Medication Guide App

Generic Name: Silodosin
Class: Selective alpha-1-Adrenergic Blocking Agents
ATC Class: G04CA04
VA Class: GU900
Chemical Name: 1 - (3 - hydroxypropyl) - 5 - [(2R) - 2 - [[2 - [2 - (2,2,2 - trifluoroethoxy)phenoxy]ethyl]amino]propyl] - 2,3 - dihydro - 1H - indole - 7 - carboxamide
Molecular Formula: C25H32F3N3O4
CAS Number: 160970-54-7

Introduction

α1-Adrenergic blocker with selectivity for α1A-adrenergic receptors;1 trifluoroethoxy-phenoxyethyl amine derivative.10

Uses for Rapaflo

Benign Prostatic Hyperplasia (BPH)

Reduction of urinary obstruction and relief of associated manifestations (e.g., hesitancy, weak stream, sensation of incomplete bladder emptying, frequency, urgency, nocturia) in patients with symptomatic BPH.1 3 4 5 6

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May be a useful alternative to surgery, particularly in those who are awaiting surgical correction of hyperplasia or who are not candidates for such surgery.3 5

May consider combined therapy with an α1A-adrenergic blocking agent and a 5α-reductase inhibitor for men with bothersome moderate to severe BPH.8 9 Has been more effective than therapy with either drug alone in preventing long-term BPH symptom progression.8 9 Men at risk for BPH progression are most likely to benefit from combination therapy.8

Other Uses

Manufacturer states that silodosin should not be used for the treatment of hypertension.1

Rapaflo Dosage and Administration

Administration

Oral Administration

Administer orally once daily with a meal.1 4

Dosage

Adults

BPH
Oral

8 mg once daily.1 4

Special Populations

Hepatic Impairment

Dosage adjustment not necessary in patients with mild or moderate hepatic impairment (Child-Pugh class A or B).1 Not recommended for use in patients with severe hepatic impairment (Child-Pugh class C).1 7

Renal Impairment

Dosage adjustment not necessary in patients with mild renal impairment (Clcr 50–80 mL/minute).1 Reduce dosage to 4 mg once daily in patients with moderate renal impairment (Clcr 30–50 mL/minute).1 7 Not recommended for use in patients with severe renal impairment (Clcr <30 mL/minute).1 7

Cautions for Rapaflo

Contraindications

  • Severe hepatic impairment (Child-Pugh class C).1 7

  • Severe renal impairment (Clcr <30 mL/minute).1 7

  • Concomitant use with potent inhibitors of CYP3A4 (e.g., clarithromycin, itraconazole, ketoconazole, ritonavir).1 7 (See Interactions.)

Warnings/Precautions

Warnings

Orthostatic Hypotension

Potential for orthostatic hypotension, dizziness, or syncope.1 (See Advice to Patients.)

General Precautions

Prostate Cancer

Exclude possibility of prostate cancer prior to initiation of therapy.1

Intraoperative Floppy Iris Syndrome

Intraoperative floppy iris syndrome (IFIS) observed during phacoemulsification cataract surgery in some patients currently receiving or previously treated with α1-adrenergic blocking agents.1 3 7 8 11

Specifically question male patients being considered for cataract surgery to determine whether they have received silodosin or other α1-adrenergic blockers.1 11 If patient has received α1-adrenergic blockers, ophthalmologist should consider modification of the surgical technique through use of iris hooks or iris dilator rings or pharmacologic intervention with intracameral phenylephrine or preoperative administration of atropine to minimize complications of IFIS.11 Benefit of discontinuing α1-blocker therapy prior to cataract surgery not established.8 11

Specific Populations

Pregnancy

Category B.1 Not indicated for use in women.1

Lactation

Not indicated for use in women.1

Pediatric Use

Not indicated for use in children.1

Geriatric Use

Higher incidence of orthostatic hypotension reported in patients ≥65 years of age compared with younger adults.1 No other substantial differences in safety and efficacy relative to younger adults.1

Hepatic Impairment

Use not recommended in patients with severe hepatic impairment.1 7 (See Contraindications under Cautions.)

Renal Impairment

Use not recommended in patients with severe renal impairment.1 7 Use caution and reduce dosage in patients with moderate renal impairment.1 7

Common Adverse Effects

Retrograde ejaculation, dizziness, diarrhea, orthostatic hypotension, headache, nasopharyngitis, nasal congestion.1 4 7

Interactions for Rapaflo

Extensively metabolized by CYP3A4 and UGT2B7.1 7

Drugs Affecting Hepatic Microsomal Enzymes

Pharmacokinetic interaction (increased plasma silodosin concentrations) with potent inhibitors of CYP3A4.1 Concomitant use contraindicated.1 7

Drugs Affecting or Affected by P-glycoprotein Transport

Silodosin is a substrate for the P-glycoprotein transport system.1 Potential pharmacokinetic interaction (increased plasma silodosin concentrations) with inhibitors of P-glycoprotein transport.1 7 Concomitant use with a potent P-glycoprotein inhibitor not recommended.1 7

Drugs Affecting Uridine Diphosphate-glucuronosyltransferase (UGT) 2B7

Potential pharmacokinetic interaction (increased silodosin exposure) with inhibitors of UGT2B7.1

Specific Drugs

Drug

Interaction

Comments

α-Adrenergic blocking agents

Possible pharmacodynamic interaction1

Concomitant use not recommended1

Antihypertensive agents

Higher incidence of dizziness and orthostatic hypotension1

Use with caution;1 monitor for adverse effects1

Clarithromycin

Increased plasma silodosin concentrations1

Concomitant use contraindicated1

Cyclosporine

Potential for increased plasma silodosin concentrations1

Concomitant use not recommended1

Digoxin

No substantial change in digoxin pharmacokinetics1

Dosage adjustment not required1

Diltiazem

Potential for increased plasma silodosin concentrations1

Use with caution;1 monitor for adverse effects1

Erythromycin

Potential for increased plasma silodosin concentrations1

Use with caution;1 monitor for adverse effects1

Fluconazole

Potential for increased silodosin exposure1

Itraconazole

Increased plasma silodosin concentrations1

Concomitant use contraindicated1

Ketoconazole

Substantially increased plasma silodosin concentrations and silodosin exposure1

Concomitant use contraindicated1

Phosphodiesterase (PDE) type 5 inhibitors (e.g., sildenafil, tadalafil)

Possible orthostatic effects7

Probenecid

Potential for increased silodosin exposure1

Ritonavir

Increased plasma silodosin concentrations1

Concomitant use contraindicated1

Valproic acid

Potential for increased silodosin exposure1

Verapamil

Potential for increased plasma silodosin concentrations1

Use with caution;1 monitor for adverse effects1

Rapaflo Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability of approximately 32% following oral administration under fed conditions.1 Peak plasma concentrations attained in about 2.6 hours.1

Food

When administered with a moderate-fat, moderate-calorie meal, AUC and peak plasma concentrations are decreased by 4–49% and 18–43%, respectively, compared with administration in the fasting state.1 Administration with a high-fat, high-calorie meal not evaluated.1

Distribution

Plasma Protein Binding

Approximately 97%.1

Elimination

Metabolism

Extensively metabolized in the liver via glucuronidation, alcohol and aldehyde dehydrogenases, and CYP3A4 isoenzymes.1 The primary active metabolite, KMD-3213G, is formed via UGT2B7-mediated glucuronidation.1 Another major metabolite, KMD-3293, is formed via alcohol and aldehyde dehydrogenases.1 KMD-3293 is not expected to contribute substantially to the overall pharmacologic activity of silodosin.1

Elimination Route

Excreted in urine (33.5%) and feces (54.9%).1

Half-life

Approximately 13.3 hours.1

Special Populations

In patients with moderate hepatic impairment, the pharmacokinetics of silodosin were not substantially altered following administration of a single dose.1 The pharmacokinetics of silodosin in patients with severe hepatic impairment have not been evaluated.1

In patients with moderate renal impairment, AUC, peak plasma concentrations, and elimination half-life were 3.2, 3.1, and 2 times higher, respectively, than in healthy individuals.1

In geriatric individuals, AUC and elimination half-life were increased by approximately 15% and 20%, respectively, compared with younger individuals.1

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).1 Protect from moisture and light.1

Actions

  • Blocks α1-adrenergic receptors in the lower urinary tract to cause relaxation of smooth muscle in the bladder neck and prostate,1 2 3 4 5 7 resulting in improved urinary flow and reduced symptoms of BPH.1 3 5

  • Higher affinity for α1A-adrenergic receptors, which are in nonvascular smooth muscle (e.g., prostate), than for α1B-adrenergic receptors located in vascular smooth muscle;1 2 3 5 may result in reduced incidence of cardiovascular effects (e.g., syncope, dizziness, hypotension).3 4 5

Advice to Patients

  • Risk of orthostatic hypotension (e.g., feeling faint or dizzy), particularly following initiation of therapy;1 importance of exercising caution when driving, operating machinery, or performing hazardous tasks.1

  • Importance of taking silodosin once daily with a meal.1

  • Risk of retrograde ejaculation.1 Importance of advising patients that this adverse effect occurs frequently and is reversible upon discontinuance of therapy.1

  • Importance of advising male patients being considered for cataract surgery that they should inform their ophthalmologist of current or prior α1-blocker (e.g., silodosin) therapy.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Silodosin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

4 mg

Rapaflo

Watson

8 mg

Rapaflo

Watson

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Rapaflo 8MG Capsules (WATSON LABS): 30/$137.93 or 90/$380.90

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions December 1, 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Watson Pharma. Rapaflo (silodosin) capsules prescribing information. Corona, CA; 2008 Oct.

2. Anon. KMD 3213: KAD 3213, Silodosin. Drugs R D. 2004; 5:50-1.

3. Yoshida M, Homma Y, Kawabe K. Silodosin, a novel selective alpha 1A-adrenoceptor selective antagonist for the treatment of benign prostatic hyperplasia. Expert Opin Investig Drugs. 2007; 16:1955-65. [PubMed 18042003]

4. Marks LS, Gittelman MC, Hill LA et al. Rapid efficacy of the highly selective alpha1A-adrenoceptor antagonist silodosin in men with signs and symptoms of benign prostatic hyperplasia: pooled results of 2 phase 3 studies. J Urol. 2009; 181:2634-40. [PubMed 19371887]

5. Kawabe K, Yoshida M, Homma Y et al. Silodosin, a new alpha1A-adrenoceptor-selective antagonist for treating benign prostatic hyperplasia: results of a phase III randomized, placebo-controlled, double-blind study in Japanese men. BJU Int. 2006; 98:1019-24. [PubMed 16945121]

6. Takao T, Tsujimura A, Kiuchi H et al. Early efficacy of silodosin in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Int J Urol. 2008; 15:992-6. [PubMed 18775032]

7. Anon. Silodosin (Rapaflo) for benign prostatic hyperplasia. Med Lett Drugs Ther. 2009; 51:3-4.

8. American Urological Association. Guideline on the management of benign prostatic hyperplasia (BPH) (2003/updated 2006). Available from website. Accessed 2009 Aug 13.

9. Madersbacher S, Alivizatos G, Nordling J et al. EAU 2004 guidelines on assessment, therapy and follow-up of men with lower urinary tract symptoms suggestive of benign prostatic obstruction (BPH guidelines). Eur Urol. 2004; 46:547-54. [PubMed 15474261]

10. Watson Pharmaceuticals. Morristown, NJ: Personal communication.

11. Cantrell MA, Bream-Rouwenhorst HR, Steffensmeier A et al. Intraoperative floppy iris syndrome associated with alpha1-adrenergic receptor antagonists. Ann Pharmacother. 2008; 42:558-63. [PubMed 18364408]

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