Doxazosin drug interactions

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


Most (98%) of plasma Doxazosin is protein bound. In vitro data in human plasma indicate that Doxazosin mesylate has no effect on protein binding of digoxin, warfarin, phenytoin or indomethacin. There is no information on the effect of other highly plasma protein bound drugs on Doxazosin binding. Doxazosin mesylate has been administered without any evidence of an adverse drug interaction to patients receiving thiazide diuretics, beta-blocking agents, and nonsteroidal anti-inflammatory drugs. In a placebo-controlled trial in normal volunteers, the administration of a single 1 mg dose of Doxazosin on day 1 of a four-day regimen of oral cimetidine (400 mg twice daily) resulted in a 10% increase in mean AUC of Doxazosin (p = 0.006), and a slight but not statistically significant increase in mean Cmax and mean half-life of Doxazosin. The clinical significance of this increase in Doxazosin AUC is unknown.

In clinical trials, Doxazosin mesylate tablets have been administered to patients on a variety of concomitant medications; while no formal interaction studies have been conducted, no interactions were observed. Doxazosin mesylate tablets have been used with the following drugs or drug classes: 1) analgesic/anti-inflammatory (e.g., acetaminophen, aspirin, codeine and codeine combinations, ibuprofen, indomethacin); 2) antibiotics (e.g., erythromycin, trimethoprim and sulfamethoxazole, amoxicillin); 3) antihistamines (e.g., chlorpheniramine); 4) cardiovascular agents (e.g., atenolol, hydrochlorothiazide, propranolol); 5) corticosteroids; 6) gastrointestinal agents (e.g., antacids); 7) hypoglycemics and endocrine drugs; 8) sedatives and tranquilizers (e.g., diazepam); 9) cold and flu remedies.

Cardiac Toxicity in Animals: An increased incidence of myocardial necrosis or fibrosis was displayed by Sprague-Dawley rats after 6 months of dietary administration at concentrations calculated to provide 80 mg Doxazosin/kg/day and after 12 months of dietary administration at concentrations calculated to provide 40 mg Doxazosin/kg/day (AUC exposure in rats 8 times the human AUC exposure with a 12 mg/day therapeutic dose). Myocardial fibrosis was observed in both rats and mice treated in the same manner with 40 mg Doxazosin/kg/day for 18 months (exposure 8 times human AUC exposure in rats and somewhat equivalent to human Cmax exposure in mice). No cardiotoxicity was observed at lower doses (up to 10 or 20 mg/kg/day, depending on the study) in either species. These lesions were not observed after 12 months of oral dosing in dogs at maximum doses of 20 mg/kg/day [maximum plasma concentrations (Cmax) in dogs 14 times the Cmax exposure in humans receiving a 12 mg/day therapeutic dose] and in Wistar rats at doses of 100 mg/kg/day (Cmax exposures 15 times human Cmax exposure with a 12 mg/day therapeutic dose). There is no evidence that similar lesions occur in humans.

List of Doxazosin Drug Interactions

Major Interactions

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Moderate Interactions

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0-9

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Minor Interactions

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Adapted from the FDA Package Insert.