a seven-day period. RaNITIdine produced smaller and nonsignificant increases 25.
d) Concomitant administration of oral cimetidine 300 mg four times a day and oral NIFEdipine in single doses of 20 mg or multiple doses of 10 to 20 mg three times a day resulted in increases in the area under the plasma concentration-time curve (AUC) for NIFEdipine in 23 healthy patients. With both single and multiple NIFEdipine doses, cimetidine decreased the apparent oral clearance (dose/AUC) and prolonged the elimination half-life of NIFEdipine. NIFEdipine pharmacokinetics did not differ when single versus multiple dose elimination were compared. In addition, the elevations in heart rate were greater during the combined therapy when compared to NIFEdipine alone, but blood pressure reductions were similar. There was a trend towards a greater incidence of headache during combined therapy 6.
e) A 60% increase in area under the plasma concentration versus time curve (p less than 0.05) occurred in six individuals following administration of cimetidine 1 gram daily during chronic NIFEdipine (10 mg every six hours) administration. The mean peak plasma level of NIFEdipine increased by 80% during coadministration of cimetidine. A reduction in mean arterial blood pressure was also observed in these individuals suggesting an enhanced blood pressure reduction from NIFEdipine in combination with cimetidine. Even though no toxicity resulted from the combination of cimetidine and NIFEdipine, it is likely to be of clinical importance 7.
f) Cimetidine in particular among H2 receptor antagonists can cause serum level elevations for most available calcium channel blockers, although clinically significant changes in hemodynamic response (heart rate, blood pressure) are most apparent only with NIFEdipine or dilTIAZem 89.
Common questions
Can I take Cimetidine and Nifedipine together?
Increased NIFEdipine exposure and an increased risk of NIFEdipine-related adverse reactions (headache, peripheral edema, hypotension, tachycardia) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Cimetidine and Nifedipine interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Cimetidine or Nifedipine need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (9)
- Product Information: NIFEDIPINE oral tablet, extended-release, nifedipine oral tablet, extended-release. Aurobindo Pharma Limited (per DailyMed), East Windsor, NJ, 2024. DailyMed
- Product Information: PROCARDIA XL(R) oral extended-release tablets, nifedipine oral extended-release tablets. Pfizer Labs (per Dailymed), New York, NY, 2023. DailyMed
- Baciewicz AM & Baciewicz FA Jr: Effect of cimetidine and ranitidine on cardiovascular drugs. Am Heart J 1989; 118:144-154. PubMed
- McAuley BJ & Schroeder JS: The use of diltiazem hydrochloride in cardiovascular disorders. Pharmacotherapy 1982; 2:121-133. PubMed
- Renwick AG, Le Vie J, Challenor VF, et al: Factors affecting the pharmacokinetics of nifedipine. Eur J Clin Pharmacol 1987; 32:351-355. PubMed
- Schwartz JB, Upton RA, Lin ET, et al: Effect of cimetidine or ranitidine administration on nifedipine pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther 1988; 43:673-680. PubMed
- Somogyi A & Muirhead M: Pharmacokinetic interactions of cimetidine. Clin Pharmacokinet 1987; 12:321-366.
- Winship LC, McKenney JM, Wright JT Jr, et al: The effect of ranitidine and cimetidine on single-dose diltiazem pharmacokinetics. Pharmacotherapy 1985; 5:16-19. PubMed
- Piepho RW, Culbertson VL, & Rhodes RS: Drug interactions with the calcium entry blockers. Circulation 1987; 75(Suppl V):V181-V194.
Keep reading about Cimetidine
Keep reading about Nifedipine
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