Calcium Channel Blockers: Nifedipine
Indication
Nifedipine is used in adults for the treatment of angina, hypertrophic cardiomyopathy, and hypertension (extended-release forms of the drug). In pediatric patients, it is predominantly used to treat systemic hypertension and hypertrophic cardiomyopathy.
Mechanism of Action
Nifedipine prevents calcium ions from entering both vascular smooth muscle cells and myocardial cells via specific slow calcium channels. Thus, it decreases the intracellular concentration of calcium such that less calcium is available to bind to contractile proteins in these cells. This results in vasodilation, including the coronary arteries, and a negative inotropic effect. The negative inotropic effect of nifedipine is less clinically significant than its vasodilatory effect.
Dosing
Neonates (premature and full term) and infants: specific dosing information has not been obtained for neonates and infants
Children:
Oral or sublingual (S.L.): hypertensive emergencies, 0.25 to 0.5mg/kg/ dose P.O./S.L. every 4 to 6 hours, as needed. Maximum single dose is 10 mg/dose; and the daily dose is 1 to 2 mg/kg/day
Hypertrophic cardiomyopathy: 0.6 to 0.9mg/kg/24 hours in three to four divided doses
Hypertension (chronic treatment) extended-release forms: initial, 0.25 to 0.5 mg/kg/day P.O./S.L. in one to two doses per day. Titrate to desired effect. Maximum dose is 3 mg/kg/day, up to 180mg/day
Adults:
Oral or S.L:
Capsules: initial, 10 mg three times per day. Maintenance, 10 to 30mg, three to four times per day Extended-release tablets: initial, 30 to 60mg once daily. Usual dosage for hypertension is 30 to 60mg once daily. Maximum dose is 120mg/ day
Note: Doses are typically titrated to achieve the desired effect (e.g., reduce hypertension) over 1 to 2 weeks.
Pharmacokinetics
Onset of action:
S.L. or “bite and swallow”: within 1 to 5 minutes
Oral:
Immediate release: within 20 to 30 minutes Extended release: 2 to 2.5 hours Absorption: bioavailability:
Capsules: 45 to 75%
Extended release: 65 to 85% Half-life:
Healthy adults: 2 to 5 hours
Adults with cirrhosis: 7 hours
Duration:
Immediate release: 4 to 8 hours
Extended release: 24 hours
Protein binding: 92 to 98%
Metabolism: in the liver, to inactive metabolites
Elimination: in urine, with greater than 90% excreted as inactive metabolites
Monitoring Parameters
Blood pressure, CBC, and liver enzymes.
Contraindications
Hypersensitivity to nifedipine (any component) and recent myocardial infarction.
Adverse Effects
Cardiovascular: hypotension, tachycardia, flushing, palpitations, syncope, peripheral edema
Respiratory: shortness of breath
Central nervous system: headache, dizziness
Gastrointestinal: nausea, diarrhea, constipation, gingival hyperplasia
Hepatic: elevated liver enzymes, cholestasis, jaundice, allergic hepatitis (rare)
Neuromuscular and skeletal: joint stiffness, arthritis with an elevated antinuclear antibody
Hematological: thrombocytopenia, leukopenia, anemia
Ophthalmological: blurred vision, transient blindness
Cutaneous/peripheral: dermatitis, urticaria, purpura, photosensitivity (rare)
Other: fever, chills, diaphoresis
Precautions
Initiation of antihypertensive therapy with nifedipine should be performed cautiously and with close blood pressure monitoring, because significant hypotension can occur. Upward titrations of dosing should be monitored similarly. Patients receiving concomitant treatment with β-blockers are at increased risk of hypotension. Angina and acute myocardial infarction in adults has been reported with initiation of nifedipine therapy. Patients with either congestive heart failure or aortic stenosis are also at increased risk.
Drug-Drug Interactions
Concomitant use of β-blockers may increase cardiovascular adverse events. Hypotension may be accentuated with anesthetic doses of fentanyl. Nifedipine may increase the serum concentrations of phenytoin, cyclosporin, and possibly digoxin. It may decrease serum quinidine concentration. Cimetidine and saquinavir may increase serum nifedipine concentration. Combined administration with cyclosporin in transplant patients seems to increase significantly the incidence of gingival hyperplasia. Delavirdine may decrease nifedipine metabolism and, thus, increase serum level. Administration of calcium typically reduces the effects of a calcium channel-blocking agent.
Compatible Diluents/Administration
Administer tablets with food. Avoid coadministration with grapefruit juice, because this may increase oral bioavailability. Sustained-release tablets should be swallowed whole. Nifedipine from liquid-filled capsules can be removed and administered either S.L. or swallowed (only a small amount of a S.L. dose is absorbed in the mouth).
This post has been viewed 771 times.
Comments are closed.
