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Amlodipine and Caffeine Interaction: What You Need to Know

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At a glance

  • Amlodipine class / dihydropyridine calcium channel blocker, labeled once daily
  • Amlodipine half-life / about 30 to 50 hours, per the Norvasc label
  • Amlodipine interaction route / CYP3A [1]
  • Caffeine main enzyme / CYP1A2, for which it is the FDA clinical index substrate [2][3]
  • Caffeine half-life / group means about 3.4 to 6.0 hours in healthy adults in these studies, with wide individual spread [6][7][8]
  • FDA caffeine benchmark / 400 mg a day, about two to three 12-fluid-ounce cups of coffee [4]
  • Brewed coffee per 12 fl oz / 113 to 247 mg [4]

Do amlodipine and caffeine interact?

Amlodipine is a dihydropyridine calcium channel blocker that widens peripheral arteries and lowers blood pressure. The Norvasc label gives a terminal half-life of about 30 to 50 hours and a once-daily regimen. Its interaction data point to CYP3A involvement: in a study of older adults taking calcium channel blockers, more than half of them on amlodipine, hospitalization for acute kidney injury was more common when clarithromycin was prescribed than when azithromycin was [1].

Caffeine is cleared mainly by CYP1A2, the enzyme for which the FDA uses it as a clinical index substrate [3]; 3-N-demethylation by CYP1A2 is the main human pathway [2]. A smaller 8-hydroxylation route has been attributed to CYP3A4, though the same review says that reaction is not specific enough to measure CYP3A4 activity [2].

Does caffeine raise blood pressure?

The FDA cites 400 mg of caffeine a day, about two to three 12-fluid-ounce cups of coffee, as an amount not generally associated with negative effects in most adults. It also notes wide variation in sensitivity and in how fast people clear caffeine, and that some conditions and medications raise sensitivity [4]. A review of coffee and health found coffee consumption associated with increases in blood pressure, and listed people with hypertension among those who may be more vulnerable to caffeine's adverse effects [9].

Per 12 fluid ounces, the FDA gives brewed coffee 113 to 247 mg and energy drinks 41 to 246 mg. Decaffeinated coffee typically has 2 to 15 mg per 8-fluid-ounce cup [4].

What about grapefruit juice with amlodipine?

In a study of 20 healthy men given a single 10 mg dose of amlodipine, grapefruit juice or water was given daily for nine days. Oral availability was 88% with juice versus 81% with water, and AUC, peak concentration and clearance were not markedly changed [10]. A separate study of 12 healthy men given a single 5 mg dose with 250 mL of grapefruit juice found peak concentration 115% and AUC 116% of water values, with no significant difference in blood pressure or heart rate [11].

Frequently asked questions

Does caffeine change amlodipine levels?
Amlodipine interaction data point to CYP3A, while caffeine is cleared mainly by CYP1A2 [1][2][3].
How much coffee can I drink while taking amlodipine?
The FDA cites 400 mg a day, about two to three 12-fluid-ounce cups, as an amount not generally associated with negative effects in most adults, and notes wide variation in sensitivity and clearance [4]. A review listed people with hypertension among those who may be more vulnerable to caffeine adverse effects [9].
Does grapefruit juice interact with amlodipine?
In 20 healthy men given a single 10 mg dose of amlodipine, nine days of daily grapefruit juice did not markedly change exposure measures [10]. A separate study of 12 healthy men found a small increase in peak concentration and AUC [11].
Does the timing of coffee relative to my amlodipine dose matter?
The Norvasc label gives a terminal half-life of about 30 to 50 hours and a once-daily regimen, with peak plasma concentration at 6 to 12 hours and bioavailability not altered by food.

References

  1. Gandhi S, Fleet JL, Bailey DG, McArthur E, Wald R, Rehman F, et al. Calcium-channel blocker-clarithromycin drug interactions and acute kidney injury. JAMA. 2013;310(23):2544-53. Calcium-channel blocker-clarithromycin drug interactions and acute kidney injury
  2. Kot M, Daniel WA. Caffeine as a marker substrate for testing cytochrome P450 activity in human and rat. Pharmacol Rep. 2008;60(6):789-97. Caffeine as a marker substrate for testing cytochrome P450 activity in human and rat
  3. Drug Development and Drug Interactions | Table of Substrates, Inhibitors and Inducers | FDA. Drug Development and Drug Interactions | Table of Substrates, Inhibitors and Inducers | FDA
  4. Spilling the Beans: How Much Caffeine is Too Much? | FDA. Spilling the Beans: How Much Caffeine is Too Much? | FDA
  5. Drugs@FDA: FDA-Approved Drugs. Drugs@FDA: FDA-Approved Drugs
  6. Knutti R, Rothweiler H, Schlatter C. Effect of pregnancy on the pharmacokinetics of caffeine. Eur J Clin Pharmacol. 1981;21(2):121-6. Effect of pregnancy on the pharmacokinetics of caffeine
  7. Abernethy DR, Todd EL. Impairment of caffeine clearance by chronic use of low-dose oestrogen-containing oral contraceptives. Eur J Clin Pharmacol. 1985;28(4):425-8. Impairment of caffeine clearance by chronic use of low-dose oestrogen-containing oral contraceptives
  8. Parsons WD, Neims AH. Effect of smoking on caffeine clearance. Clin Pharmacol Ther. 1978;24(1):40-5. Effect of smoking on caffeine clearance
  9. Higdon JV, Frei B. Coffee and health: a review of recent human research. Crit Rev Food Sci Nutr. 2006;46(2):101-23. Coffee and health: a review of recent human research
  10. Vincent J, Harris SI, Foulds G, Dogolo LC, Willavize S, Friedman HL. Lack of effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of amlodipine. Br J Clin Pharmacol. 2000;50(5):455-63. Lack of effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of amlodipine
  11. Josefsson M, Zackrisson AL, Ahlner J. Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers. Eur J Clin Pharmacol. 1996;51(2):189-93. Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers
Evidence overview for interactions amlodipine: Amlodipine and Caffeine Interaction: What You Need to Know