Acemiso 200 μg Tablets

ACEMISO is indicated for co-administration with non-steroidal anti-inflammatory drugs (NSAIDs) for the prevention of gastric and duodenal ulcers, haemorrhagic lesions and erosions induced by NSAIDs.

Posology
For the prevention of gastric ulcers, haemorrhagic lesions and erosions induced by NSAIDs : A minimum of 200 mcg (one tablet) with food twice daily, together with the prescribed NSAID. Dosage may be increased to 200 mcg three times daily or to a maximum of 200 mcg four times daily, to correspond to the NSAID administration schedule or if indicated by the clinical condition of the patient.
For the prevention of duodenal ulcers induced by NSAIDs : 800 mcg (four tablets) daily in divided doses, with food. Antacids containing aluminium may be given as needed for relief of pain.
Special populations
Elderly
The usual dosage may be used.
Paediatric population
Safety and effectiveness in children under the age of 18 years have not been established.
Method of administration
For oral use
To minimise the risk of diarrhoea, ACEMISO should be taken with food, and magnesium containing antacids should be avoided.

Misoprostol is contraindicated:
Hypersensitivity to misoprostol, other prostaglandins or to any of the excipients of ACEMISO listed in section 6.1.
u2022 In women of childbearing potential who are not using effective contraception (see sections 4.4, 4.6 and 4.8)
u2022 In women who are pregnant, or in whom pregnancy has not been excluded, or who are planning a pregnancy as misoprostol increases uterine tone and contractions in pregnancy which may cause partial or complete expulsion of the products of conception (see sections 4.4, 4.6 and 4.8). Use in pregnancy has been associated with birth defects.
In patients with moderate to severe impaired renal function.

ACEMISO should not be used in pregnant women as teratogenicity in animals have been demonstrated and it induces uterine contractions and therefore has abortifacient potential.
In women of childbearing potential ACEMISO must not be started until pregnancy is excluded and should be fully counselled on the importance of adequate contraception while undergoing treatment. If pregnancy is suspected, use ACEMISO should be discontinued (see sections 4.3, 4.6 and 4.8).
In such patients it is advised that ACEMISO should only be used if the patient:
u2022 takes effective contraceptive measures
u2022 has been advised of the risks of taking ACEMISO if pregnant (see section 4.3)
Gastrointestinal bleeding, ulceration, and perforation have occurred in NSAID-treated patients receiving misoprostol. Medical practitioners and patients should remain alert for ulceration, even in the absence of gastrointestinal symptoms, and, where appropriate, endoscopy and biopsy should be carried out before use to ensure that malignant disease is absent in the upper gastrointestinal tract. These investigations and any others considered necessary by the clinician should be repeated at appropriate intervals for follow-up purposes.
Symptomatic responses to misoprostol do not preclude the presence of gastric malignancy.
Misoprostol should be used with caution in patients with conditions that predispose them to diarrhoea, such as inflammatory bowel disease. To minimise the risk of diarrhoea, misoprostol should be taken with food, and magnesium containing antacids should be avoided (see section 4.5).
Misoprostol should be used with caution in patients in whom dehydration would be dangerous. These patients should be monitored carefully.
ACEMISO should be used with caution in the presence of disease states where hypotension might precipitate severe complications, e.g. cerebrovascular disease, coronary artery disease or severe peripheral vascular disease including hypertension.
There is no evidence that ACEMISO has adverse effects on glucose metabolism in human volunteers or patients with diabetes mellitus.

Concomitant administration of NSAIDs and misoprostol in rare cases can cause a transaminase increase and peripheral oedema. ACEMISO is predominantly metabolised via fatty acid oxidising systems and has shown no adverse effect on the hepatic microsomal mixed function oxidase (P450) enzyme system. A modest increase in propranolol concentrations (mean approximately 20% in AUC, 30% in C max ) has been observed with multiple dosing of misoprostol. Medicine interaction studies with misoprostol and several NSAIDs showed no clinically significant effect on the kinetics of ibuprofen, diclofenac, piroxicam, aspirin, naproxen or indomethacin. Magnesium-containing antacids should be avoided during treatment with misoprostol as this may worsen the misoprostol-induced diarrhoea.

Women of childbearing potential
Women of childbearing potential must be informed about the risk of teratogenicity prior to treatment with ACEMISO . Treatment must not be initiated until pregnancy is excluded, and women should be fully counselled on the importance of adequate contraception while undergoing treatment. If pregnancy is suspected, treatment must be immediately discontinued (see sections 4.3 and 4.4).
Pregnancy
ACEMISO is contraindicated during pregnancy (see section 4.3) Misoprostol induces uterine contractions and is associated with abortion, premature birth, foetal death and foetal malformations.
Breast-feeding
Misoprostol is rapidly metabolised in the mother to misoprostol acid, which is biologically active and is excreted in breast milk. Misoprostol should not be administered to nursing mothers because the excretion of misoprostol acid could cause undesirable effects such as diarrhoea in nursing infants.

ACEMISO can cause dizziness. Patients should be cautioned about operating machinery and driving.

Tabulated summary of adverse reactions
The table below lists the adverse reactions observed during use of misoprostol.
Immune System Disorder
Frequency unknown Anaphylactic reaction
Nervous System Disorders
Frequent Dizziness, headache
Gastrointestinal Disorders
Frequent Diarrhoea * Abdominal pain*, constipation, dyspepsia, flatulence, nausea, vomiting
Skin and Subcutaneous Tissue Disorders
Frequent Rash
Pregnancy, puerperium, and perinatal conditions
Less frequent Frequency unknown Uterine rupture** Amniotic fluid embolism, abnormal uterine contractions, foetal death, incomplete abortion, premature birth, retained placenta, uterine perforation
Reproductive System and Breast Disorders
Less frequent Frequency unknown Vaginal haemorrhage (including postmenopausal bleeding), intermenstrual bleeding, menstrual disorder, uterine cramping
Menorrhagia, dysmenorrhoea Uterine haemorrhage
Congenital, Familial and Genetic Disorders
Frequent Foetal malformations
General Disorders and Administration Site Conditions
Frequency unknown Less frequent Chills Pyrexia
Description of selected adverse reactions
* Diarrhoea and abdominal pain were dose-related, usually developed early in the course of therapy, and were typically self-limiting. Rare instances of profound diarrhoea leading to severe dehydration has been reported.
**Uterine rupture has been uncommonly reported after prostaglandin intake during the second or third trimester of pregnancy. Uterine ruptures occurred particularly in multiparous women or in women with a caesarean section scar.
Diarrhoea can be minimised by using single doses not exceeding 200 micrograms with food and by avoiding the use of predominantly magnesium containing antacids when an antacid is required.
The pattern of adverse events associated with ACEMISO is similar when an NSAID is given concomitantly.
Special populations: There were no significant differences in the safety profile of misoprostol in patients who were 65 years of age or older, compared with younger patients.
The use of misoprostol in children has not been evaluated.
Reporting of suspected adverse reactions
Reporting 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 to SAHPRA via the u201c6.04 Adverse Drug Reaction Reporting Formu201d , found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

Clinical signs that may indicate an overdose are sedation, tremor, convulsions, dyspnoea, abdominal pain, diarrhoea, fever, palpitations, hypotension, or bradycardia.
Treatment of overdose
Because misoprostol is metabolized like a fatty acid, it is unlikely that dialysis would be appropriate treatment for overdosage. In cases of overdose, standard supportive measures should be adopted as required.