Published in:
01-11-2005 | Adis Drug Evaluation
Naftidrofuryl
A Review of its Use in the Treatment of Intermittent Claudication
Published in: Drugs & Aging | Issue 11/2005
Login to get accessSummary
Abstract
Naftidrofuryl (Praxilene®) is a vasodilator that has been used in the treatment of intermittent claudication for >30 years in Europe to improve walking distance and provide symptomatic relief. However, earlier trials had inconsistencies in design and the clinical relevance of the treatment effect has been controversial.
Recent randomised, double-blind, placebo-controlled trials, however, have generally been conducted in accordance with updated methodology guidelines. In these studies, naftidrofuryl 200mg three times daily improved pain-free and maximal walking distances and health-related quality of life by a significantly greater extent than placebo in patients with intermittent claudication. The magnitude of these effects appears to support claims that the effects of naftidrofuryl are clinically relevant in these patients.
Pharmacological Properties
Naftidrofuryl is a vasodilator, but its mechanism of action is complex and not fully understood. The drug is a selective inhibitor of serotonin receptors and may involve nitric oxide in some actions. Naftidrofuryl appears to reduce the vasoconstrictive effects of serotonin released from damaged endothelia, inhibits platelet aggregration and platelet-induced vasospasm, and improves erythrocyte flexibility and aggregability.
Naftidrofuryl also appears to improve aerobic metabolism in the blood vessel wall. The lactate: pyruvate ratio is reduced in healthy volunteers during exercise and the transcutaneous oxygen pressure improved in patients with intermittent claudication.
Oral naftidrofuryl is absorbed relatively quickly. The mean peak plasma concentration in healthy volunteers who received a single 200mg dose of naftidrofuryl occurred after a median of 2.75 hours. About 80% of the drug is bound to plasma proteins. Excretion is predominantly via the urine in the form of metabolites. A short terminal elimination half-life requires the dosage to be administered in three divided daily doses. No dosage adjustment appears necessary in the elderly.
Therapeutic Efficacy
Oral naftidrofuryl 600 mg/day in three divided doses for 6 or 12 months improved pain-free walking distance (PFWD) and maximal walking distance (MWD), assessed on a treadmill or physiologically via the PADHOC™ (Peripheral Arterial Disease HOlter Control) device, by a significantly greater extent than placebo in patients with intermittent claudication in two recent randomised, double-blind, placebo-controlled trials (n = 181 and 168 in the intent-to-treat population). The absolute between-group difference in increase in both PFWD and MWD from baseline (≈70%) in the treadmill-based study, which was designed to conform with current European guidelines, exceeded the 30% figure considered to be clinically relevant.
Naftidrofuryl 600 mg/day significantly improved aspects of health-related quality of life after 6 months (primary endpoint), measured by the disease-specific Claudication Scale (CLAU-S) instrument, to a significantly greater extent than placebo in patients with intermittent claudication in three recent randomised, double-blind, placebo-controlled studies (n = 709). The effect was greatest in reducing the limitation on activities of daily living caused by intermittent claudication, and in reducing pain.
Tolerability
Oral naftidrofuryl was well tolerated in patients with intermittent claudication in clinical trials. The most common adverse events were mild gastrointestinal complaints that rarely required discontinuation of treatment. Less commonly occurring adverse events in naftidrofuryl recipients include headache, dizziness, flushing, erythema, insomnia and vertigo. Hepatitis and calcium oxalate stones rarely occur.