Consumer medicine information

Voltaren Tablets and Suppositories

Diclofenac sodium

BRAND INFORMATION

Brand name

Voltaren

Active ingredient

Diclofenac sodium

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Voltaren Tablets and Suppositories.

What is in this leaflet

This leaflet answers some common questions about Voltaren tablets and suppositories. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

The information in this leaflet was last updated on the date listed on the final page. More recent information on the medicine may be available.

You should ensure that you speak to your pharmacist or doctor to obtain the most up to date information on the medicine. You can also download the most up to date leaflet from www.novartis.com.au. Those updates may contain important information about the medicine and its use of which you should be aware.

All medicines have risks and benefits. Your doctor has weighed the risks of you using this medicine against the benefits they expect it will provide.

If you have any concerns about this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What Voltaren is used for

Voltaren belongs to a group of medicines called non-steroidal anti-inflammatory drugs (NSAIDs), which are used to treat pain and reduce inflammation (swelling and redness).

Voltaren is used to treat:

  • different types of arthritis including rheumatoid arthritis and osteoarthritis
  • other painful conditions where swelling is a problem such as back pain, rheumatism, muscle strains, sprains and tendonitis (e.g. tennis elbow)
  • menstrual cramps (period pain)
  • relieve pain in children after they have had an operation.

It can relieve the symptoms of pain and inflammation but it will not cure your condition.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another purpose.

Voltaren is only available with a doctor's prescription. It is not addictive.

Voltaren suppositories should not be used in children under 12 months of age. Because of their strength, Voltaren 100mg suppositories are not suitable for children and adolescents.

There is not enough information to recommend the use of Voltaren tablets in children.

Before you use Voltaren

When you must not use it

Do not use Voltaren if you are allergic (hypersensitive) to:

  • diclofenac (the active ingredient in Voltaren) or any of the other ingredients listed at the end of this leaflet
  • other medicines containing diclofenac (e.g. Voltaren Rapid tablets, Voltaren Emulgel)
  • aspirin
  • ibuprofen
  • any other NSAID

If you are not sure if you are taking any of the above medicines, ask your doctor or pharmacist.

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue, throat, and/or extremities (signs of angioedema)
  • rash, itching or hives on the skin.

Many medicines used to treat headache, period pain and other aches and pains contain aspirin or NSAID medicines. If you are allergic to aspirin or NSAID medicines and you use Voltaren, these symptoms may be severe.

Do not use Voltaren if you have had any of the following medical conditions:

  • a stomach or intestinal ulcer
  • bleeding from the stomach or bowel (symptoms of which may include blood in your stools or black stools)
  • kidney or liver problems
  • severe heart failure
  • heart bypass surgery

Do not use Voltaren suppositories if you suffer from inflammation of the rectum (back passage) or if your rectum is painful (sometimes with bleeding or discharge).

Do not use Voltaren during the first 6 months of pregnancy, except on doctor's advice. Do not use during the last three months of pregnancy. Use of this medicine during the last 3 months of pregnancy may affect your baby and may delay labour and birth.

Use of non-aspirin NSAIDs can increase the risk of miscarriage, particularly when taken close to the time of conception.

Do not use Voltaren after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. In that case, return it to your pharmacist.

Before you start to use it

Tell your doctor if you have any of the following health problems / medical conditions:

  • established disease of the heart or blood vessels (also called cardiovascular disease, including uncontrolled high blood pressure, congestive heart failure, established ischemic heart disease, peripheral arterial disease or atherosclerotic cardiovascular disease), as treatment with Voltaren is generally not recommended
  • established cardiovascular disease (see above) or significant risk factors such as high blood pressure, abnormally high levels of fat (cholesterol, triglycerides) in your blood, diabetes, or if you smoke, and your doctor decides to prescribe Voltaren, you must not increase the dose above 100 mg per day if you are treated for more than 4 weeks.
  • a past history of ulcers (stomach or intestinal)
  • gastrointestinal problems such as stomach ulcer, bleeding or black stools, or have experienced stomach discomfort or heartburn after taking anti-inflammatory medicines in the past
  • diseases of the bowel or inflammation of the intestinal tract (Crohn's disease) or colon (ulcerative or ischemic colitis)
  • past history of haemorrhoids (piles) or irritation of the rectum (back passage)
  • liver or kidney problems
  • a rare liver condition called porphyria
  • bleeding disorders or other blood disorders (e.g. anaemia)
  • asthma or any other chronic lung disease that causes difficulty in breathing
  • hay fever (seasonal allergic rhinitis)
  • repeated chest infections
  • polyps in the nose
  • diabetes
  • dehydration (e.g. by sickness, diarrhoea, before or after recent major surgery
  • swollen feet

Your doctor may want to take special precautions if you have any of the above conditions.

It is generally important to take the lowest dose of Voltaren that relieves your pain and/or swelling and for the shortest time possible in order to keep your risk for cardiovascular side effects as small as possible.

Tell your doctor if you are pregnant or trying to become pregnant. There is not enough information to recommend the use of Voltaren during the first 6 months of pregnancy and it must not be used during the last 3 months. Voltaren may also reduce fertility and affect your chances of becoming pregnant. Your doctor can discuss with you the risks and benefits involved.

Tell your doctor if you currently have an infection. If you use Voltaren while you have an infection, some of the signs of the infection such as pain, fever, swelling and redness may be hidden. You may think, mistakenly, that you are better or that the infection is not serious.

Tell your doctor if you are breast-feeding. Breast-feeding is not recommended while you are using this medicine. The active ingredient in Voltaren passes into breast milk and may affect your baby.

Tell your doctor if you are lactose intolerant. Voltaren tablets contain lactose.

Tell your doctor if you are allergic to any other medicines, foods, dyes or preservatives. Your doctor will want to know if you are prone to allergies, especially if you get skin reactions with redness, itching or rash.

Taking other medicines

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

Some medicines that are important to mention include:

  • other anti-inflammatory medicines, e.g. aspirin, salicylates or ibuprofen
  • warfarin or other "blood thinners" (medicines used to prevent blood clotting)
  • digoxin (a medicine for heart problems)
  • lithium or selective serotonin-reuptake inhibitors (SSRIs), a medicine used to treat some types of depression
  • diuretics (medicines used to increase the amount of urine)
  • ACE inhibitors or beta-blockers (medicines used to treat high blood pressure, heart conditions, glaucoma and migraine)
  • prednisone, cortisone, or other corticosteroids (medicines used to provide relief for inflamed areas of the body)
  • medicines (such as metformin) used to treat diabetes, except insulin
  • methotrexate (a medicine used to treat arthritis and some cancers)
  • cyclosporin, tacrolimus (a medicine used in patients who have received organ transplants)
  • trimethoprim (a medicine used to prevent or treat urinary tract infections)
  • some medicines used to treat infection (quinolone antibacterials)
  • glucocorticoid medicines, used to treat arthritis
  • sulfinpyrazone (a medicine used to treat gout)
  • voriconazole (a medicine used to treat fungal infections)
  • phenytoin (a medicine used to treat seizures)
  • Rifampicin (an antibiotic medicine used to treat bacterial infections)

You may need to take different amounts of your medicines or to take different medicines while you are using Voltaren. Your doctor and pharmacist have more information.

If you have not told your doctor about any of these things, tell him/her before you start using this medicine.

How to use Voltaren

When to take it

Voltaren Tablets

It is recommended to take the tablets before meals or on an empty stomach. If they upset your stomach, you can take them with food or immediately after food. They will work more quickly if you take them on an empty stomach but they will still work if you have to take them with food to prevent stomach upset.

Voltaren suppositories

Use the suppositories at bedtime to relieve pain during the night and early morning stiffness; or to relieve pain after an operation.

How much Voltaren to take/use

Follow all directions given to you by your doctor and pharmacist carefully. These instructions may differ from the information contained in this leaflet.

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

There are different ways to take Voltaren tablets and suppositories, depending on your condition. Your doctor will tell you exactly how many tablets or suppositories to take.

Do not exceed the recommended dose.

To treat arthritis or other painful conditions

The usual starting dose of Voltaren tablets is 75mg to 150mg each day. After the early stages of treatment, it is usually possible to reduce the dose to 75mg to 100mg each day.

To treat menstrual cramps (period pain)

The tablets are usually taken during each period as soon as cramps begin and continued for a few days until the pain goes away.

The usual starting dose of Voltaren tablets is 50mg to 100mg each day, beginning as soon as cramps begin and continuing until the pain goes away, but for no longer than 3 days.

If necessary, the dose can be raised over several menstrual periods to a maximum of 200mg each day.

To treat post-operative pain in children

Your doctor will advise what strength and dose of Voltaren suppositories is suitable for your child.

How to take the tablets

Voltaren tablets are usually taken in 2 or 3 doses during the day.

Swallow the tablets whole with a full glass of water or other liquid. Do not chew them. The tablets have a special coating to keep them from dissolving until they have passed through the stomach into the bowel. Chewing the tablets would destroy the coating.

How to use Voltaren suppositories

Do not take suppositories by mouth.

When used in children, the strength of the Voltaren suppository used depends on the weight of the child. Your doctor will decide which strength is suitable for your child and how often it can be used.

If possible, go to the toilet and empty your bowels before using the suppository.

Follow these steps:

  1. Wash your hands thoroughly with soap and water.
  2. If the suppository feels soft, chill it before removing the wrapper by placing it in the fridge or holding it under cold water for a few minutes.
  3. Put on a disposable glove, if desired (available from a pharmacy).
  4. Remove the entire wrapper from the suppository.
  5. Moisten the suppository by dipping it briefly in cool water.
  6. Lie on your side and raise your knees to your chest.
  7. Push the suppository, blunt end first, gently into your rectum (back passage). Do not break the suppository.
  8. Remain lying down for a few minutes so that the suppository dissolves.
  9. Wash your hands again thoroughly.

Try not to go to the toilet to empty your bowels for at least one hour after using the suppository.

If you are not sure how to use a suppository, ask your pharmacist or doctor.

How long to take/use it

Do not use Voltaren for longer than your doctor says.

If you are using Voltaren for arthritis, it will not cure your disease but it should help to control pain and inflammation. It usually begins to work within a few hours but several weeks may pass before you feel the full effects of the medicine.

Voltaren suppositories should not be used for more than 3 days in children.

If you forget to take/use it

If it is almost time for your next dose (e.g. within 2 or 3 hours), skip the dose you missed and take the next dose when you are meant to.

Otherwise, take it as soon as you remember, and then go back to taking it as you would normally.

Do not take a double dose to make up for the one that you missed. This may increase the chance of you getting an unwanted side effect.

If you have trouble remembering when to take your medicine, ask your pharmacist for some hints.

If you take/use too much Voltaren (Overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone 13 11 26), or go to Accident and Emergency at your nearest hospital if you think that you or anyone else may have used too much Voltaren. Do this even if there are no signs of discomfort or poisoning. Keep the telephone numbers for these places handy.

If you take too much Voltaren, you may experience:

  • vomiting
  • bleeding from the stomach or bowel
  • diarrhoea
  • dizziness
  • ringing in the ears
  • convulsions (fits)

While you are taking/ using Voltaren

Things you must do

If you take Voltaren for more than a few weeks, you should make sure to visit your doctor for regular check-ups to ensure that you are not suffering from unnoticed undesirable effects.

If you become pregnant whilst taking or using Voltaren, tell your doctor immediately. Your doctor can discuss with you the risks of using it while you are pregnant.

Be sure to keep all of your doctor's appointments so that your progress can be checked. Your doctor will periodically re-evaluate whether you should continue treatment with Voltaren, if you have established heart disease or significant risks for heart disease, especially in case you are treated for more than 4 weeks.

Your doctor may want to check your kidneys, liver and blood from time to time to help prevent unwanted side effects.

If, at any time while taking Voltaren you experience any signs or symptoms of problems with your heart or blood vessels such as chest pain, shortness of breath, weakness, or slurring of speech, contact your doctor immediately. These may be signs of cardiovascular toxicity.

If you are going to have surgery, make sure the surgeon and anaesthetist know that you are using Voltaren. NSAID medicines can slow down blood clotting and affect kidney function.

If you get an infection while using Voltaren, tell your doctor. This medicine may hide some of the signs of an infection (pain, fever, swelling, redness). You may think, mistakenly, that you are better or that the infection is not serious.

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

Tell any other doctor, dentist or pharmacist who treats you that you are using Voltaren.

Things you must not do

Do not take any of the following medicines while you are using Voltaren without first telling your doctor:

  • aspirin (also called ASA or acetylsalicylic acid)
  • other salicylates
  • other medicines containing diclofenac (e.g. Voltaren Rapid tablets, Voltaren Emulgel)
  • ibuprofen
  • any other NSAID medicine

If you take these medicines together with Voltaren, they may cause unwanted side effects.

If you need to take something for headache or fever, it is usually okay to take paracetamol. If you are not sure, your doctor or pharmacist can advise you.

Do not stop any other forms of treatment for arthritis that your doctor has told you to follow. This medicine does not replace exercise or rest programs or the use of heat/cold treatments.

Do not give this medicine to anyone else, even if their condition seems similar to yours.

Do not use it to treat any other complaints unless your doctor tells you to.

Things to be careful of

Be careful driving, operating machinery or doing jobs that require you to be alert until you know how Voltaren affects you. This medicine may cause dizziness, drowsiness, spinning sensation (vertigo) or blurred vision in some people. If you have any of these symptoms, do not drive, use machines, or do anything else that could be dangerous.

Elderly patients should take the minimum number of tablets or suppositories that provides relief of symptoms. Elderly patients, especially those with a low body weight, may be more sensitive to the effects of Voltaren than other adults.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are using Voltaren.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

If you are over 65 years old, you should be especially careful while taking this medicine. Report any side effects promptly to your doctor. As people grow older, they are more likely to get side effects from medicines.

Do not be alarmed by these lists of possible side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

  • stomach upset including nausea (feeling sick), vomiting, indigestion, cramps, loss of appetite, wind
  • heartburn or pain behind or below the breastbone (possible symptoms of an ulcer in the tube that carries food from the throat to the stomach)
  • stomach or abdominal pain
  • constipation, diarrhoea
  • sore mouth or tongue
  • altered taste sensation
  • headache
  • dizziness, spinning sensation
  • drowsiness, disorientation, forgetfulness
  • feeling depressed, anxious or irritable
  • strange or disturbing thoughts or moods
  • shakiness, sleeplessness, nightmares
  • tingling or numbness of the hands or feet
  • feeling of fast or irregular heart beat
  • unusual weight gain or swelling of arms, hands, feet, ankles or legs due to fluid build-up
  • symptoms of sunburn (such as redness, itching, swelling, blistering of the lips, eyes, mouth, and/or skin) that happen more quickly than normal
  • skin inflammation with flaking or peeling
  • vision disorders* (e.g. blurred or double vision)
  • buzzing or ringing in the ears, difficulty hearing
  • hypertension (high blood pressure)
  • hair loss or thinning
  • application site irritation, painful rectum or discomfort in the rectum (back passage) or worsening of haemorrhoids (piles) when using the suppositories

NSAIDs, including diclofenac, may be associated with increased risk of gastro-intestinal anastomotic leak. Close medical surveillance and caution are recommended when using this medicine after gastrointestinal surgery.

*If symptoms of vision disorders occur during treatment with Voltaren, contact your doctor as an eye examination may be considered to exclude other causes.

If any of the following signs appear, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

  • red or purple skin (possible signs of blood vessel inflammation)
  • severe pain or tenderness in the stomach, vomiting blood or material that looks like coffee grounds, bleeding from the back passage, black sticky bowel motions (stools) or bloody diarrhoea (possible stomach problems)
  • rash, skin rash with blisters, itching or hives on the skin; swelling of the face, lips, mouth, tongue, throat, or other part of the body which may cause difficulty to swallow, low blood pressure (hypotension), fainting, shortness of breath (possible allergic reaction)
  • wheezing, troubled breathing, or feelings of tightness in the chest (signs of asthma)
  • yellowing of the skin and/or eyes (signs of hepatitis/liver failure)
  • persistent nausea, loss of appetite, unusual tiredness, vomiting, pain in the upper right abdomen, dark urine or pale bowel motions (possible liver problems)
  • constant "flu-like" symptoms including chills, fever, sore throat, aching joints, swollen glands, tiredness or lack of energy, bleeding or bruising more easily than normal (possible blood problem)
  • painful red areas, large blisters, peeling of layers of skin, bleeding in the lips, eyes, mouth, nose or genitals, which may be accompanied by fever and chills, aching muscles and feeling generally unwell (possible serious skin reaction)
  • signs of a possible effect on the brain, such as sudden and severe headache, stiff neck (signs of viral meningitis), severe nausea, dizziness, numbness, difficulty in speaking, paralysis (signs of cerebral attack), convulsions (fits)
  • change in the colour or amount of urine passed, frequent need to urinate, burning feeling when passing urine, blood or excess of protein in the urine (possible kidney disorders)
  • sudden and oppressive chest pain (which may be a sign of myocardial infarction or a heart attack)
  • breathlessness, difficulty breathing when lying down, swelling of the feet or legs (signs of cardiac failure)
  • Coincidental occurrence of chest pain and allergic reactions (signs of Kounis syndrome)

Tell your doctor if you notice anything else that is making you feel unwell. Some people may have other side effects not yet known or mentioned in this leaflet.

After using Voltaren

Storage

  • Keep your medicine in the original container until it is time to use it.
  • Store it in a cool dry place.
  • Do not store Voltaren or any other medicine in the bathroom or near a sink.
  • Do not leave it in the car or on window sills.

Keep the medicine where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop using Voltaren or the expiry date has passed, ask your pharmacist what to do with any medicine you have left over.

Product description

What it looks like

Voltaren tablets

Voltaren 25mg tablets are round, yellow, coated tablets marked "CG" on one side and "BZ" on the other side; blisters of 50.

Voltaren 50mg tablets are round, pale brown, coated tablets marked "CG" on one side and "GT" on the other side; blisters of 50.

Voltaren suppositories

Voltaren suppositories are yellowish-white, torpedo shaped suppositories. The 100mg strength is in packs of 20 and the lower strength suppositories are in packs of 10.

Ingredients

Voltaren tablets

Contain 25mg or 50mg diclofenac sodium as the active ingredient in gastro-resistant tablets.

The tablets also contain:

  • silica colloidal anhydrous
  • microcrystalline cellulose (E460)
  • lactose
  • magnesium stearate (E572)
  • maize starch
  • povidone (E1201)
  • hypromellose (E463)
  • iron oxide yellow CI77492 (E172)
  • iron oxide red CI77491 (50mg tablet only) (E172)
  • titanium dioxide (E171)
  • sodium starch glycolate
  • purified talc (E553b)
  • macrogol 8000
  • PEG-40 hydrogenated castor oil
  • acrylates copolymer

Voltaren tablets do not contain sucrose, gluten, tartrazine or any other azo dyes.

Voltaren suppositories

Contain either 12.5mg, 25mg, 50mg or 100mg diclofenac sodium as the active ingredient in a triglyceride base.

Voltaren suppositories do not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

Sponsor

Voltaren is supplied in Australia by:

NOVARTIS Pharmaceuticals Australia Pty Limited
ABN 18 004 244 160
54 Waterloo Road
Macquarie Park NSW 2113
Telephone: 1800 671 203

®= Registered Trademark

This leaflet was prepared in October 2019.

Australian Registration Numbers:

25mg tablet blister AUST R 166496

50mg tablet blister AUST R 66880

12.5mg suppository AUST R 96797

25mg suppository AUST R 96810

50mg suppository AUST R 96811

100mg suppository AUST R 37582

(vlt031019c.doc) based on PI (vlt031019i.doc)

Published by MIMS December 2019

BRAND INFORMATION

Brand name

Voltaren

Active ingredient

Diclofenac sodium

Schedule

S4

 

1 Name of Medicine

Active ingredient: Diclofenac sodium.

6.7 Physicochemical Properties

The active ingredient of Voltaren is diclofenac sodium, a phenylacetic acid derivative, structurally similar to both the phenylalkanoic acid and the anthranilic acid series of compounds. Diclofenac sodium is an odourless, yellowish-white, crystalline powder sparingly soluble in water.
Chemical name: sodium-[O-[(2,6-dichlorophenyl)-amino] phenyl]-acetate.
Molecular weight: 296.15.
Molecular formula: C14H11Cl2NO2.

Chemical structure.


CAS number.

15307-86-5.

2 Qualitative and Quantitative Composition

Voltaren Tablets are enteric coated and contain either 25 mg or 50 mg of diclofenac sodium.

List of excipients with known effect.

Lactose monohydrate.
For the full list of excipients, see Section 6.1 List of Excipients.
Voltaren Suppositories contain either 12.5 mg, 25 mg, 50 mg or 100 mg diclofenac sodium in a triglyceride base.

3 Pharmaceutical Form

Enteric coated tablets.

25 mg.

Yellow, round, slightly biconvex tablets with bevelled edges. Debossed with BZ on one side and CG on reverse side.

50 mg.

Light brown, round, slightly convex, coated tablets. Imprinted with CG on one side and GT on the other.

Suppositories.

12.5 mg, 25 mg and 50 mg.

White to yellowish torpedo-shaped with smooth surfaces.

100 mg.

Yellowish white "torpedo shaped" suppository, rounded one end, flat at other, being 30 mm long 12 mm diameter at widest part tapering to 9 mm small end.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Diclofenac sodium, a non-steroidal compound, exhibits pronounced antirheumatic, anti-inflammatory, analgesic, and antipyretic properties.
As with other NSAIDs, its mode of action is not known; however, its ability to inhibit prostaglandin synthesis may be involved in the anti-inflammatory effect.

Clinical trials.

In rheumatic diseases, the anti-inflammatory and analgesic properties of Voltaren elicit a clinical response characterised by relief from signs and symptoms such as pain at rest, pain on movement, morning stiffness, and swelling of the joints, as well as by an improvement in function.
In addition, clinical studies have revealed that in primary dysmenorrhoea, Voltaren is capable of relieving the pain and reducing the extent of bleeding. Low concentrations of diclofenac sodium inhibit the aggregation of platelets induced in vitro by collagen and by adenosine diphosphate. Diclofenac sodium in vitro does not suppress proteoglycan biosynthesis in canine cartilage at concentrations equivalent to the concentrations reached in humans. It is unknown whether or not diclofenac sodium affects the integrity of human osteoarthritic cartilage.

5.2 Pharmacokinetic Properties

Absorption.

Diclofenac is completely absorbed from the enteric coated tablets after their passage through the stomach. Following ingestion of one tablet with or after a meal, its passage through the stomach is slower than when it is taken before a meal, but the amount of active substance absorbed remains the same. In fasting subjects, the mean peak plasma concentration of 1.5 microgram/mL (5 micromol/L) is attained on average 2 hours after ingestion of one tablet of 50 mg. Suppositories of 50 mg produce a corresponding mean peak plasma concentration of 1.2 microgram/mL (4 micromol/L). The plasma concentrations, as measured by the area under the time-concentration curve, are in linear relation to the size of the dose.
In a comparative bioavailability study of Voltaren 50 mg enteric coated tablets and Voltaren 100 mg suppositories, the rectal absorption of diclofenac was almost immediate (Tmax 0.62 hr) and the Cmax was lower but more sustained, suggesting slower absorption from this formulation compared with the tablet. The t1/2 was significantly longer for the suppository, however, the total AUC was not significantly different for the two formulations.

Distribution.

Diclofenac becomes bound to serum proteins to the extent of 99.7%, chiefly to albumin (99.4%).

Metabolism.

Following oral or rectal administration, about half the active substance is metabolised during its first passage through the liver ("first-pass" effect). The biotransformation of diclofenac involves partly glucuronidation of the intact molecule, but mainly single and multiple hydroxylation followed by glucuronidation.

Excretion.

The total systemic clearance of diclofenac in plasma is 263 ± 56 mL/min (mean value ± SD). The terminal half-life in plasma is 1 to 2 hours.
After administration of diclofenac for 15 days in an oral dose of 25 mg three times daily, there was no evidence of drug accumulation in plasma.
In a study in 16 patients with rheumatoid arthritis and knee joint effusions it was found that diclofenac enters the synovial fluid, where maximum concentrations were measured 2 to 4 hours after oral administration. The apparent half-life for elimination from the synovial fluid was 3 to 6 hours. Only 4 to 6 hours after administration, therefore, concentrations of the active substance were already higher in the synovial fluid than they were in the plasma and remained higher for up to 12 hours. These results could possibly explain that the duration of clinical effect is longer than might be inferred from the short plasma half-life of Voltaren.
The biotransformation of diclofenac involves partly glucuronidation of the intact molecule, but mainly single and multiple hydroxylation followed by glucuronidation. About 60% of the administered dose is excreted in the urine in the form of metabolites from one of these two processes. Less than 1% is excreted as unchanged substance. The remainder of the dose is eliminated as metabolites through the bile in the faeces.

Special patient populations.

No relevant age-dependent differences in the drug's absorption, metabolism or excretion have been observed.
In patients suffering from renal impairment, no accumulation of the unchanged active substance could be inferred from the single-dose kinetics when applying the usual dosage schedule. At a creatinine clearance of < 10 mL/min, the theoretical steady-state plasma levels of metabolites are about four times higher than in normal subjects. However, the metabolites appear to be satisfactorily cleared through the bile.
In the presence of impaired hepatic function (chronic hepatitis, non-decompensated cirrhosis), the kinetics and metabolism of diclofenac were the same as in patients without liver disease.

5.3 Preclinical Safety Data

Genotoxicity.

Diclofenac showed no mutagenic effects in the studies conducted.

Carcinogenicity.

Dietary administration of diclofenac to mice and rats at doses up to 0.5 mg/kg/day revealed no carcinogenic activity. However, the plasma concentration of diclofenac at this dose level was 20 to 100 times lower than that in humans. Administration of higher doses to rats and mice resulted in increased mortality due to gastrointestinal ulceration. Diclofenac showed no carcinogenic effects in the studies conducted.

4 Clinical Particulars

4.1 Therapeutic Indications

Tablets.

Inflammatory and degenerative forms of rheumatism: rheumatoid arthritis and osteoarthritis.
Relief of acute or chronic pain states in which there is an inflammatory component.
Symptomatic treatment of primary dysmenorrhoea.

Suppositories.

Inflammatory and degenerative forms of rheumatism: rheumatoid arthritis and osteoarthritis.
Short term (up to three days) treatment of post-operative pain in children.

4.3 Contraindications

Tablets and suppositories.

Gastric or duodenal ulcer, gastrointestinal bleeding or perforation.
Patients who are hypersensitive to the active ingredient, diclofenac, or any of the excipients contained in the tablets or suppositories.
Last trimester of pregnancy (see Section 4.6 Fertility, Pregnancy and Lactation).
Patients with severe hepatic impairment (see Section 4.4 Special Warnings and Precautions for Use).
Renal failure (see Section 4.4 Special Warnings and Precautions for Use).
Severe cardiac failure (see Section 4.4 Special Warnings and Precautions for Use).
Treatment of perioperative pain in setting of coronary artery bypass surgery (CABG).
Patients in whom diclofenac, aspirin or other NSAIDs induce asthma, angioedema, urticaria or other allergic-type reactions, because severe, rarely fatal, anaphylactic type reactions to diclofenac have been reported in such patients.

Suppositories.

Proctitis.

4.4 Special Warnings and Precautions for Use

Cardiovascular thrombotic events.

Observational studies have indicated that non-selective NSAIDs may be associated with an increased risk of serious cardiovascular events, including myocardial infarction and stroke, which may increase with dose or duration of use. Patients with cardiovascular disease, history of atherosclerotic cardiovascular disease or cardiovascular risk factors may also be at greater risk (see Section 4.2 Dose and Method of Administration).
Treatment with Voltaren is generally not recommended in patients with established cardiovascular disease (congestive heart failure, established ischemic heart disease, peripheral arterial disease) or uncontrolled hypertension. If needed, patients with established cardiovascular disease, uncontrolled hypertension, or significant risk factors for cardiovascular disease (e.g. hypertension, hyperlipidemia, diabetes mellitus and smoking) should be treated with Voltaren only after careful consideration and only at doses ≤ 100 mg daily when treatment continues for more than 4 weeks.
As the cardiovascular risks of diclofenac may increase with dose and duration of exposure, the lowest effective daily dose should be used for the shortest duration possible. The patient's need for symptomatic relief and response to therapy should be re-evaluated periodically, especially when treatment continues for more than 4 weeks.
Physicians and patients should remain alert for the signs and symptoms of serious arteriothrombotic events (e.g. chest pain, shortness of breath, weakness, slurring of speech), which can occur without warnings. Patients should be informed about signs and/or symptoms of serious cardiovascular toxicity and be instructed to see a physician immediately in case of such an event.
There is no consistent evidence that the concurrent use of aspirin mitigates the possible increased risk of serious cardiovascular thrombotic events associated with NSAID use.

Hypertension.

NSAIDs may lead to the onset of new hypertension or worsening of pre-existing hypertension and patients taking anti-hypertensives with NSAIDs may have an impaired anti-hypertensive response. Caution is advised when prescribing NSAIDs to patients with hypertension. Blood pressure should be monitored closely during initiation of NSAID treatment and at regular intervals thereafter.

Heart failure.

Fluid retention and oedema have been observed in some patients taking NSAIDs, including diclofenac, therefore, caution is advised in patients with fluid retention or heart failure.

Gastrointestinal effects.

Close medical surveillance is imperative and particular caution should be exercised when prescribing NSAIDs, including diclofenac, in patients with symptoms indicative of gastrointestinal disorders (GI) or with a history suggestive of gastrointestinal ulceration, bleeding or perforation (see Section 4.8 Adverse Effects (Undesirable Effects)).
Upper GI ulcers, gross bleeding or perforation caused by NSAIDs, including diclofenac, occur in approximately 1% of patients treated for 3-6 months and in about 2-4% of patients treated for one year. The risk of GI bleeding is higher with increasing NSAID doses, with increasing duration of use and in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation, and in the elderly.
Gastric or duodenal ulceration, perforation or gastrointestinal bleeding, which can be fatal, have been reported in patients receiving Voltaren. Studies to date have not identified any subset of patients who are not at risk of developing these problems.
Caution is advised in patients with risk factors for gastrointestinal events who may be at greater risk of developing serious gastrointestinal events, e.g. the elderly, those with a history of serious gastrointestinal events, smoking and alcoholism.
The concurrent use of aspirin and NSAIDs, including diclofenac, also increases the risk of serious gastrointestinal adverse events.
To reduce the risk of GI toxicity in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation, and in the elderly, the treatment should be initiated and maintained at the lowest effective dose. Gastrointestinal bleeding, ulceration and perforation in general have more serious consequences in the elderly. They can occur at any time during treatment with or without warning symptoms or a previous history. In instances where gastrointestinal bleeding or ulcerations occur in patients receiving Voltaren, the drug should be withdrawn immediately. Physicians should warn patients about the signs and symptoms of serious gastrointestinal toxicity and what steps to take if they occur.
Combination therapy with protective agents (e.g. proton pump inhibitors or misoprostol) should be considered for these patients, and also for patients requiring concomitant use of medicinal products containing low-dose acetylsalicylic acid (ASA)/ aspirin or other medicinal products likely to increase gastrointestinal risk.
Patients with a history of GI toxicity, particularly the elderly, should report any unusual abdominal symptoms (especially GI bleeding). Caution is recommended in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as systemic corticosteroids, anticoagulants, anti-platelet agents or selective serotonin-reuptake inhibitors (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Close medical surveillance and caution should also be exercised in patients with ulcerative colitis, or with Crohn's disease, as well as in patients suffering from pre-existing dyshaemopoiesis or disorders of blood coagulation, as their condition may be exacerbated (see Section 4.8 Adverse Effects (Undesirable Effects)).
NSAIDs, including diclofenac, may be associated with increased risk of gastrointestinal anastomotic leak. Close medical surveillance and caution are recommended when using Voltaren after gastrointestinal surgery.

Serious skin reactions.

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs, including Voltaren (see Section 4.8 Adverse Effects (Undesirable Effects)). These serious adverse events are idiosyncratic and are independent of dose or duration of use. Patients appear to be at highest risk of these reactions early in the course of therapy, the onset of the reaction occurring in the majority of cases within the first month of treatment. Patients should be advised of the signs and symptoms of serious skin reactions and to consult their doctor at the first appearance of skin rash, mucosal lesion or any other sign of hypersensitivity, and Voltaren should be discontinued.

Pre-existing asthma.

In patients with asthma, seasonal allergic rhinitis, swelling of the nasal mucosa (i.e. nasal polyps), chronic obstructive pulmonary diseases or chronic infections of the respiratory tract (especially if linked to allergic rhinitis-like symptoms), reactions to NSAIDs such as asthma exacerbations (so-called intolerance to analgesics/ analgesics-asthma), Quincke's oedema or urticaria, are more frequent than in other patients. Therefore, special precaution is recommended in such patients. This is applicable as well for patients who are allergic to other substances, e.g. with skin reactions, pruritus or urticaria.

Infection.

Like other NSAIDs, Voltaren may mask the usual signs and symptoms of infection due to its pharmacodynamic properties.

Hypersensitivity.

As with NSAIDs, allergic reactions, including anaphylactic/ anaphylactoid reactions, have been reported with diclofenac. These reactions can occur without earlier exposure to the drug.

Lactose intolerance.

Voltaren tablets contain lactose and therefore are not recommended for patients with rare hereditary problems of galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption.

Perioperative bleeding.

Pre-operative administration of Voltaren may increase the risk of post-operative bleeding. The safety of Voltaren suppositories in children has not been established in major operations or in procedures where minor bleeding could pose a critical safety risk (e.g. patients undergoing intracranial surgery or receiving spinal anaesthesia). The use of Voltaren suppositories in children for such procedures is not recommended.
Since Voltaren may temporarily inhibit platelet aggregation, children undergoing minor procedures such as tonsillectomy, myringotomy, circumcision, orchidopexy and strabismus surgery, should be carefully monitored.

Use in hepatic impairment.

Close medical surveillance is required when prescribing Voltaren to patients with impaired hepatic function, as their condition may be exacerbated (see Section 4.3 Contraindications).
As with other NSAIDs, including diclofenac, elevations of one or more liver enzymes may occur during Voltaren therapy. These laboratory abnormalities may progress, remain unchanged, or revert to normal despite continued therapy. Borderline elevations (i.e. 1.2 to 3 times the upper limit of normal (ULN)), or greater elevations of transaminases occurred in about 15% of Voltaren-treated patients. In clinical trials, meaningful elevations (i.e. more than 3 times the ULN) of AST and/or ALT occurred in about 4% of patients treated for several months, including marked elevations (i.e. more than 8 times the ULN) in about 1% of patients. Transaminase elevations were seen more frequently in patients with osteoarthritis than in those with rheumatoid arthritis (see Section 4.8 Adverse Effects (Undesirable Effects)).
Transaminase elevations were reversible on cessation of therapy, and even among patients with marked elevations, signs and symptoms of liver disease occurred only in isolated cases. Most patients with borderline elevations did not have therapy interrupted, and transaminase elevations in most of these cases disappeared or did not progress. There were no identifying features to distinguish those patients who developed marked elevations from those who did not.
In addition to the enzyme elevations seen in clinical trials, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, have been reported.
Severe hepatotoxicity may develop without prodromal symptoms, so transaminases should be measured periodically in patients receiving long-term therapy with Voltaren. The optimum times for making the measurements are not known. In most patients who have developed marked transaminase elevations, abnormal tests occurred during the first 2 months of therapy with Voltaren. Based on this experience the first transaminase measurement should be made no later than 8 weeks after the start of Voltaren treatment. As with other NSAIDs, including diclofenac, if abnormal liver tests persist or worsen, if clinical signs and/or symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g. eosinophilia, rash, etc.), Voltaren should be discontinued.
To minimise the possibility of hepatic injury becoming severe between transaminase measurements, physicians should inform patients of the warning signs and symptoms of hepatotoxicity (e.g. nausea, fatigue, lethargy, pruritus, jaundice, abdominal tenderness in the right upper quadrant and "flu-like" symptoms) and the appropriate action to take should these signs and symptoms appear.
Caution should be exercised when using Voltaren in patients with hepatic porphyria, since Voltaren may trigger an attack.

Use in renal impairment.

As a class, NSAIDs have been associated with renal papillary necrosis and other pathology during long-term administration in animals.
Fluid retention and oedema have been reported in association with NSAID therapy, including diclofenac. Owing to the importance of prostaglandins for maintaining renal blood flow, particular caution is called for in patients with impaired cardiac or renal function, history of hypertension, in the elderly, in patients being treated with diuretics or medicinal products that can significantly impact renal function, and in those with extracellular volume depletion from any cause, e.g. in the peri- or post-operative phase of major surgical operations (see Section 4.3 Contraindications). Monitoring of renal function as a precautionary measure is, therefore, recommended when using Voltaren in such cases. Discontinuation of therapy is typically followed by recovery to the pre-treatment state.

Combination use of ACE inhibitors or angiotensin receptor antagonists, anti-inflammatory drugs and thiazide diuretics.

The use of an ACE inhibiting drug (ACE-inhibitors or angiotensin receptor antagonist), an anti-inflammatory drug (NSAID or COX-2 inhibitor) and a thiazide diuretic at the same time increases the risk of renal impairment. This includes use in fixed combination products containing more than one class of drug. Combined use of these medications should be accompanied by increased monitoring of serum creatinine, particularly at the institution of the combination. The combination of drugs from these three classes should be used with caution particularly in elderly patients or those with pre-existing renal impairment.

Use in the elderly.

In elderly patients, who are generally more prone to side effects, particular caution should be exercised. It is recommended that the lowest effective dosage be used in elderly patients or those with a low body weight.

Paediatric use.

The safety and efficacy of Voltaren suppositories in children under 12 months has not been established. Therefore, the use of Voltaren suppositories for peri-operative pain, is not recommended in this population.

Effects on laboratory tests.

Haematological effects.

Like other NSAIDs, Voltaren may temporarily inhibit platelet aggregation. Patients with haemostatic disorders should be carefully monitored.
During prolonged treatment with Voltaren, a slight reduction in haemoglobin has been noted in some patients. On rare occasions, blood dyscrasias have been reported. Periodic blood counts are, therefore, recommended.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The following interactions include those observed with Voltaren tablets/ suppositories and/or other pharmaceutical forms of diclofenac.

Lithium/ digoxin.

When given together with preparations containing lithium or digoxin, diclofenac may raise their plasma concentrations and these concentrations should be monitored during treatment with Voltaren.

Diuretics and antihypertensive agents.

Like other NSAIDs, concomitant use of diclofenac with diuretics or antihypertensive agents (e.g. beta-blockers, angiotensin converting enzyme (ACE) inhibitors) may cause a decrease in their antihypertensive effect. Therefore, the combination should be administered with caution and patients, especially the elderly, should have their blood pressure periodically monitored. When NSAIDs, including diclofenac, are combined with diuretics, ACE inhibitors or angiotensin II receptor antagonists, the risk of worsening of renal function, including possible acute renal failure (which is usually reversible), may be increased in some patients, especially when renal function is compromised (e.g. dehydrated or elderly patients). Patients should be adequately hydrated and monitoring of renal function is recommended after initiation of concomitant therapy and periodically thereafter (see Section 4.4 Special Warnings and Precautions for Use).

Other NSAIDs and corticosteroids.

The concomitant use of diclofenac with systemic NSAIDs, including cyclooxygenase-2 selective inhibitors, should be avoided due to the absence of any evidence demonstrating synergistic benefits and the potential for additive undesirable effects. Concomitant administration of diclofenac and other systemic NSAIDs or corticosteroids may increase the frequency of gastrointestinal undesirable effects. Concurrent treatment with aspirin lowers the plasma concentration, peak plasma levels and AUC values of diclofenac. The use of both drugs concurrently is not recommended.

Anticoagulants and anti-platelet agents.

Caution is recommended since concomitant administration could increase the risk of bleeding (see Section 4.4 Special Warnings and Precautions for Use). The concurrent use of NSAIDs and warfarin has been associated with severe, sometimes fatal, haemorrhage. The exact mechanism of the interaction between NSAIDs and warfarin is unknown, but may involve enhanced bleeding from NSAID-induced gastrointestinal ulceration or an additive effect of anticoagulation by warfarin and inhibition of platelet function by NSAIDs. Diclofenac should be used with caution in combination with warfarin and such patients should be closely monitored.

Selective serotonin reuptake inhibitors (SSRIs).

Concomitant administration of systemic NSAIDs, including diclofenac, and SSRIs may increase the risk of gastrointestinal bleeding (see Section 4.4 Special Warnings and Precautions for Use).

Antidiabetic agents.

Diclofenac can be given together with oral antidiabetic agents without influencing their clinical effect. However, there are isolated reports of both hypoglycaemic and hyperglycaemic effects in the presence of diclofenac which necessitated changes in the dosage of the antidiabetic agents. For this reason, monitoring of the blood glucose level is recommended as a precautionary measure during concomitant therapy.
There have also been isolated reports of metabolic acidosis when diclofenac was co-administered with metformin, especially in patients with pre-existing renal impairment.

Methotrexate.

Caution should be exercised when NSAIDs, including diclofenac, are administered less than 24 hours before or after treatment with methotrexate, since the blood concentration of methotrexate may rise and the toxicity of this substance be increased.

Cyclosporin and tacrolimus.

Nephrotoxicity of cyclosporin may be enhanced through effects of NSAIDs, including diclofenac, on renal prostaglandins. Therefore, diclofenac should be given at doses lower than those that would be used in patients not receiving cyclosporin or tacrolimus.

Drugs known to cause hyperkalaemia.

Concomitant treatment with potassium-sparing drugs (e.g. diuretics, cyclosporin, tacrolimus or trimethoprim) may be associated with increased serum potassium levels, which should therefore be monitored frequently (see Section 4.4 Special Warnings and Precautions for Use).

Glucocorticoids.

The addition of glucocorticoids to NSAIDs, though sometimes necessary for therapeutic reasons, may aggravate gastrointestinal side effects.

Quinolone antibacterials.

There have been isolated reports of convulsions which may have been due to concomitant use of quinolones and NSAIDs.

CYP2C9 inhibitors.

Caution is recommended when co-prescribing diclofenac with potent CYP2C9 inhibitors (such as sulfinpyrazone and voriconazole), which could result in a significant increase in peak plasma concentrations and exposure to diclofenac due to inhibition of diclofenac metabolism. Concomitant administration of voriconazole with diclofenac may increase plasma diclofenac levels.

CYP2C9 inducers.

Caution is recommended when co-prescribing diclofenac with CYP2C9 inducers (such as rifampicin), which could result in a significant decrease in plasma concentration and exposure to diclofenac.

Phenytoin.

When using phenytoin concomitantly with diclofenac, monitoring of phenytoin plasma concentrations is recommended due to an expected increase in exposure to phenytoin.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

The use of Voltaren may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of Voltaren should be considered.
(Category C)
NSAIDs inhibit prostaglandin synthesis and, when given during the latter part of pregnancy, may cause closure of the foetal ductus arteriosus, foetal renal impairment, inhibition of platelet aggregation, and delay labour and birth.
The use of diclofenac in pregnant women has not been studied and safety in pregnancy has not been established. Therefore, Voltaren should not be used in pregnant women during the first two trimesters or in women who are likely to become pregnant unless the potential benefit to the mother outweighs the risk to the foetus. Use of Voltaren during the third trimester of pregnancy is contraindicated owing to the possibility of uterine inertia, fetal renal impairment with subsequent oligohydramnios and/or premature closure of the ductus arteriosus (see Section 4.3 Contraindications).
Data from epidemiological studies suggest an increased risk of miscarriage after the use of a prostaglandin synthesis inhibitor in early pregnancy.
Following oral doses of 50 mg administered every 8 hours, the active substance, diclofenac, passes into the breast milk. As with other drugs that are excreted in milk, Voltaren is not recommended for use in nursing women.

4.8 Adverse Effects (Undesirable Effects)

Adverse reactions are ranked under heading of frequency, the most frequent first, using the following convention: common (≥ 1/100, < 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, < 1/1,000); very rare (< 1/10,000), including isolated reports.
The following undesirable effects include those reported with Voltaren tablets/ suppositories and/or other pharmaceutical forms of diclofenac, with either short-term or long-term use.

Blood and lymphatic system disorders.

Very rare: Thrombocytopenia, leucopoenia, anaemia (including haemolytic and aplastic anaemia), agranulocytosis, positive Coombs' test.

Immune system disorders.

Rare: Hypersensitivity, anaphylactic and anaphylactoid reactions (including hypotension and shock).
Very rare: Angioneurotic oedema (including face oedema).

Psychiatric disorders.

Very rare: Disorientation, depression, insomnia, nightmare, irritability, psychotic disorder.

Nervous system disorders.

Common: Headache, dizziness.
Rare: Somnolence.
Very rare: Paraesthesia, memory impairment, convulsion, anxiety, tremor, aseptic meningitis, taste disturbances, cerebrovascular accident, myoclonic encephalopathy (described in two patients).

Eye disorders.

Very rare: Visual disturbance, blurred vision, diplopia.

Ear and labyrinth disorders.

Common: Vertigo.
Very rare: Tinnitus, impaired hearing.

Cardiac disorders.

Uncommon*: Myocardial infarction, cardiac failure, palpitations, chest pain.
Frequency unknown: Kounis syndrome.

Vascular disorders.

Very rare: Hypertension, vasculitis.

Respiratory, thoracic and mediastinal disorders.

Rare: Asthma (including dyspnoea).
Very rare: Pneumonitis.

Gastrointestinal disorders.

Common: Nausea, vomiting, diarrhoea, dyspepsia, abdominal pain, flatulence, anorexia.
Rare: Gastritis, gastrointestinal haemorrhage, haematemesis, haemorrhagic diarrhoea, melaena, gastrointestinal ulcer (with or without bleeding or perforation), gastrointestinal stenosis, or perforation, which may lead to peritonitis, proctitis (Voltaren suppositories).
Very rare: Colitis (including haemorrhagic colitis, ischemic colitis and exacerbation of ulcerative colitis or Crohn's disease), constipation, stomatitis, glossitis, oesophageal disorder, diaphragm-like intestinal strictures, pancreatitis, haemorrhoids aggravated (Voltaren suppositories).

Hepatobiliary disorders.

Common: Transaminases increased.
Rare: Hepatitis, jaundice, liver disorder.
Very rare: Fulminant hepatitis, hepatic necrosis, hepatic failure.

Skin and subcutaneous tissue disorders.

Common: Rashes or skin eruptions.
Rare: Urticaria.
Very rare: Bullous eruptions, eczema, erythema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), exfoliative dermatitis, loss of hair, photosensitivity reaction, purpura, allergic purpura, pruritus.

Renal and urinary disorders.

Very rare: Acute kidney injury (acute renal failure), haematuria, proteinuria, nephrotic syndrome, interstitial nephritis, renal papillary necrosis.

General disorders and administration site conditions.

Common: Application site irritation.
Rare: Oedema.
Very rare: Impotence (association with Voltaren intake is doubtful). Worsening of haemorrhoids has been reported with use of Voltaren suppositories. Toxic shock syndrome has been reported in patients administered NSAIDs postoperatively.
* The frequency reflects data from long-term treatment with a high dose (150 mg/day).

Description of selected adverse drug reactions.

Arteriothrombotic events.

Meta-analysis and pharmacoepidemiological data point towards an increased risk of arteriothrombotic events (for example myocardial infarction) associated with the use of diclofenac, particularly at a high dose (150 mg daily) and during long-term treatment (see Section 4.4 Special Warnings and Precautions for Use). A recent meta-analysis (CNT) estimates that, in comparison with placebo, allocation to diclofenac caused around 3 additional major vascular events per 1000 participants per year. This estimate reflects data from long-term treatment with high dose diclofenac (150 mg/day).

Visual effects.

Visual disturbances such as visual impairment, blurred vision or diplopia appear to be NSAID class effects and are usually reversible on discontinuation. A likely mechanism for the visual disturbances is the inhibition of prostaglandin synthesis and other related compounds that alter the regulation of retinal blood flow resulting in potential changes in vision. If such symptoms occur during diclofenac treatment, an ophthalmological examination may be considered to exclude other causes.

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.

4.2 Dose and Method of Administration

After assessing the risk/ benefit ratio in each individual patient, the lowest effective dose for the shortest possible duration should be used. Adverse effects may be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see Section 4.4 Special Warnings and Precautions for Use). Patients on long-term treatment should be reviewed regularly with regards to efficacy, risk factors and ongoing need for treatment.
The tablets should be swallowed whole with liquid, preferably before meals, and must not be divided or chewed.

Dose.

Adults.

Initial dosage is 75 to 150 mg daily.
For long-term therapy, 75 to 100 mg daily is usually sufficient.
The daily dosage should generally be prescribed in 2 or 3 fractional doses. To suppress nocturnal pain and morning stiffness, treatment with tablets during the day can be supplemented by the administration of a suppository at bedtime (up to a maximum daily dose of 150 mg).
In primary dysmenorrhoea the daily dosage, which should be individually adapted, is generally 50 to 150 mg. Initially, a dose of 50 to 100 mg should be given and, if necessary, raised in the course of several menstrual cycles up to a maximum of 200 mg/day. Treatment should be started upon appearance of the first symptoms and, depending on the symptomatology, continued for a few days.

Post-operative analgesia in children.

A first dose of 1-2 mg/kg followed by 1 mg/kg three times daily for a maximum of three days total therapy. The maximum daily dose is 3 mg/kg. Voltaren suppositories should not be used in children under 12 months of age.
A maximum daily dose of 150 mg should not be exceeded.
Voltaren 100 mg suppositories are not suitable for children and adolescents.
There is some evidence that post-operative analgesia is improved if the first dose of diclofenac is given one hour prior to surgery, however this may increase the risk of intra-operative bleeding (see Section 4.4 Special Warnings and Precautions for Use).

Method of administration.

Tablets.

The tablets should be swallowed whole with liquid, preferably before meals, and must not be divided or chewed.

Suppositories.

The suppositories should be inserted well into the rectum. It is recommended to insert the suppositories after passing stools. The suppositories are not to be taken by mouth.

4.7 Effects on Ability to Drive and Use Machines

Patients experiencing visual disturbances, dizziness, vertigo, somnolence or other central nervous disturbances while taking Voltaren should refrain from driving a vehicle or operating machines (see Section 4.8 Adverse Effects (Undesirable Effects)).

4.9 Overdose

Management of acute poisoning with NSAIDs, including diclofenac, consists essentially of supportive measures and symptomatic treatment. There is no typical clinical picture resulting from an overdosage of diclofenac. Overdosage can cause symptoms such as vomiting, gastrointestinal haemorrhage, diarrhoea, dizziness, tinnitus or convulsions. In the event of significant poisoning, acute renal failure and liver damage are possible.
Activated charcoal may reduce absorption of the medicine if given within one or two hours after ingestion. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via nasogastric tube, once the airway is protected.
Supportive and symptomatic treatment should be given for complications such as hypotension, renal failure, convulsions, gastrointestinal disorder, and respiratory depression. Haematological and biochemical parameters, and the presence or absence of blood in the stools, should be monitored.
Specific therapies such as forced diuresis, dialysis, or haemoperfusion, are probably of no help in eliminating NSAIDs, including diclofenac, because of their high protein-binding rate and extensive metabolism.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Tablets.

Colloidal anhydrous silica, microcrystalline cellulose, lactose monohydrate, magnesium stearate, maize starch, povidone, hypromellose, iron oxide yellow, titanium dioxide, sodium starch glycollate, purified talc, macrogol 8000, PEG-40 hydrogenated castor oil, acrylates copolymer, iron oxide red (50 mg tablet only), Wacker Silicone Fluid Emulsion E 2 (proprietary ingredient).

Suppositories.

Triglyceride base.

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

Tablets.

Store below 30°C. Keep out of reach of children.

Suppositories.

Store below 25°C. Keep out of the reach of children.

6.5 Nature and Contents of Container

Tablets.

25 mg.

PVC/PE/PVDC/Al blister packs of 20 (not marketed) and 50; HDPE bottle packs of 20 (not marketed) and 50.

50 mg.

PVC/PE/PVDC/Al or PVC/Al blister packs of 10 (samples), and 50; HDPE bottle packs of 16, 20, and 50.

Suppositories.

12.5 mg, 25 mg and 50 mg.

PVC/PE blister packs of 10.

100 mg.

PVC/PE blister packs of 5 (not currently marketed), 20.

6.6 Special Precautions for Disposal

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

Summary Table of Changes