Consumer medicine information

Urorec

Silodosin

BRAND INFORMATION

Brand name

Urorec

Active ingredient

Silodosin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Urorec.

SUMMARY CMI

UROREC®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I taking UROREC?

UROREC contains the active ingredient silodosin. It is used in men for the relief of lower urinary tract symptoms associated with a medical condition called benign prostatic hyperplasia or BPH.

For more information, see Section 1. Why am I taking UROREC? in the full CMI.

2. What should I know before I take UROREC?

Do not take if you are a woman or a child, or if you have ever had an allergic reaction to silodosin or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions or take any other medicines.

For more information, see Section 2. What should I know before I take UROREC? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with UROREC and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I take UROREC?

  • The usual dose is one capsule of UROREC 8 mg taken once each day at about the same time. If you have moderate kidney problems, your doctor may start you on a lower 4 mg dose. Swallow the capsule whole, with or straight after food, with a glass of water.

More instructions can be found in Section 4. How do I take UROREC? in the full CMI.

5. What should I know while taking UROREC?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are taking UROREC.
  • If you are going to have surgery, tell the surgeon or anaesthetist that you are taking this medicine.
  • If you are going to have eye surgery for cataracts, please tell your surgeon that you are taking or have ever taken UROREC.
Things you should not do
  • Do not take UROREC to treat any other complaints unless your doctor tells you to.
  • Do not give your medicine to anyone else, even if they have the same condition as you.
Driving or using machines
  • UROREC may cause dizziness in some people. If you feel dizzy, do not drive, operate machinery or do anything else that could be dangerous.
Drinking alcohol
  • Tell your doctor if you drink alcohol.
Looking after your medicine
  • Keep your capsules in the pack until it is time to take them.
  • Store it in a cool dry place away from moisture, heat or sunlight.

For more information, see Section 5. What should I know while taking UROREC? in the full CMI.

6. Are there any side effects?

Common side effects include: changes or problems with ejaculation (decrease in the amount of semen released during sex), dizziness, runny or blocked nose and diarrhoea. Serious side effects include: swelling of the face, lips, mouth or throat which may cause difficulty in swallowing or breathing.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

UROREC®

Active ingredient: silodosin

Consumer Medicine Information (CMI)

This leaflet provides important information about taking UROREC. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about taking UROREC.

Where to find information in this leaflet:

1. Why am I taking UROREC?
2. What should I know before I take UROREC?
3. What if I am taking other medicines?
4. How do I take UROREC?
5. What should I know while taking UROREC?
6. Are there any side effects?
7. Product details

1. Why am I taking UROREC?

UROREC contains the active ingredient silodosin. Silodosin belongs to a group of medicines called alpha-blockers. UROREC works by helping relax the smooth muscles in the prostate, in that way it improves flow of urine. This makes it easier for you to pass urine and relieves your symptoms.

UROREC is for use by men only. It is used for the relief of lower urinary tract symptoms associated with a medical condition called benign prostatic hyperplasia or BPH. BPH is a condition where the prostate gland (which is near your bladder) has become bigger making it more difficult for you to pass urine. This can lead to symptoms such as:

  • weak or interrupted stream of urine
  • feeling that you cannot empty your bladder completely
  • delay before you start to pass urine
  • needing to pass urine often, especially at night
  • feeling that you must pass urine straight away.

BPH occurs only in men and is common over the age of 50 years. In some men, BPH can lead to serious problems, including urinary tract infections and the sudden inability to pass urine at all.

Ask your doctor if you have any questions about why this medicine has been prescribed for you.

Your doctor may have prescribed it for another reason.

UROREC is not addictive.

2. What should I know before I take UROREC?

Warnings

Do not take UROREC if:

  • you are allergic to silodosin, or any of the ingredients listed at the end of this leaflet.
    Always check the ingredients to make sure you can take this medicine.
  • you are a woman or a child.
    The condition for which UROREC is prescribed occurs only in men.

Check with your doctor if you:

  • have allergies to any other medicines, foods, preservatives or dyes.
  • take any medicines for any other condition
  • have any other medical conditions such as:
    - severe liver problems
    - kidney problems
    - feeling dizzy or light-headedness when you sit up or stand abruptly
    - prostate symptoms
    Since a benign enlargement of the prostate and prostate cancer may present the same symptoms, your doctor will check you for prostate cancer before starting treatment with UROREC. UROREC does not treat prostate cancer.
    - changes or problems with ejaculation
    The treatment with UROREC may lead to an abnormal ejaculation (decrease in the amount of semen released during sex) that may temporarily affect male fertility. This effect normally disappears after discontinuation of UROREC. Please inform your doctor if you are planning to have children.
    - planning to have eye surgery.
    If you are undergoing eye surgery because of cloudiness of the lens (cataract surgery), it is important that you immediately inform your eye specialist that you are taking or have previously taken or about to start taking UROREC.
    This is because some patients treated with this kind of medicine may experience a loss of muscle tone in the iris (the coloured part of the eye) during eye surgery.
    The period of time between discontinuing the medicine and eliminating the risk of loss of muscle tone in the iris is unknown. It is important therefore that you tell your eye surgeon if you have ever taken UROREC. The surgeon can take appropriate precautions with respect to medicine and surgical techniques to be used.
    Ask your eye specialist whether or not you should postpone or temporarily stop taking UROREC when undergoing cataract surgery.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and UROREC may interfere with each other. These include:

  • medicines which lower blood pressure (in particular, medicines called alpha-blockers, such as prazosin or doxazosin)
  • antifungal medicines (such as ketoconazole or itraconazole)
  • medicines used for HIV-AIDS (such as ritonavir)
  • medicines used after transplants to prevent organ rejection (such as cyclosporine)
  • medicines used for treating problems in getting or keeping an erection (such as sildenafil or tadalafil)
  • medicines for epilepsy (such as carbamazepine and phenytoin)
  • rifampicin (a medicine to treat tuberculosis).

These medicines may be affected by UROREC or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect UROREC.

4. How do I take UROREC?

How much to take

  • The usual dose is one capsule of UROREC 8 mg taken once each day.

Patients with kidney conditions:

  • If you have moderate kidney problems, your doctor may start you on a lower dose. UROREC is also available as a 4 mg hard capsule.
  • Follow the instructions provided and take UROREC until your doctor tells you to stop.
    If you stop treatment, your symptoms may re-appear.

When to take UROREC

  • Take your medicine at about the same time each day.
  • Taking it at the same time each day will have the best effect. It will also help you remember when to take it.

How to take UROREC

  • Swallow the UROREC capsule whole, with or straight after food, preferably with a glass of water.
  • Do not break or chew the capsule.

If you forget to take UROREC

UROREC should be taken regularly at about the same time each day. If you miss your dose at the usual time take your dose as soon as you remember, continue to take it as you would normally.

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

If you miss a whole day, continue to take your normal daily dose the next day.

Do not take a double dose to make up for the dose you missed.

If you take too much UROREC

If you think that you have taken too much UROREC, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while taking UROREC?

Things you should do:

Remind any doctor, dentist or pharmacist you visit that you are taking UROREC.

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking UROREC.

If you are going to have surgery, tell the surgeon or anaesthetist that you are taking this medicine.

It may affect other medicines used during surgery.

If you are going to have eye surgery for cataracts, please tell your surgeon that you are taking or have ever taken UROREC (see Section 6. Are there any side effects?)

Keep all of your doctor's appointments so that your progress can be checked.

Things you should not do:

  • Do not take UROREC to treat any other complaints unless your doctor tells you to.
  • Do not give your medicine to anyone else, even if they have the same condition as you.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how UROREC affects you.

UROREC may cause dizziness in some people

If you feel dizzy, do not drive, operate machinery or do anything else that could be dangerous.

If you feel light-headed, dizzy or faint when getting out of bed or standing up, get up slowly.

Standing up slowly, especially when you get up from bed or chairs, will help your body get used to the change in position and blood pressure. If this problem continues or gets worse, talk to your doctor.

Drinking alcohol

Tell your doctor if you drink alcohol.

Looking after your medicine

Keep your capsules in the pack until it is time to take them. This will protect the capsules from light and moisture.

If you take the capsules out of the pack they may not keep well.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on windowsills.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
Very Common:
  • changes or problems with ejaculation, such as decreased amount of semen released during sex (this decrease does not appear to interfere with normal sexual function)
Common
  • dizziness
  • runny or blocked nose
  • diarrhoea
Uncommon:
  • decreased sexual drive
  • nausea
  • dry mouth
  • difficulties in getting or keeping an erection
  • fast heartbeats
  • skin rash, itchiness
  • hives (pinkish, itchy swellings on the skin)
  • abnormal liver enzyme levels
  • low blood pressure.
Rare:
  • fast or irregular heartbeats (called palpitations)
  • fainting/loss of consciousness
Speak to your doctor if you have any of these less serious side effects and they worry you

Serious side effects

Serious side effectsWhat to do
Swelling of the face, lips, mouth or throat which may cause difficulty in swallowing or breathing.
These are symptoms of very rare serious allergic reaction. You may need urgent medical attention or hospitalisation		Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

UROREC may cause complications during a cataract surgery.

Some patients treated with UROREC can experience a loss of muscle tone in the iris (the coloured circular part of the eye) during such a surgery.

It is important that you immediately inform your eye specialist if you are taking or have previously taken UROREC. The specialist can take appropriate precautions with respect to the medicine and surgical techniques to be used.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What UROREC contains

Active ingredient
(main ingredient)
  • each UROREC 8 mg capsule contains 8 mg silodosin
  • each UROREC 4 mg capsule contains 4 mg silodosin
Other ingredients
(inactive ingredients)
  • pregelatinised maize starch
  • mannitol
  • magnesium stearate
  • sodium lauryl sulfate
  • gelatin
  • titanium dioxide
  • iron oxide yellow (in UROREC 4 mg capsule only)
Potential allergensUROREC does not contain lactose, sucrose or gluten

Do not take this medicine if you are allergic to any of these ingredients.

What UROREC looks like

UROREC 8 mg are white, opaque, hard gelatine capsules (AUST R 275265).

UROREC 4 mg are yellow, opaque, hard gelatine capsules (AUST R 275256).

Trade packs are available in blister packs of 30 capsules, and starter packs available in blister packs of 10 capsules.

Who distributes UROREC?

Mayne Pharma International Pty Ltd
1538 Main North Road
Salisbury South, SA 5106

This leaflet was prepared in May 2025.

Published by MIMS July 2025

BRAND INFORMATION

Brand name

Urorec

Active ingredient

Silodosin

Schedule

S4

 

1 Name of Medicine

Silodosin.

2 Qualitative and Quantitative Composition

Urorec hard gelatin capsules contain either 4 mg or 8 mg of silodosin.

3 Pharmaceutical Form

Urorec 4 mg is presented as yellow, opaque, hard gelatin capsules.
Urorec 8 mg is presented as white, opaque, hard gelatin capsules.

4 Clinical Particulars

4.1 Therapeutic Indications

Urorec is indicated for the relief of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) in adult men.

4.2 Dose and Method of Administration

Dosage.

The recommended dose is one capsule of Urorec 8 mg daily.

Method of administration.

A capsule should be taken with food, preferably at the same time every day. It should not be broken or chewed but swallowed whole, preferably with a glass of water.

Dosage adjustment.

Use in the elderly.

No dose adjustment is required in the elderly.

Use in renal impairment.

No dose adjustment is required for patients with mild renal impairment (CLCR ≥ 60 to ≤ 89 mL/min; eGFR ≥ 60 to ≤ 89 mL/min/1.73 m2; CKD stage G2).
A starting dose of 4 mg once daily is recommended in patients with moderate renal impairment (CLCR ≥ 30 to ≤ 59 mL/min; eGFR ≥ 30 to ≤ 59 mL/min/1.73 m2; CKD stage G3a and G3b). After a minimum of one week a dose increase may be considered. The dose can be carefully increased to 8 mg once daily depending on the individual patient's response (see Section 4.4 Special Warnings and Precautions for Use; Section 5.2 Pharmacokinetic Properties, Use in renal impairment).
The use in patients with severe renal impairment (CLCR < 30 mL/min; eGFR < 30 mL/min/1.73 m2; CKD stage G4 and G5) is not recommended (see Section 4.4 Special Warnings and Precautions for Use).

Use in hepatic impairment.

No dose adjustment is required for patients with mild to moderate hepatic impairment. As no data are available, the use in patients with severe hepatic impairment is not recommended (see Section 4.4 Special Warnings and Precautions for Use).

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients.

4.4 Special Warnings and Precautions for Use

Identified precautions.

Orthostatic effects.

The incidence of orthostatic effects with silodosin is very low. However, a reduction in blood pressure can occur in individual patients, leading in rare cases to syncope. At the first signs of orthostatic hypotension (such as postural dizziness), the patient should sit or lie down until the symptoms have disappeared. In patients with orthostatic hypotension, treatment with silodosin is not recommended.

Carcinoma of the prostate.

Since BPH and prostate carcinoma may present the same symptoms and can co-exist, patients thought to have BPH should be examined prior to starting therapy with silodosin, to rule out the presence of carcinoma of the prostate. Digital rectal examination and, when necessary, determination of prostate specific antigen (PSA) should be performed before treatment and at regular intervals afterwards.

Retrograde ejaculation.

Treatment with silodosin leads to a decrease in the amount of semen released during orgasm that may temporarily affect male fertility. This effect disappears after discontinuation of silodosin (see Section 4.8 Adverse Effects (Undesirable Effects)).

Intraoperative floppy iris syndrome (IFIS).

IFIS (a variant of small pupil syndrome) has been observed during cataract surgery in a significant proportion of patients on α1-blockers or previously treated with α1-blockers. This may lead to increased procedural complications during the operation and an increase in post-operative complications.
The initiation of therapy with silodosin is not recommended in patients for whom cataract surgery is scheduled. The benefit and duration of stopping the therapy prior to cataract surgery has not yet been established.
During pre-operative assessment, eye surgeons and ophthalmic teams should consider whether patients scheduled for cataract surgery are being or have ever been treated with silodosin, in order to ensure that appropriate measures will be in place to minimise the effects of peri-operative IFIS.

Concomitant use with other alpha-blockers.

Since there is inadequate information about the safe use of silodosin in association with other α-adrenoreceptor antagonists, this use is not recommended.

Use in hepatic impairment.

Since no data are available in patients with severe hepatic impairment, the use of silodosin in these patients is not recommended (see Section 4.2 Dose and Method of Administration; also see Section 5.2 Pharmacokinetic Properties, Special populations).

Use in renal impairment.

Since only limited experience exists in patients with moderate renal impairment (CLCR ≥ 30 to ≤ 59 mL/min; eGFR ≥ 30 to ≤ 59 mL/min/1.73 m2; CKD stage G3a and G3b) (n = 35), a lower starting dose of 4 mg is recommended, caution should be exercised if the dose is increased to 8 mg once daily, based on the individual patient's response.
Since there are no clinical safety data in patients with severe renal impairment (CLCR < 30 mL/min; eGFR < 30 mL/min/1.73 m2; CKD stage G4 and G5) the use of silodosin in these patients is not recommended (see Section 4.2 Dose and Method of Administration; also see Section 5.2 Pharmacokinetic Properties, Special populations).

Use in the elderly.

Exposure to silodosin and its main metabolites does not change significantly with age, even in subjects of age over 75 years. Orthostatic hypotension occurs more commonly in patients aged > 75 years although it is usually mild and resolves with continued treatment.

Paediatric use.

Silodosin has not been evaluated in patients less than 18 years of age. Urorec is not indicated for use in the paediatric population.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Silodosin is metabolised extensively, mainly via CYP3A4, alcohol dehydrogenase and UGT2B7. Co-administration of silodosin with agents that interfere with these enzymes may increase circulating levels of unchanged silodosin. Silodosin is also a substrate for P-glycoprotein and exposure may be enhanced by P-glycoprotein inhibitors. Substances that inhibit (such as ketoconazole, itraconazole, ritonavir or cyclosporine) or induce (such as rifampicin, barbiturates, carbamazepine, phenytoin) these enzymes and transporters may affect the plasma concentrations of silodosin and its active metabolite.

Alpha-blockers.

There is inadequate information about the safe use of silodosin in association with other α-adrenoreceptor antagonists. Consequently, the concomitant use of other α-adrenoreceptor antagonists is not recommended.

CYP3A4 inhibitors.

In an interaction study, a 3.7-fold increase in maximum silodosin plasma concentrations and a 3.1-fold increase in silodosin exposure (i.e. AUC) were observed with concurrent administration of a potent CYP3A4 inhibitor (ketoconazole 400 mg). Concomitant use with potent CYP3A4 inhibitors (such as ketoconazole, itraconazole, ritonavir or cyclosporine) is not recommended.
When silodosin was co-administered with a CYP3A4 inhibitor of moderate potency such as diltiazem, an increase in silodosin AUC of approximately 30% was observed, but Cmax and half-life were not affected. This change is clinically not relevant and no dose adjustment is required.

Strong P-glycoprotein (P-gp) inhibitors.

Since in vitro studies indicated that silodosin is a P-gp substrate, inhibition of P-gp may lead to increased silodosin concentrations. Therefore, coadministration with strong P-gp inhibitors is not recommended.

PDE-5 inhibitors.

Minimal pharmacodynamic interactions have been observed between silodosin and maximum doses of sildenafil or tadalafil. In a placebo-controlled study in 24 subjects 45-78 years of age receiving silodosin, the co-administration of sildenafil 100 mg or tadalafil 20 mg induced no clinically meaningful mean decreases in systolic or diastolic blood pressure, as assessed by orthostatic tests (standing versus supine). In the subjects over 65 years, the mean decreases at the various time points were between 5 and 15 mmHg (systolic) and 0 and 10 mmHg (diastolic). Positive orthostatic tests were only slightly more common during co-administration; however, no symptomatic orthostasis or dizziness occurred. Patients taking PDE-5 inhibitors concomitantly with silodosin should be monitored for possible adverse reactions.

Antihypertensives.

In the clinical study program, many patients were on concomitant antihypertensive therapy (mostly agents acting on the renin-angiotensin system, beta-blockers, calcium antagonists and diuretics) without experiencing an increase in the incidence of orthostatic hypotension.
Nevertheless, caution should be exercised when starting concomitant use with antihypertensives and patients should be monitored for possible adverse reactions.

Digoxin.

Steady state levels of digoxin, a substrate of P-glycoprotein, were not significantly affected by co-administration with silodosin 8 mg once daily. No dose adjustment is required.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

In male rats, decreased fertility was observed from exposures which were approximately twice the exposure at the maximum recommended human dose. The observed effect was reversible.
In clinical studies, the occurrence of ejaculation with reduced or no semen has been observed during treatment with silodosin, due to the pharmacodynamic properties of silodosin. Before starting treatment, the patient should be informed that this effect may occur, temporarily affecting male fertility.
(Category B3)
Silodosin is not indicated for use in female patients. Embryo-foetal development studies in rats and rabbits did not find evidence of teratogenic effects at doses up to 1000 mg/kg/day in rats (> 1000 times the clinical dose, based on body surface area comparisons) and 60 mg/kg/day in rabbits (2.9 times the clinical AUC at the maximum recommended human dose [MRHD]). There were treatment-related increases in foetal losses and abortions in rabbits at doses ≥ 200 mg/kg/day (23 times the clinical AUC), which were secondary to maternotoxic effects of silodosin. As well, findings from a pre-/ postnatal development study in rats indicated treatment-related impairments to development (impaired suckling and ambulation at doses ≥ 300 mg/kg/day or > 340 times the clinical dose, based on body surface area comparisons).
 Silodosin is indicated for use in males only. No animal data are available on whether silodosin passes into milk.

4.7 Effects on Ability to Drive and Use Machines

Urorec has minor or moderate influence on the ability to drive and use machines. Patients should be informed about the possible occurrence of symptoms related to postural hypotension (such as dizziness) and should be cautioned about driving or operating machines until they know how silodosin will affect them.

4.8 Adverse Effects (Undesirable Effects)

Summary of the safety profile.

The safety of silodosin has been evaluated in four phase II-III double-blind controlled clinical studies (with 931 patients receiving silodosin 8 mg once daily and 733 patients receiving placebo) and in two long-term open-label extension phase studies. In total, 1,581 patients have received silodosin at a dose of 8 mg once daily, including 961 patients exposed for at least 6 months and 384 patients exposed for 1 year.
The most frequent adverse events reported with silodosin in placebo controlled clinical studies and during long-term use were ejaculatory disorders such as retrograde ejaculation and anejaculation (ejaculatory volume reduced or absent), with a frequency of 23%. This may temporarily affect male fertility. It is reversible within a few days upon discontinuation of treatment (see Section 4.4 Special Warnings and Precautions for Use).

List of adverse events.

Adverse events with incidence ≥ 1% reported in the four phase II-III placebo controlled clinical studies with silodosin 8 mg are listed by MedDRA system organ class in Table 1.
Adverse events with incidence ≥ 1% recorded in the European phase III active and placebo controlled clinical trial are listed by MedDRA system organ class in Table 2.
Adverse reactions reported in all clinical studies and in the worldwide post-marketing experience for which a reasonable causal relationship exists are listed by MedDRA system organ class and frequency: very common 10%; common (≥ 1% to < 10%); uncommon (≥ 0.1% to < 1%); rare (≥ 0.01% to < 0.1%); very rare (< 0.01%), not known (cannot be estimated from available data). Within each frequency grouping, the observed adverse events are presented in order of decreasing seriousness.

Immune system disorders.

Very rare: allergic-type reactions including facial swelling, swollen tongue and pharyngeal oedema.

Psychiatric disorders.

Uncommon: libido decreased.

Nervous system disorders.

Common: dizziness. Rare: syncope loss of consciousness.

Cardiac disorders.

Uncommon: tachycardia. Rare: palpitations.

Vascular disorders.

Common: orthostatic hypotension**. Uncommon: hypotension.

Respiratory, thoracic and mediastinal disorders.

Common: nasal congestion.

Gastrointestinal disorders.

Common: diarrhoea. Uncommon: nausea, dry mouth.

Hepatobiliary disorders.

Uncommon: abnormal liver function tests.

Skin and subcutaneous tissue disorders.

Uncommon: skin rash, pruritus, urticaria, drug eruption.

Reproductive system and breast disorders.

Very common: ejaculatory disorders, including retrograde ejaculation, anejaculation. Uncommon: erectile dysfunction.

Injury, poisoning and procedural complication.

Unknown: intraoperative floppy iris syndrome*.
* IFIS has been reported during cataract surgery (see Section 4.4 Special Warnings and Precautions for Use).
** Orthostatic hypotension. The incidence of orthostatic hypotension in placebo-controlled clinical studies was 1.2% with silodosin and 1.0% with placebo. Orthostatic hypotension may occasionally lead to syncope (see Section 4.4 Special Warnings and Precautions for Use).

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Silodosin was evaluated at doses of up to 48 mg/day in healthy male subjects. The dose-limiting adverse reaction was postural hypotension. Should overdose of silodosin lead to hypotension, cardiovascular support has to be provided. Dialysis is unlikely to be of significant benefit since silodosin is highly (approximately 95%) protein bound.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

Pharmacotherapeutic group: urologicals, α-adrenoreceptor antagonists, ATC code: G04CA04.

5.1 Pharmacodynamic Properties

Mechanism of action.

Silodosin is a selective antagonist of α1A-adrenoreceptors primarily located in the human prostate, bladder base, bladder neck, prostatic capsule and prostatic urethra. Data from an in vitro study showed that silodosin has lower affinity for α1B-adrenoreceptors that are primarily located in the cardiovascular system than for the α1A-adrenoreceptor subtype. Blockade of α1A-adrenoreceptors causes smooth muscle in these tissues to relax, thus decreasing bladder outlet resistance, without affecting detrusor smooth muscle contractility. This causes an improvement of both storage (irritative) and voiding (obstructive) symptoms (LUTS) associated with BPH.

Clinical trials.

A total number of 837 patients with moderate to severe symptoms of BPH (International Prostate Symptom Score [IPSS] baseline value ≥ 13) received silodosin 8 mg once daily in two phase III placebo-controlled clinical studies conducted in the United States and in one placebo- and active-controlled clinical study conducted in Europe. In all studies, patients who did not respond to placebo during a 4-week placebo run-in phase were randomised to receive the study treatment. The primary efficacy parameter in all three studies was the change from baseline to endpoint in total IPSS scores. The secondary efficacy analyses contained the changes from baseline in voiding and storage IPSS sub-scores, and IPSS Quality-of-Life scores. In all studies, patients treated with silodosin had a greater decrease in both storage and voiding symptoms of BPH as compared to placebo as assessed after 12 weeks of treatment. Data observed in the intent-to-treat populations of each study are shown in Table 3.
The IPSS questionnaire was developed and validated by the American Urological Association (IPSS previously called the American Urological Association [AUA] Symptom Index) to aid diagnosis and consisted of 7 questions evaluating the frequency of 7 urinary symptoms. These included 4 voiding symptoms (poor stream, hesitancy, intermittency and incomplete bladder emptying) and 3 storage symptoms (daytime frequency, nocturia and urgency). The patient rated each of the 7 symptoms on a scale of 0-5 of increasing symptom severity. The total score could therefore range from 0-35, the voiding sub-score from 0-20 and the storage sub-score from 0-15. The questionnaire was adopted by the World Health Organization, who added a further question assessing the impact of the urinary symptoms on the Quality of Life. The Quality-of-Life question asked how the patient would feel about his current level of symptoms for the rest of his life, ranging from 1 (delighted) to 6 (terrible).
The outcomes were comparable in subgroups based on age and race.
In the active-controlled clinical study conducted in Europe, silodosin 8 mg once daily was shown to be noninferior to tamsulosin 0.4 mg once daily: the adjusted mean difference (95% CI) in the IPSS total score between treatments in the per-protocol population was 0.4 (-0.4 to 1.1). The responder rate (i.e. improvement in the IPSS total score by at least 25%) was significantly higher in the silodosin (68%) and tamsulosin group (65%), as compared to placebo (53%).
In the long-term open-label extension phase of these controlled studies, in which patients received silodosin for up to 1 year, the symptom improvement induced by silodosin at week 12 of treatment was maintained over 1 year.
A centralised reading of the maximum urinary flow rate (Qmax) was performed in the two phase III US placebo-controlled clinical studies. Statistically significant treatment effects on Qmax were noted already within 2 to 6 hours after the first dose and at the end of both studies. See Table 4.
An improvement in Qmax was also observed at all study visits for all treatment groups in the analysis derived from the post hoc centralised reading of the European study, but the difference from placebo did not reach the statistical significance because of a particularly high placebo response seen in this study. See Table 5.
In a phase II dose-finding, double-blind, placebo-controlled clinical study with silodosin 4 or 8 mg once daily, a greater improvement in American Urologic Association (AUA) symptom index score was observed with silodosin 8 mg (-6.8 ± 5.8, n = 90; p = 0.0018) and silodosin 4 mg (-5.7 ± 5.5, n = 88; p = 0.0355) as compared to placebo (-4.0 ± 5.5, n = 83).
In a phase IV clinical trial performed in Europe (N=1036) involving men aged ≥ 60 years with a clinical diagnosis of BPH and with a mean baseline IPSS total score of 18.9 points, 77.1% were responders to silodosin (as assessed by a change from baseline in the IPSS total score of at least 25%). Approximately half of the patients reported an improvement in the most bothersome symptoms complained at baseline by the patients (i.e. nocturia, frequency, decreased stream, urgency, terminal dribbling and incomplete emptying), as assessed by the ICS-male questionnaire.
No significant reduction in supine blood pressure was observed in all clinical studies conducted with silodosin.
Silodosin 8 mg and 24 mg daily had no statistically significant effect on ECG intervals or cardiac repolarisation relative to placebo.

5.2 Pharmacokinetic Properties

The pharmacokinetics of silodosin and its main metabolites have been evaluated in adult male subjects with and without BPH after single and multiple administrations with doses ranging from 0.1 mg to 48 mg per day. The pharmacokinetics of silodosin is linear throughout this dose range.
The exposure to the main metabolite in plasma, silodosin glucuronide (KMD-3213G), at steady-state is about 3-fold that of the parent substance. Silodosin and its glucuronide reach steady state after 3 days and 5 days of treatment, respectively.

Absorption.

Silodosin administered orally is well absorbed and absorption is dose proportional. The absolute bioavailability is approximately 32%.
An in vitro study with Caco-2 cells showed that silodosin is a substrate for P-glycoprotein.
Food decreases Cmax by approximately 30%, increases tmax by approximately 1 hour and has little effect on AUC.
In healthy male subjects of the target age range (n = 16, mean age 55 ± 8 years) after once-a-day oral administration of 8 mg immediately after breakfast for 7 days, the following pharmacokinetic parameters were obtained: Cmax 87 ± 51 nanogram/mL (sd), tmax 2.5 hours (range 1.0-3.0), AUC 433 ± 286 nanogram.h/mL.

Distribution.

Silodosin has a volume of distribution of 0.81 L/kg and is approximately 95% bound to plasma proteins, while binding of silodosin glucuronide is approximately 92%. Silodosin did not distribute into blood cells under in vitro conditions.

Metabolism.

Silodosin undergoes extensive metabolism through glucuronidation (UGT2B7), alcohol and aldehyde dehydrogenase and oxidative pathways, mainly CYP3A4. The main metabolite in plasma, the glucuronide conjugate of silodosin (KMD-3213G), that has been shown to be active in vitro, has an extended half life (approximately 24 hours) and reaches plasma concentrations approximately four times higher than those of silodosin. In vitro data indicate that silodosin does not inhibit or induce cytochrome P450 enzyme systems.

Excretion.

Following oral administration of 14C-labelled silodosin, the recovery of radioactivity after 7 days was approximately 33.5% in urine and 54.9% in faeces. Body clearance of silodosin was approximately 0.28 L/h/kg. Silodosin is excreted mainly as metabolites, very low amounts of unchanged drug are recovered in urine. The terminal half life of parent drug and its glucuronide is approximately 11 hours and 18 hours, respectively.

Special populations.

Use in hepatic impairment.

In a single-dose study, the pharmacokinetics of silodosin was not altered in nine patients with moderate hepatic impairment (Child-Pugh scores 7 to 9), compared to nine healthy subjects. Results from this study should be interpreted with caution, since enrolled patients had normal biochemistry values, indicating normal metabolic function, and they were classified as having moderate liver impairment based on ascites and hepatic encephalopathy.
The pharmacokinetics of silodosin in patients with severe hepatic impairment has not been studied.

Use in renal impairment.

In a single-dose study, exposure to silodosin (unbound) in subjects with mild (CLCR ≥ 60 to ≤ 89 mL/min; eGFR ≥ 60 to ≤ 89 mL/min/1.73 m2; CKD stage G2) (n = 8) and moderate renal impairment (CLCR ≥ 30 to ≤ 59 mL/min; eGFR ≥ 30 to ≤ 59 mL/min/1.73 m2; CKD stage G3a and G3b) (n = 8) resulted, on average, in an increase of Cmax (1.6-fold) and AUC (1.7-fold) relative to subjects with normal renal function (n = 8). In subjects with severe renal impairment (CLCR < 30 mL/min; eGFR < 30 mL/min/1.73 m2; CKD stage G4 and G5) (n = 5) increase of exposure was 2.2-fold for Cmax and 3.7-fold for AUC. Exposure to the main metabolites, silodosin glucuronide and KMD3293, was also increased.
Plasma level monitoring in a phase III clinical study showed that levels of total silodosin after 4 weeks of treatment did not change in patients with mild impairment (n = 70), compared to patients with normal renal function (n = 155), while the levels were doubled on average in patients with moderate impairment (n = 7).
A review of safety data of patients enrolled in all clinical studies does not indicate that mild renal impairment (n = 487) poses an additional safety risk during silodosin therapy (such as an increase in dizziness or orthostatic hypotension) as compared to patients with normal renal function (n = 955). Accordingly, no dose adjustment is required in patients with mild renal impairment. Since only limited experience exists in patients with moderate renal impairment (n = 35), a lower starting dose of 4 mg is recommended. After a minimum of one week a dose increase may be considered. The dose can be carefully increased to 8 mg once daily, depending on the individual patient's response (see Section 4.2 Dose and Method of Administration; Section 4.4 Special Warnings and Precautions for Use). In patients with severe renal impairment administration of Urorec is not recommended.

5.3 Preclinical Safety Data

Genotoxicity.

Silodosin was not found to be genotoxic in the in vitro Ames assay, mouse lymphoma assay, unscheduled DNA synthesis assay and the in vivo mouse micronucleus assay. A weakly positive response in two in vitro Chinese Hamster Lung (CHL) tests for chromosomal aberration was observed at high, cytotoxic concentrations of silodosin.

Carcinogenicity.

Increase in thyroid tumours (follicular cell adenoma and carcinoma) were observed in male rats in a two-year carcinogenicity study at doses ≥ 50 mg/kg/day (5.1 times the clinical AUC at the MRHD). Chronic stimulation of TSH secretion resulting from a silodosin-induced increased metabolism of T4 was determined to be the cause of proliferative changes to the rat thyroid. The clinical relevance of these findings is not known but rodents are more sensitive to changes in thyroid hormone metabolism than humans.
In a two year oral carcinogenicity study in mice, silodosin resulted in significantly higher incidences of mammary gland tumours (adenocarcinoma and adenoacanthoma) in females at doses ≥ 150 mg/kg/day (≥ 41 times the clinical AUC at the MRHD). In males benign testicular tumours (Leydig cell adenoma, gonadostromal tumour) were seen at doses ≥ 60 mg/kg/day (≥ 5 times the clinical AUC at the MRHD). Both mammary gland and testicular tumours are likely secondary to silodosin-induced hyperprolactinaemia, which can directly induce proliferative changes in mammary glands or induce neoplasms in reproductive tissue by altering gonadotropin release. The clinical relevance of these findings is uncertain but hyperprolactinaemia-associated tumours have been observed in rodents with other α adrenoceptor antagonists that have an established history of clinical use. Silodosin has not been shown to elevate prolactin levels in clinical trials.

6 Pharmaceutical Particulars

6.1 List of Excipients

Urorec contains silodosin, pregelatinised maize starch, mannitol, magnesium stearate and sodium lauryl sulfate. The 4 mg hard capsule shell contains gelatin, titanium dioxide and iron oxide yellow. The 8 mg hard capsule shell contains gelatin and titanium dioxide.

6.2 Incompatibilities

See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store Urorec below 25°C in the original package in order to protect from light and moisture.

6.5 Nature and Contents of Container

Urorec trade packs contain 30 capsules and starter packs contain 10 capsules. Both trade and starter packs are provided in PVC/PVDC/aluminium foil blisters, packed in a carton.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Silodosin is a white to pale yellowish powder. It is very slightly soluble in water (0.17 mg/mL) and slightly soluble in alcohol (119 mg/mL) with a partition coefficient Log P = 2.87 (2.45-3.34). Silodosin present two pKa (pKa1: 8.53, N-ethylaminopropyl group and pKa2: 4.03, N-indoline ring).

Chemical structure.

The chemical structure is:
The chemical name is 1-(3-Hydroxypropyl)-5-[(2R)-2-({2-[2- (2,2,2-trifluoroethoxy) phenoxy]ethyl}amino) propyl]-2,3-dihydro-1H-indole-7-carboxamide.
The molecular weight is 495.53.

CAS number.

The CAS registry number is 160970-54-7.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes