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 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; 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.
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