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Silodosin: Drug information

Silodosin: Drug information
(For additional information see "Silodosin: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Rapaflo
Brand Names: Canada
  • AURO-Silodosin;
  • PMS-Silodosin;
  • Rapaflo [DSC];
  • Sandoz Silodosin
Pharmacologic Category
  • Alpha 1 Blocker
Dosing: Adult
Benign prostatic hyperplasia

Benign prostatic hyperplasia (monotherapy or combination therapy):

Note: In patients with moderate to severe predominant storage lower urinary tract symptoms, use in combination with beta-3 agonist or anticholinergic agent. In patients with a significantly enlarged prostate (prostate volume >30 mL, prostate specific antigen >1.5 ng/dL, or palpable prostate enlargement on digital rectal exam), use in combination with 5-alpha reductase inhibitor (AUA [Lerner 2021]).

Oral: 8 mg once daily with a meal.

Ureteral stone(s) expulsion

Ureteral stone(s) expulsion (off-label use):

Note: Consider for use in patients with ureteral stones >5 and ≤10 mm (Campschroer 2018; Hollingsworth 2016). Although most evidence exists for distal ureteral stones, given the low side effect profile of alpha-blockers, may consider use in patients with stones in any location of ureter (AUA/ES [Assimos 2016]). Additionally, may consider for use after shock wave lithotripsy to help pass stone fragments (AUA/ES [Assimos 2016]; Oestreich 2020).

Oral: 8 mg once daily with a meal until stone passage or for up to 4 weeks (Campschroer 2018; Dell’Atti 2015; Kumar 2015; Wang 2016).

Dosing: Kidney Impairment: Adult

CrCl >50 mL/minute: No dosage adjustment necessary.

CrCl 30-50 mL/minute: 4 mg once daily.

CrCl <30 mL/minute: Use is contraindicated.

Dosing: Hepatic Impairment: Adult

Mild-to-moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.

Severe impairment (Child-Pugh class C): Use is contraindicated (has not been studied).

Dosing: Older Adult

Refer to adult dosing.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Rapaflo: 4 mg, 8 mg

Generic: 4 mg, 8 mg

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral:

Rapaflo: 4 mg [DSC]

Rapaflo: 8 mg [DSC] [contains fd&c blue #1 (brill blue) aluminum lake]

Generic: 4 mg, 8 mg

Administration: Adult

Administer with a meal. Capsules may be opened and the powder sprinkled onto a tablespoon of applesauce (not hot). The applesauce should be swallowed within 5 minutes without chewing and followed with 8 oz of cool water. Subdividing the capsule contents is not recommended. Do not store for future use.

Use: Labeled Indications

Benign prostatic hyperplasia: Treatment of signs and symptoms of benign prostatic hyperplasia.

Use: Off-Label: Adult

Ureteral stone(s)

Medication Safety Issues
Sound-alike/look-alike issues:

Rapaflo may be confused with Rapamune

Silodosin may be confused with sildenafil, sirolimus

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%: Genitourinary: Retrograde ejaculation (28%)

1% to 10%:

Cardiovascular: Orthostatic hypotension (3%; increased in elderly ≥65 years up to 5%)

Central nervous system: Dizziness (3%), headache (2%), insomnia (1% to 2%)

Gastrointestinal: Diarrhea (3%), abdominal pain (1% to 2%)

Genitourinary: Prostate specific antigen increased (1% to 2%)

Neuromuscular & skeletal: Weakness (1% to 2%)

Respiratory: Nasal congestion (2%), rhinorrhea (1% to 2%), sinusitis (1% to 2%)

<1%, postmarketing, and/or case reports: Hepatic insufficiency, hypersensitivity reaction, increased serum transaminases, intraoperative floppy iris syndrome, jaundice, pharyngeal edema, priapism, pruritus, purpura, skin rash (including toxic), swollen tongue, syncope, urticaria

Contraindications

US labeling: Hypersensitivity to silodosin or any component of the formulation, concurrent use with strong CYP3A4 inhibitors (eg, clarithromycin, itraconazole, ketoconazole, ritonavir); severe renal impairment (CrCl <30 mL/minute); severe hepatic impairment (Child-Pugh class C)

Canadian labeling: Additional contraindications (not in US labeling): Concurrent use with other alpha-blockers (eg, prazosin, terazosin, doxazosin)

Warnings/Precautions

Concerns related to adverse effects:

• Floppy iris syndrome: Intraoperative floppy iris syndrome has been observed in cataract surgery patients who were on or were previously treated with alpha1-blockers; causality has not been established and there appears to be no benefit in discontinuing alpha-blocker therapy prior to surgery.

• Orthostatic hypotension/syncope: May cause significant orthostatic hypotension with or without syncope, especially with first dose; anticipate a similar effect if therapy is interrupted for a few days, if dosage is rapidly increased, or if another antihypertensive drug (particularly vasodilators) or a PDE-5 inhibitor (eg, sildenafil, tadalafil, vardenafil) is introduced although coadministration of sildenafil or tadalafil with silodosin was not associated with a clinically significant risk of orthostatic hypotension in one clinical trial (MacDiarmid 2010). “First-dose” orthostatic hypotension may occur 4 to 8 hours after dosing; may be dose related. Patients should be cautioned about performing hazardous tasks, driving, or operating heavy machinery when starting new therapy or adjusting dosage upward.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with mild-to-moderate hepatic impairment; contraindicated with severe impairment; not studied.

• Prostate cancer: It is recommended to rule out prostatic carcinoma before beginning therapy.

• Renal impairment: Use with caution in patients with moderate renal impairment; dosage adjustment recommended. Contraindicated in patients with severe impairment (CrCl <30 mL/minute).

Concurrent drug therapy issues:

• High potential for interactions: Contraindicated in patients on strong CYP3A4 inhibitors.

Special populations:

• Older adult: Use with caution in the elderly; risk of orthostatic hypotension increases with increasing age. Patients ≥65 years of age experienced an incidence of up to 5% in clinical trials.

• Females: Not indicated for use in women.

• Pediatric: Not indicated for use in children.

Other warnings/precautions:

• Antihypertensive use: Not intended for use as an antihypertensive drug.

Metabolism/Transport Effects

Substrate of CYP3A4 (major), P-glycoprotein/ABCB1 (minor), UGT2B7; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Alpha-/Beta-Agonists: Alpha1-Blockers may diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Similarly, Alpha-/Beta-Agonists may antagonize Alpha1-Blocker vasodilation. Risk C: Monitor therapy

Alpha1-Agonists: Alpha1-Blockers may diminish the vasoconstricting effect of Alpha1-Agonists. Similarly, Alpha1-Agonists may antagonize Alpha1-Blocker vasodilation. Risk C: Monitor therapy

Alpha1-Blockers: May enhance the antihypertensive effect of other Alpha1-Blockers. Risk X: Avoid combination

Beta-Blockers: May enhance the orthostatic hypotensive effect of Alpha1-Blockers. The risk associated with ophthalmic products is probably less than systemic products. Risk C: Monitor therapy

Calcium Channel Blockers: Alpha1-Blockers may enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Silodosin. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Silodosin. Risk X: Avoid combination

Dapoxetine: May enhance the orthostatic hypotensive effect of Alpha1-Blockers. Risk C: Monitor therapy

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of Silodosin. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: Alpha1-Blockers (Uroselective) may enhance the hypotensive effect of Phosphodiesterase 5 Inhibitors. Risk C: Monitor therapy

Rilmenidine: Alpha1-Blockers may enhance the hypotensive effect of Rilmenidine. Risk C: Monitor therapy

Food Interactions

AUC decrease by 4% to 49% and Cmax decreased by ~18% to 43% with moderate calorie/fat meal. Management: Take once daily with a meal.

Pregnancy Considerations

Silodosin is used off label for the treatment of ureteral calculi. Medical expulsive therapy has not been adequately studied in pregnant patients and is not recommended as initial therapy (AUA/ES [Assimos 2016]).

Monitoring Parameters

International Prostate Symptom Score (baseline and 4 to 12 weeks after treatment initiation); urinalysis (baseline); BP; objective and subjective signs of relief of benign prostatic hyperplasia and lower urinary tract symptoms (AUA [Lerner 2021]).

Mechanism of Action

Silodosin is a selective antagonist of alpha1A-adrenoreceptors in the prostate and bladder. Smooth muscle tone in the prostate is mediated by alpha1A-adrenoreceptors; blocking them leads to relaxation of smooth muscle in the bladder neck and prostate causing an improvement of urine flow and decreased symptoms of BPH. Approximately 75% of the alpha1-receptors in the prostate are of the alpha1A subtype.

Pharmacokinetics

Absorption: Rapidly absorbed (Lepor 2010)

Distribution: Vd: 49.5 L

Protein binding: ~97%

Metabolism: Extensive, via CYP3A4, glucuronidation, and alcohol and aldehyde dehydrogenase pathways; KMD-3213G (active in vitro) and KMD-3293 (not significant) metabolites formed

Bioavailability: ~32%; bioavailability not altered if contents of capsule sprinkled on a tablespoonful of applesauce and administered

Half-life elimination: Healthy volunteers: Silodosin: ~13 hours (mean); KMD-3213G: ~24 hours

Time to peak, plasma: Silodosin: ~3 hours; KMD-3213G: ~5.5 hours (Lepor 2010)

Excretion: Feces (55%); urine (34%)

Pharmacokinetics: Additional Considerations

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

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

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

Pricing: US

Capsules (Rapaflo Oral)

4 mg (per each): $10.46

8 mg (per each): $10.46

Capsules (Silodosin Oral)

4 mg (per each): $7.98 - $9.41

8 mg (per each): $7.98 - $9.41

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Congdosin (EG);
  • Curepass (KR);
  • Flopadex (EG);
  • Lisoflak (EG);
  • Niksol (HR);
  • Rapasin (BD);
  • Sidarso (HR);
  • Siliflo (TW);
  • Silodyx (BE, CZ, EE, ES, FR, GR, LT, LU, MT, NL, PL, PT, SK);
  • Siloflo (BD);
  • Silosin (AE, KW, LB, QA);
  • Silotrif (LK);
  • Thrupas (KR);
  • Truwin (KR);
  • Unipass (KR);
  • Urief (CN, JP, PH, TH, TW);
  • Urorec (AT, AU, EE, ES, FR, GR, HR, IE, LT, MT, NL, PL, PT, RO, RU, SI, SK, TR, UA)


For country code abbreviations (show table)
  1. Assimos D, Krambeck A, Miller NL, et al. Surgical management of stones: American Urological Association/Endourological Society guideline, PART I. J Urol. 2016;196(4):1153-1160. doi:10.1016/j.juro.2016.05.090 [PubMed 27238616]
  2. Campschroer T, Zhu X, Vernooij RW, Lock MT. Alpha-blockers as medical expulsive therapy for ureteral stones. Cochrane Database Syst Rev. 2018;4(4):CD008509. doi:10.1002/14651858.CD008509.pub3 [PubMed 29620795]
  3. Chang DF and Campbell JR, “Intraoperative Floppy Iris Syndrome Associated With Tamsulosin,” J Cataract Refract Surg, 2005, 31(4):664-73. [PubMed 15899440]
  4. Dell'Atti L. Silodosin versus tamsulosin as medical expulsive therapy for distal ureteral stones: a prospective randomized study. Urologia. 2015;82(1):54-57. [PubMed 25198942]
  5. Hollingsworth JM, Canales BK, Rogers MA, et al. Alpha blockers for treatment of ureteric stones: systematic review and meta-analysis. BMJ. 2016;355:i6112. doi:10.1136/bmj.i6112 [PubMed 27908918]
  6. Kumar S, Jayant K, Agrawal MM, Singh SK, Agrawal S, Parmar KM. Role of tamsulosin, tadalafil, and silodosin as the medical expulsive therapy in lower ureteric stone: a randomized trial (a pilot study). Urology. 2015;85(1):59-63. [PubMed 25530364]
  7. Lepor H and Hill LA, "Silodosin for the Treatment of Benign Prostatic Hyperplasia: Pharmacology and Cardiovascular Tolerability,” Pharmacotherapy, 2010, 30(12):1303-12. [PubMed 21114397]
  8. Lerner LB, McVary KT, Barry MJ, et al. Management of lower urinary tract symptoms attributed to benign prostatic hyperplasia: AUA guideline part I-initial work-up and medical management. J Urol. 2021;206(4):806-817. doi:10.1097/JU.0000000000002183 [PubMed 34384237]
  9. MacDiarmid SA, Hill LA, Volinn W, et al, “Lack of Pharmacodynamic Interaction of Silodosin, a Highly Selective Alpha 1a-Adrenoceptor Antagonist, With the Phosphodiesterase-5 Inhibitors Sildenafil and Tadalafil in Healthy Men,” Urology, 2010, 75(3):520-5. [PubMed 20080287]
  10. Oestreich MC, Vernooij RW, Sathianathen NJ, et al. Alpha-blockers after shock wave lithotripsy for renal or ureteral stones in adults. Cochrane Database Syst Rev. 2020;11(11):CD013393. doi:10.1002/14651858.CD013393.pub2 [PubMed 33179245]
  11. Preminger GM, Tiselius HG, Assimos DG, et al. 2007 guideline for the management of ureteral calculi. J Urol. 2007;178(6):2418-2434.
  12. Rapaflo (silodosin) [prescribing information]. Parsippany, NJ: Actavis; December 2020.
  13. Rapaflo (silodosin) [product monograph]. Markham, Ontario, Canada: Allergan Pharma Co; March 2018.
  14. Sur RL, Shore N, L'Esperance J, et al. Silodosin to facilitate passage of ureteral stones: a multi-institutional, randomized, double-blinded, placebo-controlled trial. Eur Urol. 2015;67(5):959-964. [PubMed 25465978]
  15. Wang CJ, Tsai PC, Chang CH. Efficacy of silodosin in expulsive therapy for distal ureteral stones: a randomized double-blinded controlled trial. Urol J. 2016;13(3):2666-2671. [PubMed 27351320]
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