Consumer medicine information

Sildenafil-WGR

Sildenafil

BRAND INFORMATION

Brand name

Sildenafil-WGR

Active ingredient

Sildenafil

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Sildenafil-WGR.

SUMMARY CMI

SILDENAFIL-WGR

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 using SILDENAFIL-WGR?

SILDENAFIL-WGR contains the active ingredient sildenafil citrate. SILDENAFIL-WGR is used to treat erectile dysfunction also commonly called impotence in men.

For more information, see Section 1. Why am I using SILDENAFIL-WGR? in the full CMI.

2. What should I know before I use SILDENAFIL-WGR?

Do not use if you have ever had an allergic reaction to sildenafil citrate or any of the ingredients listed at the end of the CMI.

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

For more information, see Section 2. What should I know before I use SILDENAFIL-WGR? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with sildenafil citrate 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 use SILDENAFIL-WGR?

  • Take SILDENAFIL-WGR as your doctor has prescribed.
  • Your doctor will decide the correct dose for you depending on your condition and response.

More instructions can be found in Section 4. How do I use SILDENAFIL-WGR? in the full CMI.

5. What should I know while using SILDENAFIL-WGR?

Things you should do
  • Remind any doctor, dentist, or pharmacist you visit that you are using SILDENAFIL-WGR.
  • Stop taking SILDENAFIL-WGR if you have sudden vision problems including blurred, decreased or distorted vision, objects appear smaller or further away than they are, changes to colour vision, loss of eyesight in one or both eyes, experience loss of hearing or have an erection that persists for more than 4 hours. Seek medical attention urgently.
  • If you are about to start taking any new medicines, especially nitrates, or riociguat, tell your doctor and pharmacist that you are taking SILDENAFIL-WGR.
Things you should not do
  • Do not use drugs containing amyl nitrite (sometimes called "poppers") while you are taking SILDENAFIL-WGR.
  • If you get an angina attack do not take nitrate medicines to relieve the pain but tell your doctor immediately.
  • Do not give SILDENAFIL-WGR to anyone else, even if they have the same condition as you.
Driving or using machines
  • If you experience changes in vision, or dizziness, when taking SILDENAFIL-WGR, you should not drive or operate machinery.
Drinking alcohol
  • Be careful drinking alcohol while taking SILDENAFIL-WGR.
Looking after your medicine
  • Keep SILDENAFIL-WGR in a locked cupboard where children cannot reach it.
  • Keep your tablets in cool dry place where temperature stays below 25°C

For more information, see Section 5. What should I know while using SILDENAFIL-WGR? in the full CMI.

6. Are there any side effects?

Tell your doctor or pharmacist if you notice any of the following and they worry you: headache, dizziness, flushing, hot flushes, indigestion, heartburn, nasal or sinus congestion, swelling of your nose, diarrhoea, rash, tightness in your throat, feeling hot or irritable, redness in your mouth or tongue. Tell your doctor or go straight to the Emergency Department if you notice any of the following: unusual heartbeat, persistent headache or fainting, bleeding from the nose, pain or tingling in your hands, toes or feet, red eye(s), swollen, puffy or pain in or around the eye(s), blood in the urine, sudden vision problems, changes to your normal vision, shortness of breath, wheezing or difficulty breathing, swelling of the face, lips, tongue or other parts of the body, chest pain, increased heart rate, seizures, fits or convulsions or your erection is increased, painful or persists for longer than four hours. 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

SILDENAFIL-WGR

Active ingredient(s): sildenafil (as citrate)

Consumer Medicine Information (CMI)

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

Where to find information in this leaflet:

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

1. Why am I using SILDENAFIL-WGR?

SILDENAFIL-WGR contains the active ingredient sildenafil (as citrate). SILDENAFIL-WGR belongs to a group of medicines called phosphodiesterase type 5 inhibitors.

SILDENAFIL-WGR is used to treat erectile dysfunction, also commonly called impotence in men. This is when a man cannot get, or keep, a hard erect penis, suitable for sexual activity.

It works by relaxing the blood vessels in your penis when you are sexually excited. This allows blood to flow into your penis, allowing you to get an erection in the natural way.

SILDENAFIL-WGR will not increase your sex drive and will work only if you are sexually excited.

SILDENAFIL-WGR is not for use in women.

2. What should I know before I use SILDENAFIL-WGR?

Warnings

YOU MUST NOT TAKE SILDENAFIL-WGR IF YOU ARE TAKING NITRATES OR NITRITE MEDICATIONS. IT MAY LEAD TO A SEVERE DROP IN YOUR BLOOD PRESSURE, WHICH MAY BE DIFFICULT TO TREAT.

BECAUSE SEXUAL ACTIVITY MAY PLACE A STRAIN ON YOUR HEART, YOUR DOCTOR WILL NEED TO CHECK WHETHER YOU ARE FIT ENOUGH TO TAKE SILDENAFIL-WGR.

Do not use SILDENAFIL-WGR if:

  • you are allergic to sildenafil or similar medicines, or any of the ingredients listed at the end of this leaflet. An allergic reaction can include:
    - hives, itching or skin rash
    - swelling of the face, lips or tongue which may lead to difficulty swallowing or breathing.
    Always check the ingredients to make sure you can take this medicine.
  • you are being treated for angina (chest pain) or other heart conditions with medicines called nitrates. These are available in multiple dosage forms, such as tablets, patches, sprays and injections. These include but not limited to:
    - glyceryl trinitrate (also called nitroglycerin)
    - isosorbide mononitrate, isosorbide dinitrate
    - nicorandil
    - sodium nitroprusside.
  • you are taking guanylate cyclase stimulators (GCS), such as riociguat.
    GCS is a type of medicine used to treat high blood pressure in the blood vessels in the lungs caused by blood clots in the lungs (chronic thromboembolic pulmonary hypertension or CTEPH) or narrowing of the vessels that carry blood from the heart to the lungs (pulmonary arterial hypertension or PAH).
  • you have heart or blood vessel problems that make sexual intercourse inadvisable
  • you have suffered a heart attack or stroke in the last 6 months
  • you have severe liver problems
  • you have blood pressure that is unusually high or low or is not effectively treated
  • you have sudden vision problems including loss of vision in one or both eyes from an eye disease called non-arteritic anterior ischaemic optic neuropathy (NAION)
  • you have an eye disease called retinitis pigmentosa
  • the packaging is torn or shows signs of tampering, or does not look quite right even if the tablets may look alright
  • the expiry date on the pack has passed
    If it has expired or is damaged, return it to your pharmacist for disposal.

Check with your doctor if you:

  • have any allergies to any other medicines or any other substances such as foods, preservatives or dyes
  • have any other heart or blood vessel problems
  • have previously had sudden vision problems including blurred, decreased or distorted vision, objects appear smaller or further away than they are, changes to colour vision, loss of eyesight in one or both eyes
  • have any of the following medical conditions:
    - diabetes, especially if you also have eye problems
    - kidney or liver problems
    - leukaemia (cancer of the blood cells)
    - multiple myeloma (a cancer of the bone marrow)
    - any disease or deformity of your penis
    - any bleeding disorder such as haemophilia
    - stomach ulcer
    - a disease of the blood called sickle cell anaemia
    - colour vision problems
    - previously experienced sudden decrease or loss of hearing
  • are taking or using any other treatment for impotence
  • are taking any medicines to treat high blood pressure in the vessels of the lungs (pulmonary arterial hypertension) including bosentan or Revatio which also contains sildenafil
  • have any other medical conditions.

If you have not told your doctor or pharmacist about any of the above, tell them before you start taking SILDENAFIL-WGR.

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.

Do not take SILDENAFIL-WGR if you are taking or using nitrate medicines for angina.

Do not take SILDENAFIL-WGR if you are taking guanylate cyclase stimulators (GCS), such as riociguat.

Some medicines and SILDENAFIL-WGR may interfere with each other. These include:

  • cimetidine, a medicine used to treat ulcers
  • some medicines used to treat fungal infections including ketoconazole and itraconazole
  • some antibiotics including erythromycin and rifampicin
  • some protease inhibitors such as ritonavir and saquinavir for the treatment of HIV infection
  • medicines called alpha-blockers. These are used to treat high blood pressure or prostate problems
  • bosentan, a medicine used to treat high blood pressure in the vessels of the lungs.

You may need different amounts of your medicine or you may need to take different medicines. Your doctor or pharmacist can tell you what to do if you are taking any of these medicines. They also have a more complete list of medicines to be careful with or avoid while taking SILDENAFIL-WGR.

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

4. How do I use SILDENAFIL-WGR?

Take SILDENAFIL-WGR exactly as your doctor has prescribed.

Follow all directions given to you by your doctor and pharmacist carefully.

They may differ from the information contained in this leaflet.

If you do not understand the instructions on the box, ask your doctor or pharmacist for help.

How much to take

  • Your doctor will decide the correct dose for you depending on your condition and response.
  • This can be either one 25 mg tablet, one 50 mg tablet, or one 100 mg tablet per day.
  • Do not take more than one dose of SILDENAFIL-WGR a day.

How to take it

Swallow the tablet whole with a full glass of water.

When to take SILDENAFIL-WGR

  • Take your dose of SILDENAFIL-WGR about one hour before you intend to have sex.
  • The amount of time SILDENAFIL-WGR takes to start working varies from person to person, but it normally takes between half an hour and one hour.
  • You may find SILDENAFIL-WGR takes longer to work if you take it with a heavy meal.
  • SILDENAFIL-WGR will work only if you are sexually excited.

If you take too much SILDENAFIL-WGR

If you think that you or anyone else may have taken too much SILDENAFIL-WGR, urgent medical attention may be needed.

You should immediately:

  • phone the Poisons Information Centre (Australia telephone 13 11 26) for advice, 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 using SILDENAFIL-WGR?

Things you should do

  • Stop taking SILDENAFIL-WGR if you have sudden vision problems including blurred, decreased or distorted vision, objects appear smaller or further away than they are, changes to colour vision, loss of eyesight in one or both eyes, experience loss of hearing or have an erection that persists for more than 4 hours. Seek medical attention urgently.
  • If SILDENAFIL-WGR does not help you get an erection or if your erection does not last long enough to complete sexual intercourse, tell your doctor.
  • In these cases, your doctor may decide that you need a higher dose.
  • If you are about to start taking any new medicines, especially nitrates, or riociguat, tell your doctor and pharmacist that you are taking SILDENAFIL-WGR.
    See " 2. What should I know before I take SILDENAFIL-WGR?" for a list of common nitrate medications.
  • Tell any other doctors, dentists and pharmacists who are treating you that you are taking SILDENAFIL-WGR.

Things you should not do

  • Do not use drugs containing amyl nitrite (sometimes called "poppers") while you are taking SILDENAFIL-WGR.
  • If you get an angina attack do not take nitrate medicines to relieve the pain but tell your doctor immediately. Make sure your doctor knows you are taking SILDENAFIL-WGR.
  • Do not give SILDENAFIL-WGR to anyone else, even if they have the same condition as you.

Driving or using machines

Be careful before you drive or take any machines or tools until you know how SILDENAFIL-WGR affects you.

If you experience changes in vision, or dizziness when taking SILDENAFIL-WGR, you should not drive or operate machinery.

Drinking alcohol

Be careful drinking alcohol while taking SILDENAFIL-WGR.

Drinking alcohol can temporarily impair the ability to get an erection.

Do not drink large amounts of alcohol before sexual activity.

Looking after your medicine

  • Store below 30°C
  • Keep the tablets in their pack until it is time to take them. If you take your tablets out of the pack, they will not keep as well.

Follow the instructions in the carton on how to take care of your medicine properly.

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 window sills.

Heat and dampness can destroy some medicines.

Keep it where young children cannot reach it.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Getting rid of any unwanted medicine

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

Do not take this medicine after the expiry date.

6. Are there any side effects?

While SILDENAFIL-WGR helps most people, it can cause some unwanted side effects in a few people. 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.

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking SILDENAFIL-WGR.

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

Do not be alarmed by this list of possible side effects.

You may not get any of them.

Less serious side effects

Less serious side effectsWhat to do
Nervous system related:
  • headache
  • dizziness
Vascular related:
  • flushing
  • hot flushes
Gastrointestinal related:
  • indigestion
  • heartburn
  • diarrhoea
  • dry mouth or dry throat
Respiratory related:
  • nasal congestion
  • sinus congestion
  • dry nose
Skin related:
  • rash
Eye related:
  • dry eyes
Other side effects:
  • swelling of your nose
  • tightness in your throat
  • feeling hot or irritable
  • redness in your mouth or tongue
Speak to your doctor or pharmacist if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Heart related:
  • unusual heartbeat
Urogenital related:
  • urinary tract infection (stinging or burning urine, more frequent need to pass urine)
  • blood in the urine
Nervous system related:
  • persistent headache or fainting
  • pain or tingling in your hands, toes or feet
  • decreased sensitivity or numbness in your mouth
Eye related:
  • irritation or feeling of having something in the eye
  • swollen or puffy eye(s)
  • fatigue, pain in or around the eyes
  • "red eye" due to swollen blood vessels in the white part of the eye and in the eyelids
Other side effects:
  • bleeding from the nose
Call your doctor straight away if you notice any of these serious side effects.

More serious side effects

More serious side effectsWhat to do
Allergy related:
  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts
Heart related:
  • chest pain
  • increased heart rate
Nervous system related:
  • seizures, fits or convulsions
Urogenital related:
  • your erection is increased, painful or persists for longer than usual
    If your erection continues for four hours, or sooner if there is pain, you should seek medical attention urgently.
Eye related:
  • sudden vision problems
    - blurred, decreased or distorted vision
    - objects appear smaller or further away than they are
    - changes to colour vision
  • changes to your normal vision such as:
    - red or yellow colour tinges to your vision or colourless objects appear coloured
    - you see a halo around lights, sparks or lights when your eyes are closed

Rarely, men have lost eyesight after taking drugs to treat erectile dysfunction. If you lose eyesight in one or both eyes or experience changes in vision such as blurring, a blue colour to your vision or a greater awareness of light, seek medical attention urgently.

Other side effects:
  • sudden decrease or loss of hearing
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these more serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell or if you don't understand anything in this list.

This is not a complete list of all possible side effects. Other side effects not listed here may occur in some people.

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 SILDENAFIL-WGR contains

Active ingredient
(main ingredient)		Sildenafil (as citrate)
Other ingredients
(inactive ingredients)		brilliant blue FCF aluminium lake
calcium hydrogen phosphate
croscarmellose sodium
macrogol 3350
magnesium stearate
microcrystalline cellulose
polyvinyl alcohol
purified talc
quinoline yellow aluminium lake
titanium dioxide
Potential allergensn/a

The tablet does not contain gluten or lactose.

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

What SILDENAFIL-WGR looks like

SILDENAFIL-WGR comes in 3 strengths of tablets.

  • SILDENAFIL-WGR 25 – green coloured, round shape, convex film coated tablet break line on one side and plain on the other side
  • SILDENAFIL-WGR 50 – green coloured, round shape, convex film coated tablet cross break line on one side and plain on the other side
  • SILDENAFIL-WGR 100 – green coloured, round shape, convex film coated tablet cross break line on one side and plain on the other side

All strengths come in packs of 4 tablets. SILDENAFIL-WGR 100mg also comes in a pack of 12 tablets.

Australian registration numbers:

SILDENAFIL-WGR 25mg - AUST R 425510

SILDENAFIL-WGR 50mg - AUST R 425511

SILDENAFIL-WGR 100mg - AUST R 425512

Who distributes SILDENAFIL-WGR

Wagner Pharmaceuticals Pty Ltd
6 Albert Street
Preston VIC 3072
Tel: 1800 936 140

This leaflet was prepared in February 2025.

Published by MIMS April 2025

BRAND INFORMATION

Brand name

Sildenafil-WGR

Active ingredient

Sildenafil

Schedule

S4

 

1 Name of Medicine

Sildenafil citrate.

2 Qualitative and Quantitative Composition

Sildenafil-WGR tablets come in three strengths and contain 25 mg, 50 mg or 100 mg of sildenafil (as sildenafil citrate).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Sildenafil-WGR 25 mg.

Green coloured, round shape, convex film coated tablet break line on one side and plain on the other side.

Sildenafil-WGR 50 mg.

Green coloured, round shape, convex film coated tablet with cross break line on one side and plain on the other side.

Sildenafil-WGR 100 mg.

Green coloured, round shape, convex film coated tablet with cross break line on one side and plain on the other side.

4 Clinical Particulars

4.1 Therapeutic Indications

Sildenafil is indicated for the treatment of erectile dysfunction in adult males.
It is not indicated for use by women.

4.2 Dose and Method of Administration

Dosage.

Adults.

The recommended dose is 50 mg taken as needed approximately one hour before sexual activity. Based on efficacy and tolerance, the dose may be increased to 100 mg or decreased to 25 mg. The maximum recommended dose is 100 mg. The maximum recommended dosing frequency is once per day.

Children.

Sildenafil is not indicated for use in children.

Method of administration.

Sildenafil tablets are for oral administration.

Dosage adjustment.

Use in the elderly.

Since sildenafil clearance is reduced in elderly patients, a first dose of 25 mg should be considered. Based on efficacy and tolerance, the dose may be increased to 50 and 100 mg.

Impaired renal function.

The dosing recommendations for adults should be followed for patients with mild to moderate renal impairment (creatinine clearance = 30 to 80 mL/minute).
Since sildenafil clearance is reduced in patients with severe renal impairment (creatinine clearance < 30 mL/minute) a 25 mg starting dose should be considered. Based on efficacy and tolerance, the dose may be increased to 50 and 100 mg.

Impaired hepatic function.

Since sildenafil clearance is reduced in patients with hepatic impairment (e.g. cirrhosis) a 25 mg starting dose should be considered. Based on efficacy and tolerance, the dose may be increased to 50 and 100 mg.

Use in patients using other medicines.

Concomitant use of potent CYP3A4 inhibitors has been associated with increased plasma levels of sildenafil (e.g. erythromycin 182%, saquinavir 210%). It can also be expected that more potent CYP3A4 inhibitors such as ketoconazole and itraconazole would result in increased plasma levels of sildenafil. (See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions, Effects of other medicines on sildenafil.) Since higher plasma levels may increase both the efficacy and incidence of adverse events, a starting dose of 25 mg should be considered in these patients.
Given the extent of the interaction with patients receiving concomitant therapy with ritonavir, it is recommended not to exceed a maximum single dose of 25 mg of sildenafil in a 48 hour period. (See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions, Effects of other medicines on sildenafil.)
In order to minimise the potential for developing postural hypotension, patients should be stable on α-blocker therapy prior to initiating sildenafil treatment. In addition, initiation of sildenafil at lower doses should be considered (see Section 4.4 Special Warnings and Precautions for Use; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

4.3 Contraindications

Known hypersensitivity to any component of the tablet.
Nitrates and sildenafil must not be used concomitantly. Sildenafil was shown to potentiate the hypotensive effects of both acute and chronic nitrate administration and, therefore, its coadministration with NO donors, organic nitrates or organic nitrites in any form either regularly or intermittently is contraindicated. Medicines which must not be used concomitantly include glyceryl trinitrate (injection, tablets, sprays or patches), isosorbide salts, sodium nitroprusside, amyl nitrite, nicorandil or organic nitrates in any form.
The co-administration of PDE5 inhibitors, including , with guanylate cyclase stimulators, such as riociguat, is contraindicated as it may potentially lead to symptomatic hypotension.
Sildenafil is contraindicated in men for whom sexual intercourse is inadvisable due to cardiovascular risk factors (e.g. patients with severe cardiovascular disease such as established cardiac failure and unstable angina pectoris) (see Section 4.4 Special Warnings and Precautions for Use). The possibility of undiagnosed cardiovascular disorders in men with erectile dysfunction should be considered before prescribing sildenafil.
Sildenafil is not recommended in patients with male erectile dysfunction with a previous episode of nonarteritic anterior ischaemic optic neuropathy (NAION) (see Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects), Postmarketing data, Other events).
The safety of sildenafil has not been studied in the following subgroups of patients and its use is, therefore, contraindicated until further information is available: severe hepatic impairment, hypotension (blood pressure < 90/50 mmHg), hypertension (blood pressure > 170/110 mmHg), recent history of stroke or myocardial infarction and known hereditary degenerative retinal disorders such as retinitis pigmentosa (a minority of these patients have genetic disorders of retinal phosphodiesterases).

4.4 Special Warnings and Precautions for Use

A thorough medical history and physical examination should be undertaken to diagnose erectile dysfunction, determine potential underlying causes, and identify appropriate treatment.
Prior to initiating any treatment for erectile dysfunction, doctors should consider the cardiovascular status of their patients, including those with recent onset angina, since there is a degree of cardiovascular risk associated with sexual intercourse. Sildenafil has vasodilator properties, resulting in mild and transient decreases in blood pressure and, as such, potentiates the hypotensive effect of nitrates (see Section 4.3 Contraindications).
Visual defects including central serous chorioretinopathy (CSCR) have been reported in connection with the intake of sildenafil and other phosphodiesterase type 5 (PDE5) inhibitors. Most cases of CSCR resolved spontaneously after stopping sildenafil. Doctors should advise patients to stop use of all PDE5 inhibitors, including Sildenafil-WGR, and seek immediate medical attention in the event of sudden visual defect, visual acuity impairment, visual distortion and/or loss of vision in one or both eyes. Such an event may be a sign of nonarteritic anterior ischaemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, that has been reported rarely postmarketing in temporal association with the use of all PDE5 inhibitors. An observational study evaluating whether recent use of PDE5 inhibitors, as a class, was associated with acute onset of NAION suggests an increase in the risk of NAION with PDE5 inhibitor use. In case of sudden visual loss, patients should be advised to stop taking sildenafil and consult a physician immediately.
Individuals who have already experienced NAION are at increased risk of NAION recurrence.
PDE 5 inhibitors, including sildenafil, are not recommended in patients with male erectile dysfunction with a previous episode of NAION (see Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects), Postmarketing data, Other events).
In clinical trials, sildenafil has been shown to have systemic vasodilatory properties that result in transient decreases in blood pressure (see Section 5.1 Pharmacodynamic Properties, Clinical trials). This is of little or no consequence in most patients. However, prior to prescribing sildenafil, doctors should carefully consider whether their patients with certain underlying conditions could be adversely affected by such vasodilatory effects, especially in combination with sexual activity. Patients with increased susceptibility to vasodilators include those with left ventricular outflow obstruction (e.g. aortic stenosis, hypertrophic obstructive cardiomyopathy), or those with the rare syndrome of multiple system atrophy manifesting as severely impaired autonomic control of blood pressure.
Agents for the treatment of erectile dysfunction should be used with caution in patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis or Peyronie's disease) or in patients who have conditions which may predispose them to priapism (such as sickle cell anaemia, multiple myeloma or leukaemia).
The safety and efficacy of combinations of sildenafil with other PDE5 inhibitors, or other pulmonary arterial hypertension (PAH) treatments containing sildenafil or with other treatments for erectile dysfunction have not been studied. Therefore, the use of such combinations is not recommended.
Caution is advised when sildenafil is administered to patients taking an α-blocker, as the coadministration may lead to symptomatic hypotension in a few susceptible individuals (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). In order to minimise the potential for developing postural hypotension, patients should be haemodynamically stable on α-blocker therapy prior to initiating sildenafil treatment. Initiation of sildenafil at lower doses should be considered (see Section 4.2 Dose and Method of Administration). In addition, doctors should advise patients what to do in the event of postural hypotensive symptoms.
Sildenafil had no effect on bleeding time, including during coadministration with aspirin. In vitro studies with human platelets indicate that sildenafil potentiates the antiaggregatory effect of sodium nitroprusside (a nitric oxide donor). There is no safety information on the administration of sildenafil to patients with bleeding disorders or active peptic ulceration. Therefore, sildenafil should be administered with caution to these patients.
There are limited safety data in patients with diabetic retinopathy. The safety of sildenafil in patients with untreated diabetic retinopathy has not been studied and therefore it should be administered to these patients only after careful benefit/ risk assessment.
Sudden decrease or loss of hearing, which may be accompanied by tinnitus and dizziness, has been reported in a small number of postmarketing and clinical trials cases with the use of all PDE5 inhibitors, including sildenafil. Most of these patients had risk factors for sudden decrease or loss of hearing. No causal relationship has been made between the use of PDE5 inhibitors and sudden decrease or loss of hearing. In case of sudden decrease or loss of hearing patients should be advised to stop taking sildenafil and consult a doctor promptly.
The incidence of adverse events may be greater in those patients who require the maximum recommended dose of 100 mg (e.g. some diabetic and spinal cord injury patients).
Patients with cardiovascular disease who have not engaged in sexual intercourse for a number of years should have their cardiovascular status carefully assessed prior to initiating treatment with sildenafil.
Prolonged erections greater than four hours and priapism (painful erections greater than six hours) have been reported infrequently since market approval of sildenafil. In the event of an erection that persists longer than four hours, the patient should seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency could result.

Use in the elderly.

See Section 4.2 Dose and Method of Administration, Use in the elderly.

Paediatric use.

Sildenafil is not indicated for use in children.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Effects of other medicines on sildenafil.

In vitro studies.

Sildenafil metabolism is principally mediated by the cytochrome P450 isoforms CYP3A4 (major route) and CYP2C9 (minor route). Therefore, inhibitors of these isoenzymes may reduce sildenafil clearance and inducers of these isoenzymes may increase sildenafil clearance.

In vivo studies.

Population pharmacokinetic analysis of clinical trial data indicated a reduction in sildenafil clearance when coadministered with CYP3A4 inhibitors such as ketoconazole, erythromycin or cimetidine. However, there was no increased incidence of adverse events in these patients.
Cimetidine (800 mg), a nonspecific CYP3A4 inhibitor, caused a 56% increase in plasma sildenafil concentrations when coadministered with sildenafil (50 mg) to healthy volunteers.
When a single 100 mg dose of sildenafil was administered with erythromycin, a specific CYP3A4 inhibitor, at steady state (500 mg twice daily for five days), there was a 182% increase in sildenafil systemic exposure (AUC).
Coadministration of the HIV protease inhibitor saquinavir, also a CYP3A4 inhibitor, at steady state (1,200 mg three times daily) with sildenafil (100 mg single dose) resulted in a 140% increase in sildenafil Cmax and a 210% increase in sildenafil AUC (see Section 4.2 Dose and Method of Administration). Stronger CYP3A4 inhibitors such as ketoconazole and itraconazole would be expected to have still greater effects.
Coadministration with the HIV protease inhibitor ritonavir, which is a highly potent P450 inhibitor, at steady state (500 mg twice daily) with sildenafil (100 mg single dose) resulted in a 300% (fourfold) increase in sildenafil Cmax and a 1,000% (elevenfold) increase in sildenafil plasma AUC. At 24 hours the plasma levels of sildenafil were still approximately 200 nanogram/mL, compared to approximately 5 nanogram/mL when sildenafil was dosed alone. This is consistent with ritonavir's marked effects on a broad range of P450 substrates (see Section 4.2 Dose and Method of Administration).
Since systemic exposure to sildenafil increases on coadministration with inhibitors of CYP3A4, the sildenafil dose may have to be reduced depending on tolerability.
Single doses of antacid (magnesium hydroxide/aluminium hydroxide) did not affect the bioavailability of sildenafil.
There is no information on the interaction between sildenafil and cyclosporin.
It can be expected that concomitant administration of CYP3A4 inducers, such as rifampicin, will decrease plasma levels of sildenafil.
Population pharmacokinetics analysis showed no effect of concomitant medication on sildenafil pharmacokinetics when grouped as CYP2C9 inhibitors, CYP2D6 inhibitors (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and related diuretics, loop and potassium sparing diuretics, ACE inhibitors, calcium channel blockers, β-adrenoreceptor antagonists or inducers of CYP450 metabolism (such as barbiturates).
In a study of healthy male volunteers, co-administration of the endothelin antagonist, bosentan, (an inducer of CYP3A4 [moderate], CYP2C9 and possibly of CYP2C19) at steady state (125 mg twice a day) with sildenafil at steady state (80 mg three times a day) resulted in 62.6% and 55.4% decrease in sildenafil AUC and Cmax, respectively. Sildenafil (80 mg three times a day) increased bosentan AUC and Cmax bv 49.8% and 42%, respectively.
Preclinical studies showed an additive systemic blood pressure lowering effect when PDE5 inhibitors were combined with riociguat. In clinical studies, riociguat has been shown to augment the hypotensive effects of sildenafil. There was no evidence of favourable clinical effect of the combination in the population studied. Concomitant use of riociguat with PDE5 inhibitors, including sildenafil, is contraindicated as it may potentially lead to symptomatic hypotension (see Section 4.3 Contraindications).

Effects of sildenafil on other medicines.

In vitro studies.

Sildenafil is a weak inhibitor of the cytochrome P450 isoforms CYP1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50 > 150 micromolar). Given sildenafil peak plasma concentrations of approximately 1 microM after recommended doses, it is unlikely that sildenafil will alter the clearance of substrates of these isoenzymes.
There are no data on the interaction of sildenafil and nonspecific phosphodiesterase inhibitors such as theophylline or dipyridamole.

In vivo studies.

In three specific drug-drug interaction studies, the α-blocker doxazosin (4 and 8 mg) and sildenafil (25, 50 or 100 mg) were administered simultaneously to patients with benign prostatic hyperplasia (BPH) stabilised on doxazosin therapy. In these study populations, mean additional reductions of supine blood pressure of 7/7, 9/5 and 8/4 mmHg, and mean additional reductions of standing blood pressure of 6/6, 11/4 and 4/5 mmHg, respectively, were observed. When sildenafil and doxazosin were administered simultaneously to patients stabilised on doxazosin therapy, there were infrequent reports of patients who experienced symptomatic postural hypotension. These reports included dizziness and lightheadedness, but not syncope. Concomitant administration of sildenafil to patients taking α-blocker therapy may lead to symptomatic hypotension in a few susceptible individuals (see Section 4.4 Special Warnings and Precautions for Use; Section 4.2 Dose and Method of Administration).
No significant interactions were shown when sildenafil 50 mg was coadministered with tolbutamide (250 mg) or warfarin (40 mg), both of which are metabolised by CYP2C9.
Sildenafil (50 mg) did not potentiate the increase in bleeding time caused by aspirin (150 mg).
Sildenafil causes a small reduction in supine and tilted diastolic blood pressure (3.5 and 6.1 mmHg respectively) in healthy subjects who had a blood alcohol level of 80 mg/dL.
No interaction was seen when sildenafil (100 mg) was coadministered with amlodipine in hypertensive patients. The mean additive reduction on supine blood pressure (systolic, 8 mmHg; diastolic, 7 mmHg) was of a similar magnitude to that seen when sildenafil was administered alone to healthy volunteers (see Section 5.1 Pharmacodynamic Properties).
Analysis of the safety database showed no difference in the side effect profile in patients taking sildenafil with and without antihypertensive medication.
Sildenafil was shown to potentiate the hypotensive effect of acute and chronic nitrate administration. Therefore, use of nitric oxide donors, organic nitrates, or organic nitrites in any form either regularly or intermittently with sildenafil is contraindicated (see Section 4.3 Contraindications).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There was no impairment of fertility in rats given sildenafil for 36 days (females) and 102 days (males) at a dose producing an AUC value of more than 25 times the human male AUC.
There is no information on the effects of sildenafil on semen production or sperm motility/morphology in patients suffering from erectile dysfunction. There was no effect on sperm motility or morphology after single 100 mg oral doses of sildenafil in healthy volunteers.
(Category B1)
Sildenafil is not indicated for use by women.
No evidence of teratogenicity, embryotoxicity or fetotoxicity was observed in rats and rabbits which received up to 200 mg/kg/day during organogenesis. The dose results in total systemic drug exposure (AUC) for unbound sildenafil and its major metabolite of greater than 60 times the exposure observed in human males given the MRHD of 100 mg. In the rat prenatal and postnatal development study, the no observed adverse effect dose was 30 mg/kg/day given for 36 days. In nonpregnant rats the AUC at this dose was about 20 times the human AUC. There are no adequate and well controlled studies of sildenafil in pregnant women.
 Sildenafil is not indicated for use in women. No information is available on its secretion into breast milk.

4.7 Effects on Ability to Drive and Use Machines

As transient visual disturbances and dizziness have been reported in some patients taking sildenafil, particularly at the 100 mg dose, patients should be aware of how they react to sildenafil before driving or operating machinery, and the doctor should advise accordingly.

4.8 Adverse Effects (Undesirable Effects)

Clinical trial data.

Sildenafil was administered to over 3,700 patients (aged 19 to 87) during clinical trials worldwide. Over 550 patients were treated for longer than one year.
Treatment with sildenafil was well tolerated. In placebo controlled clinical studies, the discontinuation rate due to adverse events was low and similar to placebo. The adverse events were generally transient and mild to moderate in nature.
Across trials of all designs, the profile of adverse events reported by patients receiving sildenafil was similar. In fixed dose studies, the incidence of adverse events increased with dose. The nature of the adverse events in flexible dose studies, which more closely reflect the recommended dosage regimen, was similar to that for fixed dose studies.
When sildenafil was taken as recommended (on an as needed basis in flexible dose placebo controlled clinical trials) the adverse events shown in Table 1 were reported.
Other adverse reactions occurred at a rate of > 2%, but equally commonly on placebo: respiratory tract infection, back pain, flu syndrome and arthralgia.
In fixed dose studies, dyspepsia (17%) and abnormal vision (11%) were more common at 100 mg than at lower doses.
At doses above the recommended dose range, adverse events were similar to those detailed above but generally were reported more frequently.
No cases of priapism were reported during controlled clinical trials.
The following events occurred in < 2% of patients in controlled clinical trials; a causal relationship to sildenafil is uncertain. Reported events include those with a plausible relation to drug use; omitted are minor events and reports too imprecise to be meaningful.

General disorders and administrative site conditions.

Face oedema, oedema, peripheral oedema, asthenia, pain, chills, chest pain, thirst.

Immune systems disorders.

Hypersensitivity.

Cardiac disorders.

Angina pectoris, A-V block, tachycardia, palpitations, myocardial ischaemia, cardiac arrest, heart failure, cardiomyopathy.

Vascular disorders.

Hypotension, postural hypotension, vasodilation, shock.

Gastrointestinal disorders.

Nausea, vomiting, glossitis, colitis, dysphagia, gastritis, oesophagitis, stomatitis, dry mouth, rectal haemorrhage, abdominal pain.

Blood and lymphatic systems disorders.

Anaemia and leukopenia.

Metabolic and nutritional disorders.

Gout, unstable diabetes, hyperglycaemia, hyperuricaemia, hypoglycaemic reaction, hypernatraemia.

Musculoskeletal and connective tissue disorders.

Arthritis, arthrosis, myalgia, tenosynovitis, bone pain, myasthenia, synovitis.

Injury, poisoning and procedural complications.

Accidental fall, accidental injury, tendon rupture.

Nervous system disorders.

Ataxia, hypertonia, neuralgia, neuropathy, paraesthesia, tremor, vertigo, somnolence, hyporeflexia, hypaesthesia, migraine, syncope, cerebral thrombosis.

Psychiatric disorders.

Depression, insomnia, abnormal dreams.

Respiratory thoracic and mediastinal disorders.

Rhinitis, respiratory disorder, asthma, dyspnoea, sputum increased, cough increased.

Infections and infestations.

Infection, rhinitis, sinusitis bronchitis, laryngitis, pharyngitis, herpes simplex, gastroenteritis, gingivitis, cystitis.

Skin and subcutaneous tissue disorders.

Urticaria, pruritus, sweating, skin ulcer, contact dermatitis, exfoliative dermatitis, photosensitivity reaction.

Eye disorders.

Mydriasis, conjunctivitis, photophobia, eye pain, eye haemorrhage, cataract, dry eyes.

Ear and labyrinth disorders.

Sudden decrease or loss of hearing, ear pain, tinnitus.

Reproductive and breast disorders.

Prostatic disorder, breast enlargement, abnormal ejaculation, genital oedema and anorgasmia.

Renal and urinary disorders.

Nocturia, urinary frequency, urinary incontinence.

Investigations.

Abnormal electrocardiogram, liver tests abnormal.
Adverse reactions reported in clinical trials that are not included in the above section include:

Eye disorders.

Visual disturbance, cvanopsia, photopsia, chromatopsia, ocular hvperaemia, visual brightness, eye oedema, eye swelling, dry eye, asthenopia, halo vision, xanthopsia, erythropsia, eye disorder, conjunctival hyperaemia, eye irritation, abnormal sensation in eye, evelid oedema.

Vascular disorders.

Hot flush.

Respiratory, thoracic and mediastinal disorders.

Sinus congestion, epistaxis, throat tightness, nasal dryness, nasal oedema.

Gastrointestinal disorders.

Gastro-oesophageal reflux disease, hypaesthesia oral.

Musculoskeletal and connective tissue disorders.

Pain in extremity.

Reproductive system and breast disorders.

Erection increased.

General disorders and administration site conditions.

Feeling hot, irritability.

Investigations.

Heart rate increased.

Postmarketing data.

Cardiac disorders and Vascular disorders.

Serious cardiovascular events, including myocardial infarction, sudden cardiac death, ventricular arrhythmia, cerebrovascular haemorrhage, transient ischaemic attack and hypertension have been reported postmarketing in temporal association with the use of sildenafil. Most, but not all, of these patients had pre-existing cardiovascular risk factors. Many of these events were reported to occur during or shortly after sexual activity, and a few were reported to occur shortly after the use of sildenafil without sexual activity. Others were reported to have occurred hours to days after the use of sildenafil and sexual activity. It is not possible to determine whether these events are related directly to sildenafil, to sexual activity, to the patient's underlying cardiovascular disease, to a combination of these factors or to other factors. Tachycardia, hypotension, syncope and epistaxis have also been reported postmarketing. Rare spontaneous reports have been received of hypotensive events after the use of sildenafil in combination with α-blockers.

Other events.

Other events reported postmarketing to have been observed in temporal association with sildenafil and not listed in the clinical trials adverse reactions section include the following.

Nervous system disorders.

Seizure, seizure recurrence and anxiety.

Reproductive system and breast disorders.

Priapism and prolonged erection.

Renal disorders.

Haematuria.

Eye disorders.

Diplopia, temporary vision loss/decreased vision, ocular redness or bloodshot appearance, ocular burning, ocular swelling/ pressure, increased intraocular pressure, retinal vascular disease or bleeding, vitreous detachment/ traction and paramacular oedema, central serous chorioretinopathy (CSCR).
Nonarteritic anterior ischaemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported rarely postmarketing in temporal association with the use of phosphodiesterase type 5 (PDE5) inhibitors, including sildenafil. Most, but not all, of these patients had underlying anatomical or vascular risk factors for developing NAION, including but not necessarily limited to low cup to disc ratio (crowded disc), age over 50, diabetes, hypertension, coronary artery disease, hyperlipidaemia and smoking. An observational study evaluating whether recent use of PDE5 inhibitors, as a class, was associated with acute onset of NAION suggests an increase in the risk of NAION with PDE5 inhibitor use (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use).

Immune system disorders.

Hypersensitivity reaction.

Ear and labyrinth disorders.

Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including sildenafil. In some of the cases, medical conditions and other factors were reported that may have also played a role in the otologic adverse events. In many cases, medical follow-up information was limited. It is not possible to determine whether these reported events are related directly to the use of sildenafil, to the patient's underlying risk factors for hearing loss, a combination of these factors, or to other factors (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

Overdose information is limited.

Symptoms.

In studies with healthy volunteers of single doses up to 800 mg, adverse events were similar to those seen at lower doses but incidence rates and severities were increased.

Treatment.

In cases of overdose, standard supportive measures should be adopted as required. Sildenafil blood levels are not clinically useful. Monitor electrocardiogram (ECG) and blood pressure in symptomatic patients. Renal dialysis is not expected to accelerate clearance as sildenafil is highly bound to plasma proteins and not eliminated in the urine.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Sildenafil is an oral therapy for erectile dysfunction which restores impaired erectile function by increasing blood flow to the penis, resulting in a natural response to sexual stimulation.
The physiological mechanism responsible for erection of the penis involves the release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. NO then activates the enzyme, guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood.
Sildenafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP in the corpus cavernosum. Sildenafil has a peripheral site of action on erections. Sildenafil has no direct relaxant effect on isolated human corpus cavernosum but potently enhances the relaxant effect of NO on this tissue. When the NO/cGMP pathway is activated, as occurs with sexual stimulation, inhibition of PDE5 by sildenafil results in increased corpus cavernosum levels of cGMP. Therefore, sexual stimulation is required in order for sildenafil to produce its beneficial pharmacological effects.
Single oral doses of sildenafil up to 100 mg in healthy volunteers produced no clinically relevant effects on the electrocardiogram. The mean maximum decrease in supine systolic blood pressure following 100 mg oral dosing was 8.4 mmHg. The corresponding change in supine diastolic blood pressure was 5.5 mmHg. These decreases in blood pressure are consistent with the vasodilatory effects of sildenafil, probably due to increased cGMP levels in vascular smooth muscle.
Sildenafil has no effect on visual acuity or contrast sensitivity. Mild and transient differences in colour discrimination (blue/green) were detected in some subjects using Farnsworth-Munsell 100 hue test at one hour following a 100 mg dose, with no effects evident two hours after the dose. The postulated mechanism for this change in colour discrimination is related to inhibition of PDE6, which is involved in the phototransduction cascade of the retina. In vitro studies show that sildenafil is tenfold less potent against PDE6 than PDE5.
Human platelets contain the PDE5 enzyme system. Sildenafil, in limited studies, did not affect platelet function in vivo. In in vitro studies sildenafil was shown to potentiate the antiaggregatory effect of the nitric oxide donor, sodium nitroprusside.
Studies in vitro have shown that sildenafil has between 10 and 10,000-fold greater selectivity for PDE5 than for other phosphodiesterase isoforms (PDEs 1, 2, 3, 4, 6, 7 to 11). In particular, sildenafil has greater than 4,000-fold selectivity for PDE5 over PDE3, the cyclic adenosine monophosphate specific phosphodiesterase isoform involved in the control of cardiac contractility.

Clinical trials.

The efficacy and safety of sildenafil was evaluated in 21 randomised, double blind placebo controlled trials up to six months duration. Sildenafil was administered to more than 3,000 patients aged 19 to 87, with erectile dysfunction of various aetiologies (organic, psychogenic, mixed). The efficacy was evaluated by global assessment questions, diary of erections, the International Index of Erectile Function (IIEF, a validated sexual function questionnaire) and a partner questionnaire.
Sildenafil efficacy, determined as the ability to achieve and maintain an erection sufficient for sexual intercourse, was demonstrated in all 21 studies and was maintained in long-term extension studies (one year). In fixed dose studies the proportions of patients reporting that treatment improved their erections were 62% (25 mg), 74% (50 mg), 82% (100 mg) compared to 25% on placebo. In addition to improvements in erectile function, analysis of IIEF showed that sildenafil treatment also improved the domains of orgasm, satisfaction with intercourse and overall satisfaction.
Across all trials, the proportion of patients reporting improvement on sildenafil were 59% of diabetic patients, 43% of radical prostatectomy patients and 83% of patients with spinal cord injury (versus 16, 15 and 12% on placebo, respectively).

5.2 Pharmacokinetic Properties

Absorption.

Sildenafil is rapidly absorbed. Maximum observed plasma concentrations are reached within 30 to 120 minutes (median 60 minutes) of oral dosing in the fasted state. The mean absolute oral bioavailability is 41% (range 25 to 63%). The oral pharmacokinetics of sildenafil are proportional over the recommended dose range (25 to 100 mg).
When sildenafil is taken with a high fat meal, the rate of absorption is reduced with a mean delay in Tmax of 60 minutes and a mean reduction in Cmax of 29%. Patients may need to individualise their dosing relative to their food intake based on their own experienced clinical response.

Distribution.

The mean steady-state volume of distribution (Vss) for sildenafil is 105 L, indicating distribution into the tissues. Sildenafil and its major circulating N-desmethyl metabolite are both approximately 96% bound to plasma proteins. Protein binding is independent of total drug concentrations.
In 16 healthy volunteers receiving sildenafil (100 mg single dose), the mean semen concentrations of sildenafil 1.5 and 4 hours after dosing were 18 and 17%, respectively, of the plasma concentration at the same time point. The amount in the ejaculate at 90 minutes after dosing was less than 0.0002% of the administered dose.

Metabolism.

Sildenafil is cleared predominantly by the CYP3A4 (major route) and CYP2C9 (minor route) hepatic microsomal isoenzymes. The major circulating metabolite results from N-demethylation of sildenafil. This metabolite has a PDE selectivity profile similar to sildenafil and an in vitro potency for PDE5 approximately 40% that of the parent drug. Plasma concentrations of this metabolite are approximately 40% of those seen for sildenafil. The N-desmethyl metabolite is further metabolised with a terminal half-life of approximately four hours.

Excretion.

The total body clearance of sildenafil is 41 L/hour with a resultant terminal phase half-life of three to five hours. After either oral or intravenous administration, sildenafil is excreted as metabolites predominantly in the faeces (approximately 80% of administered oral dose) and to a lesser extent in the urine (approximately 13% of administered oral dose).

Pharmacokinetics in special patient groups.

Use in the elderly.

Healthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil, with free plasma concentrations approximately 40% greater than those seen in younger volunteers (18 to 45 years). However, analysis of the safety database showed that age had no effect on the incidence of adverse events.

Use in renal insufficiency.

In volunteers with mild (creatinine clearance = 50 to 80 mL/minute) and moderate (creatinine clearance = 30 to 49 mL/minute) renal impairment, the pharmacokinetics of a single oral dose of sildenafil (50 mg) were not altered. In volunteers with severe (creatinine clearance < 30 mL/minute) renal impairment, sildenafil clearance was reduced, resulting in increases in AUC (100%) and Cmax (88%) compared to age matched volunteers with no renal impairment.

Use in hepatic insufficiency.

In volunteers with hepatic cirrhosis (Child-Pugh A and B), sildenafil clearance was reduced, resulting in increases in AUC (84%) and Cmax (47%) compared to age matched volunteers with no hepatic impairment. The pharmacokinetics of sildenafil in patients with severe hepatic impairment have not been studied.

5.3 Preclinical Safety Data

Genotoxicity.

Sildenafil was negative in in vitro bacterial and Chinese hamster ovary cell assays to detect mutagenicity, and in vitro human lymphocytes and in vivo mouse micronucleus assays to detect clastogenicity.

Carcinogenicity.

Sildenafil was not carcinogenic when administered to rats for 24 months at a dose resulting in total systemic drug exposure (AUC) for unbound sildenafil and its major metabolite of 35 and 39 times, for male and female rats, respectively, the exposures observed in human males given the maximum recommended human dose (MRHD) of 100 mg. Sildenafil was not carcinogenic when administered to mice for 18 to 21 months at dosages up to the maximum tolerated dose of 10 mg/kg/day, but resulting in total systemic drug exposure for unbound sildenafil and its major metabolite of less than the exposures observed in human males given the MRHD.

6 Pharmaceutical Particulars

6.1 List of Excipients

The tablets also contain microcrystalline cellulose, calcium hydrogen phosphate, croscarmellose sodium, magnesium stearate and Opadry II complete film coating system 85F510057 Green. The tablets are gluten free.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

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 below 25°C.

6.5 Nature and Contents of Container

Sildenafil-WGR 25 mg.

Blister packs of 4 tablets (PVC/PVDC/Al).

Sildenafil-WGR 50 mg.

Blister packs of 4 tablets (PVC/PVDC/Al).

Sildenafil-WGR 100 mg.

Blister packs of 4 and 12 tablets (PVC/PVDC/Al).

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

Sildenafil citrate is an off white, crystalline powder. Its aqueous solubility is equivalent to sildenafil 2.6 mg/mL at 25°C. The chemical name for sildenafil citrate is 1-[4-ethoxy- 3-(6,7-dihydro- 1-methyl- 7-oxo- 3-propyl- 1H-pyrazolo [4,3-d]pyrimidin-5-yl) phenylsulfonyl]- 4-methylpiperazine citrate.

Chemical structure.

Its structural formula is:
C22H30N6O4S.C6H807.
Molecular weight: 666.7.

CAS number.

171599-83-0.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes