Siloin

Siloin Uses, Dosage, Side Effects, Food Interaction and all others data.

Siloin is a selective antagonist of post-synaptic alpha-1 adrenoreceptors, which are located in the human prostate, bladder base, bladder neck, prostatic capsule and prostatic urethra. Blockade of these alpha-1 adrenoreceptors can cause smooth muscle in these tissues to relax, resulting in an improvement in urine flow and a reduction in BPH symptoms.

Siloin is an antagonist of α1-adrenoceptors. It has the highest selectivity for the α1A-adrenoceptor subtype, with a 162-fold greater affinity than α1B-adrenoceptor and about a 50-fold greater affinity than for α1D-adrenoceptor. In clinical trials, silodosin improved maximum urinary flow rate, voiding symptoms, and storage symptoms of benign prostatic hyperplasia. Following oral administration, silodosin had a rapid onset of effect in men, with early effects of relieving lower urinary tract symptoms occurring within two to six hours post-dose.

Siloin inhibited the human ether-a-go-go-related gene (HERG) tail current; however, it has weak cardiovascular effects. As with all α1-adrenoceptor antagonists blocking α1-adrenoceptors in the iris dilator muscle, silodosin may cause intraoperative floppy iris syndrome (IFIS), which is characterized by small pupils and iris billowing during cataract surgery in patients taking α1-AR antagonists.

Trade Name Siloin
Availability Prescription only
Generic Silodosin
Silodosin Other Names Silodosin, Silodosina
Related Drugs tamsulosin, finasteride, Flomax, prazosin, tadalafil, Cialis
Type Capsule
Formula C25H32F3N3O4
Weight Average: 495.5345
Monoisotopic: 495.234491142
Protein binding

Silodosin is approximately 97% protein bound.

Groups Approved
Therapeutic Class BPH/ Urinary retention/ Urinary incontinence
Manufacturer Elio Bio Care Lifesciences Pvt Ltd
Available Country India
Last Updated: September 19, 2023 at 7:00 am
Siloin
Siloin

Uses

Siloin, a selective alpha-1 adrenergic receptor antagonist, is used for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH). Siloin is not used for the treatment of hypertension.

Siloin is also used to associated treatment for these conditions: Benign Prostatic Hyperplasia (BPH)

How Siloin works

The pathogenesis of benign prostatic hyperplasia is not fully understood: it is believed to involve several pathways, including inflammation, apoptosis, and cellular proliferation. Most drug therapies aim to alleviate symptoms of benign prostatic hyperplasia, silodosin included. Lower urinary tract symptoms of benign prostatic hyperplasia are categorized into three main groups: voiding or obstructive (hesitancy, slow stream, intermittency, incomplete emptying), storage or irritative (frequency, urgency, nocturia, urge urinary incontinence), and postmicturition (postvoid dribbling). Prostate contraction is the main contributor to lower urinary tract symptoms of benign prostatic hyperplasia. The smooth muscle tone of the prostate is regulated by α1A-adrenoceptors, which are the most highly expressed subtype of α1adrenoceptors in the human prostate tissue. It has been reported that blockade of α1A-adrenoceptors relieves bladder outlet obstruction. Blockade of α1D-adrenoceptors, another subtype found in prostate tissue, is believed to alleviate storage symptoms due to detrusor overactivity.

α1-adrenoceptors are G protein-coupled receptors: upon binding of its natural ligand, norepinephrine and epinephrine, leads to the activation of phospholipase C and downstream signalling molecules, including inositol triphosphate and diacylglycerol. Ultimately, there is an increase in intracellular calcium levels and, consequently, smooth muscle contraction. Siloin is an antagonist of α1-adrenoceptors, with the highest selectivity for the α1A-adrenoceptor subtype. By blocking the α1A-adrenoceptor signalling pathway, silodosin promotes prostatic and urethral smooth muscle relaxation, thereby improving lower urinary tract symptoms such as voiding. Siloin also targets afferent nerves in the bladder, relieving bladder overactivity and storage symptoms.

Dosage

Siloin dosage

The recommended dose is Siloin 8 mg orally once daily with a meal.4 mg capsules taken orally once daily with a meal for those with moderate renal impairment (CrCl 30-50 mL/min).

Side Effects

Most common adverse reactions are retrograde ejaculation, dizziness, diarrhea, orthostatic hypotension, headache, nasopharyngitis and nasal congestion.

Toxicity

Oral LD50 is 800 mg/kg in rats.

In clinical trials, postural hypotension was the most common dose-limiting adverse event. In case of drug overdose leading to hypotension, the patient should be placed in a supine position to restore blood pressure and normalize heart rate. Further measures, such as administration of intravenous fluids, may be initiated. In case of the use of vasopressors, renal function should be monitored and supported as needed. Since silodosin is highly bound to plasma proteins, dialysis is unlikely to be beneficial.

Precaution

Postural hypotension with or without symptoms (e.g. dizziness) may develop when beginning Siloin treatment. Siloin should not be used in combination with other alpha-blocker. Inform patients planning cataract surgery to notify their ophthalmologist that they are taking Siloin because of the possibility of Intraoperative Floppy Iris Syndrome (IFIS)

Interaction

Strong P-glycoprotein inhibitors (e.g., cyclosporine): Co-administration may increase plasma Siloin concentration. Concomitant use of PDE5 inhibitors with alpha-blockers including Siloin can potentially cause symptomatic hypotension.

Food Interaction

  • Take with food. A moderate fat or calorie meal decreases drug exposure as well as the risk of adverse effects.

[Moderate] ADJUST DOSING INTERVAL: Food may reduce the oral bioavailability of silodosin.

The effect of a moderate-fat, moderate-calorie meal on silodosin pharmacokinetics was variable and decreased silodosin maximum plasma concentration (Cmax) by approximately 18% to 43% and systemic exposure (AUC) by 4% to 49% across three different studies.

The maximum effect of food (i.e., coadministration with a high-fat, high-calorie meal) on the pharmacokinetics of silodosin was not evaluated.

Safety and efficacy clinical trials for silodosin were always conducted in the presence of food intake.

MANAGEMENT: Patients should be instructed to take silodosin with a meal to reduce the risk of adverse events.

Siloin Alcohol interaction

[Moderate] GENERALLY AVOID:

The concurrent use of ethanol and alpha-1 adrenergic blockers may cause increased hypotensive effects.

Patients with aldehyde dehydrogenase deficiencies (primarily Asians) may be at a higher risk of this interaction.

The mechanism has not been determined.

Data exist for prazosin and other alpha adrenergic blockers are expected to interact also.

In addition, any patients taking alpha adrenergic blockers may experience excessive orthostatic hypotension with ethanol ingestion, due to ethanol's unopposed vasodilatory effects in the presence of alpha adrenergic blockade.

Patients who develop

a flushing reaction after ethanol ingestion (indicates a possible aldehyde dehydrogenase deficiency) should be advised to avoid ethanol or limit their intake.

All patients should be warned about the possibility of orthostatic hypotension with concurrent ethanol use.

Volume of Distribution

Siloin has an apparent volume of distribution of 49.5 L.

Elimination Route

The absolute bioavailability is approximately 32%. Following oral administration of silodosin 8 mg once daily in healthy male subjects, Cmax was 61.6 ± 27.54 ng/mL and AUC was 373.4 ± 164.94 ng x hr/mL. The Tmax was 2.6 ± 0.90 hours. Siloin glucuronide or KMD-3213G, the main metabolite of silodosin, has an AUC three- or four fold higher than for the parent compound.

A moderate fat or calorie meal reduces Cmax by 18% to 43% and AUC by 4% to 49%, as well as Tmax by about one hour. However, the US prescribing information recommends drug intake with meals to avoid the potential adverse effects associated with high plasma drug concentrations.

Half Life

The elimination half-life of silodosin is 13.3 ± 8.07 hours. KMD-3213G, the main metabolite of silodosin, has an extended half-life of approximately 24 hours.

Clearance

After intravenous administration, the plasma clearance of silodosin was approximately 10 L/hour.

Elimination Route

At 10 days following oral administration of radiolabelled silodosin, about 33.5% of the dose was recovered in urine and 54.9% was recovered in feces.

Pregnancy & Breastfeeding use

Pregnancy Category B. Siloin is not indicated for use in women. An embryo/fetal study in rabbits showed decreased maternal body weight at 200 mg/kg/day (approximately 13-25 times the maximum recommended human exposure or MRHE of Siloin via AUC). No statistically significant teratogenicity was observed at this dose. Siloin was not teratogenic when administered to pregnant rats during organogenesis at 1000 mg/kg/day (estimated to be approximately 20 times the MRHE). No maternal or fetal effects were observed at this dose. Rats and rabbits do not produce glucuronidated Siloin, which is present in human serum at approximately 4 times the level of circulating Siloin and which has similar pharmacological activity to Siloin. No effects on physical or behavioral development of offspring were observed when rats were treated during pregnancy and lactation at up to 300 mg/kg/day.

Contraindication

Patients with severe renal & hepatic impairment, concomitant administration with strong Cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ketoconazole, clarithromycin, itraconazole, ritonavir) and patients with a history of hypersensitivity to Siloin.

Special Warning

Pediatric patients: Siloin is not indicated for use in pediatric patients.

Geriatric use: In double-blind, placebo-controlled, 12-week clinical studies of Siloin, 259 (55.6%) were under 65 years of age, 207 (44.4%) patients were 65 years of age and over, while 60 (12.9%) patients were 75 years of age and over. Orthostatic hypotension was reported in 2.3% of Siloin patients < 65 years of age (1.2% for placebo), 2.9% of Siloin patients > 65 years of age (1.9% for placebo), and 5.0% of patients > 75 years of age (0% for placebo). There were otherwise no significant differences in safety or effectiveness between older and younger patients.

Renal impairment: Siloin is contra-indicated in patients with severe renal impairment (CCr <30 mL/min). In patients with moderate renal impairment (CCr 30-50 mL/min), the dose should be reduced to Siloin 4 mg once daily taken with a meal. No dosage adjustment is needed in patients with mild renal impairment (CCr 50-80 mL/min).

Hepatic impairment: Siloin has not been studied in patients with severe hepatic impairment (Child-Pugh score > 10) and is therefore contra-indicated in these patients. No dosage adjustment is needed in patients with mild or moderate hepatic impairment.

Acute Overdose

Siloin was evaluated at doses of up to 48 mg/day in healthy male subjects. The dose-limiting adverse event was postural hypotension. Should overdose of Siloin lead to hypotension, support of the cardiovascular system is of first importance. Restoration of blood pressure and normalization of heart rate may be accomplished by maintaining the patient in the supine position. If this measure is inadequate, administration of intravenous fluid should be considered. If necessary, vasopressors could be used, and renal function should be monitored and supported as needed. Dialysis is unlikely to be of significant benefit since Siloin is highly (97%) protein bound.

Storage Condition

Store in a cool and dry place, protected from light.

Innovators Monograph

You find simplified version here Siloin

Siloin contains Silodosin see full prescribing information from innovator Siloin Monograph, Siloin MSDS, Siloin FDA label

FAQ

What is Siloin used for?

Siloin is an alpha-blocker that is used to improve urination in men with benign prostatic hyperplasia (enlarged prostate).
Siloin may also be used for purposes not listed in this medication guide.

How should I take Siloin?

Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose. Use the medicine exactly as directed.Take once daily with a meal.If you cannot swallow a capsule whole, open it and mix the medicine with applesauce. Swallow the mixture right away without chewing.

How safe is Siloin?

Siloin is an effective and safe agent in elderly men who are taking antihypertensive medications. Siloin has an advantage in the treatment of LUTS in this population, even if the patients have orthostatic hypotension before treatment.

What are the common side effects of Siloin?

The most common side effects are include:

  • dizziness
  • diarrhea
  • orthostatic hypotension (low blood pressure when you stand up after sitting or lying down)
  • headache
  • retrograde ejaculation (occurs when semen enters the bladder instead of out the tip of the penis)
  • common cold
  • stuffy nose

Is Siloin safe during pregnancy?

Women should not take Siloin, especially if they are or could become pregnant .

Is Siloin safe during breastfeeding?

This drug is not indicated for use in female patients.

Can I drink alcohol with Siloin?

avoid or limit alcohol-containing beverages while taking Siloin.

Can I drive after taking Siloin?

Siloin may cause some people to become dizzy or less alert than they are normally. Do not drive or do anything else that could be dangerous until you know how this medicine affects you.

When is the best time to take Siloin?

This drug should be taken with a meal.Taking this drug on an empty stomach may increase your risk of side effects, such as a drop in blood pressure when rising after sitting or lying down.Take this drug at the same time every day.

How long does Siloin stay in my system?

The terminal half-life of Siloin is about 11 hours.

How quickly does Siloin work?

Most people in studies saw improvements in their prostate symptoms within the first month of the study.

Does Siloin make me tired?

You should know that Siloin may make you drowsy or dizzy, especially when you first start taking it. Do not drive a car or operate machinery until you know how this medication affects you.

Can I take Siloin at night?

Your first dose of Siloin with food at bedtime so that your body can get used to its effects. The dosage is based on your medical condition and response to treatment. Take this medication regularly to get the most benefit from it.

Does Siloin cause retrograde?

The ejaculatory dysfunction caused by Siloin was a loss of seminal emission, not retrograde ejaculation.

What happens if I miss a dose of Siloin?

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

Does Siloin help in erection?

Most patients using Siloin per day for BPH treatment experienced improvement in their erectile function, estimated IELT, and premature ejaculation profile in the third month of the treatment.

Can Siloin cause incontinence?

Siloin can cause problems in urinating, such as a need to urinate often, a weak stream when urinating, or a feeling of not being able to empty the bladder completely.

How long can I take Siloin?

It may take up to 4 weeks to notice an improvement in symptoms but keep taking them regularly. Tell your doctor if your symptoms do not improve after 4 weeks or if they get worse

What happens if I take too much Siloin?

If you take too much, you may experience low blood pressure, especially when you stand up after sitting or lying down. Symptoms may include: feeling dizzy or lightheaded. fainting.

*** Taking medicines without doctor's advice can cause long-term problems.
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