Version May 2024
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/mL, or palpable prostate enlargement on digital rectal exam), use in combination with 5-alpha reductase inhibitor (Ref).
Oral: 8 mg once daily with a meal.
Ureteral stone(s) expulsion (off-label use):
Note: Consider for use in patients with ureteral stones >5 and ≤10 mm (Ref). 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 (Ref). Additionally, may consider for use after shock wave lithotripsy to help pass stone fragments (Ref).
Oral: 8 mg once daily with a meal until stone passage or for up to 4 weeks (Ref).
CrCl >50 mL/minute: No dosage adjustment necessary.
CrCl 30-50 mL/minute: 4 mg once daily.
CrCl <30 mL/minute: Use is contraindicated.
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).
Refer to adult dosing.
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
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).
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Concurrent use with other alpha-blockers (eg, prazosin, terazosin, doxazosin).
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.
• Pediatric: Not indicated for use in children.
Other warnings/precautions:
• Antihypertensive use: Not intended for use as an antihypertensive drug.
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
Yes
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.
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
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.
Benign prostatic hyperplasia: Treatment of signs and symptoms of benign prostatic hyperplasia.
Ureteral stone(s)
Rapaflo may be confused with Rapamune
Silodosin may be confused with sildenafil, sirolimus
Substrate of CYP3A4 (major), P-glycoprotein/ABCB1 (minor), UGT2B7; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
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
Blood Pressure Lowering Agents: Silodosin may enhance the hypotensive effect of Blood Pressure Lowering Agents. 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
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.
Silodosin may cause ejaculatory dysfunction, including anejaculation. Small studies conducted in healthy patients with normal semen parameters found anejaculation to be reversible when silodosin is discontinued. As a result, silodosin has been evaluated as an on-demand, reversible, nonhormonal, nonbarrier form of contraception (additional study needed) (Bearelly 2021; Bhat 2020; Kobayashi 2008).
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]).
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]).
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.
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%)
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.
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