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Medication Safety Issues
Sound-alike/look-alike issues:
NIFEdipine may be confused with niCARdipine, niMODipine, nisoldipine
Procardia XL® may be confused with Cartia® XT
International issues:
Nipin® [Italy and Singapore] may be confused with Nipent® which is a brand name for pentostatin in the U.S.
Pronunciation
(nye FED i peen)
U.S. Brand Names
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Angina and hypertension (sustained release only), pulmonary hypertension
Pregnancy Risk Factor
C
Pregnancy Considerations
Use in pregnancy only when clearly needed and when the benefits outweigh the potential hazard to the fetus. No data on crossing the placenta. Hypotension, IUGR reported. IUGR probably related to maternal hypertension. May exhibit tocolytic effects. Available evidence suggests safe use during pregnancy.
Lactation
Enters breast milk/compatible
Breast-Feeding Considerations
Crosses into breast milk. Available evidence suggests safe use during breast-feeding. AAP considers compatible with breast-feeding.
Contraindications
Hypersensitivity to nifedipine or any component of the formulation; immediate release preparation for treatment of urgent or emergent hypertension; acute MI
Warnings/Precautions
Concerns related to adverse effects:
• Angina/MI: Increased angina and/or MI has occurred with initiation or dosage titration of calcium channel blockers.
• Hypotension/syncope: Symptomatic hypotension with or without syncope can rarely occur; blood pressure must be lowered at a rate appropriate for the patient's clinical condition. The use of sublingual short-acting nifedipine in hypertensive emergencies and urgencies is neither safe nor effective and SHOULD BE ABANDONED! Serious adverse events (eg, cerebrovascular ischemia, syncope, stroke, acute myocardial infarction, and fetal distress) have been reported in relation to such use.
• Peripheral edema: The most common side effect is peripheral edema; occurs within 2-3 weeks of starting therapy.
• Reflex tachycardia: May occur with use.
Disease-related concerns:
• Aortic stenosis: Use with caution in patients with severe aortic stenosis.
• Heart failure (HF): Use with caution in patients with HF; may cause worsening of symptoms.
• Hepatic impairment: Use with caution in patients with hepatic impairment; may require lower starting dose.
• Idiopathic hypertrophic subaortic stenosis (IHSS): Use with caution in patients with IHSS.
Concurrent drug therapy issues:
• Beta-blockers and fentanyl: Severe hypotension may occur in patients taking immediate release nifedipine concurrently with beta-blockers when undergoing CABG with high dose fentanyl anesthesia. When considering surgery with high dose fentanyl, may consider withdrawing nifedipine (>36 hours) before surgery if possible.
Special populations:
• Elderly: The elderly may be more susceptible to adverse effects.
Dosage form specific issues:
• Extended release formulation: Consists of drug within a nondeformable matrix; following drug release/absorption, the matrix/shell is expelled in the stool. The use of nondeformable products in patients with known stricture/narrowing of the GI tract has been associated with symptoms of obstruction.
Other warnings/precautions:
• Withdrawal: Abrupt withdrawal may cause rebound angina in patients with CAD.
Adverse Reactions
>10%:
Cardiovascular: Flushing (10% to 25%), peripheral edema (dose related 7% to 10%; up to 50%)
Central nervous system: Dizziness/lightheadedness/giddiness (10% to 27%), headache (10% to 23%)
Gastrointestinal: Nausea/heartburn (10% to 11%)
Neuromuscular & skeletal: Weakness (10% to 12%)
?1% to 10%:
Cardiovascular: Palpitation (?2% to 7%), transient hypotension (dose related 5%), CHF (2%)
Central nervous system: Nervousness/mood changes (?2% to 7%), shakiness (?2%), jitteriness (?2%), sleep disturbances (?2%), difficulties in balance (?2%), fever (?2%), chills (?2%)
Dermatologic: Dermatitis (?2%), pruritus (?2%), urticaria (?2%)
Endocrine & metabolic: Sexual difficulties (?2%)
Gastrointestinal: Diarrhea (?2%), constipation (?2%), cramps (?2%), flatulence (?2%), gingival hyperplasia (?10%)
Neuromuscular & skeletal: Muscle cramps/tremor (?2% to 8%), inflammation (?2%), joint stiffness (?2%)
Ocular: Blurred vision (?2%)
Respiratory: Cough/wheezing (6%), nasal congestion/sore throat (?2% to 6%), chest congestion (?2%), dyspnea (?2%)
Miscellaneous: Diaphoresis (?2%)
<1% (Limited to important or life-threatening): Syncope, erythromelalgia, thrombocytopenia, anemia, leukopenia, purpura, allergic hepatitis, angioedema, gingival hyperplasia, depression, paranoid syndrome, transient blindness, tinnitus, nocturia, photosensitivity, polyuria, arthritis with positive ANA, exfoliative dermatitis, gynecomastia, myalgia, memory dysfunction, fever, bezoars (sustained-release preparations), reflux, myoclonus, angina, ischemia, myoclonus
Postmarketing and/or case reports: EPS, aplastic anemia, agranulocytosis, purpura, Stevens-Johnson syndrome, cerebral ischemia, parotitis, dysgeusia, dysosmia, nocturnal enuresis, erythema multiforme
Reported with use of sublingual short-acting nifedipine: Cerebrovascular ischemia, syncope, heart block, stroke, sinus arrest, severe hypotension, acute MI, ECG changes, and fetal distress
Metabolism/Transport Effects
Substrate of CYP2D6 (minor), 3A4 (major); Inhibits CYP1A2 (moderate), 2C9 (weak), 2D6 (weak), 3A4 (weak)
Drug Interactions
Alcohol (Ethyl): May increase the serum concentration of NIFEdipine. Risk C: Monitor therapy
Alpha1-Blockers: May enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of Calcium Channel Blockers. Risk D: Consider therapy modification
Barbiturates: May increase the metabolism of Calcium Channel Blockers. Risk D: Consider therapy modification
Calcium Channel Blockers (Nondihydropyridine): May enhance the hypotensive effect of Calcium Channel Blockers (Dihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy
Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Risk C: Monitor therapy
Carbamazepine: May increase the metabolism of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy
Cimetidine: May decrease the metabolism of Calcium Channel Blockers. Risk D: Consider therapy modification
Cisapride: May increase the serum concentration of NIFEdipine. Reported with sustained release nifedipine product. Risk C: Monitor therapy
CycloSPORINE: May decrease the metabolism of Calcium Channel Blockers (Dihydropyridine). Nicardipine may likewise inhibit the metabolism of cyclosporine. Cyclosporine dosage adjustments might be needed. Risk C: Monitor therapy
CYP1A2 Substrates: CYP1A2 Inhibitors (Moderate) may decrease the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Fluconazole: May decrease the metabolism of Calcium Channel Blockers. Risk C: Monitor therapy
Grapefruit Juice: May decrease the metabolism of Calcium Channel Blockers. Risk C: Monitor therapy
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Macrolide Antibiotics: May decrease the metabolism of Calcium Channel Blockers. Exceptions: Azithromycin; Dirithromycin [Off Market]; Spiramycin. Risk D: Consider therapy modification
Magnesium Salts: Calcium Channel Blockers may enhance the adverse/toxic effect of Magnesium Salts. Magnesium Salts may enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Nafcillin: May increase the metabolism of Calcium Channel Blockers. Risk D: Consider therapy modification
Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Nitroprusside: Calcium Channel Blockers may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Phenytoin: Calcium Channel Blockers may decrease the metabolism of Phenytoin. Risk D: Consider therapy modification
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Protease Inhibitors: May decrease the metabolism of Calcium Channel Blockers (Dihydropyridine). Risk D: Consider therapy modification
Quinidine: Calcium Channel Blockers (Dihydropyridine) may decrease the serum concentration of Quinidine. Risk C: Monitor therapy
Quinupristin: May decrease the metabolism of Calcium Channel Blockers. Risk C: Monitor therapy
Rifamycin Derivatives: May increase the metabolism of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers. Risk D: Consider therapy modification
Rituximab: Antihypertensives may enhance the hypotensive effect of Rituximab. Risk D: Consider therapy modification
Tacrolimus: Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of Tacrolimus. Risk C: Monitor therapy
VinCRIStine: NIFEdipine may decrease the excretion of VinCRIStine. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may increase CNS depression and may increase the effects of nifedipine). Monitor.
Food: Nifedipine serum levels may be decreased if taken with food. Food may decrease the rate but not the extent of absorption of Procardia XL®. Increased therapeutic and vasodilator side effects, including severe hypotension and myocardial ischemia, may occur if nifedipine is taken by patients ingesting grapefruit.
Herb/Nutraceutical: St John's wort may decrease nifedipine levels. Avoid dong quai if using for hypertension (has estrogenic activity). Avoid ephedra, yohimbe, ginseng (may worsen hypertension). Avoid garlic (may have increased antihypertensive effect).
Mechanism of Action
Inhibits calcium ion from entering the “slow channels” or select voltage-sensitive areas of vascular smooth muscle and myocardium during depolarization, producing a relaxation of coronary vascular smooth muscle and coronary vasodilation; increases myocardial oxygen delivery in patients with vasospastic angina
Pharmacodynamics/Kinetics
Onset of action: Immediate release: ~20 minutes
Protein binding (concentration dependent): 92% to 98%
Metabolism: Hepatic to inactive metabolites
Bioavailability: Capsule: 40% to 77%; Sustained release: 65% to 89% relative to immediate release capsules
Half-life elimination: Adults: Healthy: 2-5 hours, Cirrhosis: 7 hours; Elderly: 6.7 hours
Excretion: Urine (as metabolites)
Dosage
Oral:
Children:
Hypertrophic cardiomyopathy: 0.6-0.9 mg/kg/24 hours in 3-4 divided doses
Hypertension: Children 1-17 years: Extended release tablet: Initial: 0.25-0.5 mg/kg/day once daily or in 2 divided doses; maximum: 3 mg/kg/day up to 120 mg/day
Adults: (Note: When switching from immediate release to sustained release formulations, total daily dose will start the same)
Initial: 30 mg once daily as sustained release formulation, or if indicated, 10 mg 3 times/day as capsules
Usual dose: 10-30 mg 3 times/day as capsules or 30-60 mg once daily as sustained release
Maximum dose: 120-180 mg/day
Increase sustained release at 7- to 14-day intervals
Hemodialysis: Supplemental dose is not necessary.
Peritoneal dialysis effects: Supplemental dose is not necessary.
Dosing adjustment in hepatic impairment: Reduce oral dose by 50% to 60% in patients with cirrhosis.
Administration: Oral
Immediate release: In general, may be administered with or without food.
Extended release: Tablets should be swallowed whole; do not crush or chew.
Adalat®CC, Afeditab™ CR, Nifediac™ CC: Administer on an empty stomach (per manufacturer). Other extended release products may not have this recommendation; consult product labeling.
Monitoring Parameters
Heart rate, blood pressure, signs and symptoms of CHF, peripheral edema
Dietary Considerations
Avoid grapefruit juice with all products.
Immediate release: Capsule is rapidly absorbed orally if it is administered without food, but may result in vasodilator side effects; if flushing is problematic, administration with low-fat meals may decrease. In general, can take with or without food.
Extended release: Adalat®CC, Afeditab™ CR, Nifediac™ CC: Take on an empty stomach (manufacturer recommendation). Other extended release products may not have this recommendation; consult product labeling.
Patient Education
Do not take any new medication or over-the-counter medications, or herbal products during therapy unless approved by prescriber (especially anything that may act as a stimulant or depressant). Take exactly as directed; do not alter dose or decrease without consulting prescriber. Do not crush or chew sustained release forms, swallow whole. Avoid grapefruit juice and excess alcohol or caffeine. Consult prescriber before increasing exercise routine (decreased angina does not mean it is safe to increase exercise). May cause orthostatic hypotension (change position slowly from sitting or lying to standing, or when climbing stairs); sore mouth (inspect gums for swelling or redness, use soft toothbrush, waxed dental floss, and frequent mouth rinses); dizziness, difficulties in balance, or fatigue (use caution when driving or engaging in tasks that require alertness until response to drug is known); or nausea or heartburn (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help). Report chest pain, palpitations, rapid heartbeat; swelling of extremities; muscle weakness or pain; respiratory difficulty; nervousness or mood change, rash; or vision changes. Pregnancy precaution: Inform prescriber if you are or intend to become pregnant.
Geriatric Considerations
Elderly may experience a greater hypotensive response. Theoretically, constipation may be more of a problem in elderly patients. The half-life of nifedipine is extended in elderly patients (6.7 hours) as compared to younger subjects (3.8 hours).
Additional Information
When measuring smaller doses from the liquid-filled capsules, consider the following concentrations (for Procardia®) 10 mg capsule = 10 mg/0.34 mL; 20 mg capsule = 20 mg/0.45 mL; may be used preoperative to treat hypertensive urgency.
Considerable attention has been directed to potential increases in mortality and morbidity when short-acting nifedipine is used in treating hypertension. The rapid reduction in blood pressure may precipitate adverse cardiovascular events. At this time, there is no indication for the use of short-acting calcium channel blocker therapy. Nifedipine also has potent negative inotropic effects and can worsen heart failure.
Anesthesia and Critical Care Concerns/Other Considerations
Considerable attention has been directed to potential increases in mortality and morbidity when short-acting nifedipine is used in treating hypertension. The rapid reduction in blood pressure may precipitate adverse cardiovascular events. At this time, there is no indication for the use of short-acting calcium channel blocker therapy for angina and hypertension. Nifedipine also has potent negative inotropic effects and can worsen heart failure.
Cardiovascular Considerations
Considerable attention has been directed to potential increases in mortality and morbidity when short-acting nifedipine is used in treating hypertension. The rapid reduction in blood pressure may precipitate adverse cardiovascular events. At this time, there is no indication for the use of short-acting calcium channel blocker therapy for angina and hypertension. Nifedipine also has potent negative inotropic effects and can worsen heart failure.
In the treatment of unstable angina/non-ST-segment elevation MI, a nondihydropyridine calcium antagonist (diltiazem or verapamil) may be considered in patients with continuing or frequently recurring ischemia when beta-blockers are contraindicated (Class I). Oral long-acting calcium antagonists may also be considered in addition to beta-blockers and nitrates (Class IIa).
Dental Health: Effects on Dental Treatment
Nifedipine has been reported to cause 10% incidence of gingival hyperplasia; effects from 30-100 mg/day have appeared after 1-9 months. Discontinuance results in complete disappearance or marked regression of symptoms; symptoms will reappear upon remedication. Marked regression occurs after 1 week and complete disappearance of symptoms has occurred within 15 days. If a gingivectomy is performed and use of the drug is continued or resumed, hyperplasia usually will recur. The success of the gingivectomy usually requires that the medication be discontinued or that a switch to a noncalcium channel blocker be made. If for some reason nifedipine cannot be discontinued, hyperplasia has not recurred after gingivectomy when extensive plaque control was performed. If nifedipine is changed to another class of cardiovascular agent, the gingival hyperplasia will probably regress and resolve. Switching to another calcium channel blocker may result in continued hyperplasia.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Dizziness is common; may cause nervousness, sedation, or mood changes
Mental Health: Effects on Psychiatric Treatment
May cause leukopenia; use caution with clozapine and carbamazepine; concurrent use with propranolol may increase AV nodal effects; barbiturates may decrease effects of nifedipine
Nursing: Physical Assessment/Monitoring
Use caution in severe aortic stenosis or severe hepatic impairment. Assess potential for interactions with other pharmacological agents or herbal products patient is taking that may increase risk of hypotension and toxicity. Assess therapeutic effectiveness (blood pressure and cardiac status) and adverse reactions (eg, hypotension, peripheral edema, gastrointestinal upset, CNS changes) when starting, adjusting dose, or discontinuing. Teach patient proper use, possible side effects/appropriate interventions (eg, orthostatic precautions), and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, softgel: 10 mg, 20 mg
Procardia®: 10 mg
Tablet, extended release: 30 mg, 60 mg, 90 mg
Adalat® CC, Procardia XL®: 30 mg, 60 mg, 90 mg
Afeditab™ CR, Nifedical™ XL: 30 mg, 60 mg
Nifediac™ CC: 30 mg, 60 mg, 90 mg [90 mg tablet contains tartrazine]
Pricing: U.S. (www.drugstore.com)
Capsules (NIFEdipine)
10 mg (90): $65.99
20 mg (90): $109.99
Capsules (Procardia)
10 mg (90): $92.73
Tablet, 24-hour (Adalat CC)
30 mg (30): $49.99
90 mg (30): $90.99
Tablet, 24-hour (Afeditab CR)
30 mg (30): $39.99
60 mg (30): $57.92
Tablet, 24-hour (Nifediac CC)
30 mg (100): $108.99
60 mg (30): $49.99
90 mg (30): $60.99
Tablet, 24-hour (Nifedical XL)
30 mg (30): $32.99
60 mg (30): $55.99
Tablet, 24-hour (NIFEdipine CR Osmotic)
30 mg (30): $33.99
60 mg (30): $59.99
90 mg (30): $67.99
Tablet, 24-hour (Procardia XL)
30 mg (30): $64.99
60 mg (30): $104.99
90 mg (30): $115.49
References
Braunwald E, Antman EM, Beasley JW, et al, “ACC/AHA Guidelines for the Management of Patients With Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina),” J Am Coll Cardiol, 2000, 36(3):970-1062.
Chobanian AV, Bakris GL, Black HR, et al, “The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report,” JAMA, 2003, 289(19):2560-71.
Furberg Cd, Psaty BM, and Meyer JV, “Nifedipine: Dose-Related Increase in Mortality in Patients With Coronary Heart Disease,” Circulation, 1995, 92(5):1326-31.
Grossman E, Messerli FH, Grodzicki T, et al, “Should a Moratorium Be Placed on Sublingual Nifedipine Capsules Given for Hypertensive Emergencies and Pseudoemergencies?” JAMA, 1996, 276(16):1328-31.
Ishikawa K, Nakai S, Takenaka T, et al, “Short-Acting Nifedipine and Diltiazem Do Not Reduce the Incidence of Cardiac Events in Patients With Healed Myocardial Infarction. Secondary Prevention Group,” Circulation, 1997, 95(10):2368-73.
Messerli FH, Kowey P, and Grodzicki T, “Sublingual Nifedipine for Hypertensive Emergencies,” Lancet, 1991, 338(8771):881.
National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents, “The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents,” Pediatrics, 2004, 114(2 Suppl):555-76.
Psaty BM, Heckbert SR, Koepsell TD, et al, “The Risk of Myocardial Infarction Associated With Antihypertensive Therapies,” JAMA, 1995, 274(8):620-5.
Scognamiglio R, Rahimtoola SH, Fasoli G, et al, “Nifedipine in Asymptomatic Patients With Severe Aortic Regurgitation and Normal Left Ventricular Function,” N Engl J Med, 1994, 331(11):689-94.
Steele RM, Schuna AA, and Schreiber RT, “Calcium Antagonist-Induced Gingival Hyperplasia,” Ann Intern Med, 1994, 120(8):663-4.
International Brand Names
Lexi-Comp.com
Last full review/revision August 2008
Content last modified August 2008
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