Coffee-Antihypertensive Drug Interaction: A Hemodynamic and Pharmacokinetic Study With Felodipine

Am J Hypertens. 2016 Dec 1;29(12):1386-1393. doi: 10.1093/ajh/hpw081.


Objectives: A period of abstinence from coffee to permit caffeine elimination appears to enable increased blood pressure on subsequent exposure. We hypothesized that this would offset the antihypertensive effect of the dihydropyridine calcium channel blocker felodipine.

Methods: A randomized, single-dose, crossover study assessed hemodynamic and pharmacokinetic effects following 2 days without coffee and caffeine-containing foods. Consistently brewed black coffee (2×300ml), felodipine maximum recommended dose (10mg), and coffee plus felodipine were tested in middle-aged normotensive subjects.

Results: Pretreatment plasma caffeine concentrations were unquantifiable. After coffee, blood pressure changes (mm Hg) averaged over study hours 1-4 were increased for brachial systolic (7.6, P < 0.001) and diastolic (4.9, P < 0.001) and aortic systolic (7.4, P < 0.001), pulse (3.0, P < 0.05) and augmentation (1.4, P < 0.05) relative to baseline. After coffee plus felodipine, they were higher for brachial systolic (4.0, P < 0.05) and diastolic (3.9, P < 0.001) and aortic systolic (4.6, P < 0.05) compared to felodipine alone. The pressor effects of coffee and its modulation by felodipine were variable among individuals. Coffee containing caffeine (127mg) caused maximum pressor effect. Caffeine and felodipine pharmacokinetics were similar for coffee and felodipine given alone or in combination indicating an interaction having a pharmacodynamic basis. Plasma felodipine concentration-diastolic blood pressure reduction relationship shifted with coffee such that doubling the felodipine concentration would eliminate the pressor effect. However, this may increase the risk of adverse drug events particularly during the timeframe without coffee.

Conclusion: Intermittent coffee ingestion might complicate hypertension diagnosis and management for many individuals.

Trial registration: NCT02232269.

Keywords: blood pressure; calcium channel blockers; coffee; drug interactions; felodipine; hypertension; pharmacodynamics; pharmacokinetics..

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Area Under Curve
  • Arterial Pressure / drug effects*
  • Caffeine / administration & dosage
  • Caffeine / adverse effects
  • Caffeine / blood
  • Caffeine / pharmacokinetics*
  • Calcium Channel Blockers / administration & dosage
  • Calcium Channel Blockers / blood
  • Calcium Channel Blockers / pharmacokinetics*
  • Coffee* / adverse effects
  • Cross-Over Studies
  • Felodipine / administration & dosage
  • Felodipine / blood
  • Felodipine / pharmacokinetics*
  • Female
  • Food-Drug Interactions*
  • Half-Life
  • Humans
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Vascular Resistance / drug effects
  • Vasodilator Agents / administration & dosage
  • Vasodilator Agents / blood
  • Vasodilator Agents / pharmacokinetics*


  • Calcium Channel Blockers
  • Coffee
  • Vasodilator Agents
  • Caffeine
  • Felodipine

Associated data