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 4 mg, which could be increased by the investigator
to 8 mg after seven weeks if an adequate response was not seen (see Clinical Pharmacology;
Clinical Studies). 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.
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 Occuring in ≥1% of BPH Patients Treated
with CARDURA XL and More Frequently Than with Placebo in the Two Controlled Clinical
Studies
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; Musculoskeletal System: arthralgia; Nervous System: libido
decreased; Urogenital System: impotence; dysuria. Of these, the following
events were reported more frequently with CARDURA XL than with placebo: syncope,
tachycardia, palpitations and 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 13-week controlled trials.
In post-marketing experience, the following additional adverse reactions have been
reported with doxazosin IR: Autonomic nervous system: priapism; Cardiovascular
System: cerebrovascular accidents, dizziness postural, myocardial infarction;
Central and Peripheral Nervous System: hypoesthesia, paresthesia; Endocrine
System: gynecomastia; Gastrointestinal System: 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; Special Senses:
blurred vision, Intraoperative Floppy Iris Syndrome (see PRECAUTIONS, Cataract Surgery);
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.