Consumer medicine information

Sildenafil Sandoz

Sildenafil

BRAND INFORMATION

Brand name

Sildenafil Sandoz

Active ingredient

Sildenafil

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Sildenafil Sandoz.

SUMMARY CMI

Sildenafil Sandoz®

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 Sandoz?

Sildenafil Sandoz contains the active ingredient sildenafil. Sildenafil Sandoz is used to d to treat erectile dysfunction, more commonly known as impotence, in men.

For more information, see Section 1. Why am I using Sildenafil Sandoz? in the full CMI.

2. What should I know before I use Sildenafil Sandoz?

Do not use if you have ever had an allergic reaction to sildenafil 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, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use Sildenafil Sandoz? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Sildenafil Sandoz 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 Sandoz?

  • Take Sildenafil Sandoz exactly 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 Sandoz? in the full CMI.

5. What should I know while using Sildenafil Sandoz?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are taking Sildenafil Sandoz.
  • Stop taking Sildenafil Sandoz 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 Sandoz.
Things you should not do
  • Do not use drugs containing amyl nitrite (sometimes called "poppers") while you are taking Sildenafil Sandoz.
  • If you get an angina attack, do not take nitrate medicines to relieve the pain but tell your doctor immediately.
  • Do not give Sildenafil Sandoz 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 Sandoz, you should not drive or operate machinery.
Drinking alcohol
  • Be careful drinking alcohol while taking Sildenafil Sandoz.
Looking after your medicine
  • Keep Sildenafil Sandoz in a cool, dry place where the temperature stays below 30°C.
  • Keep this medicine where children cannot reach it.

For more information, see Section 5. What should I know while using Sildenafil Sandoz? 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 Sandoz®

Active ingredient(s): sildenafil (as citrate)

Consumer Medicine Information (CMI)

This leaflet provides important information about using Sildenafil Sandoz. 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 Sandoz.

Where to find information in this leaflet:

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

1. Why am I using Sildenafil Sandoz?

Sildenafil Sandoz contains the active ingredient sildenafil (as citrate). Sildenafil Sandoz belongs to a group of medicines called phosphodiesterase type 5 (PDE5) inhibitors.

Sildenafil Sandoz is used to treat erectile dysfunction, more commonly known as 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 Sandoz will not increase your sex drive and will work only if you are sexually excited.

Sildenafil Sandoz is not for use in women.

2. What should I know before I use Sildenafil Sandoz?

Warnings

YOU MUST NOT TAKE SILDENAFIL SANDOZ 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 SANDOZ.

Do not use Sildenafil Sandoz 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 use 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 Sandoz.

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 Sandoz if you are taking or using nitrate medicines for angina.

Do not take Sildenafil Sandoz if you are taking guanylate cyclase stimulators (GCS), such as riociguat.

Some medicines and Sildenafil Sandoz 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 Sandoz.

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 Sandoz.

4. How do I use Sildenafil Sandoz?

Take Sildenafil Sandoz 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 Sandoz a day.

How to take Sildenafil Sandoz

Swallow the tablet with a full glass of water.

Sildenafil Sandoz tablets have a breaking notch and may be broken if necessary

When to take Sildenafil Sandoz

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

If you take too much Sildenafil Sandoz

If you think that you or anyone else may have taken too much Sildenafil Sandoz, 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 using Sildenafil Sandoz?

Things you should do

  • Stop taking Sildenafil Sandoz 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 Sandoz 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 Sandoz.
  • See Section 2. What should I know before I use Sildenafil Sandoz? for a list of common nitrate medications.
  • Tell any other doctors, dentists and pharmacists who are treating you that you are taking Sildenafil Sandoz.

Things you should not do

  • Do not use drugs containing amyl nitrite (sometimes called "poppers") while you are taking Sildenafil Sandoz.
  • 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 Sandoz.
  • Do not give Sildenafil Sandoz 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 Sildenafil Sandoz affects you.

If you experience changes in vision, or dizziness when taking Sildenafil Sandoz, you should not drive or operate machinery

Drinking alcohol

Be careful drinking alcohol while taking Sildenafil Sandoz.

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 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?

While Sildenafil Sandoz 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 Sandoz.

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 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.

Very serious side effects

Very 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 very serious side effect.

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 Sandoz contains

Active ingredient
(main ingredient)		sildenafil (as citrate) equivalent to 25 mg, 50 mg or 100 mg sildenafil per tablet
Other ingredients
(inactive ingredients)		microcrystalline cellulose
calcium hydrogen phosphate anhydrous
copovidone
croscarmellose sodium
magnesium stearate
sodium saccharin
indigo carmine (E132) aluminium lake.

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

What Sildenafil Sandoz looks like

Sildenafil Sandoz tablets are available in three strengths:

Sildenafil Sandoz 25mg - light blue, slightly dotted, round tablets, with a breaking notch and marked "25". Available in blisters of 4 tablets (AUST R 148570).

Sildenafil Sandoz 50mg - light blue, slightly dotted, round tablets, with a cross breaking notch and marked "50". Available in blisters of 4 and 12 tablets (AUST R 148567).

Sildenafil Sandoz 100mg - light blue, slightly dotted, round tablets, with a cross breaking notch and marked "100". Available in blisters of 4 and 12 tablets (AUST R 148568).

Who distributes Sildenafil Sandoz

Sandoz Pty Ltd
100 Pacific Highway
North Sydney, NSW 2060
Australia

Tel 1800 726 369

This leaflet was prepared in January 2025.

® Registered Trade Mark. The trade marks mentioned in this material are the property of their respective owners.

Published by MIMS March 2025

BRAND INFORMATION

Brand name

Sildenafil Sandoz

Active ingredient

Sildenafil

Schedule

S4

 

1 Name of Medicine

Sildenafil (as citrate).

2 Qualitative and Quantitative Composition

Each Sildenafil Sandoz 25 mg tablets contains 25 mg Sildenafil (as citrate).
Each Sildenafil Sandoz 50 mg tablets contains 50 mg Sildenafil (as citrate).
Each Sildenafil Sandoz 100 mg tablets contains 100 mg Sildenafil (as citrate).
Sildenafil citrate is an off-white, crystalline powder. Its aqueous solubility is equivalent to 2.6 mg sildenafil per millilitre at 25°C.
For the full list of excipients, see Section 6.1 List of Excipients.
Not all presentations may be marketed in Australia.

3 Pharmaceutical Form

Sildenafil Sandoz 25 mg tablets.

Light blue round slightly dotted tablets with breaking notch and embossment "25".

Sildenafil Sandoz 50 mg tablets.

Light blue round slightly dotted tablets with cross breaking notch and embossment "50".

Sildenafil Sandoz 100 mg tablets.

Light blue round slightly dotted tablets with cross breaking notch and embossment "100".

4 Clinical Particulars

4.1 Therapeutic Indications

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

4.2 Dose and Method of Administration

Dosage.

Use in adults.

The recommended dose is 50 mg taken as needed approximately one hour before sexual activity. Based on the efficacy and toleration, 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.

Use in children.

Sildenafil Sandoz is not indicated for use in children.

Method of administration.

Sildenafil Sandoz tablets are for oral administration. Sildenafil Sandoz tablets have a breaking notch and may be broken if necessary.

Dosage adjustment.

Renal impairment.

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

Hepatic impairment.

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 toleration, the dose may be increased to 50 mg and 100 mg.

Elderly.

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

Patients using other medication.

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 drugs 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 drugs on sildenafil.)
In order to minimise the potential for developing postural hypotension, patients should be stable on alpha-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

Use of Sildenafil Sandoz is contraindicated in patients with 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 nitric oxide donors, organic nitrates or organic nitrites in any form, either regularly or intermittently is contraindicated. Drugs 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 coadministration of PDE5 inhibitors, including sildenafil, 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 non-arteritic anterior ischaemic optic neuropathy (NAION) (see Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects), Post marketing experience).
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), 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, physicians 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 PDE5 inhibitors. Most cases of CSCR resolved spontaneously after stopping sildenafil. Physicians should advise patients to stop use of all PDE5 inhibitors, including sildenafil, and seek immediate medical attention in the event of a sudden loss of vision in one or both eyes. Such an event may be a sign of non-arteritic anterior ischaemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, that has been reported rarely post marketing in temporal association with the use of all PDE-5 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. PDE5 inhibitors, including Sildenafil Sandoz, are not recommended in patients with male erectile dysfunction with a previous episode of NAION (see Section 4.3 Contraindications; Section 4.8 Adverse Effects (Undesirable Effects), Post marketing experience).
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, physicians 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 including sildenafil, 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 alpha-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 alpha-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, physicians 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 anti-aggregatory 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 sildenafil 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 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 physician 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 in duration and priapism (painful erections greater than 6 hours) have been reported infrequently since market approval of sildenafil. In the event of an erection that persists longer than 4 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.

No data available.

Paediatric use.

See Section 4.2 Dose and Method of Administration.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Effects of other drugs on sildenafil.

Sildenafil metabolism is principally mediated by the cytochrome P450 (CYP) isoforms 3A4 (major route) and 2C9 (minor route). Therefore, inhibitors of these isoenzymes may reduce sildenafil clearance and inducers of these isoenzymes may increase sildenafil clearance.
Population pharmacokinetics analysis of clinical trial data indicated a reduction in sildenafil clearance when coadministered with CYP3A4 inhibitors (such as ketoconazole, erythromycin, cimetidine). However, there was no increased incidence of adverse events in these patients.
Cimetidine (800 mg), a non-specific 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 5 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 (1200 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% (4-fold) increase in sildenafil Cmax and a 1000% (11-fold) 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.
Grapefruit juice is a weak inhibitor of CYP3A4 gut wall metabolism and may give rise to moderate increase in plasma levels of sildenafil.
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, beta-adrenoreceptor antagonists or inducers of CYP450 metabolism (such as barbiturates).
In a study of healthy male volunteers, coadministration 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 by 49.8% and 42% respectively.
Riociguat: 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).
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.
Nicorandil should not be used concomitantly with sildenafil (see Section 4.3 Contraindications).

Effects of sildenafil on other medicines.

Sildenafil is a weak inhibitor of the cytochrome P450 isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50 > 150 micromolar). Given sildenafil peak plasma concentrations of approximately 1 micromolar 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 non-specific phosphodiesterase inhibitors such as theophylline or dipyridamole.
In three specific drug-drug interaction studies, the alpha-blocker doxazosin (4 mg and 8 mg) and sildenafil (25 mg, 50 mg, or 100 mg) were administered simultaneously to patients with benign prostatic hyperplasia (BPH) stabilized on doxazosin therapy. In these study populations, mean additional reductions of supine blood pressure of 7/7 mmHg, 9/5 mmHg, and 8/4 mmHg, and mean additional reductions of standing blood pressure of 6/6 mmHg, 11/4 mmHg, and 4/5 mmHg, respectively, were observed. When sildenafil and doxazosin were administered simultaneously to patients stabilized 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 alpha-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 to females and 102 days to 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, 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)
Pregnancy Category B1: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human foetus having been observed. Studies in animals have not shown evidence of an increased occurrence of foetal damage.
Sildenafil Sandoz 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 maximum recommended human dose (MRHD) of 100 mg. In the rat pre- and postnatal development study, the no observed adverse effect dose was 30 mg/kg/day given for 36 days. In nonpregnant rat the AUC at this dose was about 20 times human AUC. There are no adequate and well controlled studies of sildenafil in pregnant women.
 Sildenafil Sandoz 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 3700 patients (aged 19-87) 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 following adverse events were reported (see Table 1).
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 system disorders.

Hypersensitivity.

Cardiac disorders.

Angina pectoris, AV block, tachycardia, palpitation, 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, hyperuricemia, hypoglycaemic reaction, hypernatremia.

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.

Respiratory disorder, asthma, dyspnoea, sputum increased, cough increased, epistaxis.

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, Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), photosensitivity reactions.

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 system.

Haematospermia, penile haemorrhage, priapism, prolonged erection.

Urogenital 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 disturbances, cyanopsia, photopsia, chromatopsia, ocular hyperaemia, visual brightness, eye oedema, eye swelling, dry eye, asthenopia, halo vision, xanthopsia, erythropsia, eye disorder, conjunctival hyperaemia, eye irritation, abnormal sensation in eye, eyelid oedema.

Vascular disorders.

Hot flush.

Respiratory, thoracic and mediastinal disorders.

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

Gastrointestinal disorders.

Gastroesophageal reflux disease, hypoaesthesia oral.

Musculoskeletal and connective tissue disorder.

Pain in extremity.

Reproductive system and breast disorders.

Erection increased.

General disorders and administration site conditions.

Feeling hot, irritability.

Investigations.

Heart rate increased.

Post marketing experience.

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 post marketing 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 post marketing. Rare spontaneous reports have been received of hypotensive events after the use of sildenafil in combination with alpha blockers.
Other events reported postmarketing to have been observed in temporal association with sildenafil and not listed in the clinical trials adverse reactions section include:

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 post marketing in temporal association with the use of phosphodiesterase type 5 (PDE5) inhibitors, including sildenafil. Most, but not all, of these patients had underlying anatomic 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 post marketing 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 http://www.tga.gov.au/reporting-problems.

4.9 Overdose

Symptoms.

Overdose information is limited. 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 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 Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Sildenafil Sandoz 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. Nitric oxide 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 ECG. The mean maximum decreases 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 1 hour following a 100 mg dose, with no effects evident after 2 hours post-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 10-fold less potent against PDE6 than PDE5.
Human platelets contain PDE5 enzyme system. Sildenafil, in limited studies, did not affect platelet function in vivo. In in vitro studies, sildenafil was shown to potentiate the anti-aggregatory 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 cAMP 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 6 months duration. Sildenafil was administered to more than 3000 patients aged 19-87, 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 after oral administration. 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 25-63%). The oral pharmacokinetics of sildenafil are proportional over the recommended dose range (25 mg - 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 sixteen healthy volunteers receiving sildenafil (100 mg single dose), the mean semen concentrations of sildenafil 1.5 and 4 hours post-dose 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 50% 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 4 hours.

Excretion.

The total body clearance of sildenafil is 41 L/h with a resultant terminal phase half-life of 3-5 hours. After either oral or intravenous administration, sildenafil is excreted as metabolites predominantly in the faeces (approximately 80% of administered oral dose) to a lesser extent in the urine (approximately 13% of administered oral dose).

Pharmacokinetics in special patient groups.

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 (18-45 years). However, analysis of the safety database showed that age had no effect on the incidence of adverse events.

Renal insufficiency.

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

Hepatic insufficiency.

In volunteers with hepatic cirrhosis (Child-Pugh A and B), sildenafil clearance was reduced, resulting in increases in AUC (85%) and Cmax (47%) compared to age matched volunteers with no hepatic impairment. The pharmacokinetics of sildenafil in patients with severe hepatic impairment has 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 18-21 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

Each Sildenafil Sandoz tablet contains the following inactive (excipients) ingredients: microcrystalline cellulose, calcium hydrogen phosphate, copovidone, croscarmellose sodium, magnesium stearate, saccharin sodium and indigo carmine aluminium lake.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.
For information on interactions with other medicines and other forms of interactions, see Section 4.5.

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 30°C.

6.5 Nature and Contents of Container

Sildenafil Sandoz 25 mg tablets: Blister packs of 4 tablets.
Sildenafil Sandoz 50 mg tablets: Blister packs of 1, 2, 4, 8 and 12 tablets.
Sildenafil Sandoz 100 mg tablets: Blister packs of 4 and 12 tablets.
Sildenafil Sandoz tablets are available in blister packs (PVC/PCTFE (Aclar)/Al).
Not all presentations are marketed in Australia.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

The chemical name of 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. Its empirical formula is C22H30N6O4S.C6H8O7 (MW: 666.7).

Chemical structure.

Its chemical structure is:

CAS number.

171599-83-0.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes