Cardura XL

Product Type: HUMAN PRESCRIPTION DRUG

Route: ORAL

Dosage Form:

NDC: 58151-078

Application: NDA021269

Effective: 20230515

1 INDICATIONS AND USAGE CARDURA ® XL is indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH). CARDURA XL is not indicated for the treatment of hypertension. CARDURA XL is an alpha 1 adrenergic antagonist indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia. ( 1 ) CARDURA XL is not indicated for the treatment of hypertension. ( 1 )

2 DOSAGE AND ADMINISTRATION Recommended starting dose (initial therapy or switching from immediate-release): 4 mg once daily with breakfast ( 2.1 , 2.2 ) Dose range: 4 to 8 mg once daily ( 2.1 ) 2.1 General Dosing Information The initial dose of CARDURA XL, 4 mg given once daily, should be administered with breakfast. Depending on the patient’s symptomatic response and tolerability, the dose may be increased to 8 mg, the maximum recommended dose. The recommended titration interval is 3-4 weeks. If CARDURA XL administration is discontinued for several days, therapy should be restarted using the 4 mg once daily dose. Tablets should be swallowed whole, and must not be chewed, divided, cut, or crushed. 2.2 Patients Switching from CARDURA to CARDURA XL If switching from CARDURA immediate-release (IR) to CARDURA XL, therapy should be initiated with the lowest dose (4 mg once daily). Prior to starting therapy with CARDURA XL, the final evening dose of CARDURA should not be taken. 2.3 Concomitant Administration with PDE-5 Inhibitors Concomitant administration of CARDURA XL with a PDE-5 inhibitor can result in additive blood pressure lowering effects and symptomatic hypotension; therefore, PDE-5 inhibitor therapy should be initiated at the lowest dose in patients taking CARDURA XL.

4 CONTRAINDICATIONS CARDURA XL is contraindicated in patients with a known hypersensitivity to doxazosin, other quinazolines (e.g., prazosin, terazosin), or any of the inert ingredients. Allergic reactions to doxazosin and other quinazolines have included skin rash, urticaria, pruritus, angioedema, and respiratory symptoms [see Adverse Reactions (6.2) ] . Patients with known sensitivity to doxazosin, other quinazolines, or any of the inert ingredients ( 4 )

Not available.

6 ADVERSE REACTIONS The most commonly reported adverse reactions from clinical trials are asthenia, headache, hypotension, and dizziness. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Viatris at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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. TABLE 1 Adverse Reactions, Derived from All Adverse Events Exceeding Placebo Rate and Occurring in ≥ 1% of BPH Patients Treated with CARDURA XL 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% Asthenia 3.9% 6.9% 1.3% 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, 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.