(SI lo doe sin)
Treatment of signs and symptoms of benign prostatic hyperplasia (BPH)
U.S. 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 U.S. labeling): Concurrent use with other alpha-blockers (eg, prazosin, terazosin, doxazosin)
BPH: Oral: 8 mg once daily with a meal
Refer to adult dosing.
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).
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.
Take with a meal.
Store at room temperature of 25 � �C (77 � �F); excursions permitted to 15 � �C to 30 � �C (59 � �F to 86 � �F). Protect from light. Protect from moisture.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Rapaflo: 4 mg, 8 mg
Alpha-/Beta-Agonists: Alpha1-Blockers may diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Similarly, Alpha-/Beta-Agonists may antagonize Alpha1-Blocker vasodilation. Monitor therapy
Alpha1-Agonists: Alpha1-Blockers may diminish the vasoconstricting effect of Alpha1-Agonists. Similarly, Alpha1-Agonists may antagonize Alpha1-Blocker vasodilation. Monitor therapy
Alpha1-Blockers: May enhance the antihypertensive effect of other Alpha1-Blockers. Avoid combination
Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Beta-Blockers: May enhance the orthostatic hypotensive effect of Alpha1-Blockers. The risk associated with ophthalmic products is probably less than systemic products. Exceptions: Levobunolol; Metipranolol. Monitor therapy
Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Calcium Channel Blockers: Alpha1-Blockers may enhance the hypotensive effect of Calcium Channel Blockers. Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Silodosin. Avoid combination
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Dapoxetine: May enhance the orthostatic hypotensive effect of Alpha1-Blockers. Monitor therapy
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification
Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of Silodosin. Avoid combination
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Alpha1-Blockers. Management: Ensure patient is stable on one agent prior to initiating the other, and always initiate combination using the lowest possible dose of the drug being added. When tadalafil is used for treatment of BPH, concurrent alpha 1-blockers are not recommended. Consider therapy modification
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
St Johns Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Blood pressure; urinary symptoms
>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% (Limited to important or life-threatening): Hepatic insufficiency, hypersensitivity reaction, increased serum transaminases, intraoperative floppy iris syndrome, jaundice, priapism, purpura, syncope, skin rash (including toxic)
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.
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 years compared with subjects with a mean age of 24 years.
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 4-8 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:
- Elderly: 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.
B
Teratogenic effects were not observed in animal studies; however, silodosin is not approved for use in women.
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.
Rapidly absorbed (Lepor, 2010)
Vd: 49.5 L
Extensive, via CYP3A4, glucuronidation, and alcohol and aldehyde dehydrogenase pathways; KMD-3213G (active in vitro) and KMD-3293 (not significant) metabolites formed
Feces (55%); urine (34%)
Silodosin: ~3 hours; KMD-3213G: ~5.5 hours (Lepor, 2010)
Healthy volunteers: Silodosin: ~13 hours (mean); KMD-3213G: ~24 hours
~97%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience sexual dysfunction. Have patient report immediately to prescriber signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), severe dizziness, passing out, angina, or priapism (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.