Important Drug Interactions for the Hypertension and Angina Drug Nifedipine

Patients taking the widely prescribed calcium channel blocker nifedipine (PROCARDIA, PROCARDIA XL) should be aware that it has clinically important interactions with many other prescription medications, as well as certain dietary supplements.

Nifedipine initially was approved by the Food and Drug Administration in 1981 and is used to treat hypertension (high blood pressure) and angina (chest pain that often spreads to the shoulders, arms and neck and that is caused by inadequate blood flow to the heart through the coronary arteries).[1] It is often used in combination with other medications.

Public Citizen’s Health Research Group has designated the short-acting form of nifedipine, sold under the brand name Procardia, as Do Not Use because it can cause dangerously low blood pressure, heart attacks and strokes.[2]

We have designated the extended-release form of nifedipine, marketed under the brand name Procardia XL, as Limited Use.[3] The extended-release form of nifedipine should be used by hypertension patients who have not responded to lifestyle modifications (such as weight loss, exercise and decreased dietary sodium) and first-line drug therapy with a thiazide diuretic, such as hydrochlorothiazide (MICROZIDE). For patients with typical stable angina (angina that occurs predictably with the same level of exertion), extended-release nifedipine should be reserved for those who remain symptomatic despite adequate doses of beta blockers (such as metoprolol [KAPSPARGO SPRINKLE, LOPRESSOR, TOPROL-XL]) and nitrate medications (such as isosorbide dinitrate [ISORDIL]).[4]

Drugs that may increase risk of nifedipine toxicity[5],[6]

Like many drugs, nifedipine is metabolized (broken down or chemically modified) by substances in the liver called enzymes. One important liver enzyme, known as CYP3A4, breaks down nifedipine and helps eliminate it from the body.

Table 1 (below) provides examples of oral drugs that can inhibit CYP3A4. The list includes certain antibiotics, antidepressants, antifungal drugs and antiviral drugs for HIV infection, as well as the stomach-acid–suppressing histamine-2 receptor blocker cimetidine [TAGAMET HB].

When taken concomitantly with nifedipine, these CYP3A4-inhibiting drugs, because they decrease the rate of nifedipine breakdown, can thereby increase nifedipine levels in the blood to toxic levels. Nifedipine toxicity may result in dangerously low blood pressure, slow heart rate and acute kidney damage.

For example, one study in six healthy volunteers found that concomitant use of cimetidine and nifedipine over a seven-day period resulted in an approximately 75% increase in blood nifedipine levels.

Table 1: Examples of Oral Drugs That Can Increase Risk of Nifedipine Toxicity

†Brand-name combination products were excluded.
*Designated as Limited Use by Worst Pills, Best Pills News
**Designated as Do Not Use except for serious fungal infection by Worst Pills, Best Pills News
***Designated as Do Not Use by Worst Pills, Best Pills News

Drugs that may decrease nifedipine’s effectiveness[7],[8]

Table 2 (below) provides examples of oral medications that can increase the activity of the CYP3A4 liver enzyme. The list includes certain anti-inflammatory corticosteroids, drugs for daytime sleepiness and seizure drugs, as well as the antibiotic/tuberculosis drug rifampin (RIFADIN, RIMACTANE) and the diabetes drug pioglitazone (ACTOS).

When taken concomitantly with nifedipine, these CYP3A4-stimulating drugs, because they increase the rate of nifedipine breakdown, can thereby decrease nifedipine levels in the blood, possibly resulting in inadequate treatment of hypertension and angina.

The dietary supplement St. John’s wort also can increase the activity of the CYP3A4 liver enzyme. Concomitant use of this supplement with nifedipine thus can potentially lead to decreased nifedipine blood levels and inadequate treatment of hypertension and angina.

Table 2: Examples of Oral Drugs That Can Decrease the Effectiveness of Nifedipine

†Brand-name combination products were excluded.
*Designated as Limited Use by Worst Pills, Best Pills News
**Designated as Do Not Use by Worst Pills, Best Pills News

Other important interactions[9],[10]

Clopidogrel (PLAVIX)

Concomitant use of nifedipine with the antiplatelet drug clopidogrel, which is used to reduce the risks of heart attack and stroke in certain patients at high risk of such events, may block the activation of clopidogrel and thus interfere with its antiplatelet effects and ability to prevent a heart attack or stroke.

Digoxin (LANOXIN)

Concomitant use of nifedipine with the heart drug digoxin, which is used to treat heart failure and control the heart rate in atrial fibrillation, may result in increased levels of digoxin, which could lead to digoxin toxicity. Symptoms of digoxin toxicity include loss of appetite, nausea, vomiting and fatigue. Patients taking digoxin may need a dosage change and should undergo more frequent monitoring of blood digoxin levels after starting, stopping or adjusting the dosage of nifedipine.

Grapefruit juice

Grapefruit contains a substance that inhibits the CYP3A4 liver enzyme. Consuming grapefruit juice while taking nifedipine has been shown to cause an approximately twofold increase in nifedipine blood levels, potentially leading to nifedipine toxicity. Patients taking nifedipine should avoid ingesting grapefruit and grapefruit juice.

What You Can Do

If you need treatment with nifedipine, review all your other medications and dietary supplements with your doctor to assess for potentially significant drug interactions. If you are taking certain medications that interact with nifedipine, you may need to adjust the dosage of the interacting drug or undergo more frequent monitoring of the blood levels of the interacting drug, or your doctor may advise you to take a different drug for your hypertension or angina. Be aware that other drugs not listed in this article also may have dangerous interactions with nifedipine.
 

References

[1] Pfizer Inc. Label: nifedipine (PROCARDIA XL). May 2021. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=8ebcb33c-f43b-4b36-9f94-9774b2a59e06. Accessed June 8, 2021.

[2] Drug profile: short acting nifedipine. March 31, 2021. https://www.worstpills.org/monographs/view/182. Accessed June 8, 2021.

[3] Drug profile for calcium channel blockers: felodipine (PLENDIL); nisoldipine (SULAR); verapamil (CALAN, CALAN SR, COVERA-HS, VERELAN, VERELAN-PM); amlodipine (CONSENSI, KATERZIA, NORVASC); diltiazem (CARDIZEM, CARDIZEM CD, CARDIZEM LA, CARTIA XT, DILACOR XR, DILT-CD, DITZAC, TAZTIA, TAZTIA XT, TIAZAC); isradipine; nicardipine (CARDENE, CARDENE SR); nifedipine (ADALAT CC, AFEDITAB CR, PROCARDIA XL). March 31, 2021. https://www.worstpills.org/monographs/view/183. Accessed June 8, 2021.

[4] Pfizer Inc. Label: nifedipine (PROCARDIA XL). May 2021. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=8ebcb33c-f43b-4b36-9f94-9774b2a59e06. Accessed June 8, 2021.

[5] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “nifedipine.” Accessed June 8, 2021.

[6] Pfizer Inc. Label: nifedipine (PROCARDIA XL). May 2021. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=8ebcb33c-f43b-4b36-9f94-9774b2a59e06. Accessed June 8, 2021.

[7] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “nifedipine.” Accessed June 8, 2021.

[8] Pfizer, Inc. Label: nifedipine (PROCARDIA XL). May 2021. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=8ebcb33c-f43b-4b36-9f94-9774b2a59e06. Accessed June 8, 2021.

[9] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “nifedipine.” Accessed June 8, 2021.

[10] Pfizer Inc. Label: nifedipine (PROCARDIA XL). May 2021. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=8ebcb33c-f43b-4b36-9f94-9774b2a59e06. Accessed June 8, 2021.