U.S. Brand Names:
Adalat® CC; Afeditab™; Nifediac™ CC; Nifedical™ XL; Procardia®; Procardia XL®
Generic Available:
Yes
Canadian Brand Names:
Adalat® XL®; Apo-Nifed®; Apo-Nifed PA®; Novo-Nifedin; Nu-Nifed; Procardia®
Use:
Angina and hypertension (sustained release only), pulmonary hypertension
Pregnancy Risk Factor:
C
Pregnancy Implications:
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
Contraindications:
Hypersensitivity to nifedipine or any component of the formulation; immediate release preparation for treatment of urgent or emergent hypertension; acute MI
Warnings/Precautions:
The use of sublingual short-acting nifedipine in hypertensive emergencies and pseudoemergencies is neither safe nor effective and SHOULD BE ABANDONED! Serious adverse events (cerebrovascular ischemia, syncope, heart block, stroke, sinus arrest, severe hypotension, acute myocardial infarction, ECG changes, and fetal distress) have been reported in relation to such use.
Blood pressure lowering should be done at a rate appropriate for the patient's condition. Rapid drops in blood pressure can lead to arterial insufficiency. Increased angina and/or MI has occurred with initiation or dosage titration of calcium channel blockers. Use caution in severe aortic stenosis. Use caution in patients with severe hepatic impairment (may need dosage adjustment). Abrupt withdrawal may cause rebound angina in patients with CAD. Use caution in CHF (may cause worsening of symptoms). The 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. Avoid grapefruit juice during treatment with nifedipine.
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: Palpitations (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%), weakness (10%), 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
Overdosage/Toxicology:
Primary cardiac symptoms of calcium blocker overdose include hypotension and bradycardia. Noncardiac symptoms include confusion, stupor, nausea, vomiting, metabolic acidosis, and hyperglycemia. Following initial gastric decontamination, treat symptomatically.
Drug Interactions:
Substrate of CYP2D6 (minor), 3A4 (major);
Inhibits CYP1A2 (moderate), 2C8/9 (weak), 2D6 (weak), 3A4 (weak)
Azole antifungals may inhibit the calcium channel blocker's metabolism; avoid this combination. Try an antifungal like terbinafine (if appropriate) or monitor closely for altered effect of the calcium channel blocker.
Beta-blockers may have increased pharmacokinetic or pharmacodynamic interactions with nifedipine.
Calcium may reduce the calcium channel blocker's effects, particularly hypotension.
Cimetidine: Cimetidine may increase nifedipine serum concentrations.
Cisapride increases nifedipine's effects; monitor blood pressure.
CYP1A2 substrates: Nifedipine may increase the levels/effects of CYP1A2 substrates. Example substrates include aminophylline, fluvoxamine, mexiletine, mirtazapine, ropinirole, theophylline, and trifluoperazine.
CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of nifedipine. Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins.
CYP3A4 inhibitors: May increase the levels/effects of nifedipine. Example inhibitors include azole antifungals, ciprofloxacin, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, and verapamil.
Ethanol increased nifedipine's AUC by 53%; watch for a greater hypotensive effect.
Grapefruit juice increases the bioavailability of nifedipine; avoid grapefruit juice.
Nafcillin decreases plasma concentration of nifedipine; avoid this combination.
Phenobarbital reduces the plasma concentration of nifedipine. May require much higher dose of nifedipine.
Protease inhibitor like amprenavir and ritonavir may increase nifedipine's serum concentration.
Quinidine's serum concentration is reduced and nifedipine's is increased; adjust doses as needed.
Rifampin increases the metabolism of the calcium channel blocker; adjust the dose of the calcium channel blocker to maintain efficacy.
Sildenafil, tadalafil, vardenafil: Blood pressure-lowering effects may be additive; use caution
Tacrolimus's serum concentrations are increased by nifedipine; avoid the combination. Use another calcium channel blocker or monitor tacrolimus trough levels and renal function closely.
Vincristine's half-life is increased by nifedipine; monitor closely for vincristine dose adjustment.
Ethanol/Nutrition/Herb Interactions:
Ethanol: Avoid ethanol (may increase CNS depression).
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: ~20 minutes
Protein binding (concentration dependent): 92% to 98%
Metabolism: Hepatic to inactive metabolites
Bioavailability: Capsules: 45% to 75%; Sustained release: 65% to 86%
Half-life elimination: Adults: Healthy: 2-5 hours, Cirrhosis: 7 hours; Elderly: 6.7 hours
Excretion: Urine
Dosage:
Oral:
Children: Hypertrophic cardiomyopathy: 0.6-0.9 mg/kg/24 hours in 3-4 divided doses
Adolescents and 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:
Extended release tablets should be swallowed whole; do not crush or chew.
Monitoring Parameters:
Heart rate, blood pressure, signs and symptoms of CHF, peripheral edema
Dietary Considerations:
Capsule is rapidly absorbed orally if it is administered without food, but may result in vasodilator side effects; administration with low-fat meals may decrease flushing. Avoid grapefruit juice.
Patient Education:
Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. Take as directed; do not alter dose or decrease without consulting prescriber. Do not crush or chew sustained release forms, swallow whole. Take with nonfatty food. Avoid caffeine, alcohol, and grapefruit juice. 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.
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
Dosage Forms:
[DSC] = Discontinued product
Capsule, liquid-filled: 10 mg, 20 mg
Procardia®: 10 mg; 20 mg [DSC]
Tablet, extended release: 30 mg, 60 mg, 90 mg
Adalat® CC, Nifediac™ CC, Procardia XL®: 30 mg, 60 mg, 90 mg
Afeditab™, Nifedical™ XL: 30 mg, 60 mg
International Brand Names:
Adalat® (AR, AT, AU, BE, BR, CH, CL, CY, CZ, DE, DK, EG, ES, FI, GB, HK, HR, HU, ID, IE, IT, JO, JP, KW, LB, LU, MT, MX, NL, NO, NZ, PL, PT, SE, SI, TH, TR, ZA); Adalat CC® (MX, PL); Adalat® CR (RO, TH); Adalate® (FR); Adalat® Eins (RO); Adalat LA® (GB, SG); Adalat Oros® (AR, AU, BE, BR, CL, CO, CR, DO, EC, FI, GT, HN, ID, MX, NO, PA, SE, SI, SV); Adalat Retard® (AR, BE, BR, CH, CL, GB, ID, MX, TH); Adalat SL® (PL); Adalat® XL® (CA); Adipine® (GB); Alpha-Nifedipine® (NZ); Ampine® (BD); Angiodisten® (CL); Angiopine® (GB); Apo-Nifed® (CA, CZ, PL); Apo-Nifedipine® (ZA); Apo-Nifed PA® (CA, SG); Aprical® (DE, LU); Atanaal® (JP); Biocord® (BR); BSP Nifedipine® (ZA); Buconif® (AT); Calcianta® (ID); Calcigard® (IN, RU, TH); Cardalin® (BR); Cardicon® (CL); Cardicon Retard® (CL); Cardicon S/R® (CL); Cardifen® (ZA); Cardilate MR® (GB); Cardilat® (ZA); Cardipin® (CH); Carvas® (ID); Chronadalate® (FR); Cipalat® (ZA); Cisday® (DE); Citilat® (IT); Coracten® (CY, HK, JO, KW, LB, SY, TH); Coracten SR® (GB); Coracten XL® (GB); Coral® (IT); Cordafen® (CZ, PL, RU); Cordaflex® (HU, RO, RU); Cordalat® (ID); Cordicant® (DE); Cordipin® (CZ, HR, HU, PL, RO, RU, SG, SI, YU); Corinfar® (CZ, DE, HU, PL, RO, RU); Coroday MR® (GB); Coronovo® (CL); Corotrend® (CH, DE, MX); Depin-E® (RU, ZA); Dignokonstant® (DE); Dilaflux® (BR); Dilcor® (ES); Ditrenil® (TH); duranifin® (DE); Ecodipin® (CH); Epilat® (JO, KW, LB, RO); Euxat® (IT); Farmalat® (ID); Fedip® (AT); Fedipin® (ID); Fenamon® (HK, RU, SG, TH); Fenidina® (IT); Ficard® (BD); Fortipine LA 40® (GB); Hexadilat® (DK); Hypan® (BE); Hypolar® (GB); It-Nifedichem® (EC); Jedipin® (DE); Jutadilat® (DE); Kardilat® (TR); Kemolat® (ID); Majolat® (AT); Megalat® (IL); MTW-Nifedipin retard® (DE); Myogard® (IN); Nadipinia® (HK); Nelapine® (TH); Nicardia® (IN, RU); Nicodin® (BD); Nidicard® (TR); Nidilat® (TR); Nidipine/Nidipine SR® (BD); Nifadil® (RO); Nifangin® (FI); Nifdemin® (FI); Nife 1A Pharma® (DE); Nife AbZ® (DE); Nife-basan® (CH); Nifebene® (AT, CZ, RU); Nife Biochemie® (DE); Nifecard® (AU, HK, ID, LB, PL, RO, RU, SI, TH); Nifecard XL® (CZ, HU, SG); Nifeclair® (DE); Nifecodan® (DK); Nifecor® (AR, DE); Nifedalat® (ZA); Nifedate® (PT); Nifedicor® (CH, IT, PL, RU); Nifedicron® (IT); Nifed® (IE); Nifedin® (BR, EC, ID); Nifedine® (IN); Nifedipat® (DE); Nifedip® (DO); Nifedipin 1 A Pharma® (DE); Nifedipin 20 SR® (RO); Nifedipina Alter® (PT); Nifedipina® (AR, BR); Nifedipina BIG® (IT); Nifedipin acis® (DE); Nifedipina DOC® (IT); Nifedipina Dorom® (IT); Nifedipina Edmond® (IT); Nifedipina EG® (IT); Nifedipina GNR® (IT); Nifedipina Hexan® (IT); Nifedipin AL® (DE, HU); Nifedipina Merck® (IT); Nifedipina-ratiopharm® (IT); Nifedipina Retard® (AR); Nifedipina Retard Feltrex® (DO); Nifedipin Atid® (DE); Nifedipin Basics® (DE); Nifedipin® (BG); Nifedipin-Cophar® (CH); Nifedipin "Crosspharma"® (DK); Nifedipine Alpharma Aps® (SG); Nifedipine-BC (AU); Nifedipine® (GB, PL); Nifedipine LA® (SG); Nifedipine-Teva® (IL); Nifedipin Genericon® (AT); Nifedipin Helvepharm® (CH); Nifedipin Heumann® (DE); Nifedipin® (HR, NO, RO, RU, YU); Nifedipin-Mepha® (CH); Nifedipino Bayvit® (ES); Nifedipino® (BR, CL); Nifedipino Genfar® (EC); Nifedipino Juste® (ES); Nifedipino L.CH.® (CL); Nifedipino MK® (CR, DO, GT, HN, PA, SV); Nifedipino Ratiopharm® (ES); Nifedipino Retard® (CL); Nifedipino Retard L.CH.® (CL); Nifedipin PB® (DE); Nifedipin Pharmavit® (HU, RO); Nifedipin Pliva® (HR); Nifedipin-ratiopharm® (BE, DE, LU, RU); Nifedipin Sandoz® (DE); Nifedipin Stada® (AT, DE, LU, SG, TH); Nifedipin T 20 Stada Ret.® (RO); Nifedipin Verla® (DE); Nifedipres® (MX); Nifedipress® (GB); Nifegis® (PL); Nifehexal® (AT, AU, DE, LU, PL, RU); Nife-Isis® (DE); Nifelan® (NO); Nifelat® (AR, BR, CY, DE, IN, RO, RU, TH, YU); Nifelat Q® (TH); Nifelease® (IE); Nifensar® (IE); Nife-Puren® (DE); Nifesan® (CZ); Nifeslow® (BE, LU); nife von ct® (DE, RO); Nife-Wolff® (DE); Nifical® (DE); Nifical-Tablinen® (DE); Nificard® (RU); Nifidine® (ZA); Nifin® (BD); Nifiran® (TH); Nifopress® (GB); Nipidin® (YU); Nipin® (IT, SG); Novo-Nifedin (CA); Nu-Nifed (CA); Nyefax® (AU, TH); Nyefax Retard® (NZ); Osmo-Adalat® (IL, RU); Ospocard® (AT); Oxcord® (BR); Pabalat® (CL); Pertensal® (ES); Pidilat® (CZ, DE); Pincard® (ID); Pinifed® (IE); Pressolat® (IL); Procardia® (CA); Prudencial® (AR); Rolab-Diltiazem HCl® (ZA); Rolab-Nifedipine® (ZA); Sanfidipin® (RO); Slofedipine® (GB); Slofedipine XL® (GB); Slow-Nifine® (LU); Sponif® (RU); Sulotil Retard® (CL); Supracordin® (CZ); Systepin® (IE); Tensipine MR® (GB); Tensomax® (CR, DO, GT, PA, SV); Tensopin® (CR, DO, GT, PA, SV); Unidipin® (AT, LU); Vascard® (ZA); Vasdalat® (ID, SG); Vasofed® (IE); Xepalat® (ID); Zenusin® (PL, PT)
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.
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.
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