Voltaren Tablets/ Ampoules/ Suppositories

Inflammatory and degenerative forms of rheumatism: rheumatoid arthritis, ankylosing spondylitis, osteoarthrosis and spondylarthritis. Painful musculoskeletal conditions. Non-articular rheumatism. Acute attacks of gout.

Mild to moderately painful post-operative and post-traumatic inflammation and swelling, pain following dental surgery or orthopaedic surgery. Symptomatic treatment of primary dysmenorrhoea. Migraine attacks. VOLTAREN 75 AMPOULES used for Intramuscular injection For initial therapy for inflammatory and degenerative rheumatic diseases, as well as for the treatment of mild to moderately painful conditions due to inflammation of non-rheumatic origin. VOLTAREN 75 AMPOULES used for the preparation of Intravenous infusion Treatment or prevention of post-operative mild to moderate pain of inflammatory origin in the absence of any infection.

Because of their dosage strength, the following dosage strengths are not suitable for use in children and adolescents below 14 years of age; VOLTAREN 25 tablets could be used in these patients.

• VOLTAREN GT 50 TABLETS
• VOLTAREN 75 TABLETS
• VOLTAREN SIMPLE REGIMEN 100 TABLETS
• VOLTAREN 75 AMPOULES
• VOLTAREN 100 SUPPOSITORIES

Adults As a general recommendation, the dose should be individually adjusted, and the lowest effective dose given for the shortest possible duration. VOLTAREN 25; VOLTAREN GT 50 The tablets should be swallowed whole with a glass of water and must not be divided or chewed. For the relief of acute pain, the tablets should preferably be taken on an empty stomach. The recommended initial daily dose is 100 to 150 mg. In milder cases, as well as for long-term therapy, 75 mg to 100 mg daily is usually sufficient. The maximum daily dose of 150 mg should not be exceeded. The total daily dose should generally be divided into 2 to 3 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 total maximum daily dose of 150 mg). In primary dysmenorrhoea, the daily dose should be individually adjusted and is generally 50 mg to 150 mg. A dose of 50 mg to 100 mg should be given initially and, if necessary, increased over the course of several menstrual cycles up to a maximum of 200 mg/day. Treatment should be started on appearance of the first symptoms and, depending on the symptomatology, continued for a few days.

Geriatrics (Patients aged 65 or above) No adjustment of the starting dose is generally required for elderly patients. However, caution is indicated on basic medical grounds, especially for frail elderly patients or patients with a low body weight. (see section 4.4)

VOLTAREN 75 TABLETS and VOLTAREN SIMPLE REGIMEN 100 TABLETS As a rule, the initial daily dosage is 100 mg to 150 mg administered as 1 tablet of VOLTAREN SIMPLE REGIMEN 100 as a single dose or as 2 tablets of VOLTAREN 75 TABLETS taken in two divided doses. In milder cases, as well as for long-term therapy, 1 tablet of VOLTAREN 75 TABLETS daily is usually sufficient. The VOLTAREN 75 TABLETS and VOLTAREN SIMPLE REGIMEN 100 tablets should neither be fragmented nor chewed and should preferably be taken at mealtimes. Where the symptoms are most pronounced during the night or in the morning. VOLTAREN SIMPLE REGIMEN 100 tablets should preferably be taken in the evening. VOLTAREN 75 AMPOULES should not be given for more than two days; if necessary, the treatment can be continued with VOLTAREN tablets or suppositories.

Intramuscular injection The following directions for intramuscular injection must be followed in order to avoid damage to a nerve or other tissue at the injection site. Only for deep intragluteal injection into the upper outer quadrant. After inserting the needle, the plunger should be pulled back to avoid inadvertent intra-arterial injection. For adults the dose is generally one VOLTAREN 75 AMPOULE daily. VOLTAREN 75 AMPOULES should not be mixed with other injection solutions. By way of exception, in severe cases, two injections of 75 mg, separated by an interval of a few hours, can be given per day (one into each buttock). Alternatively, it is possible to combine one ampoule of 75 mg with either VOLTAREN 25 or VOLTAREN GT 50 tablets up to a maximum daily dosage of 150 mg.

VOLTAREN 75 AMPOULES used for the preparation of intravenous infusion. VOLTAREN 75 AMPOULES must not be given as an intravenous bolus injection and must not be mixed with other injection solutions. Infusion solutions of sodium chloride 0,9 % or glucose 5 % without sodium bicarbonate as an additive present a risk of supersaturation, possibly leading to formation of crystals or precipitates. Only clear solutions should be used. If crystals or precipitates are observed, the infusion solution should not be used. Do not use infusion solutions other than those recommended. To prepare an intravenous infusion, one VOLTAREN 75 AMPOULE should be diluted with 100 mL u2013 500 mL of either sodium chloride solution (0,9 %) or glucose solution (5 %). Both solutions should first be buffered with bicarbonate solution (0,5 mL 8,4 % or 1 mL 4,2 %). Only clear infusion solutions should be used. VOLTAREN infusions should be freshly made up and used immediately. Once prepared, the infusion should not be stored. VOLTAREN should not be administered as an intravenous bolus injection.

Two alternative dosage regimens of VOLTAREN IV Infusion are recommended u2022 For the treatment of moderate to severe postoperative pain, 75 mg should be infused continuously over a period of 30 minutes to 2 hours. If necessary, treatment may be repeated, but a total dosage of 150 mg within any period of 24 hours must not be exceeded. u2022 For the prevention of postoperative pain, a loading dose of 25 mg to 50 mg should be infused after surgery over 15 minutes to 1 hour, followed by a continuous infusion of approximately 5 mg per hour up to a maximum daily dosage of 150 mg. VOLTAREN infusion should not be given for more than 2 days; if necessary, treatment to be continued with tablets or suppositories.

VOLTAREN 25 SUPPOSITORIES Children aged 2 years or over and adolescents should be given 0.5 to 2 mg/kg body weight daily in 2 to 3 divided doses, depending on the severity of the disorder. For treatment of juvenile rheumatoid arthritis, the daily dose can be raised up to a maximum of 3 mg/kg daily, given in divided doses.

VOLTAREN 100 SUPPOSITORIES The average adult dose is one VOLTAREN 100 SUPPOSITORIES daily. To suppress nocturnal pain and morning stiffness, treatment with tablets during the day can be supplemented by the administration of one VOLTAREN 100 SUPPOSITORIES at bedtime, up to a maximum dosage of 150 mg daily. Note: Not to be taken by mouth, as per rectal use only. The suppositories should be inserted well into the rectum. It is recommended to take the suppositories after passing stools. Suppositories should never be divided for administration as incorrect storage conditions could have led to an uneven distribution of active substance in the suppository. Do not use suppositories deformed by exposure to temperatures above 30 u00b0C.

• History of gastrointestinal perforation, ulceration, or bleeding. Active or history of recurrent ulcer/haemorrhage/perforations
• Known hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
• Patients with porphyria.
• Last trimester of pregnancy and during lactation due to the risk of oligohydramnios/ foetal renal dysfunction (see section 4.6).
• Hepatic failure
• Renal failure (GFR <15 MLml/MINmin/1.73mu00b2)
• Severe cardiac failure
• Heart failure, established ischaemic heart disease and/or cerebrovascular disease (stroke) and peripheral arterial disease.
• Patients in whom the use of acetylsalicylic acid or other NSAIDs can precipitate asthma, angioedema, urticaria, or acute rhinitis (i.e. NSAID-induced cross-reactivity reactions)
• Children under the age of two years.

VOLTAREN 75 AMPOULES u2022 The intravenous use in children is contraindicated due to insufficient evidence. u2022 Known sensitivity to sodium metabisulphite. u2022 NB: The intravenous use of VOLTAREN 75 AMPOULES is absolutely contraindicated in patients with impaired renal function and/or any form of shock.

VOLTAREN 25 SUPPOSITORIES and VOLTAREN 100 SUPPOSITORIES u2022 Proctitis

Gastrointestinal (GI) bleeding (haematemesis, melaena), ulceration or perforation, which can be fatal, have been reported with VOLTAREN and may occur at any time during treatment, with or without warning symptoms or a previous history of serious gastrointestinal events. They generally have more serious consequences in the elderly. If gastrointestinal bleeding or ulceration occurs in patients receiving VOLTAREN, the treatment should be discontinued.

As with all NSAIDs, including diclofenac, close medical surveillance is imperative, and particular caution should be exercised when prescribing VOLTAREN in patients with symptoms indicative of gastrointestinal disorders or with a history suggestive of gastric or intestinal ulceration, bleeding or perforation. The risk of GI bleeding is higher with increasing NSAID doses and in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation and in the elderly.

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.

Combination therapy with protective medicines (e.g. proton pump inhibitors or misoprostol) should be considered for these patients, and also for patients requiring concomitant use of low-dose acetylsalicylic acid (ASA) or other drugs 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 medicines or selective serotonin-reuptake inhibitors.

Close medical surveillance and caution should be exercised in patients with ulcerative colitis or Crohnu2019s disease, as their condition may be exacerbated. When gastrointestinal bleeding or ulceration occurs in patients receiving VOLTAREN, treatment with VOLTAREN should be stopped.

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

Cardiovascular and cerebrovascular effects: Treatment with NSAIDs including diclofenac, particularly at high dose and in long term, may be associated with a small increased risk of serious cardiovascular thrombotic events (including myocardial infarction and stroke). Treatment with VOLTAREN is generally not recommended in patients with established cardiovascular disease (congestive heart failure, established ischaemic 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, hyperlipidaemia, diabetes mellitus and smoking) should be treated with VOLTAREN only after careful consideration and only at doses u2264 100 mg daily when treatment continues form 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 patients need for symptomatic relief and response to therapy should be re-evaluated periodically, especially when treatment continues for more than 4 weeks. 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 instructed to see a medical practitioner immediately in case of such an event.

Caution is required in patients with a history of hypertension and/or heart failure as fluid retention and oedema have been reported in association with VOLTAREN therapy. In view of VOLTARENu2019s inherent potential to cause fluid retention, heart failure may be precipitated in some compromised patients.

Haematological effects: During prolonged treatment with VOLTAREN, as with other NSAIDs, monitoring of the blood count is recommended. Like other NSAIDs, diclofenac may temporarily inhibit platelet aggregation. Patients with defects of haemostasis, bleeding diathesis or haematological abnormalities should be carefully monitored.

Respiratory effects (Pre-existing asthma): In patients with asthma, seasonal allergic rhinitis, swelling of the nasal mucosa (i.e. nasal polyps), chronic obstructive pulmonary disease or chronic infections of the respiratory tract (especially if linked to allergic rhinitis-like symptoms), reactions on NSAIDs like asthma exacerbations (so-called intolerance to analgesics/analgesics-asthma), Quinckeu2019s oedema or urticaria are more frequent than in other patients. Therefore, special caution is recommended in such patients (readiness for emergency). This is applicable as well for patients who are allergic to other substances, e.g. with skin reactions, pruritus, or urticaria.

Like other medicines that inhibit prostaglandin synthetase activity, diclofenac sodium and other NSAIDs can precipitate bronchospasm if administered to patients suffering from, or with a previous history of bronchial asthma. VOLTAREN 75 AMPOULES Special caution is recommended when used parenterally especially in patients with bronchial asthma because symptoms may be exacerbated. The presence of sodium metabisulphite can, lead to isolated hypersensitivity reactions, which may manifest as an acute asthma attack, clouding of consciousness, or shock.

Hepatobiliary effects: Close medical surveillance is required when prescribing VOLTAREN to patients with impaired hepatic function as their condition may be exacerbated. As with other NSAIDs, including diclofenac, values of one or more liver enzymes, may increase. During prolonged treatment with VOLTAREN, regular monitoring of hepatic function is indicated as a precautionary measure. If abnormal liver function tests persist or worsen, or if clinical signs or symptoms consistent with liver disease develop, or if other manifestations occur (e.g. eosinophilia, rash) VOLTAREN should be discontinued. Hepatitis may occur with the use of diclofenac without prodromal symptoms. Caution is called for when using VOLTAREN in patients with hepatic porphyria, since it may trigger attack.

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 VOLTAREN (see sections 4.4 and 4.8). 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. VOLTAREN should be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity. Allergic reactions, including anaphylactic/anaphylactoid reactions, can also occur in rare cases without earlier exposure to diclofenac.

Renal Effects: As fluid retention and oedema have been reported in association with NSAID therapy, including diclofenac, particular caution is called for in patients with impaired cardiac or renal function, history of hypertension, the elderly, patients receiving concomitant treatment with diuretics or medicinal products that can significantly impact renal function, and in those patients with substantial extracellular volume depletion from any cause, e.g. before or after major surgery. Monitoring of renal function is recommended as a precautionary measure when using VOLTAREN in such cases. Discontinuation of therapy is usually followed by recovery to the pre-treatment state.

The concomitant use of VOLTAREN with systemic NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided due to the potential for additive undesirable effects. (see section 4.5). VOLTAREN may mask the signs and symptoms of infection due to its pharmacodynamic properties.

Note: VOLTAREN 25 and VOLTAREN GT 50 contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine. VOLTAREN 75 mg and VOLTAREN SR 100 tablets contain sucrose. Patients with rare hereditary conditions such as fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take VOLTAREN 75 mg and VOLTAREN SR 100 tablets. VOLTAREN 75 mg and VOLTAREN SR 100 tablets contain sucrose which may have an effect on the glycaemic control of patients with diabetes mellitus.

Pregnancy Use during the third trimester of pregnancy is contraindicated owing to the possibility of uterine inertia, foetal renal impairment with subsequent oligohydramnios/ foetal renal dysfunction and/or premature closure of the ductus arteriosus and pulmonary hypertension (see section 4.3). Complications of prolonged oligohydramnios include limb contractures and delayed lung maturation, which may require invasive procedures such as exchange transfusion or dialysis, in some cases. The onset of labour may be delayed, and its duration increased.

Lactation VOLTAREN passes into the breast milk in small amounts. Therefore, VOLTAREN should not be administered during breast feeding in order to avoid undesirable effects in the infant (see section 4.3).

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.

Patients experiencing visual disturbances, dizziness, vertigo, somnolence or other central nervous system disturbances while taking VOLTAREN, should refrain from driving or using machines.

Adverse reactions (Table 1) are ranked under heading of frequency, the most frequent first, using the following convention: common (u2265 1/100, < 1/10); uncommon (u2265 1/1,000, < 1/100); rare (u2265 1/10,000, < 1/1,000); very rare (< 1/10,000), including isolated reports. The following undesirable effects include those reported with VOLTAREN tablets and/or other pharmaceutical forms of diclofenac, with either short-term or long-term use. Administration of the suppositories may give rise to systemic side-effects. Suppositories may cause exacerbation of haemorrhoids.

Table 1 Injections and infestations Very rare: Injection site abscess Blood and lymphatic system disorders Very rare: Thrombocytopenia, leucopenia, anaemia (including haemolytic and aplastic anaemia), agranulocytosis Immune system disorders Rare: Hypersensitivity reactions, anaphylactic and anaphylactoid reactions (including hypotension and shock). Very rare: Angioedema (including face oedema). Psychiatric disorders Very rare: Disorientation, depression, insomnia, nightmare, irritability, psychotic disorder. Nervous system disorders Common: Headache, dizziness. Rare: Somnolence. Very rare: Disturbances of sensation, paraesthesia, memory impairment, convulsion, anxiety, tremor, aseptic meningitis, taste disturbances, cerebrovascular accident. Eye disorders Very rare: Visual impairment, blurred vision, diplopia Ear and labyrinth disorders Common: Vertigo. Very rare: Tinnitus, impaired hearing. Cardiac disorders Very rare: Palpitations, chest pain, cardiac failure, myocardial infarction. 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, decreased appetite. Rare: Gastritis, gastrointestinal haemorrhage, haematemesis, haemorrhagic diarrhoea, melaena, gastro-intestinal ulcer (with or without bleeding or perforation which may lead to peritonitis). Very rare: Colitis (including haemorrhagic colitis, ischaemic colitis and exacerbation of ulcerative colitis or Crohn's disease), constipation, stomatitis, glossitis, oesophageal disorder, diaphragm-like intestinal strictures, pancreatitis. Hepatobiliary disorders Common: Transaminases increased (SGOT, SGPT). Rare: Hepatitis, jaundice, liver disorder. Very rare: Fulminant hepatitis, hepatic necrosis, hepatic failure Skin and subcutaneous tissue disorders Common: Rash. Rare: Urticaria. Very rare: Dermatitis bullous, eczema, erythema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal, necrolysis (Lyell's syndrome), dermatitis exfoliative, alopecia, photosensitivity reaction, purpura, Henoch-Schonlein purpura, pruritus. Renal and urinary disorders Very rare: Acute kidney injury (acute renal failure), haematuria, proteinuria, nephrotic syndrome, tubulointerstitial nephritis, renal papillary necrosis.

Selected adverse drug reactions: Arteriothrombotic events: Meta-analysis and pharmacoepidemiological data point to a small 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). 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 of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are requested to report any suspected adverse drug reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website. Novartis adverse drug reaction reporting: Web: www.novartis.com/report General disorders and administration site conditions Common: Injection site reactions, injection site pain, injection site induration, application site irritation (suppositories) Rare: Oedema

Symptoms There is no typical clinical picture resulting from VOLTAREN overdosage. Overdosage can cause symptoms such as headache, nausea, vomiting, epigastric pain, gastrointestinal haemorrhage, diarrhoea, dizziness, disorientation, excitation, tinnitus or convulsions and coma. In the event of significant poisoning, acute renal failure and liver damage are possible.

Therapeutic measures Management of acute poisoning with VOLTAREN essentially consists of supportive measures and symptomatic treatment. Supportive measures and symptomatic treatment should be given for complications such as hypotension, renal failure, convulsions, gastrointestinal disorder, and respiratory depression. Special measures such as forced diuresis, dialysis or haemoperfusion are probably of no help in eliminating VOLTAREN due to the high protein binding and extensive metabolism. Activated charcoal may be considered within one hour after ingestion of a potentially toxic overdose.