Amlodipine adverse effects

The pharmacokinetic properties of these drugs are set forth in Table 12-5. The choice of a particular calcium channel-blocking agent should be made with knowledge of its specific potential adverse effects as well as its pharmacologic properties. Nifedipine does not decrease atrioventricular conduction and therefore can be used more safely than verapamil or diltiazem in the presence of atrioventricular conduction abnormalities. A combination of verapamil or diltiazem with 3 blockers may produce atrioventricular block and depression of ventricular function. In the presence of overt heart failure, all calcium channel blockers can cause further worsening of heart failure as a result of their negative inotropic effect. Amlodipine, however, does not increase the mortality of patients with heart failure due to nonischemic left ventricular systolic dysfunction and can be used safely in these patients. 

Amlodipine is a long-acting dihydropyridine calcium channel blocker. It has an adverse effects profile similar to those of other dihydropyridines, but at a lower frequency (1). Along with felodipine (2), but unlike other calcium channel blockers, it may also be safer in severe chronic heart failure when there is concurrent angina or hypertension (3). 

Ciclosporin increases the survival of allografts in man. However, it causes renal vasoconstriction and increases proximal tubular reabsorption, leading in some cases to hjrperten-sion (20). The concomitant use of calcium channel blockers can prevent most of these adverse effects of ciclosporin. However, some calcium channel blockers (verapamil, dUtia-zem, nicardipine) can increase plasma concentrations of ciclosporin up to three-fold through inhibition of cjhochrome P450. Eight different studies have been performed on the combination of amlodipine and ciclosporin given for 1-6 months to kidney transplant recipients, and the results have been reviewed (21). In three studies, in a total of 41 patients, amlodipine increased ciclosporin concentrations, while in the others, a total of 85 patients, there was no evidence of an interaction. 

Syncope occurred in a hypertensive 48-year-old man who took oral chloroquine sulfate (total 600 mg base) while also taking amlodipine 5 mg/day (44). Chloroquine and amlodipine both cause vasodilatation, perhaps by release of nitric oxide, and the syncope in this case was probably due to a synergistic mechanism. Malaria itself can also provoke orthostatic reactions, which may be why syncope is not a reported adverse effect of chloroquine. However, in this patient malaria had been excluded. 

A 74-year-old woman with seronegative rheumatoid arthritis was given sulfasalazine followed by methotrexate, both of which were withdrawn because of adverse effects. She also took prednisone 10 mg/day. She developed acute abdominal pain and fever (38.7 C) with no chills. Her serum amylase was 269 IU/1, serum lipase 300 IU/1, and urinary amylase 2895 IU/1. There was no evidence of tumor, hypertriglyceridemia, or lithiasis. In addition to prednisone, she was taking amlodipine, bromazepam, and omeprazole, none of which have been reported to cause pancreatitis. A marked improvement was noted after prednisone withdrawal. 

Felodipine is a dihydropyridine derivative with diuretic properties (1). Its diuretic properties are not unique but are shared by other dihydropyridines. Its vasodilator-related adverse effects include flushing, headache, and tachycardia (2,3). Reduced arterial oxygen saturation has been seen in patients given intravenous felodipine for pulmonary hypertension (4,5). Along with amlodipine, but unlike other calcium channel blockers, felodipine may be safer in severe chronic heart failure accompanied by angina or hypertension. 

Adverse effects and contraindications of calcium channel blockers are described in Table 16. Verapamil, diltiazem, and first-generation dihydropyridines also should be avoided in patients with acute decompensated heart failure or LV dysfunction because they can worsen heart failure and potentially increase mortality secondary to their negative inotropic effects. In patients with heart failure requiring treatment with a calcium channel blocker, amlodipine is the preferred agent. ... 

Several studies have raised concerns about the long-term safety of short-acting nifedipine. The proposed mechanism for this adverse effect lies in abrupt vasodilation with reflex sympathetic activation. There does not appear to be either significant reflex tachycardia or long-term adverse outcomes from treatment with sustained-release forms of nifedipine or with dihydropyiidine Ca blockers such as amlodipine or felodipine, which have more favorable (slower) pharmacokinetics. 

In a study in 12 healthy subjects, telmisartan 120 mg daily had no clinically relevant effect on the pharmacokinetics of amlodipine 10 mg daily for 9 days, and there was no evidence of any marked effect of amlodipine on the pharmacokinetics of telmisartan. Although there were no serious adverse effects, mild to moderate adverse events (most commonly headache) occurred slightly more frequently with the comhination, compared with amlodipine alone (19 events versus 12 events). ... 

Vasodilatory calcium channel blockers have been reported to improve exercise tolerance in some preliminary studies. A multicenter, randomized, placebo-con-trolled trial was therefore performed in 437 patients with mild to moderate heart failure to assess the effects of amlodipine 10 mg/day in addition to standard therapy (5). Over 12 weeks amlodipine did not improve exercise time and did not increase the incidence of adverse events. 

The effect of sildenafil on arterial pressure has been tested in 16 hypertensive men taking amlodipine 5-10 mg/day (23). Sildenafil did not affect amlodipine pharmacokinetics, but caused a further additive fall in blood pressure. Adverse events with the combination of sildenafil and amlodipine, headache, dyspepsia, and nausea, did not require drug withdrawal. 

Manidipine is a dihydropyridine calcium channel blocker that can be given once a day for hypertension. In a comparison of manidipine 10 mg/day and amlodipine 5 mg/day in a multicenter, randomized, double-blind study in 530 patients with mild-to-moderate hypertension, the two drugs had comparable antihypertensive effects, but manidipine was associated with a significantly lower incidence of ankle edema (1). Nevertheless, adverse events caused withdrawal from treatment in a similar number of patients, 23 with manidipine and 26 with amlodipine. 

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