Silodosin

Pronunciation: SIL-oh-DOE-sin
Class: Alpha-1 adrenergic blocker

Trade Names

Rapaflo
- Capsules 4 mg
- Capsules 8 mg

Pharmacology

Selectively blocks postsynaptic alpha-1 adrenoreceptors located in the prostate, bladder base, bladder neck, prostatic capsule, and prostatic urethra.

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Pharmacokinetics

Absorption

AUC is approximately 373.4 ng•h/mL. C _max is approximately 61.6 ng/mL. T _max is approximately 2.6 h. Absolute bioavailability is approximately 32%.

Distribution

Vd is 49.5 L. Approximately 97% is protein bound.

Metabolism

Extensively metabolized through glucuronidation, alcohol and aldehyde dehydrogenase, and CYP3A4 pathways. The major metabolite is pharmacologically active.

Elimination

Half-life of silodosin is approximately 13.3 h; the half-life of the major metabolite is approximately 24 h. Excretion is approximately 54.9% in the feces and approximately 33.5% in the urine.

Special Populations

Total silodosin (bound and unbound) AUC, C _max , and elimination half-life were 3.2-, 3.1-, and 2-fold higher, respectively, in patients with moderate renal impairment. Unbound AUC and C _max were 2- and 1.5-fold higher, respectively.

Pharmacokinetics are not altered in patients with moderate hepatic impairment. Patients with severe hepatic impairment have not been studied.

Exposure and elimination half-life are approximately 15% and 20%, respectively, greater in subjects with a mean age of 69 y compared with subjects with a mean age of 24 y.

Indications and Usage

Treatment of signs and symptoms of benign prostatic hyperplasia (BPH).

Contraindications

Severe renal impairment (CrCl less than 30 mL/min); severe hepatic impairment (Child-Pugh score of 10 or more); coadministration with strong CYP3A4 inhibitors (eg, clarithromycin, itraconazole, ketoconazole, ritonavir).

Dosage and Administration

PO 8 mg once daily with a meal.

PO 4 mg once daily with a meal.

General Advice

• Should be taken with food.

Storage/Stability

Store between 59° and 86°F. Protect from light and moisture.

Drug Interactions

Additive pharmacologic effects and adverse reactions may occur. Avoid coadministration with silodosin.

Use with caution and monitor for adverse reactions. The risk of dizziness and orthostatic hypotension may be increased.

Silodosin plasma concentrations may be elevated, increasing the pharmacologic effects and adverse reactions. Use with caution and monitor for adverse reactions.

The risk of dizziness and orthostatic reactions may be increased. Use with caution and monitor BP.

Silodosin plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Coadministration with silodosin is contraindicated.

Silodosin exposure may be increased. Coadministration with silodosin is not recommended.

Adverse Reactions

Cardiovascular

Orthostatic hypotension (3%).

CNS

Dizziness (3%); headache (2%); asthenia, insomnia (1% to 2%).

Dermatologic

Purpura, toxic skin eruption (postmarketing).

EENT

Nasal congestion, nasopharyngitis (2%); rhinorrhea (1% to 2%).

GI

Diarrhea (3%).

Genitourinary

Retrograde ejaculation (28%); increased prostate-specific antigen (1% to 2%).

Hepatic

Impaired hepatic function associated with increased transaminase values, jaundice (postmarketing).

Respiratory

Sinusitis (1% to 2%).

Miscellaneous

Abdominal pain (1% to 2%).

Precautions

Pregnancy

Category B . Not indicated for use in women.

Lactation

Unknown. Not indicated for use in women.

Children

Safety and efficacy not established.

Elderly

Risk of orthostatic hypotension may be increased.

Renal Function

Plasma concentrations were approximately 3-fold higher and the half-life was prolonged 2-fold in individuals with moderate renal impairment. Use with caution and in reduced dose in patients with moderate renal impairment. Contraindicated in patients with severe renal impairment (CrCl less than 30 mL/min).

Hepatic Function

Contraindicated in patients with severe hepatic impairment.

Cognitive and motor impairment

Caution patients about driving, operating machinery, or performing hazardous tasks when initiating therapy.

Intraoperative floppy iris syndrome

Intraoperative floppy iris syndrome has been reported during cataract surgery in patients receiving or previously treated with alpha-1 blockers.

Orthostatic hypotension

Postural hypotension, with or without symptoms, may occur at the beginning of treatment.

Prostate cancer

Rule out before starting therapy.

Overdosage

Symptoms

Postural hypotension.

Patient Information

• Caution patients about driving, operating machinery, or performing hazardous tasks when initiating therapy.
• Instruct patients to take with food.
• Instruct patients to inform ophthalmologist about the use of silodosin before cataract surgery or other procedures involving the eye, even if the patient is no longer taking the drug.

Copyright © 2009 Wolters Kluwer Health.