Is syncope a known adverse drug reaction of alfuzosin and can it appear even after a single dose?/n

Fråga: Is syncope a known adverse drug reaction of alfuzosin and can it appear even after a single dose? A 64-year-old man with benign prostatic hyperplasia suffered from syncope the morning after he had taken the first dose of alfuzosin (Xatral) 5 mg. One more episode with syncope apperared one week later. Other substances used are pravastatin 40 mg x1 and and modafinil 100 mg x1.

Sammanfattning: Syncope is a documented but rare side effect of alfuzosin. Syncope can appear as early as a few hours after the first dose.

Svar: Alfuzosin is a postsynaptic alpha-1 receptor blocker. Uroselectivity has been reported in an in vivo study. Cardiovascular effects from alfuzosin occur, although they are less common than with other unselective alpha-1 antagonists like prazosin. Dose-titration, to reduce the risk of vasodilatation, when alfuzosin is initiated seems not necessary, as it is with some other alpha1-antagonists like prazosin (1).

The most common adverse effects from alfuzosin are dizziness, headache, tachycardia and postural hypotension all related to hypotension symtoms that usually appear during the first four weeks of treatment. Elderly, hypertensive patients and patients on other bloodpressure lowering treatment are at a higher risk for hypotension related adverse drug reactions (2).

In an open multicentre study with over 11500 patients, syncope was reported in six patients (0.05%) using alfuzosin. Adverse drug reactions were reported in 2.4% of patients. Two thirds of adverse these adverse drug reactions where associated with vasodilatation (3). One out of 26 patients, in a safety study, suffered from syncope after initiation of alfuzosin and four patients had adverse effects related to vasodilatation (4). One of 150 patients withdrawn from an alfuzosin study because of syncope (5). One of twelve patients suffered from syncopal episodes two hour after the first administration of alfuzosin and again on the fourth day after initiation (6).

In an open double-blind study with 311 patients 4.4 % of all patients hade adverse reactions related to vasodilatation when administered alfuzosin. No case of syncope appeared (7). In healthy volunteers alfuzosin causes a small reduction in systolic blood pressure that is followed by increased heart rate (6).

Six cases of syncope after alfuzosin intake have been reported to SADRAC (Swedish Adverse Drug Reactions Advisory Committee). In three of these cases syncope appeared after one initial dose (8).

Modafinil potentiates alpha-1 adrenergic activity in the brain and increases wakefulness. It is hypothesised that alfuzosin can reduce the effect of modafinil although it has not been shown in humans (9).