6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The incidence of adverse reactions 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 of these studies, CARDURA XL was initiated at a dose of 4 mg, which could be increased by the investigator to 8 mg after seven weeks if an adequate response was not seen [see Clinical Studies (14.1)]. Similarly, doxazosin IR was begun at a dose of 1 mg, which was increased in all patients to 2 mg after 1 week, followed by the option to increase to 4 mg after 4 weeks, and 8 mg after 7 weeks.
The most commonly reported adverse reactions leading to discontinuation in the CARDURA XL group were: dizziness, dyspnea, asthenia, headache, hypotension, postural hypotension, and somnolence. The rates of discontinuation for adverse reactions were 6%, 7% and 3% in the CARDURA XL, doxazosin IR, and placebo groups, respectively.
Table 1 lists the incidence rates of adverse reactions derived from all reported adverse events in the two controlled studies (Studies 1 and 2) combined, at a rate greater than placebo and in 1% or more of patients treated with CARDURA XL.
|Body System||CARDURA XL|
(N = 666)
(N = 651)
(N = 156)
|BODY AS A WHOLE|
|Respiratory Tract Infection||4.8%||4.5%||1.9%|
|Urinary Tract Infection||1.4%||0.8%||0.6%|
Additional adverse events reported with CARDURA XL, reported by less than 1% of patients, and those of clinical interest include: Cardiovascular System: angina pectoris, syncope, tachycardia, chest pain, palpitations; Digestive System: diarrhea; Musculoskeletal System: arthralgia; Nervous System: libido decreased; Urogenital System: impotence, dysuria.
In general, the adverse events reported in the open-label safety extension, in approximately 295 BPH patients treated for up to 37 weeks, were similar in type and frequency to the events described above in the controlled trials.
6.2 Postmarketing Experience
The following adverse events have been identified during post-approval use of doxazosin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Autonomic Nervous System: priapism; Cardiovascular System: cerebrovascular accidents, dizziness postural, myocardial infarction; Central and Peripheral Nervous System: hypoesthesia, paresthesia; Endocrine System: gynecomastia; Gastrointestinal System: gastrointestinal obstruction, vomiting; General Body System: fatigue, hot flushes, malaise; Heart Rate/Rhythm: bradycardia, cardiac arrhythmias; Hematopoietic: leukopenia, purpura, thrombocytopenia; Liver/Biliary System: abnormal liver function tests, hepatitis, hepatitis cholestatic, jaundice; Musculoskeletal System: muscle cramps, muscle weakness; Psychiatric: agitation, anorexia, nervousness; Respiratory System: bronchospasm aggravated; Skin Disorders: alopecia, urticaria, skin rash, pruritus; Special Senses: blurred vision, Intraoperative Floppy Iris Syndrome [see Warnings and Precautions (5.2)]; Urinary System: hematuria, micturition disorder, micturition frequency, nocturia, polyuria.
There have been rare reports of gastrointestinal irritation and gastrointestinal bleeding with use of another drug in this non-deformable sustained release formulation, although causal relationship to the drug is uncertain.