Silodosin (Rapaflo) - Uses, Dose, MOA, Brands, Side effects

Silodosin (Rapaflo) is a selective alpha-1A receptor blocker that inhibits the contraction of smooth muscles present in the prostate and urinary bladder resulting in improvement in the obstructive symptoms associated with benign prostatic hyperplasia.

Silodosin (Rapaflo) Uses:

  • It is indicated for the symptomatic treatment of patients with benign prostatic hyperplasia (BPH)
  • Off Label Use of Silodosin in Adults:

    • It is also used as an off-label medicine for the treatment of small distal Ureteral calculi.

Silodosin (Rapaflo) Dose in Adults

Silodosin (Rapaflo) Dose in the treatment of BPH:

  • 8 mg administered orally once a day with meals.

Silodosin (Rapaflo) Dose in the treatment of Ureteral calculi (distal) expulsion (off-label):

  • 8 mg once daily with meals. The treatment should be discontinued if the stone is successfully expelled out. The average time for stone expulsion is 3 to 18 days.
  • Patients should be advised to take fluids liberally. The efficacy of the drug has not been established in clinical studies in patients with stone size exceeding 10 mm.

Use in children:

The safety and efficacy of the drug in children have not been established.

Pregnancy Risk Factor B

  • The drug has not been shown to have teratogenic effects. Adverse pregnancy outcomes have not been documented. However, it is not approved for use in women.

Dose in Kidney Disease:

  • CrCl >50 mL/minute:
    • No dosage adjustment necessary.
  • CrCl 30-50 mL/minute:
    • 4 mg once a day.
  • CrCl <30 mL/minute:
    • Use is contraindicated.

Dose in Liver disease:

  • Mild-to-moderate impairment (Child-Pugh class A or B):
    • No dosage adjustment is necessary.
  • Severe impairment (Child-Pugh class C):
    • Use is contraindicated. The drug has not been studied in patients with advanced liver disease.

Common Side Effects of Silodosin (Rapaflo):

  • Genitourinary:

    • Retrograde Ejaculation

Less Common Side Effects of Silodosin (Rapaflo):

  • Cardiovascular:

    • Orthostatic Hypotension
  • Central Nervous System:

    • Dizziness
    • Headache
    • Insomnia
  • Gastrointestinal:

    • Diarrhea
    • Abdominal Pain
  • Genitourinary:

    • Prostate Specific Antigen Increased
  • Neuromuscular & Skeletal:

    • Weakness
  • Respiratory:

    • Nasal Congestion
    • Rhinorrhea
    • Sinusitis

Contraindications to Silodosin (Rapaflo):

US Labeling

  • Allergy reactions to silodosin and any component of the formulation
  • Concomitant use strong CYP3A4 inhibitors like clarithromycin and itraconazole or ketoconazole;
  • Severe renal impairment (CrCl >30 mL/minute);
  • Severe hepatic impairment (Child Puugh class C).

Canadian labeling:

  • Use of alpha-receptor blocking medications like prazosin and terazosin in conjunction with these medications is not recommended.

Warnings and precautions

  • Floppy iris syndrome:

    • Patients taking alpha-receptor blocking drugs have been known to develop intraoperative folly iris syndromes during cataract surgery.
    • This association is not established. Patients who stop taking alpha-blockers prior to surgery do not seem to be in any benefit.
  • Orthostatic hypotension, syncope

    • There have been cases of significant postural hypotension that could present with syncope. Patients who have received the first dose of the drug or after a long-term treatment-free period are most likely to experience the effects. Patients on blood pressure-lowering medication and patients taking rapid up-titration should be advised to increase their doses.
    • Patients taking medications to treat erectile dysfunction (e.g. sildenafil or vardenafil), or vasodilators such as hydralazine, may also experience postural hypotension.
    • One study found that orthostatic hypotension was not caused by sildenafil and tadalafil use together.
    • Orthostatic hypotension can occur between 4 and 8 hours after drug administration. It may also be dose-related.
    • Patients who are being prescribed a new drug or have had their dose titrated recently should not drive or operate heavy machinery.
  • Hepatic impairment

    • Patients with severe hepatic impairment should avoid it. It should not be used in patients with mild to moderate hepatic impairment. Adjustments to the dosage should be made.
  • Prostate cancer:

    • It is important to rule out the possibility of developing prostatic carcinoma before starting treatment.
  • Renal impairment

    • It is contraindicated for patients with severe renal impairment or those who have a CrCl lower than 30 ml/minute.
    • Moderate renal impairment should be avoided. The CrCl should be adjusted to adjust the dosage.

Silodosin: Drug Interaction

Risk Factor C (Monitor therapy)

Alpha-/Beta-Agonists

Alpha1-Blockers may diminish the vasoconstricting effect of Alpha-/BetaAgonists. Similarly, Alpha-/Beta-Agonists may antagonize Alpha1-Blocker vasodilation.

Alpha1-Agonists

Alpha1-Blockers may diminish the vasoconstricting effect of Alpha1-Agonists. Similarly, Alpha1-Agonists may antagonize Alpha1-Blocker vasodilation.

Aprepitant

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

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.

Bosentan

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).

Calcium Channel Blockers

Alpha1-Blockers may enhance the hypotensive effect of Calcium Channel Blockers.

Clofazimine

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

CYP3A4 Inducers (Moderate)

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).

CYP3A4 Inhibitors (Moderate)

May increase the serum concentration of Silodosin.

Dapoxetine

May enhance the orthostatic hypotensive effect of Alpha1-Blockers.

Deferasirox

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).

Duvelisib

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Erdafitinib

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).

Erdafitinib

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Erdafitinib

May increase the serum concentration of P-glycoprotein/ABCB1 Substrates.

Fosaprepitant

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Fosnetupitant

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Ivosidenib

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).

Larotrectinib

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Netupitant

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Palbociclib

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

P-glycoprotein/ABCB1 Inhibitors

May increase the serum concentration of Silodosin.

Phosphodiesterase 5 Inhibitors

Alpha1-Blockers (Uroselective) may enhance the hypotensive effect of Phosphodiesterase 5 Inhibitors.

Ranolazine

May increase the serum concentration of P-glycoprotein/ABCB1 Substrates.

Rilmenidine

Alpha1-Blockers may enhance the hypotensive effect of Rilmenidine.

Sarilumab

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).

Siltuximab

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).

Simeprevir

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Tocilizumab

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).

Risk Factor D (Consider therapy modification)

CYP3A4 Inducers (Strong)

May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling.

Dabrafenib

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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).

Enzalutamide

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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.

Lorlatinib

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences.

Mitotane

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane.

St John's Wort

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling.

Stiripentol

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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.

Risk Factor X (Avoid combination)

Alpha1-Blockers

May enhance the antihypertensive effect of other Alpha1-Blockers.

Conivaptan

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

CYP3A4 Inhibitors (Strong)

May increase the serum concentration of Silodosin.

Fusidic Acid (Systemic)

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Idelalisib

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Monitoring parameters:

  • Blood pressure;
  • urinary symptoms

How to administer Silodosin (Rapaflo)?

  • It is administered orally with meals once a day.
  • The capsule may be opened and sprinkled on a tablespoon of applesauce (that should not be hot) and administered within five minutes.
  • This should be followed by a glass of cool water. It is not recommended to split the capsule and use half or store the capsule for future use.

Mechanism of action of Silodosin (Rapaflo):

  • It acts as a selective inhibitor of the alpha-1A receptors in the bladder and prostate. 
  • When activated, the bladder's alpha-1A receptors and the prostatic smooth muscle cause spasm and contraction.
  • They inhibit the smooth muscles of the prostate and bladder, resulting in a relaxation that improves the flow of urine and reduces the symptoms of BPH. About three-quarters (75%) are alpha-1A receptors.

Absorption:

  • Orally administered, it is quickly absorbed.

Protein binding:

  • About 97% of the drug is protein-bound in the plasma.

Metabolism:

  • It is extensively metabolized via CYP3A4, glucuronidation, and alcohol and aldehyde dehydrogenase pathways. The resultant metabolites are KMD-3213G (active in vitro) and KMD-3293 (not significant).

Bioavailability:

  • It has a bioavailability of about 32%. The bioavailability of the drug is not altered if the contents of the capsule sprinkled on a tablespoonful of applesauce and administered.

Half-life elimination:

  • Healthy volunteers:
    • Silodosin: ~ a mean of 13 hours;
    • KMD-3213G: ~24 hours

Time to peak plasma concentration:

  • Silodosin: about 3 hours;
  • KMD-3213G: about 5.5 hours.

Excretion:

  • Feces (55%);
  • urine (34%)

International Brand Names of Silodosin:

  • Rapaflo
  • Congdosin
  • Curepass
  • Flopadex
  • Lisoflak
  • Rapasin
  • Silodyx
  • Siloflo
  • Silosin
  • Silotrif
  • Thrupas
  • Truwin
  • Unipass
  • Urief
  • Urorec

Silodosin Brand Names in Pakistan:

Sildoso ( CCL Pharma).

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