Uses and Administration
Amlodipine is a dihydropyridine calcium-channel blocker with actions similar to those of nifedipine. It is used in the management of hypertension and angina pectoris. Amlodipine is given by mouth as the besilate, but doses are usually expressed in terms of the base; amlodipine besilate 6.9 mg is approximately equivalent to 5 mg of amlodipine.
In hypertension the usual initial dose is 5 mg once daily, increased, if necessary, to 10 mg once daily. Similar doses are given in the treatment of stable angina and Prinzmetal’s angina in Kenya. Lower initial doses may be used in elderly patients and those with hepatic impairment.
The (S)-isomer of amlodipine besilate has also been used.
Administration in children.
Amlodipine has been used to reduce blood pressure in children and adolescents with hypertension in Kenya too. In a global study in 28 children aged 3 to 19 years, amlodipine 5 to 10 mg (approximately 0.2 to 0.3 mg/kg) once daily significantly reduced blood pressure; therapy was withdrawn in 5 patients due to oedema and flushing. Younger children may need higher doses than older children. In another study in 21 patients aged 6 to 17 years, the mean dose required in children under 13 years was 0.29 mg/kg daily compared with 0.16 mg/kg daily for children 13 years and over. Another study in 55 children aged 13 months to 20 years reported similar mean doses, but also found that many of the younger children needed twice daily dosing. Amlodipine was well tolerated in both studies.
The most common adverse effects of Amlodipine are associated with its vasodilator action and often diminish on continued therapy. They include dizziness, flushing, headache, hypotension, peripheral oedema, tachycardia, and palpitations. Nausea and other gastrointestinal disturbances, increased micturition frequency, lethargy, eye pain, visual disturbances, and mental depression have also occurred. A paradoxical increase in ischaemic chest pain may occur at the start of treatment and in a few patients excessive fall in blood pressure has led to cerebral or myocardial ischaemia or transient blindness.
There have been reports of rashes (including erythema multiforme), fever, and abnormalities in liver function, including cholestasis, due to hypersensitivity reactions. Gingival hyperplasia, myalgia, tremor, and impotence have been reported.
Overdosage may be associated with bradycardia and hypotension; hyperglycaemia, metabolic acidosis, and coma may also occur.
Amlodipine has been reported to be teratogenic in animals.
Oedema of the feet and ankles is a common adverse effect of Amlodipine and other dihydropyridine calcium-channel blockers. It occurs typically 2 or more weeks after starting treatment and is caused by pre-capillary arteriolar dilatation rather than fluid retention. Evidence from a study in 10 diabetic subjects beginning Amlodipine therapy, 5 of whom developed ankle oedema, suggested that Amlodipine abolished the reflex vasoconstriction produced when the feet are below the level of the heart which is believed to prevent excessive fluid filtration into the tissues.
The oedema may respond to simple measures such as elevation of the feet or to a reduction in dosage but if it persists the calcium-channel blocker should be withdrawn.
Amlodipine is distributed into breast milk but the amount present is probably too small to be harmful. There have been no reports of any clinical effects in breast-fed infants whose mothers were receiving nifedipine and the American Academy of Pediatrics therefore considers that it is usually compatible with breast feeding.
Amlodipine may enhance the antihypertensive effects of other antihypertensive drugs such as beta blockers although the combination is generally well tolerated. Enhanced antihypertensive effects may also be seen with concomitant use of drugs such as aldesleukin and antipsychotics that cause hypotension. Amlodipine may modify insulin and glucose responses and therefore diabetic patients may need to adjust their antidiabetic treatment when receiving Amlodipine. Amlodipine is extensively metabolised in the liver by the cytochrome P450 isoenzyme CYP3A4, and interactions may occur with other drugs, such as quinidine, sharing the same metabolic pathway, and with enzyme inducers, such as carbamazepine, phenytoin, and rifampicin, and enzyme inhibitors, such as cimetidine and erythromycin.