VOLTAREN Tablet / Ampoule / Suppository Ref.[115937] Active ingredients: Diclofenac

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 Crohn's 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 ≤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 VOLTAREN's 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), Quincke's 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.

Interactions with other NSAIDs

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.

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

Lithium

If used concomitantly, VOLTAREN may raise plasma concentrations of lithium. Monitoring of the serum lithium level is recommended.

Digoxin

If used concomitantly, VOLTAREN may raise plasma concentrations of digoxin. Monitoring of the serum digoxin level is recommended.

Diuretics and antihypertensive agents

Concomitant use of VOLTAREN with diuretics or antihypertensive medicines (e.g. beta-adrenoceptor 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. Patients should be adequately hydrated, and consideration should be given to monitoring of renal function after initiation of concomitant therapy and periodically thereafter, particularly for diuretics and ACE inhibitors due to the increased risk of nephrotoxicity. (see section 4.4).

Medicines known to cause hyperkalaemia

Concomitant use of VOLTAREN with potassium sparing diuretics, ciclosporin, tacrolimus or trimethoprim may be associated with increased serum potassium levels, which should be monitored frequently (see section 4.4).

Other NSAIDs and corticosteroids

Concomitant administration of VOLTAREN and other systemic NSAIDs or corticosteroids may increase the frequency of gastrointestinal undesirable effects (see section 4.4).

Anticoagulants and anti-platelet medicines

The bioavailability of VOLTAREN is reduced by acetylsalicylic acid, and that of acetylsalicylic acid by VOLTAREN, when the two products are administered together. Caution is recommended since concomitant administration could increase the risk of bleeding (see section 4.4).

There are reports of an increased risk of haemorrhage in patients receiving VOLTAREN and anticoagulants concomitantly.

Close monitoring of such patients is therefore recommended.

Selective serotonin reuptake inhibitors (SSRIs)

Concomitant administration of systemic NSAIDs and SSRIs may increase the risk of gastrointestinal bleeding (see section 4.4).

Antidiabetics

There have been isolated reports of both hypoglycaemic and hyperglycaemic effects necessitating changes in the dosage of the antidiabetic medicines during treatment with VOLTAREN. 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 renal impairment.

Methotrexate

Caution is recommended when VOLTAREN is administered less than 24 hours before or after treatment with methotrexate, since blood concentrations of methotrexate may rise, and the toxicity of this substance be increased.

Ciclosporin and tacrolimus

VOLTAREN may increase the nephrotoxicity of ciclosporin and tacrolimus due to the effect on renal prostaglandins. Therefore, it should be given at doses lower than those that would be used in patients not receiving ciclosporin or tacrolimus.

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 VOLTAREN with potent CYP2C9 inhibitors (such as voriconazole), which could result in a significant increase in peak plasma concentrations and exposure to diclofenac.

Phenytoin

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

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 (≥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 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:

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, Email: patientsafety.sacg@novartis.com, Tel: +27 11 347 6600

Not applicable.