|Drug Name:||Doxazosin Mesylate|
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 mesylate 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 mesylate 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 mesylate group was at least 0.5% or where the reaction is of particular interest.TABLE 4 Adverse Reactions During Placebo-Controlled Studies Hypertension Doxazosinmesylate(N=339)Placebo(N=336) CARDIOVASCULAR SYSTEM Dizziness19%9% Vertigo2%1% Postural hypotension0.3%0% Edema4%3% Palpitation2%3% Arrhythmia1%0% Hypotension1%0% Tachycardia0.3%1% Peripheral ischemia0.3%0% SKIN & APPENDAGES Rash1%1% Pruritus1%1% MUSCULOSKELETAL SYSTEM Arthralgia/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% AUTONOMIC Mouth dry2%2% Flushing1%0% SPECIAL SENSES Vision abnormal2%1% Conjunctivitis/eye pain1%1% Tinnitus1%0.3% PSYCHIATRIC Somnolence5%1% Nervousness2%2% Depression1%1% Insomnia1%1% Sexual dysfunction2%1% GASTROINTESTINAL Nausea3%4% Diarrhea2%3% Constipation1%1% Dyspepsia1%1% Flatulence1%1% Abdominal pain0%2% Vomiting0%1% RESPIRATORY Rhinitis3%1% Dyspnea1%1% Epistaxis1%0% URINARY Polyuria2%0% Urinary incontinence1%0% Micturition frequency0%2% GENERAL Fatigue/malaise12%6% Chest pain2%2% Asthenia1%1% Face edema1%0% Pain2%2% Additional adverse reactions have been reported, but these are, in general, not distinguishable from symptoms that might have occurred in the absence of exposure to doxazosin mesylate.
The following adverse reactions occurred with a frequency of between 0.5% and 1%: syncope, hypoesthesia, increased sweating, agitation, increased weight.
The following additional adverse reactions were reported by <0.5% of 3960 patients who received doxazosin mesylate in controlled or open, short- or long-term clinical studies, including international studies.Cardiovascular System: angina pectoris, myocardial infarction, cerebrovascular accidentAutonomic Nervous System: pallorMetabolic: thirst, gout, hypokalemiaHematopoietic: lymphadenopathy, purpuraReproductive System: breast painSkin Disorders: alopecia, dry skin, eczemaCentral Nervous System: paresis, tremor, twitching, confusion, migraine, impaired concentrationPsychiatric: paroniria, amnesia,emotional lability, abnormal thinking, depersonalizationSpecial Senses: parosmia, earache, taste perversion, photophobia, abnormal lacrimationGastrointestinal System: increased appetite, anorexia, fecal incontinence, gastroenteritisRespiratory System: bronchospasm, sinusitis, coughing, pharyngitisUrinary System: renal calculusGeneral Body System: hot flushes, back pain, infection, fever/rigors, decreased weight, influenza-like symptoms.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).In post-marketing 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.
Doxazosin mesylate tablet is indicated for the treatment of both the urinary outflow obstruction and obstructive and irritative symptoms associated with BPH: obstructive symptoms (hesitation, intermittency, dribbling, weak urinary stream, incomplete emptying of the bladder) and irritative symptoms (nocturia, daytime frequency, urgency, burning).
Doxazosin mesylate may be used in all BPH patients whether hypertensive or normotensive.
In patients with hypertension and BPH, both conditions were effectively treated with doxazosin mesylate monotherapy.
Doxazosin mesylate provides rapid improvement in symptoms and urinary flow rate in 66 to 71% of patients.Sustained improvements with doxazosin mesylate were seen in patients treated for up to 14 weeks in double-blind studies and up to 2 years in open-label studies.
Syncope and “First-Dose” Effect: Doxazosin mesylate, 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 mesylate 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 mesylate 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 mesylate, 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 mesylate 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 mesylate reported syncope.
Two of the patients were taking 1 mg doxazosin mesylate, while one patient was taking 2 mg doxazosin mesylate 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.