- diclofenac sodium
POM: Prescription only medicine
This information is intended for use by health professionals
Excipient with known effect:Each Masidemen 50 mg/200 microgram modified-release tablet contains 20 mg lactose monohydrate. For the full list of excipients, see section 6.1.
AdultsOne tablet to be taken with food, two or three times daily. Tablets should be swallowed whole, not chewed.
Elderly and patients with renal, cardiac or hepatic impairmentNo adjustment of dosage is necessary in the elderly or in patients with hepatic impairment or mild to moderate renal impairment as pharmacokinetics are not altered to any clinically relevant extent. Nevertheless, elderly patients and patients with renal, cardiac or hepatic impairment should be closely monitored (see section 4.4 and section 4.8).
Children (under 18 years)The safety and efficacy of diclofenac/misoprostol in children has not been established. Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4).
WarningsThe use of diclofenac/misoprostol with concomitant NSAIDs including COX-2 inhibitors should be avoided.
Use in pre-menopausal women (see also section 4.3)Diclofenac/misoprostol should not be used in pre-menopausal women unless they use effective contraception and have been advised of the risks of taking the product if pregnant (see section 4.6). The label will state: 'Not for use by pre-menopausal women unless using effective contraception'.
PrecautionsUndesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.2, and GI and cardiovascular risks below).
Renal, cardiac or hepatic impairmentIn patients with renal, cardiac or hepatic impairment and in the elderly, caution is required since the use of NSAIDs may result in deterioration of renal function. In the following conditions diclofenac/misoprostol should be used only in exceptional circumstances and with close clinical monitoring: advanced cardiac failure, advanced kidney failure, advanced liver disease, severe dehydration.In a large trial where patients received diclofenac for a mean of 18 months, ALT/AST elevations were observed in 3.1% of patients. ALT/AST elevations usually occur within 1-6 months. In clinical trials, hepatitis has been observed in patients who received diclofenac, and in postmarketing experience, other hepatic reactions have been reported, including jaundice and hepatic failure. During diclofenac/misoprostol therapy, liver function should be monitored periodically. If diclofenac/misoprostol is used in the presence of impaired liver function, close monitoring is necessary. If abnormal liver tests persist or worsen, if clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur treatment with diclofenac should be discontinued.Diclofenac metabolites are eliminated primarily by the kidneys (see section 5.2). The extent to which the metabolites may accumulate in patients with renal failure has not been studied. As with other NSAIDs, metabolites of which are excreted by the kidney, patients with significantly impaired renal function should be more closely monitored.In rare cases, NSAIDs, including diclofenac/misoprostol, may cause interstitial nephritis, glomerulitis, papillary necrosis and the nephrotic syndrome. NSAIDs inhibit the synthesis of renal prostaglandin which plays a supportive role in the maintenance of renal perfusion in patients whose renal blood flow and blood volume are decreased. In these patients, administration of an NSAID may precipitate overt renal decompensation, which is typically followed by recovery to pretreatment state upon discontinuation of NSAID therapy. Patients at greatest risk of such a reaction are those with congestive heart failure, liver cirrhosis, nephrotic syndrome and overt renal disease. Such patients should be carefully monitored while receiving NSAID therapy.Appropriate monitoring and advice are required for patients with a history of hypertension as fluid retention and oedema have been reported in association with NSAID therapy.As with all NSAIDS, diclofenac/misoprostol can lead to the onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of cardiovascular events. NSAIDs, including diclofenac/misoprostol, should be used with caution in patients with hypertension. Blood pressure should be monitored closely during the initiation of therapy with diclofenac/misoprostol and throughout the course of therapy. Patients with significant risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking) should only be treated with diclofenac after careful consideration. As the cardiovascular risks of diclofenac may increase with dose and duration of exposure, the shortest duration possible and the lowest effective daily dose should be used. The patient's need for symptomatic relief and response to therapy should be re-evaluated periodically.Clinical trial and epidemiological data suggest that use of diclofenac, particularly at high dose (150 mg daily) and in long term treatment may be associated with a small increased risk of serious arterial thrombotic events (for example myocardial infarction or stroke).Physicians and patients should remain alert for the development of such events, even in the absence of previous cardiovascular symptoms. Patients should be informed about the signs and/or symptoms of serious cardiovascular toxicity and the steps to take if they occur (see section 4.3).
Blood system/GastrointestinalNSAIDs, including diclofenac/misoprostol, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. When GI bleeding or ulceration occurs in patients receiving diclofenac/misoprostol, the treatment should be withdrawn. These events can occur at any time during treatment, with or without warning symptoms or in patients with a previous history of serious GI events.Patients most at risk of developing these types of GI complications with NSAIDs are those treated at higher doses, the elderly, patients with cardiovascular disease, patients using concomitant aspirin, or patients with a prior history of, or active, gastrointestinal disease, such as ulceration, GI bleeding or inflammatory conditions. Therefore, diclofenac/misoprostol should be used with caution in these patients and commence on treatment at the lowest dose available (see section 4.3).Patients with a history of GI toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment. Caution should be advised in patients receiving concomitant medicines which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin-reuptake inhibitors or anti-platelet agents such as aspirin (see section 4.5).Diclofenac/misoprostol, in common with other NSAIDs, may decrease platelet aggregation and prolong bleeding time. Extra supervision is recommended in haematopoietic disorders or in conditions with defective coagulation or in patients with a history of cerebrovascular bleeding.Caution is required in patients suffering from ulcerative colitis or Crohn's Disease as these conditions may be exacerbated (see section 4.8).Care should be taken in elderly patients and in patients treated with corticosteroids, other NSAIDs, or anti-coagulants (see section 4.5).
Skin ReactionsSerious 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 diclofenac/misoprostol (see section 4.8). Patients appear to be at highest risk for these events early in the course of therapy, the onset of the event occurring in the majority of cases within the first month of treatment. Diclofenac/misoprostol should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
HypersensitivityNSAIDs may precipitate bronchospasm in patients suffering from, or with a history of, bronchial asthma or allergic disease.
Long-term treatmentAll patients who are receiving long-term treatment with NSAIDs should be monitored as a precautionary measure (e.g. renal, hepatic function and blood counts). During long-term, high dose treatment with analgesic/anti-inflammatory drugs, headaches can occur which must not be treated with higher doses of the medicinal product.Diclofenac/misoprostol may mask fever and thus an underlying infection.Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
PregnancyDiclofenac/misoprostol is contraindicated in pregnant women and in women planning a pregnancy because misoprostol induces uterine contractions and is associated with abortion, premature birth, and foetal death. Use of misoprostol has been associated with birth defects. Also diclofenac may cause premature closure of the ductus arteriosus. Women of childbearing potential should not be started on diclofenac/misoprostol until pregnancy is excluded, and should be fully counselled on the importance of adequate contraception while undergoing treatment. If pregnancy is suspected, use of the product should be discontinued.
BreastfeedingMisoprostol is rapidly metabolised in the mother to misoprostol acid, which is biologically active and is excreted in breast milk. Diclofenac is excreted in breast milk in very small quantities. In general, the potential effects on the infant from any exposure to misoprostol and its metabolites via breast feeding are unknown. However, diarrhoea is a recognised side effect of misoprostol and could occur in infants of nursing mothers. Diclofenac/misoprostol should therefore not be administered to nursing mothers.
FertilityNo fertility data are available
|Organ System||Very common (≥1/10)||Common (≥1/100 to <1/10)||Uncommon (≥1/1,000 to <1/100)||Rare (≥1/10,000 to <1/1,000)||Very rare (<1/10,000)||Frequency unknown (cannot be estimated from the available data)|
|Infections and infestations||Aseptic meningitis1|
|Blood and lymphatic system disorders||Thrombo-cytopenia||Aplastic anaemia, agranulocytosis, haemolytic anaemia, leucopenia|
|Immune system disorders||Anaphylactic reaction||Hypersensitivity|
|Metabolism and nutrition disorders||Anorexia|
|Psychiatric disorders||Insomnia||Psychotic reaction, disorientation, depression, anxiety, nightmares, mood change, irritability|
|Nervous system disorders||Headache, dizziness||Convulsions, memory disturbance, drowsiness, tremor, taste disturbance, paraesthesia|
|Eyes disorders||Visual disturbances, blurred vision|
|Ear and labyrinth disorders||Tinnitus|
|Cardiac disorders||Cardiac failure, palpitations|
|Vascular disorders||Shock, hypertension, hypotension, vasculitis|
|Respiratory, thoracic and mediastinal disorders||Asthma, pneumonitis, dyspnoea|
|Gastrointestinal disorders||Abdominal pain, diarrhoea2 , nausea, dyspepsia||Gastritis, vomiting, flatulence, eructation, constipation, peptic ulcer||Stomatitis||GI perforation 3, gastrointestinal bleeding 3 , melaena, haematemesis, colitis, Crohn's disease, oesophageal disorder, mouth ulceration, glossitis, tongue odema, dry mouth|
|Hepato-biliary disorders||Alanine amino-transferase increased||Hepatitis, jaundice||Hepatic failure||Hepatitis fulminant, aspartate aminotransferase increased, blood bilirubin increased|
|Skin and subcutaneous tissue disorders||Erythema multiforme, rash, pruritus||Purpura, urticaria||Angioedema||Toxic epidermal necrolysis4, Stevens-Johnson syndrome4 , dermatitis exfoliative4, dermatitis bullous, Henoch Schonlein purpura, mucocutaneous rash, rash vesicular, photosensitivity reaction, alopecia, urticaria|
|Renal and urinary disorders||Renal failure, acute renal failure, renal papillary necrosis, nephritis interstitial, nephrotic syndrome, proteinuria, haematuria|
|Pregnancy, puerperium and perinatal conditions||Intra-uterine death, uterine rupture, incomplete abortion, premature baby, anaphylactoid syndrome of pregnancy, retained placenta or membranes, uterine contractions abnormal|
|Reproductive system and breast disorders||Menorrhagia, metrorrhagia, vaginal haemorrhage, postmeno-pausal haemorrhage||Uterine haemorrhage|
|Congenital, familial and genetic disorders||Birth defects|
|General disorders and administration site conditions||Oedema5 , chest pain, face oedema, fatigue, pyrexia, chills, inflammation|
|Investigations||Blood alkaline phosphatase increased||Decreased haemoglobin|
|Injury, poisoning and procedural complications||Uterine perforation|
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation 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 via the Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard.
Core:Microcrystalline cellulose (E460)Lactose monohydrateMaize starchPovidone K30Magnesium stearate (E470b)Purified talc (E553b)
Mantle/Coat:Hydroxypropylmethylcellulose type 2910 (E464)Methacrylic acid-ethyl acrylate copolymer (1:1)Purified talc (E553b)Triethyl citrate (E1505)Microcrystalline cellulose (E460)Sodium starch glycolateHydrogenated castor oil