er non-deformable material, caution should be used when administering CARDURA XL Extended Release Tablets to patients with preexisting severe gastrointestinal narrowing (pathologic or iatrogenic). There have been rare reports of obstructive symptoms in patients with known strictures in association with the ingestion of another drug in this non-deformable extended release formulation. Markedly increased GI retention times, as may occur in patients with chronic constipation, can increase systemic exposure to doxazosin and thereby potentially increase adverse reactions.
Patients with Hepatic Impairment
CARDURA XL should be administered with caution to patients with evidence of mild or moderate hepatic dysfunction (see CLINICAL PHARMACOLOGY; Pharmacokinetics in Special Populations). Since there is no clinical experience in patients with severe hepatic dysfunction, use in these patients is not recommended.
Drug Interactions
No in vivo drug interaction studies were conducted with CARDURA XL (see CLINICAL PHARMACOLOGY; Drug-Drug Interactions). In vitro studies suggest that doxazosin is a substrate of CYP3A4. Caution should be exercised when concomitantly administering a potent 3A4 inhibitor, such as atanazavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin or voriconazole with CARDURA XL. Pharmacodynamic interactions between CARDURA XL and anti-hypertensive medications or other vasodilating agents have also not been determined.
Patients with Coronary Insufficiency
Patients with congestive heart failure, angina pectoris, or acute myocardial infarction within the last 6 months were excluded from the Phase 3 studies. If symptoms of angina pectoris should newly appear or worsen, CARDURA XL should be discontinued.
Information for Patients
Patients should be told about the possible occurrence of symptoms related to postural hypotension, such as dizziness or syncope, when beginning therapy or when increasing dosage strength of CARDURA XL. Patients should be cautioned about driving, operating machinery, or performing hazardous tasks during this period, until the drug's effect has been determined.
Patients should be informed that CARDURA XL Extended Release Tablets should be swallowed whole. Patients should not chew, divide, cut or crush tablets. Patients should not be concerned if they occasionally notice in their stool something that looks like a tablet. In the CARDURA XL Extended Release Tablet, the medication is contained within a nonabsorbable shell designed to release the drug at a controlled rate. When this process is completed, the empty tablet is eliminated from the body.
CARDURA XL should be taken each day with breakfast.
Drug/Laboratory Test Interactions
Doxazosin mesylate does not affect the plasma concentration of prostate specific antigen in patients treated for up to 3 years.
No clinically significant abnormalities in white blood cell (WBC) counts were reported in patients treated with CARDURA XL in controlled clinical BPH trials. In previous studies of doxazosin IR in BPH patients, the incidence of clinically significant decreases in WBC counts was 0.4% in patients treated with doxazosin IR and 0% in patients treated with placebo. There was no statistically significant difference between these two groups.
Cardiac Toxicity in Animals
Studies in Sprague-Dawley rats after 6, 12, and 18 months, and in CD-1 mice |
