Amlodipine (Norvasc) Contraindications and Precautions
- dihydropyridine hypersensitivity
- hypotension
- acute myocardial infarction
- aortic stenosis
- bradycardia
- breast-feeding
- cardiogenic shock
- children
- coronary artery disease
- elderly
- gastroesophageal reflux disease (GERD)
- heart failure
- hepatic disease
- hiatal hernia
- pregnancy
- ventricular dysfunction
Amlodipine (Norvasc) Contraindications and Precautions
Amlodipine is structurally related to nifedipine (1,4 dihydropyridine) and is contraindicated in patients with known serious dihydropyridine hypersensitivity.
Amlodipine should be used with caution in patients with severe bradycardia or heart failure (particularly in combination with a beta-blocker) because of the risk of a slight negative inotropic effect and potent hypotensive effects. Amlodipine should be avoided in cardiogenic shock or decompensated NYHA Class IV heart failure. Patients with left ventricular dysfunction who are receiving amlodipine for the treatment of angina should be monitored for signs and symptoms of worsening heart failure. Although clinical studies (PRAISE-1, PRAISE-2) have shown that amlodipine did not worsen heart failure in patients with NYHA Class II or III heart failure, amlodipine should be used cautiously in patients with heart failure. In the Prospective Randomized Amlodipine Survival Evaluation (PRAISE) trial, 1153 patients (80% with class III heart failure, either due to ischemic or nonischemic disease) were randomized to receive amlodipine 5 - 10 mg PO once daily or placebo. One month after randomization, the average amlodipine dosage was 8.8 ± 0.6 mg/day PO. In the ischemic heart failure subgroup of PRAISE-1, the results with amlodipine therapy were similar to placebo. After an average of 14 months of follow-up, amlodipine-treated patients demonstrated a significant decrease in the primary endpoint of combined risk of either death or life-threatening cardiovascular event only in the subgroup of nonischemic dilated cardiomyopathy patients. A followup trial (PRAISE-2) of non-ischemic heart failure (NYHA Class III or IV) demonstrated no significant benefit with amlodipine. In the PRAISE-2 trial, no difference was observed in all-cause mortality vs. placebo, but there were more reports of pulmonary edema (manufacturer prescribing information).
Since the vasodilation induced by amlodipine is gradual in onset, acute hypotension has rarely been reported after oral administration. However, amlodipine can decrease peripheral resistance and worsen pre-existing hypotension. Amlodipine should not be used in patients with systolic blood pressures of less than 90 mmHg (i.e., severe hypotension). Amlodipine should be used with caution in patients with mild to moderate hypotension. Blood pressure should be monitored carefully in all patients receiving amlodipine.
Amlodipine should be used with caution in patients with hepatic disease. The amlodipine elimination half-life is prolonged in patients with hepatic disease (amlodipine-norvascreg/#1">see Pharmacokinetics) and dosage adjustment is recommended (amlodipine-norvasc-indications-and-dosage/">see Dosage). Elderly patients are more likely to experience a delayed clearance of amlodipine and can be at greater risk for toxicity.
Since the vasodilation induced by amlodipine is gradual in onset, acute hypotension has rarely been reported after oral administration. Nonetheless, caution as with any other peripheral vasodilator, should be exercised when administering amlodipine, especially patients with severe aortic stenosis. Amlodipine is relatively contraindicated in patients with advanced aortic stenosis because of the risk of worsening the abnormal valve pressure gradient associated with this condition.
Rarely, an increased frequency, duration, and/or intensity of angina or acute myocardial infarction have occurred during amlodipine therapy, particularly in patients with severe obstructive coronary artery disease. Patients should be monitored for worsening angina when amlodipine therapy is begun.
Amlodipine is classified as a pregnancy category C drug. Amlodipine has been shown to be fetotoxic in laboratory animals. No adequate or well-controlled studies have been done in humans. Amlodipine should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.
It is not known whether amlodipine is excreted into human milk, so clinicians should consider the risk/benefit ratio for women who are breast-feeding.
The safety and efficacy of amlodipine in children < 6 years has not been established. The manufacturer has data on file for pediatric patients 6 - 17 years. Adverse events are similar to those seen in adults. Sixty-two hypertensive patients aged 6 - 17 years have received doses of amlodipine between 1.25 mg and 20 mg. Weight-adjusted clearance and volume of distribution are similar to adult values. Hypertensive patients (N=268), aged 6 - 17 years, have been reported to be randomized first to amlodipine 2.5 or 5 mg once daily for 4 weeks, and then randomized again to the same dose or to placebo for another 4 weeks. Patients receiving 5 mg at the end of 8 weeks have been reported to have lower blood pressure than those secondarily randomized to placebo. The magnitude of the blood pressure lowering effect is reportedly difficult to interpret, but is probably < 5 mmHg (systolic) on the 5 mg dose.
Calcium channel blockers should be used cautiously in patients with gastroesophageal reflux disease (GERD) or hiatal hernia associated with reflux esophagitis. The drugs relax the lower esophageal sphincter.
[ Last revised: 8/9/2005 12:55:00 PM ]
References
. Packer M, O’Connor CM, Ghali JK et al. Effect of amlodipine on morbidity and mortality in severe chronic heart failure. N Engl J Med 1996;335:1107 - 14.
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