Losartan, marketed in late 1997 as the potassium salt (Cozaar), was the first of the angiotensin II receptor antagonists (ARAs) approved for the treatment of hypertension in Australia. It was followed by irbesartan (Avapro, Karvea) in mid-1998 and more drugs of this class are expected to be marketed.

Up to November 1998, the Australian Adverse Drug Reactions Advisory Committee had received 230 reports of suspected adverse reactions associated with losartan and 133 reports in association with irbesartan. Most reports (84%) implicated the ARA as the only suspected drug. Ages ranged from 25 to 93 (median: 67) years and 68% were over the age of 60. The onset of the reaction was in the first few weeks in most cases and recurrence of symptoms was documented on rechallenge in 24 reports.

Most frequently reported reactions with ARAs

As the table shows, skin reactions and neuropsychiatric disturbances comprised the largest groups of reports. Neuropsychiatric problems included insomnia (14 reports), depression (10), confusion (9), nightmares (6), and agitation (5).

Of particular interest are reports of cough and angioedema. The clinical characteristics were remarkably similar to those seen with angiotensin-coverting enzyme (ACE) inhibitors. There were 37 reports of cough which was sometimes described as persistent and dry. As with ACE inhibitors, the 24 reports of angioedema described swelling of the neck, face or tongue. Over half (19) of the reports of cough documented similar problems associated with previous use of an ACE inhibitor. Time to onset was mostly in the first month. Most patients recovered after the drug was stopped but three reports described recurrence of the cough on rechallenge.

Early expectations were that problems such as cough and angioedema associated with ACE inhibitors would be avoided with this new class of antihypertensive agent.

Two other effects occurring in association with ARAs which have come to the ADRAC’s attention:

Hepatotoxicity. There have been 14 reports of hepatic dysfunction with losartan, including 7 of abnormal liver function tests and 7 of hepatitis or jaundice. For irbesartan, there has been one report of cholestatic hepatitis, one of jaundice, and one of abnormal liver function tests.

Hyperglycaemia. Three reports were received which described irregularities in glycaemic control with losartan. In 2 reports there was an increase in blood sugar levels soon after patients with diabetes started losartan, and in the other report a patient developed an acute onset of hyperosmolar diabetes mellitus within a month of an increase in the dose of losartan.

Reference: Australian Adverse Drug Reactions Bulletin Vol. 18, No. 1, February 1999.