FDA label 7871ad1d-e39b-4673-b9f7-6c0cdbe11409

WARNINGS Syncope and "First-dose" Effect Doxazosin, like other alpha-adrenergic blocking agents, can cause marked hypotension, especially in the upright position, with syncope and other postural symptoms such as dizziness. Marked orthostatic effects are most common with the first dose but can also occur when there is a dosage increase, or if therapy is interrupted for more than a few days. To decrease the likelihood of excessive hypotension and syncope, it is essential that treatment be initiated with the 1 mg dose. The 2, 4, and 8 mg tablets are not for initial therapy. Dosage should then be adjusted slowly (see DOSAGE AND ADMINISTRATION section) with evaluations and increases in dose every two weeks to the recommended dose. Additional antihypertensive agents should be added with caution. Patients being titrated with doxazosin should be cautioned to avoid situations where injury could result should syncope occur, during both the day and night. In an early investigational study of the safety and tolerance of increasing daily doses of doxazosin in normotensives beginning at 1 mg/day, only 2 of 6 subjects could tolerate more than 2 mg/day without experiencing symptomatic postural hypotension. In another study of 24 healthy normotensive male subjects receiving initial doses of 2 mg/day of doxazosin, seven (29%) of the subjects experienced symptomatic postural hypotension between 0.5 and 6 hours after the first dose necessitating termination of the study. In this study, 2 of the normotensive subjects experienced syncope. Subsequent trials in hypertensive patients always began doxazosin dosing at 1 mg/day resulting in a 4% incidence of postural side effects at 1 mg/day with no cases of syncope. In multiple dose clinical trials in hypertension involving over 1,500 hypertensive patients with dose titration every one to two weeks, syncope was reported in 0.7% of patients. None of these events occurred at the starting dose of 1 mg and 1.2% (8/664) occurred at 16 mg/day. In placebo-controlled, clinical trials in BPH, 3 out of 665 patients (0.5%) taking doxazosin reported syncope. Two of the patients were taking 1 mg doxazosin, while one patient was taking 2 mg doxazosin when syncope occurred. In the open-label, long-term extension follow-up of approximately 450 BPH patients, there were 3 reports of syncope (0.7%). One patient was taking 2 mg, one patient was taking 8 mg and one patient was taking 12 mg when syncope occurred. In a clinical pharmacology study, one subject receiving 2 mg experienced syncope. If syncope occurs, the patient should be placed in a recumbent position and treated supportively as necessary. Priapism Rarely (probably less frequently than once in every several thousand patients), alpha 1 antagonists, including doxazosin, have been associated with priapism (painful penile erection, sustained for hours and unrelieved by sexual intercourse or masturbation). Because this condition can lead to permanent impotence if not promptly treated, patients must be advised about the seriousness of the condition (see PRECAUTIONS: Information for Patients ).

ADVERSE REACTIONS Benign Prostatic Hyperplasia The incidence of adverse events has been ascertained from worldwide clinical trials in 965 BPH patients. The incidence rates presented below (Table 3) are based on combined data from seven placebo-controlled trials involving once daily administration of doxazosin in doses of 1 to 16 mg in hypertensives and 0.5 to 8 mg in normotensives. The adverse events when the incidence in the doxazosin group was at least 1% are summarized in Table 3. No significant difference in the incidence of adverse events compared to placebo was seen except for dizziness, fatigue, hypotension, edema and dyspnea. Dizziness and dyspnea appeared to be dose-related. In these placebo-controlled studies of 665 doxazosin patients, treated for a mean of 85 days, additional adverse reactions have been reported. These are less than 1% and not distinguishable from those that occurred in the placebo group. Adverse reactions with an incidence of less than 1% but of clinical interest are (doxazosin vs. placebo): Cardiovascular System: angina pectoris (0.6% vs. 0.7%), postural hypotension (0.3% vs. 0.3%), syncope (0.5% vs. 0.0%), tachycardia (0.9% vs. 0.0%); Urogenital System: dysuria (0.5% vs. 1.3%), and Psychiatric Disorders: libido decreased (0.8% vs. 0.3%). The safety profile in patients treated for up to three years was similar to that in the placebo-controlled studies. The majority of adverse experiences with doxazosin were mild. Hypertension Doxazosin mesylate has been administered to approximately 4,000 hypertensive patients, of whom 1,679 were included in the hypertension clinical development program. In that program, minor adverse effects were frequent, but led to discontinuation of treatment in only 7% of patients. In placebo-controlled studies adverse effects occurred in 49% and 40% of patients in the doxazosin and placebo groups, respectively, and led to discontinuation in 2% of patients in each group. The major reasons for discontinuation were postural effects (2%), edema, malaise/fatigue, and some heart rate disturbance, each about 0.7%. In controlled hypertension clinical trials directly comparing doxazosin to placebo there was no significant difference in the incidence of side effects, except for dizziness (including postural), weight gain, somnolence and fatigue/malaise. Postural effects and edema appeared to be dose related. The prevalence rates presented below are based on combined data from placebo-controlled studies involving once daily administration of doxazosin at doses ranging from 1 to 16 mg. Table 4 summarizes those adverse experiences (possibly/probably related) reported for patients in these hypertension studies where the prevalence rate in the doxazosin group was at least 0.5% or where the reaction is of particular interest.