Questions about Atrial Fibrillation? Get answers from our expert.

Nifedipine

Pronunciation

Pronunciation: nye-FED-i-peen
Class: Calcium channel blocking agent

Trade Names

Adalat CC
- Tablets, ER 30 mg
- Tablets, ER 60 mg
- Tablets, ER 90 mg

Afeditab CR
- Tablets, ER 30 mg
- Tablets, ER 60 mg

Nifediac CC
- Tablets, ER 30 mg
- Tablets, ER 60 mg
- Tablets, ER 90 mg

Nifedical XL
- Tablets, ER 30 mg
- Tablets, ER 60 mg

Procardia
- Capsules 10 mg

Procardia XL
- Tablets, ER 30 mg
- Tablets, ER 60 mg
- Tablets, ER 90 mg

Adalat XL (Canada)
Apo-Nifed (Canada)
Apo-Nifed PA (Canada)

Pharmacology

Inhibits movement of calcium ions across cell membrane in systemic and coronary vascular smooth muscle and myocardium. Decreases peripheral vascular resistance. Reduces myocardial oxygen demand; relaxes and prevents coronary artery spasm.

Slideshow: Grapefruit and Medicines: A Possible Deadly Mix?

Grapefruit and grapefruit juice can react adversely with over 85 prescription medications.

Pharmacokinetics

Absorption

Nifedipine is rapidly and fully absorbed (100%). T max is approximately 30 min (immediate release) and 2.5 to 5 h (ER). Bioavailability is 84% to 89% (ER) and 45% to 75% (immediate release).

Distribution

Nifedipine protein binding is 92% to 98%.

Metabolism

Nifedipine is metabolized extensively in the liver to inactive metabolites.

Elimination

Nifedipine is eliminated in urine (0.1% unchanged) and in small amounts in feces. The half-life is approximately 7 h (ER) and 2 h (immediate release). 60% to 80% is excreted in urine and the remainder in feces in metabolized form.

Special Populations

Hepatic Function Impairment

Longer half-life, higher bioavailability, and reduced protein binding may occur in patients with liver cirrhosis.

Elderly

Mean C max is 36% higher and plasma concentration is 70% greater in elderly patients.

Indications and Usage

Chronic stable angina (except Adalat CC , Afeditab CR , Nifediac CC ); hypertension (except Procardia ); vasospastic angina (except Adalat CC , Afeditab CR , Nifediac CC ).

Contraindications

Cardiogenic shock; coadministration with strong CYP-450 inducers (eg, rifampin); known hypersensitivity to nifedipine.

Dosage and Administration

Capsules
Adults

PO Start with 10 mg 3 times daily and titrate dose over a 7- to 14-day period (usual dose range, 10 to 20 mg 3 times daily). Some patients (eg, coronary artery spasm) respond only to higher doses and/or more frequent administration (eg, 20 to 30 mg 3 to 4 times daily; max, 180 mg/day). In hospitalized patients under close observation, dose may be increased in 10 mg increments over 4- to 6-h periods as required to control pain and arrhythmias caused by ischemia. A single dose rarely exceeds 30 mg.

ER tablets
Adults Procardia XL and Nifedical XL

PO 30 or 60 mg once daily, titrated over a 7- to 14-day period (max, 120 mg/day). Administer on an empty stomach. Swallow whole. Do not crush, chew, cut, or break ER tablets.

Adalat CC , Afeditab CR , and Nifediac CC (hypertension)

PO Start with 30 mg once daily and titrate dose over a 7- to 14-day period (max, 90 mg/day). Administer on an empty stomach. Swallow whole. Do not crush, chew, cut, or break ER tablets.

Storage/Stability

Store immediate-release capsules at controlled room temperature (59° to 77°F). Protect from light and moisture. Store ER tablets below 86°F. Protect from light, moisture, and freezing.

Drug Interactions

Acarbose

Coadministration may lead to loss of glucose control. Monitor blood glucose and adjust therapy as needed.

ACE inhibitors (eg, benazepril)

Hypotensive effect of both drugs may be increased. The tachycardic effect of nifedipine may be attenuated. Monitor BP and adjust the nifedipine dose as needed.

Alpha-1 blockers (eg, doxazosin)

Nifedipine plasma concentrations may be elevated and doxazosin plasma concentrations may be decreased. Monitor BP when these agents are coadministered and adjust the nifedipine dose as needed.

Anticoagulants (eg, warfarin)

May increase PT during coadministration. Monitor coagulation parameters and adjust the warfarin dose as needed.

Antihypertensive agents

May have additive effects. Monitor BP and adjust the dose of either agent as needed.

Azole antifungal agents (eg, ketoconazole, voriconazole), cisapride, delavirdine, diltiazem, fluoxetine, imatinib, macrolide antibiotics (eg, erythromycin, telithromycin), nefazodone, protease inhibitors (eg, indinavir, ritonavir), quinupristin/dalfopristin, valproic acid, verapamil

May elevate nifedipine levels, increasing the risk of hypotension and adverse effects. Monitor BP. Consider a reduction in the nifedipine dose.

Beta-blockers (eg, propranolol)

Coadministration may increase the risk of CHF, severe hypotension, or exacerbation of angina. Hypotension is more likely to occur with coadministration of timolol. Monitor the clinical response of the patient and adjust the nifedipine dose as needed.

Cimetidine

May increase bioavailability of nifedipine. Monitor BP and consider a reduction in the nifedipine dose.

Clopidogrel

Clopidogrel platelet inhibition may be decreased. Closely monitor platelet function when starting, stopping, or changing the nifedipine dose. Adjust the clopidogrel dose as needed.

CYP3A4 strong inducers (eg, carbamazepine, dexamethasone, phenobarbital, phenytoin, rifabutin, rifampin, St. John's wort)

Strong CYP3A4 inducers may reduce the efficacy of nifedipine. Coadministration is contraindicated.

Digitalis

Reports are conflicting; however, digoxin levels may be increased. Monitor digoxin concentrations and adjust the digoxin dose as needed.

Fentanyl

The risk of hypotension may be increased. In patients receiving nifedipine where surgery using high-dose fentanyl anesthesia is being considered, allow at least 36 h for nifedipine to be washed out of the body prior to surgery, if the patient's condition permits.

Flecainide

There are too few data to recommend coadministration.

Ginkgo biloba , ginseng

Nifedipine plasma concentrations may be elevated, increasing the pharmacologic effects. If Ginkgo biloba or ginseng cannot be avoided, closely monitor BP and adjust the nifedipine dose as needed.

Grapefruit juice

Nifedipine plasma levels may be elevated, increasing the pharmacologic and adverse reactions. Avoid coadministration. Stop grapefruit juice ingestion at least 3 days prior to starting nifedipine.

Loop diuretics (eg, furosemide), methyldopa, phosphodiesterase type 5 inhibitors (eg, sildenafil), thiazide diuretics (eg, chlorothiazide)

BP-lowering effects may be increased. Monitor BP and adjust the nifedipine dose as needed.

Melatonin

May interfere with the antihypertensive effects of nifedipine. If coadministration of melatonin cannot be avoided, closely monitor BP and adjust the nifedipine dose when melatonin is started or stopped.

Metformin

Nifedipine may increase metformin C max , AUC, and amount of metformin excreted in the urine. Nifedipine appears to enhance metformin absorption. Observe the clinical response of the patient to metformin and be prepared to adjust the metformin dose as needed.

Omeprazole

Nifedipine AUC is increased and C max is decreased. The magnitude of the changes is not likely to be clinically important.

Pioglitazone

Nifedipine C max and AUC may be decreased. However, because of the high variability of nifedipine pharmacokinetics, the clinical importance of this finding is unknown.

Quinidine

Quinidine may elevate nifedipine C max and AUC. Heart rate may be increased during the initial interval after administration. Monitor heart rate and adjust the nifedipine dose when adding quinidine to a nifedipine treatment regimen.

Tacrolimus

Tacrolimus trough concentrations may be elevated, increasing the risk of toxicity. Monitor tacrolimus blood concentrations. Consider a reduction in the tacrolimus dose.

Adverse Reactions

Cardiovascular

Peripheral edema (10%); palpitation (7%); transient hypotension (5%); asthenia, fatigue, insomnia (less than 3%).

CNS

Dizziness, giddiness, light-headedness (27%); headache (23%); weakness (12%); mood changes, nervousness (7%); paresthesia, vertigo (3% or less); asthenia, fatigue, insomnia (less than 3%); difficulty in balance, jitteriness, shakiness, sleep disturbances, somnolence (2% or less).

Dermatologic

Pruritis, rash (3% or less); dermatitis, sweating, urticaria (2% or less); exfoliative or bullous skin reactions, including erythema multiforme, Stevens-Johnson syndrome, and TEN (postmarketing).

EENT

Nasal congestion, sore throat (6%); blurred vision, epistaxis, rhinitis (3% or less).

GI

Heartburn, nausea (11%); constipation, diarrhea, flatulence (3% or less); abdominal pain, dry mouth, dyspepsia (less than 3%); cramps (2% or less).

Genitourinary

Impotence, polyuria, urinary frequency (3% or less); sexual difficulties (2% or less).

Musculoskeletal

Muscle cramps, tremor (8%); arthralgia, leg cramps (3% or less); inflammation, joint stiffness (2% or less).

Respiratory

Cough, dyspnea, wheezing (6%); shortness of breath (2% or less).

Miscellaneous

Flushing/heat sensation (25%); pain (less than 3%); chills, fever (2% or less).

Precautions

Monitor

Frequently assess patient for response to treatment. Ensure that therapy is periodically reviewed to determine if it needs to be continued without change or if a dose change (eg, increase, decrease, discontinuation) is indicated. Frequently monitor BP during initial administration and following any dose escalation.


Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established.

Elderly

May experience greater hypotensive effects.

Renal Function

Absorption of nifedipine from ER form could be modified by renal disease. Use with caution.

Hepatic Function

Use drug with caution in patients with impaired hepatic function, reduced hepatic blood flow, or hepatic cirrhosis.

Acute hepatic injury

In rare instances, nifedipine has been associated with significant elevations in liver enzymes, symptoms consistent with acute hepatic injury, cholestasis with or without jaundice, and allergic hepatitis.

Antiplatelet effects

Nifedipine decreases platelet aggregation and can increase bleeding time in some patients.

Beta-blocker withdrawal

Patients withdrawn from beta-blockers while taking nifedipine may experience increased angina.

CHF

Use drug with caution in patients with CHF. New-onset CHF and worsening of preexisting CHF have been reported, usually in patients also receiving a beta-blocker.

Discontinuation

Decrease dose gradually. Abrupt withdrawal may cause increased frequency and duration of angina.

Edema

Nifedipine has been associated with edema in some cases and should be distinguished from fluid retention secondary to heart failure.

Excessive hypotension

Excessive and poorly tolerated hypotension has occurred. This appears to occur during initial titration or during upward dosage adjustment and may be more common in patients with concurrent beta-blocker use.

Fentanyl anesthesia

Severe hypotension occurred in patients receiving immediate-release nifedipine together with a beta-blocker and who underwent coronary artery bypass surgery using high-dose fentanyl anesthesia. If possible, withdraw nifedipine 36 h before surgery when using high-dose fentanyl.

GI narrowing

Use ER nifedipine with caution in patients with severe GI narrowing. Obstructive symptoms have been rarely reported in patients with known strictures in association with ingestion of ER nifedipine.

Increased angina

Occasional patients may have increased frequency, duration, or severity of angina at start of therapy or when dose is increased. Sublingual nitroglycerin may be used to control acute angina episodes.

Interchangeability

Two 30 mg Afeditab and Nifediac CC tablet may be interchanged with one 60 mg Afeditab or Nifediac CC tablets. Three 30 mg tablets are not considered interchangeable with a single 90 mg tablet.

MI

Immediate-release nifedipine should not be used within the first 2 wk following MI, and should be avoided in the setting of acute coronary syndrome.

Overdosage

Symptoms

Cardiogenic shock with pulmonary edema, dizziness, ECG abnormalities, flushing, functional rhythms, generalized edema, hypotension, hypoxia, loss of consciousness, marked and prolonged hypotension and bradycardia, metabolic acidosis, nausea, nervousness, palpitations, second- or third-degree AV block, vomiting.

Patient Information

  • Instruct patient to notify health care provider if condition does not appear to be improving or is worsening, or if bothersome side effects are noted.
  • Advise patient that dose of medication may be adjusted to obtain maximum benefit.
  • Advise patient taking immediate-release capsules to take 3 to 4 times daily as prescribed. Advise patient to swallow whole, without regard to meals, and not to chew or puncture capsule. Advise patient to take with food if stomach upset occurs.
  • Advise patient taking ER tablets to take once daily as prescribed, on an empty stomach. Caution patient to swallow ER tablets whole and not to crush, chew, cut, or break.
  • Advise patient using ER tablets that empty tablets may be seen in the stool, but they are the empty matrix that released the nifedipine for absorption. Advise patient not to be concerned because the active drug has already been absorbed.
  • Advise patient to try to take each dose at about the same time each day.
  • Inform patient that this drug controls, but does not cure, hypertension or angina and to continue taking as prescribed even when BP is not elevated or angina symptoms are not present.
  • Caution patient not to change the dose or stop taking unless advised by health care provider.
  • Instruct patient to continue taking other BP or angina medications as prescribed by health care provider.
  • Instruct patient being treated for angina to notify health care provider if frequency or severity of chest pain or need for sublingual nitroglycerin appears to be increasing.
  • Instruct patient in BP and pulse measurement skills.
  • Advise hypertensive patient to monitor and record BP and pulse at home and to inform health care provider if abnormal measurements are noted. Also advise patient to take record of BP and pulse to each follow-up visit.
  • Instruct patient to lie or sit down if experiencing dizziness or light-headedness when standing.
  • Advise patient to notify health care provider if any of the following occur: frequent episodes of dizziness when arising, swelling of lower legs or ankles, persistent fatigue, or any other unusual or unexplained symptom or sign.
  • Emphasize to hypertensive patient the importance of other modalities on BP: moderate intake of alcohol and salt, regular exercise, smoking cessation, weight control.

Copyright © 2009 Wolters Kluwer Health.

Questions about Atrial Fibrillation? Get answers from our expert. Watch Video

Close
Hide
(web5)