impairment on the pharmacokinetics of CARDURA XL. CARDURA XL should be administered with caution to patients with evidence of mild or moderately impaired hepatic function or to patients receiving drugs known to influence hepatic metabolism. Use in patients with severe hepatic impairment is not recommended.
Drug-Drug Interactions
No in vivo drug-drug interaction studies have been performed to assess the effect of concomitant medications on the pharmacokinetics of CARDURA XL or to assess the effect of CARDURA XL on the pharmacokinetics of other drugs. In one placebo-controlled trial in normal volunteers, the administration of a single 1mg dose of doxazosin IR on day 1 of a four day regimen of cimetidine (400mg twice daily) resulted in a 10% increase in the mean AUC of doxazosin, 6% increase in mean Cmax of doxazosin and no significant change in mean half-life of doxazosin. Based upon the differences in dose and formulation, the applicability of these results to CARDURA XL is unknown. Otherwise, the interaction potential with other inhibitors or substrates of cytochrome P450 enzymes has not been determined. Pharmacodynamic interactions between CARDURA XL and anti-hypertensive medications or other vasodilating agents have also not been determined. Finally, drugs which reduce gastrointestinal motility leading to markedly prolonged GI retention times (e.g. anticholinergic agents) may increase systemic exposure to doxazosin.
Clinical Studies
Two controlled clinical studies were conducted with CARDURA XL in BPH patients, followed by an open-label extension study. Study 1 was a randomized, double-blind, parallel-group, placebo- and active-controlled study that compared the safety and efficacy of CARDURA XL (4 or 8 mg/day) with that of doxazosin IR (1, 2, 4, or 8 mg/day) and placebo over 13 weeks in 795 BPH patients, of whom 317 were randomized to CARDURA XL. Study 2 was a randomized, double-blind, parallel-group, active-controlled study that compared the safety and efficacy of CARDURA XL (4 or 8 mg/day) with that of doxazosin IR (1, 2, 4, or 8 mg/day) over 13 weeks in 680 BPH patients, of whom 350 were randomized to CARDURA XL.
In both studies, men aged 50–80 years with symptomatic benign prostatic hyperplasia (BPH) were enrolled. Symptomatic BPH was defined as a total score of at least 12 points on the 35-point International Prostate Symptom Score (IPSS) and a maximum urinary flow rate of ≤ 15mL/sec but no less than 5mL/sec (total voided volume ≥ 150mL). In these two studies, conducted in a total of 1475 patients, the mean age was 64 years (range 47–83 years). Patients were Caucasian (96%), Black (1.5%), Asian (1.5%), and of Other ethnicity (1%).
In both studies, CARDURA XL dosing was initiated after a 2 week placebo-run in period at 4 mg per day increasing to 8 mg per day after 7 weeks of treatment if adequate response (defined as having both an increase in maximum urinary flow rate of at least 3 ml/sec and a decrease in total I-PSS of at least 30% from baseline) was not seen. Doxazosin IR was titrated from an initial dose of 1 mg daily to 2 mg daily after 1 week with the option to increase to 4 mg daily after 3 weeks and then to a maximum of 8 mg daily after 7 weeks if an adequate response was not seen. The final daily dose of CARDURA XL was 4 mg in 43% of patients and was 8 mg in 57% of patients. The final daily dose of doxazosin IR was 1mg in 1%, 2mg in 12%, 4 mg in 30% of patients and 8 mg in 57% of patients.
There were two primary efficacy variables in each of these two controlled clinical studies |
