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Diclofenac sodium and misoprostol oral


Modified release formulations of diclofenac sodium and misoprostol

Drugs List

  • ARTHROTEC 50 modified release tablet
  • ARTHROTEC 75 modified release tablet
  • diclofenac sodium 50mg and misoprostol 200microgram modified release tablet
  • diclofenac sodium 75mg and misoprostol 200microgram modified release tablet
  • MISOFEN 50mg+200microgram modified release tablet
  • MISOFEN 75mg+200microgram modified release tablet
  • Therapeutic Indications


    Treatment of osteo- or rheumatoid arthritis in patients at risk of ulcer



    50 mg + 200 microgram tablet
    One tablet twice or three times a day as needed.

    75 mg + 200 microgram tablet
    One tablet twice a day as needed.

    The maximum daily dose is 150 mg of diclofenac.


    50 mg + 200 microgram tablet
    One tablet twice or three times a day as needed.

    75 mg + 200 microgram tablet
    One tablet twice a day as needed.

    The maximum daily dose is 150 mg of diclofenac.

    Use the lowest effective dose and exercise caution as older patients and those with low body weight are generally more prone to adverse reactions.


    Children under 18 years
    Coronary artery bypass graft
    Females attempting to conceive
    Cerebrovascular disorder
    Gastrointestinal haemorrhage
    Gastrointestinal perforation
    Gastrointestinal ulcer
    Ischaemic heart disease
    New York Heart Association class II failure
    Peripheral arterial circulatory disorder
    Severe hepatic impairment
    Severe renal impairment

    Precautions and Warnings

    Allergic disposition
    Females of childbearing potential
    Predisposition to fluid retention
    Risk factors for cardiovascular disorder
    Congestive cardiac failure
    Crohn's disease
    Glucose-galactose malabsorption syndrome
    Haematological disorder
    Hepatic cirrhosis
    Hepatic impairment
    History of asthma
    History of gastrointestinal bleeding
    History of gastrointestinal ulceration
    History of peptic ulcer
    Lactose intolerance
    Nephrotic syndrome
    Renal impairment
    Severe dehydration
    Ulcerative colitis

    May mask fever
    May mask symptoms or signs of infections
    May precipitate bronchospasm in patients with asthma or allergy
    Advise ability to drive/operate machinery may be affected by side effects
    Contains lactose
    Exclude pregnancy prior to initiation of treatment
    Discontinue if signs of gastro-intestinal bleeding occur
    Discontinue treatment immediately if pregnancy is suspected
    May inhibit platelet aggregation - observe for signs of bleeding
    Monitor blood pressure
    Monitor hepatic function on long term therapy
    Monitor renal function on long term therapy
    Perform blood counts on prolonged use of this treatment
    Discontinue if signs of gastro-intestinal ulceration occur
    High dose/long term use may increase risk of arterial thrombotic events
    May prolong bleeding time
    Severe gastro-intestinal side effects may occur without warning
    Discontinue treatment if skin rash or other allergic reaction occurs
    Maintain treatment at the lowest effective dose
    Female: Ensure adequate contraception during treatment
    Advise patients to report any new or worsening cardiovascular symptoms

    Elderly patients have increased frequency of adverse reactions, especially gastrointestinal bleeding and perforation which may be fatal. These patients should commence treatment on the lowest dose available and be monitored for gastrointestinal bleeding for 4 weeks following initiation of therapy.

    Patients with renal or hepatic impairment and the elderly should be kept under surveillance, since the use of NSAIDs may result in deterioration of renal function. The lowest effective dose should be used and renal function monitored.

    If abnormal liver function tests persist or worsen, clinical signs or symptoms consistent with liver disease develop, or if other manifestations occur (eosinophilia, rash, etc.) treatment should be discontinued. Hepatitis may occur without prodromal symptoms.

    Diclofenac sodium may reversibly inhibit platelet aggregation. Patients with defects of haemostasis, bleeding diathesis or haematological abnormalities should be carefully monitored.

    Pregnancy and Lactation


    Diclofenac plus misoprostol is contraindicated during pregnancy.

    The manufacturer states that women of childbearing potential must be informed about the risk of teratogenicity and that treatment must be discontinued if pregnancy is suspected.

    First trimester exposure to NSAIDs has been associated with an increased risk spontaneous abortions and of birth defects (notably cardiac septal defects). There is conflicting evidence, however, from various studies and the risk appears to be low.

    When an NSAID is considered essential, a more established drug such as ibuprofen may be considered. Diclofenac should be used with caution in the first and second trimesters. Schaefer (2007) considers that use of NSAIDs in early pregnancy does not require termination of pregnancy or invasive diagnostic procedures.

    Diclofenac is a prostaglandin synthetase inhibitor and may have the following effects during the second and third trimesters:
    - Pulmonary and cardiac toxicity in the foetus/newborn (pulmonary hypertension with preterm closing of the ductus arteriosus). The risk exists from the beginning of the sixth month and increases if administration is close to full term.
    - Functional renal injury in the foetus. From the twelfth week: oligohydramnios (usually reversible after the end of treatment) or anamnios (particularly with prolonged exposure). Following birth, renal failure may persist (especially with late and prolonged exposure).
    - Inhibition of uterine contractions with delayed onset and prolongation of labour.
    - Increased possibility of bleeding in mother and child.
    - Increased risk of maternal oedema formation.
    - When used in the peri-natal period, necrotising enterocolitis and intraventricular haemorrhages have been reported in very pre-term and very low birth weight infants.

    Use of any NSAID is considered contraindicated during the third trimester of pregnancy.

    Misoprostol is a potent uterine stimulant that induces abortion in early pregnancy after oral administration. It has also been associated with birth defects. The teratogenic mechanism appears to be related to the induction of uterine contractions that deform the embryo, resulting in vascular disruption, haemorrhage and cell death (Briggs, 2011).

    The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( ) or if this is unavailable at the backup site ( ).


    Diclofenac plus misoprostol use is contraindicated during lactation.

    In limited studies so far available, NSAIDs can appear in breast milk in very low concentrations.

    When an NSAID is considered necessary during breastfeeding ibuprofen or flurbiprofen would be the drugs of choice although occasional use of diclofenac is permissible.

    The secretion in maternal milk following oral administration is minimal and probably too low to affect the infant. Diclofenac has a short half-life of 1.1 hours and a number of active metabolites although the clinical significance of these is not known.

    At the time of writing no studies describing the use of misoprostol during breastfeeding have been located. The manufacturer considers the drug to be contraindicated during breastfeeding because of the potential for severe, drug induced diarrhoea in the infant (Briggs, 2011)

    Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
    Specialist advice is available from the UK Drugs in Lactation Advisory Service at

    Side Effects

    Abdominal pain
    Acute renal insufficiency
    Altered uterine contractions
    Anaphylactic reaction
    Aplastic anaemia
    Arterial thrombosis
    Aseptic meningitis
    Cardiac failure
    Chest pain
    Decrease in haemoglobin
    Dry mouth
    Erythema multiforme
    Exacerbation of Crohn's disease
    Exfoliative dermatitis
    Facial oedema
    Fulminant hepatitis
    Gastro-intestinal perforation
    Gastrointestinal bleeding
    Haemolytic anaemia
    Hair loss
    Hypersensitivity reactions
    Incomplete abortion
    Increase of liver transaminases
    Intermenstrual bleeding
    Interstitial nephritis
    Memory disturbances
    Mood changes
    Mouth ulcers
    Nephrotic syndrome
    Oesophageal lesions
    Papillary necrosis
    Peptic ulceration
    Premature birth
    Renal failure
    Retained placenta
    Serum bilirubin increased
    Stevens-Johnson syndrome
    Taste disturbances
    Tongue oedema
    Toxic epidermal necrolysis
    Ulcerative colitis
    Uterine rupture
    Vaginal bleeding
    Visual disturbances


    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( ) or if this is unavailable at the backup site ( ).

    Further Information

    Last Full Review Date: May 2015

    Reference Sources

    Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

    Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

    Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press Accessed on 22 May 2015.

    Summary of Product Characteristics: Arthrotec 50 tablets. Pfizer Ltd. Revised September 2018.
    Summary of Product Characteristics: Arthrotec 75 tablets. Pfizer Ltd. Revised Sptember 2018.

    Summary of Product Characteristics: Masidemen 50mg/200microgram modified release tablets. Actavis UK Ltd. Revised February 2014.
    Summary of Product Characteristics: Masidemen 75mg/200microgram modified release tablets. Actavis UK Ltd. Revised February 2014.

    Summary of Product Characteristics: Misofen 50mg/200microgram modified release tablets. Morningside Healthcare Ltd. Revised February 2014.
    Summary of Product Characteristics: Misofen 75mg/200microgram modified release tablets. Morningside Healthcare Ltd. Revised February 2014.

    'PRAC recommends the same cardiovascular precautions for diclofenac as for selective COX-2 inhibitors'
    European Medicines Agency (EMA) 14th June 2013
    Available at:
    Last accessed: 11 May, 2015

    MHRA Drug Safety Update June 2013
    Available at:
    Last accessed: 22 May, 2015

    The drug database for acute porphyria (NAPOS)
    Available at:
    Diclofenac sodium + misoprostol Last revised: 1 August, 2013
    Last accessed: 22 May, 2015

    US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
    Available at:
    Diclofenac Last revised: 30 January, 2015
    Last accessed: 22 May, 2015

    US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
    Available at:
    Misoprostol Last revised: 6 March, 2014
    Last accessed: 22 May, 2015

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