) were >70 years of age.
In these two studies, the cumulative incidence of hypotension appeared to be age related. The reason for an increased incidence of hypotension in patients older than 70 years of age may be related to a modest increase in systemic exposure to doxazosin (see CLINICAL PHARMACOLOGY; Pharmacokinetics in Special Populations), to an increased propensity to orthostasis in the elderly, or to an enhanced sensitivity to vasodilatory agents in the elderly. The incidence of hypotension reported as an adverse event was higher in patients 70 years of age and older (4/136; 2.9%) as compared to patients < 70 years of age (7/530; 1.3%).
ADVERSE REACTIONS
The incidence of adverse events was derived from two controlled efficacy and safety trials involving 1473 BPH patients. In Study 1, CARDURA XL (n=317) was compared to doxazosin IR tablets (n=322) and to placebo (n=156). In Study 2, CARDURA XL (n=350) was compared just to doxazosin IR tablets (n=330). In both these studies, CARDURA XL was initiated at a dose of 4mg, which could be increased by the investigator to 8mg after seven weeks if an adequate response was not seen (see Clinical Pharmacology; Clinical Studies). Similarly, doxazosin IR was begun at a dose of 1mg, which was increased in all patients to 2mg after 1 week, followed by the option to increase to 4mg after 4 weeks, and 8mg after 7 weeks.
In these two studies, 6% of patients receiving CARDURA XL withdrew from the study due to adverse events, compared to 7% receiving doxazosin IR, and 3% receiving placebo. The most commonly reported adverse events leading to discontinuation in the CARDURA XL group were: dizziness, dyspnea, asthenia, headache, hypotension, postural hypotension, and somnolence.
The incidence rates presented below (Table 4) are based on combined data from the two controlled studies (Studies 1 and 2). Adverse events with an incidence in the CARDURA XL group of at least 1% and reported more frequently than with placebo are summarized in Table 4.
TABLE 4 Treatment-Emergent Adverse Events Occurring in ≥1% of BPH Patients Treated with CARDURA XL and More Frequently Than with Placebo in the Two Controlled Clinical Studies Body System CARDURA XL
(N = 666) Doxazosin IR
(N = 651) Placebo
(N = 156)
BODY AS A WHOLE
Abdominal Pain 1.8% 2.3% 0.6%
Astdenia 3.9% 6.9% 1.3%
Back Pain 2.9% 1.7% 2.6%
Headache 6.0% 5.1% 4.5%
CARDIOVASCULAR
Hypotension 1.7% 1.8% 0.0%
Postural Hypotension 1.2% 2.2% 0.6%
DIGESTIVE
Dyspepsia 1.4% 1.2% 0.0%
Nausea 1.2% 2.3% 0.6%
MUSCULOSKELETAL
Myalgia 1.4% 0.5% 0.0%
NERVOUS
Dizziness 5.3% 9.1% 1.9%
Somnolence 1.5% 1.2% 0.0%
Vertigo 1.5% 4.1% 0.6%
RESPIRATORY
Dyspnea 1.2% 1.2% 0.0%
Respiratory Tract Infection 4.8% 4.5% 1.9%
UROGENITAL
Urinary Tract Infection 1.4% 0.8% 0.6%
Additional adverse events reported with CARDURA XL at an incidence of less than 1% and those of clinical interest include: Cardiovascular System: angina pectoris, syncope, tachycardia, chest pain, palpitations; Digestive System: diarrhea; Musculo-skeletal System: arthralgia; Nervous System: libido decreased; Urogenital System: impotence; dysuria. Of these, the following events were reported more frequently with CARD |
