Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2021 Publisher: Pfizer Limited, Ramsgate Road, Sandwich, Kent, CT13 9NJ, United Kingdom
Pharmacotherapeutic group: Alpha-adrenoreceptor antagonists
ATC code: C02CA01
Hypovase causes a decrease in total peripheral vascular resistance through selective inhibition of postsynaptic alpha-1-adrenoreceptors in vascular smooth muscle. The results of forearm plethysmographic studies in humans demonstrate that the resultant peripheral vasodilatation is a balanced effect on both resistance vessels (arterioles) and capacitance vessels (veins).
In hypertensive patients, blood pressure is lowered in both the supine and standing positions; this effect is more pronounced on the diastolic blood pressure. Tolerance to the antihypertensive effect has not been observed in long-term clinical use; relatively little tachycardia or change in renin levels has been noted. Rebound elevation of blood pressure does not occur following abrupt cessation of Hypovase therapy.
The therapeutic efficacy of Hypovase in patients with congestive heart failure is ascribed to a reduction in left ventricular filling pressure, reduction in cardiac impedance and an augmentation of cardiac output. The use of Hypovase in congestive heart failure does not provoke a reflex tachycardia and blood pressure reduction is minimal in normotensive patients.
Hypovase has been found to successfully reduce the severity of the signs, symptoms, frequency and duration of attacks, in patients with Raynaud’s disease.
In low dosage, antagonism of alpha-1-receptors on prostatic and urethral smooth muscle has been shown to improve the urinary pressure profile in men and to improve symptoms of benign prostatic hypertrophy.
Clinical studies have shown that Hypovase therapy is not associated with adverse changes in the serum lipid profile.
Following oral administration in normal volunteers and hypertensive patients plasma concentrations of prazosin reach a peak in one to two hours with a plasma half-life of two to three hours. Pharmacokinetic data in a limited number of patients with congestive heart failure, most of whom showed evidence of hepatic congestion, indicates that peak plasma concentrations are reached in 2.5 hours and plasma half-life is approximately 7 hours. Hypovase is highly bound to plasma protein. Studies indicate that Hypovase is extensively metabolised, primarily by demethylation and conjugation, and excreted mainly via bile and faeces.
Renal blood flow and glomerular filtration rate are not impaired by long term oral administration and thus Hypovase can be used with safety in hypertensive patients with impaired renal function.
Prazosin hydrochloride was not mutagenic in genetic toxicology testing, and was not carcinogenic in rats. In chronic studies (>1 year) conducted with prazosin hydrochloride in rats and dogs, testicular changes consisting of atrophy and necrosis occurred at 25 mg/kg/day (75 times the usual maximum recommended human dose), while no such changes were observed in either species at a dose of 10 mg/kg/day (30 times the usual maximum recommended human dose).
Fertility in rats was decreased at high nonclinically relevant doses (225 times the usual maximum recommended human dose). Prazosin hydrochloride was not teratogenic at doses up to 75 mg/kg/day (225 times the maximum recommended human dose).
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