silodosin (Rx)

>10%

Retrograde ejaculation (28%)

1-10%

Diarrhea (3%)

Headache (2%)

Insomnia ((1-2%)

Dizziness (3%)

Orthostatic hypotension (3%; increased in patients >65 years)

Nasopharyngitis (2%)

Nasal congestion (2%)

Sinusitis (1-2%)

Postmarketing Reports

Skin and subcutaneous tissue disorders: Toxic skin eruption, purpura, skin rash, pruritus, urticaria

Hepatobiliary disorders: Jaundice, impaired hepatic function associated with increased transaminase values

Immune system disorders: Allergic-type reactions, not limited to skin reactions including angioedema

Genitourinary system: Priapism

Contraindications

Hypersensitivity

Severe renal impairment (CrCl <30 mL/min)

Severe hepatic impairment (Child-Pugh Score >10)

Concomitant strong CYP3A4 inhibitors or P-glycoprotein inhibitors

Cautions

Use with caution in the elderly (risk of hypotension)

Not indicated for use in women or children

Not for use as hypertensive

Postural hypotension, with or without symptoms (eg, dizziness) may develop when initiating treatment; there is potential for syncope; patients should be cautioned about driving, operating machinery, or performing hazardous tasks when initiating therapy

Dose should be reduced to 4 mg in patients with moderate renal impairment; exercise caution and monitor such patients for adverse events

Not tested in patients with severe hepatic impairment, and therefore, should not be prescribed to such patients; use with caution in patients with mid-to-moderate hepatic impairment

Patients planning cataract surgery should be told to inform their ophthalmologist that they are receiving this therapy; intraoperative floppy iris syndrome observed during cataract surgery in some patients on alpha-1 blockers or previously treated with alpha-1 blockers; variant of small pupil syndrome is characterized by combination of a flaccid iris that billows in response to intraoperative irrigation currents; progressive intraoperative miosis despite preoperative dilation with standard mydriatic drugs; and potential prolapse of iris toward phacoemulsification incisions

Carcinoma of prostate and BPH cause many of same symptoms; these two diseases frequently co-exist; patients thought to have BPH should be examined prior to starting therapy to rule out the presence of carcinoma of the prostate

Drug interaction overview

• The pharmacodynamic interactions between silodosin and other alpha-blockers have not been determined; drug should not be used in combination with other alpha-blockers
• Specific pharmacodynamic interaction study between this drug and antihypertensive agents not performed; patients in Phase 3 clinical studies taking concomitant antihypertensive medications did not experience a significant increase in incidence of syncope, dizziness, or orthostasis; exercise caution during concomitant use with antihypertensives and monitor patients for possible adverse events
• Caution also advised when alpha-adrenergic blocking agents are coadministered with PDE5 inhibitors; alpha-adrenergic blockers and PDE5 inhibitors are both vasodilators that can lower blood pressure; concomitant use of two drug classes can potentially cause symptomatic hypotension

Pregnancy

Therapy is not indicated for use in females

Infertility

• Males: Possible effects on male fertility could be observed based on findings in rats at exposures that were at least two times higher than at the MRHD (based on AUC); these findings may be reversible; clinical relevance unknown

Lactation

Therapy is not indicated for use in females

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Selective antagonist of postsynaptic alpha-1-adrenoceptors; blocking the alpha1A-adrenoreceptors in the smooth muscle of the prostate leads to relaxation of the smooth muscle in the bladder neck and prostate causing an improvement of urine flow and decreased symptom of BPH.

Pharmacokinetics

Time: 2.6 +/- 0.9 hr

Concentration: (8mg dose) 62 ng/mL

Bioavailability: 32%

Half-Life: 13 +/- 8 hr

Protein Bound: 97%

Vd: 49.5 L

Clearance: 10 L/hr

Metabolism: glucuronidation, alcohol & aldehyde dehydrogenase, CYP3A4

Excretion: feces & urine