Clinical experience with guanfacine in long-term treatment of hypertension. Part II: adverse reactions to guanfacine.

1 In 580 hypertensive patients treated with guanfacine for one year and 169 patients who continued the treatment for a second year, laboratory measurements were made before, during and after the end of treatment. Side-effects were registered every month. On completion of the one and two-year studies respectively, therapy was discontinued and blood pressure, heart rate and side-effects were recorded in order to assess the frequency of a withdrawal syndrome. 2 No impairment of laboratory values was seen during long-term treatment. There was no retention of sodium, chloride and water, and no potassium depletion. Guanfacine did not interfere with carbohydrate metabolism during the long-term treatment, and there was no deterioration of clinical diabetes. 3 The overall frequencies of dryness of the mouth and sedation were 60 and 33%, respectively. At the end of one year of treatment these figures dropped to 15 and 5.7%. Further untoward reactions in the first and second year, respectively, were orthostatic disturbances (15 and 6.5%), constipation (14 and 4.1%), male sexual dysfunction (4.6 and 0.6%), insomnia (5.5 and 2.2%), and sweating (5.3 and 1.7%). 4 The frequency and severity of side-effects were dose dependent and related to increases in dosage. Doses of 2 mg and lower caused practically no dryness of the mouth. 5 A withdrawal syndrome occurred in about 3% of patients after discontinuation of prolonged treatment. It was seen in patients with a history of very high blood pressure readings, who showed a tendency to tachycardia and who had been treated with divided doses of guanfacine exceeding 4 mg daily. 6 Only patients with clinical symptoms of increased sympathetic activity were considered to have a withdrawal syndrome (or `phenomenon'). 7 No signs of tachyphylaxis or habituation (tolerance) were seen during the long-term treatment with guanfacine.