Silodosin is a medication primarily used to treat symptoms of benign prostatic hyperplasia (BPH), which is a non-cancerous enlargement of the prostate gland in men. It belongs to a class of drugs known as alpha-1 blockers. Silodosin works by relaxing the muscles in the prostate and bladder neck, making it easier to urinate.

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:

• For treating enlarged prostate, Silodosin is taken as a pill.
• You usually take 8 milligrams once a day, along with a meal.

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

• When it comes to helping pass kidney stones through the ureter, Silodosin is sometimes used even though it's not officially approved for this purpose.
• The typical dose is 8 milligrams once a day by mouth.
• After the stone has successfully passed, usually within 3 to 18 days on average, you can stop taking Silodosin.
• It's worth mentioning that people with stones larger than 10 millimeters were not part of the studies for this use.

Use in children:

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

Pregnancy Risk Factor B

• Silodosin is rated as Pregnancy Risk Factor B, which means there haven't been any observed harmful effects on pregnancy in animal studies.
• But it's important to note that Silodosin isn't approved for use in women, so its effects during pregnancy aren't well understood.

Dose in Kidney Disease:

• If your kidneys are working well with a Creatinine Clearance (CrCl) above 50 milliliters per minute, no changes to the Silodosin dosage are needed.
• If your CrCl is between 30 and 50 milliliters per minute, the usual dose is 4 milligrams taken once a day.
• If your CrCl is less than 30 milliliters per minute, using Silodosin is not recommended.

Dose in Liver disease:

• If you have mild-to-moderate liver impairment, which is classified as Child-Pugh class A or B, there's no need to adjust the Silodosin dosage.
• If you have severe liver impairment, classified as Child-Pugh class C, it's not recommended to use Silodosin as it hasn't been studied in this population.

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):

• In the United States, Silodosin shouldn't be used if you're hypersensitive to it or any part of its formulation, if you're taking strong CYP3A4 inhibitors like clarithromycin or ritonavir, if you have severe renal impairment (CrCl less than 30 mL/minute), or if you have severe hepatic impairment (Child-Pugh class C).
• In Canada, it's also contraindicated to use Silodosin alongside other alpha-blockers like prazosin, terazosin, or doxazosin.

Warnings and precautions

Floppy iris syndrome:

• In cataract surgery, there's a condition called intraoperative floppy iris syndrome that has been seen in patients who were taking or had previously taken alpha-blockers like Silodosin.
• However, it's not clear if the alpha-blockers directly cause this syndrome, and stopping alpha-blocker therapy before surgery doesn't seem to provide any benefit.

Orthostatic hypotension, syncope

• Silodosin can lead to significant drops in blood pressure when standing up, known as orthostatic hypotension, especially after the first dose.
• This effect might also occur if you stop taking it for a few days, increase your dosage quickly, or start taking another blood pressure medication or a PDE-5 inhibitor like sildenafil.
• Although a clinical trial showed that combining sildenafil or tadalafil with silodosin didn't pose a significant risk of orthostatic hypotension, caution is still advised.
• The first dose of orthostatic hypotension might happen 4 to 8 hours after taking Silodosin, and it could be related to the dosage.
• Patients should be warned about performing risky activities like driving or operating heavy machinery when starting Silodosin or adjusting the dosage upwards.

Hepatic impairment

• Silodosin should be used cautiously in patients with mild-to-moderate hepatic impairment, but it's contraindicated in those with severe impairment.
• It hasn't been studied in this population.

Prostate cancer:

• Before starting therapy with Silodosin, it's recommended to make sure there's no prostate cancer present.

Renal impairment

• Silodosin should be used cautiously in patients with moderate renal impairment, and dosage adjustment may be necessary.
• However, it's contraindicated in patients with severe renal impairment, defined as a Creatinine Clearance (CrCl) less than 30 milliliters per minute.

Silodosin: Drug Interaction

Monitoring parameters:

Blood Pressure:

• Silodosin may cause a drop in blood pressure, especially when standing up.
• This can lead to dizziness or fainting, especially with the first dose or when changing the dosage.
• Patients should be cautious when starting or adjusting the dose of Silodosin, especially if they're doing activities like driving or operating heavy machinery.

Urinary Symptoms:

• Silodosin helps with symptoms of an enlarged prostate, like difficulty urinating or frequent urination.
• It works by relaxing the muscles in the prostate and bladder neck, making it easier to urinate.
• Silodosin is usually taken once a day with a meal for best results.

How to administer Silodosin (Rapaflo)?

• Silodosin should be taken with a meal.
• Capsules can be opened, and the powder sprinkled onto a tablespoon of applesauce (not hot).
• The applesauce mixture should be swallowed within 5 minutes without chewing.
• After swallowing the mixture, drink 8 ounces of cool water.
• Do not subdivide the capsule contents.
• Do not store the mixture for future use.

Mechanism of action of Silodosin (Rapaflo):

• Silodosin works by selectively blocking certain receptors called alpha-adrenoreceptors in the prostate and bladder.
• These receptors play a role in controlling the muscle tone in the prostate.
• By blocking these receptors, Silodosin helps relax the smooth muscle in the bladder neck and prostate.
• This relaxation improves urine flow and reduces symptoms associated with benign prostatic hyperplasia (BPH).
• About 75% of the alpha1-receptors in the prostate are of the alpha subtype, which is the main target of Silodosin's action.

Absorption:

• Silodosin is rapidly absorbed into the body.

Distribution:

• The volume of distribution is approximately 49.5 liters.

Protein Binding:

• About 97% of Silodosin binds to proteins in the blood.

Metabolism:

• Silodosin undergoes extensive metabolism primarily through the CYP3A4 enzyme, as well as through glucuronidation, alcohol, and aldehyde dehydrogenase pathways.
• It forms active (KMD-3213G) and inactive (KMD-3293) metabolites.

Bioavailability:

• The bioavailability of Silodosin is around 32%.
• This bioavailability remains unchanged even when the contents of the capsule are sprinkled onto a tablespoonful of applesauce and administered.

Half-life Elimination:

• In healthy volunteers, the half-life of Silodosin is approximately 13 hours on average, while the active metabolite KMD-3213G has a half-life of about 24 hours.

Time to Peak, Plasma:

• It takes around 3 hours for Silodosin to reach peak levels in the blood, while the active metabolite KMD-3213G peaks at about 5.5 hours.

Excretion:

• The majority of Silodosin and its metabolites are excreted through the feces (55%), with a smaller portion excreted in the 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).