4.2 - addition of cardiac impairment & cross reference to section 4.4
4.3 - deletion of lactation or breast feeding, addition of Treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery, Patients with severe renal and hepatic failure, expansion of active GI contraindication to include perforation
4.4 - expansion of warnings, especially kidney in line with Arthrotec 75 SmPC; addition of hypertension warning - blood pressure monitoring required; may prolong bleeding time; care required in elderly & patients treated with corticosteroids; addition of hypersensitivity warning; may mask fever or infection; excipient warning - sugars; monitor patients in long term treatment
4.5 - addition of information regarding potential interactions with tacrolimus, antidiabetic agents, anti-hypertensives including diuretics, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II antagonists (AIIA), antacids, quinolone antibiotics, mifepristone, corticosteroids
4.6 - expansion to explain contraindication in pregnancy, misoprostol metabolism and diclofenac excretion in milk, diarrhoea is a recognised side effect of misoprostol and could occur in infants of nursing mothers so Arthrotec shouldn't be administered to nursing mothers.
4.8 - conversion of adverse events to a table of frequencies and addition of the following adverse events in line with the Arthrotec 75 SmPC: hypotension, hypertension, palpitations, chest pain and cardiac failure, dyspnea, blurred vision, abnormal uterine contractions, uterine rupture/perforation, retained placenta, amniotic fluid embolism, incomplete abortion, premature birth, fetal death, uterine haemorrhage, birth defects, chills, fever, vasculitis, pneumonitis, cutaneous reactions (including rash and bullous eruptions with vesiculation and erythroderma), dermatitis exfoliative, mucocutaneous reactions, anaphylactoid systemic reactions, oedema of the face and tongue, hypotension and shock, changes in mood, tiredness, aseptic meningitis, proteinuria, haematuria, acute renal insufficiency, severe fulminant hepatitis, gastritis, exacerbation of colitis and Crohn’s disease.