Yes: Capsule

Calcium Channel Blocker

Angina, hypertension (sustained release only), pulmonary hypertension

C

Clinical effects on the fetus: 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 and breast-feeding.

Breast-feeding/lactation: Crosses into breast milk. American Academy of Pediatrics considers compatible with breast-feeding.

Hypersensitivity to nifedipine or any component; immediately release preparation for treatment of urgent or emergent hypertension; acute MI

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).

>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 ( less than or equal to 2% to 7%), transient hypotension (dose-related 5%), CHF (2%)

Central nervous system: Nervousness/mood changes ( less than or equal to 2% to 7%), shakiness ( less than or equal to 2%), jitteriness ( less than or equal to 2%), sleep disturbances ( less than or equal to 2%), difficulties in balance ( less than or equal to 2%), fever ( less than or equal to 2%), chills ( less than or equal to 2%)

Gastrointestinal: Diarrhea ( less than or equal to 2%), constipation ( less than or equal to 2%), cramps ( less than or equal to 2%), flatulence ( less than or equal to 2%), gingival hyperplasia ( less than or equal to 10%)

Neuromuscular & skeletal: Muscle cramps/tremor ( less than or equal to 2% to 8%), weakness (10%), inflammation ( less than or equal to 2%), joint stiffness ( less than or equal to 2%)

Respiratory: Dyspnea/cough/wheezing (6%), nasal congestion/sore throat ( less than or equal to 2% to 6%), chest congestion ( less than or equal to 2%), shortness of breath ( less than or equal to 2%)

Ocular: Blurred vision ( less than or equal to 2%)

Dermatologic: Dermatitis ( less than or equal to 2%), pruritus ( less than or equal to 2%), urticaria ( less than or equal to 2%)

Endocrine and metabolic: Sexual difficulties ( less than or equal to 2%)

Miscellaneous: Sweating ( less than or equal to 2%)

<1% (Limited to important or life-threatening symptoms): Syncope, erythromelalgia, thrombocytopenia, anemia, leukopenia, purpura, allergic hepatitis, angioedema, gingival hyperplasia, depression, paranoid syndrome, transient blindness, tinnitus, nocturia, polyuria, arthritis with positive ANA, exfoliative dermatitis, gynecomastia, myalgia, memory dysfunction, fever, bezoars (sustained-release preparations), reflux, myoclonus, angina, ischemia, myoclonus

Case reports: Phototoxicity, EPS, aplastic anemia, agranulocytosis, purpura, Stevens-Johnson syndrome, cerebral ischemia, parotitis, dysgeusia, dysosmia, nocturnal enuresis, erythema multiforme

The primary cardiac symptoms of calcium blocker overdose include hypotension and bradycardia. The hypotension is caused by peripheral vasodilation, myocardial depression, and bradycardia. Bradycardia results from sinus bradycardia, second- or third-degree atrioventricular block, or sinus arrest with junctional rhythm. Intraventricular conduction is usually not affected so QRS duration is normal.

In a few reported cases, overdose with calcium channel blockers has been associated with hypotension and bradycardia, initially refractory to atropine but becoming more responsive to this agent when larger doses (approaching 1 g/hour for more than 24 hours) of calcium chloride was administered.

CYP3A3/4 and 3A5-7 enzyme substrate

Beta-blockers may have increased pharmacokinetic or pharmacodynamic interactions with nifedipine.

Calcium may reduce the calcium channel blocker's effects, particularly hypotension.

Cimetidine reduced diltiazem's metabolism; consider an alternative H₂ antagonist.

Cisapride increases nifedipine's effects; monitor blood pressure.

Ethanol increased nifedipine's AUC by 53%; watch for a greater hypotensive effect.

Grapefruit juice increases the bioavailability of nifedipine; monitor for altered nifedipine effects.

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.

Tacrolimus's serum concentrations are increased by verapamil; 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.

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

Onset of effect: Oral: Within 20 minutes

Protein binding: 92% to 98% (concentration-dependent)

Metabolism: In the liver to inactive metabolites

Bioavailability: Capsules: 45% to 75%; Sustained release: 65% to 86%

Half-life: Adults, normal: 2-5 hours; Adults with cirrhosis: 7 hours

Elimination: In urine

Oral:

Adolescents and Adults: ( Note: When switching from immediate release to sustained release formulations, total daily dose will start the same)

Initial: 10 mg 3 times/day as capsules or 30 mg once daily as sustained release

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.

Alcohol: Avoid use

Heart rate, blood pressure, signs and symptoms of CHF, peripheral edema

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.

Dizziness is common; may cause nervousness, sedation, or mood changes

May cause leukopenia; use caution with clozapine and carbamazepine; concurrent use with propranolol may increase AV nodal effects; barbiturates may decrease effects of nifedipine

No information available to require special precautions

Nifedipine has the greatest incidence in causing gingival hyperplasia than any other calcium channel blocker. Effects from the use of nifedipine (30-100 mg/day) have appeared after 1-9 months. Discontinuance of the drug 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 disappear. A switch to another calcium channel blocker probably may result in continued hyperplasia.

Take as directed; do not alter dosage regimen or increase, decrease, or discontinue without consulting prescriber. Do not crush or chew tablets or capsules. Consult prescriber before increasing exercise routine (decreased angina does not mean it is safe to increase exercise). Change position slowly to prevent orthostatic events. May cause dizziness or fatigue; use caution when driving or engaging in tasks that require alertness until response to drug is known. Maintain good oral care and inspect gums for swelling or redness. May cause frequent urination at night. Report irregular heartbeat, swelling, difficulty breathing or new cough, unresolved fatigue, unusual weight gain, unresolved dizziness or constipation, and swollen or bleeding gums. Pregnancy precautions: Inform prescriber if you are or intend to be pregnant.

May cause some patients to urinate frequently at night; may cause inflamed gums

Capsule, liquid-filled (Adalat®, Procardia®): 10 mg, 20 mg

Tablet, extended release (Adalat® CC): 30 mg, 60 mg, 90 mg

Tablet, sustained release (Procardia XL®): 30 mg, 60 mg, 90 mg

Clifton GD, Booth DC, Hobbs S, et al, "Negative Inotropic Effect of Intravenous Nifedipine in Coronary Artery Disease: Relation to Plasma Levels," Am Heart J, 1990, 119(2 Pt 1):283-90.

Deen-Duggins L, Fry HR, Clay JR, et al, "Nifedipine-Associated Gingival Overgrowth: A Survey of the Literature and Report of Four Cases," Quintessence Int, 1996, 27(3):163-70.

Dilmen U, Çaglar MK, Senses A, et al, "Nifedipine in Hypertensive Emergencies of Children," Am J Dis Child, 1983, 137(12):1162-5.

Ferner RE, Monkman S, Riley J, et al, "Pharmacokinetics and Toxic Effects of Nifedipine in Massive Overdose," Hum Exp Toxicol, 1990, 9(5):309-11.

Harel-Raviv M, Eckler M, Lalani K, et al, "Nifedipine-Induced Gingival Hyperplasia. A Comprehensive Review and Analysis," Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 1995, 79(6):715-22.

Hata T, Manabe A, Hata K, et al, "Changes in Blood Velocities of Fetal Circulation in Association With Fetal Heart Rate Abnormalities: Effect of Sublingual Administration of Nifedipine," Am J Perinatol, 1995, 12(2):80-1.

Howarth DM, Dawson AH, Smith AJ, et al, "Calcium Channel Blocking Drug Overdose: An Australian Series," Hum Exp Toxicol, 1994, 13(3):161-6.

Kahn JK, "Nifedipine-Associated Acute Psychosis," Am J Med, 1986, 81(4):705-6.

Lederman D, Lumerman H, Reuben S, et al, "Gingival Hyperplasia Associated With Nifedipine Therapy," Oral Surg Oral Med Oral Pathol, 1984, 57(6):620-2.

Lopez-Herce J, Albajara L, Cagigas P, et al, "Treatment of Hypertensive Crisis in Children With Nifedipine," Intensive Care Med, 1988, 14(5):519-21.

Lucas RM, Howell LP, and Wall BA, "Nifedipine-Induced Gingival Hyperplasia: A Histochemical and Ultrastructural Study," J Periodontol, 1985, 56(4):211-5.

Nery EB, Edson RG, Lee KK, et al, "Prevalence of Nifedipine-Induced Gingival Hyperplasia," J Periodontol, 1995, 66(7):572-8.

Nishikawa SJ, Tada H, Hamasaki A, et al, "Nifedipine-Induced Gingival Hyperplasia: A Clinical and In Vitro Study," J Periodontol, 1991, 62(1):30-5.

Ramsdale DR, Morris JL, and Hardy P, "Gingival Hyperplasia With Nifedipine," Br Heart J, 1995, 73(2):115.

Rosen WJ and Johnson CE, "Evaluation of Five Procedures for Measuring Nonstandard Doses of Nifedipine Liquid," Am J Hosp Pharm, 1989, 46(11):2313-7.

Saito K, Mori S, Iwakura M, et al, "Immunohistochemical Localization of Transforming Growth Factor Beta, Basic Fibroblast Growth Factor and Heparin Sulphate Glycosaminoglycan in Gingival Hyperplasia Induced by Nifedipine and Phenytoin," J Periodontal Res, 1996, 31(8):545-5.

Silfvast T, Kinnunen A, and Varpula T, "Laryngeal Oedema After Isosorbide Dinitrate Spray and Sublingual Nifedipine," BMJ, 1995, 311(6999):232.

Silverstein LH, Koch JP, Lefkove MD, et al, "Nifedipine-Induced Gingival Enlargement Around Dental Implants: A Clinical Report," J Oral Implantol, 1995, 21(2):116-20.

Westbrook P, Bednarczyk EM, Carlson M, et al, "Regression of Nifedipine-Induced Gingival Hyperplasia Following Switch to a Same Class Calcium Channel Blocker, Isradipine," J Periodontol, 1997, 68(7):645-50.

Whitebloom D and Fitzharris J, "Nifedipine Overdose," Clin Cardiol, 1988, 11(7):505-6.

Wynn RL, "Calcium Channel Blockers and Gingival Hyperplasia," Gen Dent, 1991, 39(4):240-3.

Wynn RL, "Update on Calcium Channel Blocker-Induced Gingival Hyperplasia," Gen Dent, 1995, 43(3):218-22.