Silodal

Silodal capsules, a selective alpha-1 adrenergic receptor antagonist, are indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH). Silodal capsules are not indicated for the treatment of hypertension.

Silodal is used to treat men who have symptoms of an enlarged prostate gland, which is also known as benign enlargement of the prostate (benign prostatic hyperplasia or BPH). Benign enlargement of the prostate is a problem that can occur in men as they get older. The prostate gland is located below the bladder. As the prostate gland gets larger, certain muscles in the gland may become tight and get in the way of the tube that drains urine from the bladder. This 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.

Silodal helps relax the muscles in the prostate and in the opening to the bladder. This may help increase the flow of urine or decrease the symptoms.

Silodal should not be given to women.

Silodal is available only with your doctor's prescription.

Dosing Information

The recommended dose is 8 mg orally once daily with a meal.

Patients who have difficulty swallowing pills and capsules may carefully open the Silodal capsule and sprinkle the powder inside on a tablespoonful of applesauce. The applesauce should be swallowed immediately (within 5 minutes) without chewing and followed with an 8 oz glass of cool water to ensure complete swallowing of the powder. The applesauce used should not be hot, and it should be soft enough to be swallowed without chewing. Any powder/applesauce mixture should be used immediately (within 5 minutes) and not stored for future use. Subdividing the contents of a Silodal capsule is not recommended [seeClinical Pharmacology (12.3)].

Dosage Adjustment in Special Populations

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

Hepatic impairment: Silodal capsules have not been studied in patients with severe hepatic impairment (Child-Pugh score ≥ 10) and is therefore contraindicated in these patients. No dosage adjustment is needed in patients with mild or moderate hepatic impairment.

See also:
What is the most important information I should know about Silodal?

You should not take Silodal if you have severe kidney or liver disease, or if you are also using ketoconazole (Extina, Ketozole, Nizoral, Xolegal), itraconazole (Sporanox), or ritonavir (Norvir).

Do not take Silodal with other similar medicines such as alfuzosin (Uroxatral), doxazosin (Cardura), prazosin (Minipress), tamsulosin (Flomax), or terazosin (Hytrin).

Silodal may cause dizziness or fainting, especially when you first start taking it. Be careful if you drive or do anything that requires you to be alert. Avoid standing for long periods of time or becoming overheated during exercise and in hot weather. Avoid getting up too fast from a sitting or lying position, or you may feel dizzy.

Silodal can affect your pupils during cataract surgery. Tell your eye surgeon ahead of time that you are using this medication. Do not stop using Silodal before surgery unless your surgeon tells you to.

There are many other drugs that can interact with Silodal. Tell your doctor about all medications you use.

Use Silodal as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Silodal by mouth with a meal.
• Swallow Silodal whole. Do not break, crush, or chew before swallowing. If you cannot swallow the capsule whole, you may open it and sprinkle the contents over a spoonful of applesauce. Mix the medicine with the applesauce and swallow the mixture right away, followed by a glass of water. Do not crush or chew the medicine before swallowing. Do not store the mixture for future use.
• If you miss a dose of Silodal, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Silodal.

Silodal is used by men to treat the symptoms of an enlarged prostate (benign prostatic hyperplasia-BPH). It does not shrink the prostate, but it works by relaxing the muscles in the prostate and the bladder. This helps to relieve symptoms of BPH such as difficulty in beginning the flow of urine, weak stream, and the need to urinate often or urgently (including during the middle of the night).

Silodal belongs to a class of drugs known as alpha blockers.

Do not use this medication to treat high blood pressure.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

Silodal may also be used to help your body "pass," or get rid of, kidney stones through urination.

How to use Silodal

Take this medication by mouth as directed by your doctor, usually once daily with a meal.

If you have difficulty swallowing this medication whole, you may sprinkle the entire contents of a capsule on a small amount (such as a tablespoon) of cool soft applesauce just before taking. Swallow the mixture right away (within 5 minutes). Do not chew the mixture, and do not save it for future use. Do not use hot applesauce. Drink a glass of cool water after each dose.

Silodal may cause a sudden drop in your blood pressure, which could lead to dizziness or fainting. This risk is higher when you first start taking this drug, after your doctor increases your dose, or if you restart treatment after you stop taking it. During these times, avoid situations where you may be injured if you faint.

To avoid injury from dizziness or fainting, your doctor may tell you to take your first dose of Silodal 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. To help you remember, take it with the same meal each day.

Tell your doctor if your condition does not improve or if it worsens.

See also:
What other drugs will affect Silodal?

Moderate and Strong CYP3A4 Inhibitors

In a clinical metabolic inhibition study, a 3.8-fold increase in Silodal maximum plasma concentrations and 3.2-fold increase in Silodal exposure were observed with concurrent administration of a strong CYP3A4 inhibitor, 400 mg ketoconazole. Use of strong CYP3A4 inhibitors such as itraconazole or ritonavir may cause plasma concentrations of Silodal to increase. Concomitant administration of strong CYP3A4 inhibitors and Silodal is contraindicated.

The effect of moderate CYP3A4 inhibitors on the pharmacokinetics of Silodal has not been evaluated. Concomitant administration with moderate CYP3A4 inhibitors (e.g., diltiazem, erythromycin, verapamil) may increase concentration of Silodal. Exercise caution and monitor patients for adverse events when co-administering Silodal with moderate CYP3A4 inhibitors.

Strong P-glycoprotein (P-gp) Inhibitors

In vitro studies indicated that Silodal is a P-gp substrate. Ketoconazole, a CYP3A4 inhibitor that also inhibits P-gp, caused significant increase in exposure to Silodal. Inhibition of P-gp may lead to increased Silodal concentration. Silodal is therefore not recommended in patients taking strong P-gp inhibitors such as cyclosporine.

Alpha-Blockers

The pharmacodynamic interactions between Silodal and other alpha-blockers have not been determined. However, interactions may be expected, and Silodal should not be used in combination with other alpha-blockers.

Digoxin

The effect of co-administration of Silodal and digoxin 0.25 mg/day for 7 days was evaluated in a clinical trial in 16 healthy males, aged 18 to 45 years. Concomitant administration of Silodal and digoxin did not significantly alter the steady state pharmacokinetics of digoxin. No dose adjustment is required.

PDE5 Inhibitors

Co-administration of Silodal with a single dose of 100 mg sildenafil or 20 mg tadalafil was evaluated in a placebo-controlled clinical study that included 24 healthy male subjects, 45 to 78 years of age. Orthostatic vital signs were monitored in the 12-hour period following concomitant dosing. During this period, the total number of positive orthostatic test results was greater in the group receiving Silodal plus a PDE5 inhibitor compared with Silodal alone. No events of symptomatic orthostasis or dizziness were reported in subjects receiving Silodal with a PDE5 inhibitor.

Other Concomitant Drug Therapy

Antihypertensives

The pharmacodynamic interactions between Silodal and antihypertensives have not been rigorously investigated in a clinical study. However, approximately one-third of the patients in clinical studies used concomitant antihypertensive medications with Silodal. The incidence of dizziness and orthostatic hypotension in these patients was higher than in the general Silodal population (4.6% versus 3.8% and 3.4% versus 3.2%, respectively). Exercise caution during concomitant use with antihypertensives and monitor patients for possible adverse events.

Metabolic Interactions

In vitro data indicate that Silodal does not have the potential to inhibit or induce cytochrome P450 enzyme systems.

Food Interactions

The effect of a moderate fat, moderate calorie meal on Silodal pharmacokinetics was variable and decreased Silodal maximum plasma concentration (Cmax) by approximately 18 - 43% and exposure (AUC) by 4 - 49% across three different studies. Safety and efficacy clinical trials for Silodal were always conducted in the presence of food intake. Patients should be instructed to take Silodal with a meal to reduce risk of adverse events.

See also:
What are the possible side effects of Silodal?

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

In U.S. clinical trials, 897 patients with BPH were exposed to 8 mg Silodal daily. This includes 486 patients exposed for 6 months and 168 patients exposed for 1 year. The population was 44 to 87 years of age, and predominantly Caucasian. Of these patients, 42.8% were 65 years of age or older and 10.7% were 75 years of age or older.

In double-blind, placebo controlled, 12-week clinical trials, 466 patients were administered Silodal and 457 patients were administered placebo. At least one treatment-emergent adverse reaction was reported by 55.2% of Silodal treated patients (36.8% for placebo treated). The majority (72.1%) of adverse reactions for the Silodal treated patients (59.8% for placebo treated) were qualified by the investigator as mild. A total of 6.4% of Silodal treated patients (2.2% for placebo treated) discontinued therapy due to an adverse reaction (treatment-emergent), the most common reaction being retrograde ejaculation (2.8%) for Silodal treated patients. Retrograde ejaculation is reversible upon discontinuation of treatment.

Adverse Reactions observed in at least 2% of patients:

The incidence of treatment-emergent adverse reactions listed in the following table were derived from two 12-week, multicenter, double-blind, placebo-controlled clinical studies of Silodal 8 mg daily in BPH patients. Adverse reactions that occurred in at least 2% of patients treated with Silodal and more frequently than with placebo are shown in Table 1.

In the two 12-week, placebo-controlled clinical trials, the following adverse events were reported by between 1% and 2% of patients receiving Silodal and occurred more frequently than with placebo: insomnia, PSA increased, sinusitis, abdominal pain, asthenia, and rhinorrhea. One case of syncope in a patient taking prazosin concomitantly and one case of priapism were reported in the Silodal treatment group.

In a 9-month open-label safety study of Silodal, one case of Intraoperative Floppy Iris Syndrome (IFIS) was reported.

6.2 Postmarketing Experience

The following adverse reactions have been identified during post approval use of Silodal. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

Skin and subcutaneous tissue disorders: toxic skin eruption, purpura, skin rash, pruritus, and urticaria

Hepatobiliary disorders: jaundice, impaired hepatic function associated with increased transaminase values

Immune system disorders: allergic-type reactions, not limited to skin reactions including swollen tongue and pharyngeal edema resulting in serious outcomes

Silodal is an α1-adrenoceptor antagonist that is selective for the prostate. Silodal is for symptomatic treatment of benign prostatic hyperplasia. FDA approved Oct 9, 2008.