FDA label 4019b41b-ccc7-62d0-e054-00144ff88e88

WARNINGS Syncope andFirst-doseEffect 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), 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 1500 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), alpha1 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 (BPH) 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 mesylate 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 mesylate 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. TABLE 3: ADVERSE REACTIONS DURING PLACEBO-CONTROLLED STUDIES BENIGN PROSTATIC HYPERPLASIA * p0.05 for treatment differences Includes vertigoBody SystemDOXAZOSIN MESYLATE (N = 665)PLACEBO (N = 300)BODY AS A WHOLEBack Pain1.8%2.0%Chest Pain1.2%0.7%Fatigue8.0% * 1.7%Headache9.9%9.0%Influenza-like Symptoms1.1%1.0%Pain2.0%1.0%CARDIOVASCULAR SYSTEMHypotension1.7% * 0.0%Palpitation1.2%0.3%DIGESTIVE SYSTEMAbdominal Pain2.4%2.0%Diarrhea2.3%2.0%Dyspepsia1.7%1.7%Nausea1.5%0.7%METABOLIC AND NUTRITIONAL DISORDERSEdema2.7% * 0.7%NERVOUS SYSTEMDizziness 15.6% * 9.0%Mouth Dry1.4%0.3%Somnolence3.0%1.0%RESPIRATORY SYSTEMDyspnea2.6% 0.3%Respiratory Disorder1.1%0.7%SPECIAL SENSESVision Abnormal1.4%0.7%UROGENITAL SYSTEMImpotence1.1%1.0%Urinary Tract Infection1.4%2.3%SKIN & APPENDAGESSweating Increased1.1%1.0%PSYCHIATRIC DISORDERSAnxiety1.1%0.3%Insomnia1.2%0.3% The majority of adverse experiences with doxazosin mesylate were mild. Hypertension Doxazosin mesylate has been administered to approximately 4000 hypertensive patients, of whom 1679 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 mesylate 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. TABLE 4: ADVERSE REACTIONS DURING PLACEBO-CONTROLLED STUDIES HYPERTENSIONDOXAZOSIN (N = 339)PLACEBO (N = 336)CARDIOVASCULAR SYSTEMDizziness19%9%Vertigo2%1%Postural Hypotension0.3%0%Edema4%3%Palpitation2%3%Arrhythmia1%0%Hypotension1%0%Tachycardia0.3%1%Peripheral Ischemia0.3%0%SKIN & APPENDAGESRash1%1%Pruritus1%1%MUSCULOSKELETAL SYSTEMArthralgia/Arthritis1%0%Muscle Weakness1%0%Myalgia1%0%CENTRAL & PERIPHERAL N.S.Headache14%16%Paresthesia1%1%Kinetic Disorders1%0%Ataxia1%0%Hypertonia1%0%Muscle Cramps1%0%AUTONOMICMouth Dry2%2%Flushing1%0%SPECIAL SENSESVision Abnormal2%1%Conjunctivitis/Eye Pain1%1%Tinnitus1%0.3%PSYCHIATRICSomnolence5%1%Nervousness2%2%Depression1%1%Insomnia1%1%Sexual Dysfunction2%1%GASTROINTESTINALNausea3%4%Diarrhea2%3%Constipation1%1%Dyspepsia1%1%Flatulence1%1%Abdominal Pain0%2%Vomiting0%1%RESPIRATORYRhinitis3%1%Dyspnea1%1%Epistaxis1%0%URINARYPolyuria2%0%Urinary Incontinence1%0%Micturition Frequency0%2%GENERALFatigue/Malaise12%6%Chest Pain2%2%Asthenia1%1%Face Edema1%0%Pain2%2% Doxazosin mesylate has not been associated with any clinically significant changes in routine biochemical tests. No clinically relevant adverse effects were noted on serum potassium, serum glucose, uric acid, blood urea nitrogen, creatinine or liver function tests. Doxazosin mesylate has been associated with decreases in white blood cell counts (see PRECAUTIONS, Leukopenia/Neutropenia). In postmarketing experience, the following additional adverse reactions have been reported: Autonomic Nervous System: priapism; Central Nervous System: hypoesthesia; Endocrine System: gynecomastia; Gastrointestinal System: vomiting; General Body System: allergic reaction; Heart Rate/Rhythm: bradycardia; Hematopoietic: leukopenia, thrombocytopenia; Liver/Biliary System: hepatitis, hepatitis cholestatic; Respiratory System: bronchospasm aggravated; Skin Disorders: urticaria; Special Senses: Intraoperative Floppy Iris Syndrome (see PRECAUTIONS, Cataract Surgery); Urinary System: hematuria, micturition disorder, micturition frequency, nocturia.