Misoprostol

Registered South African indications:

• Prevention of gastric and duodenal ulcers, haemorrhagic lesions, and erosions induced by non-steroidal anti-inflammatory drugs (NSAIDs)

South African registered contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to other prostaglandins
• Pregnancy
• In women where pregnancy has not been excluded (see boxed warning)
• Lactation
• Moderate to severely impaired renal function

Contraindications registered in other jurisdictions

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy
• Women of childbearing potential who are not using effective contraception
• In women where 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

• Breastfeeding (Recommendations in other jurisdictions)
• Gastric malignancy
• Inflammatory bowel disease
• Conditions which predispose patient to diarrhoea 
• Dehydration 
• Hypotension
• Cerebrovascular disease 
• Cardiovascular disease 
• Severe peripheral vascular disease
• Diabetes mellitus

Forms avail. in SA and covered in this monograph: tab

Dosages below include:

• South African Standard Treatment Guidelines indications and dosages
• South African registered indications and dosages

South African Standard Treatment Guidelines indications and dosages

• Click here for the Gynaecology Chapter (Standard Treatment Guidelines And Essential Medicines List For South Africa, Hospital Level, Adults, 2019 Edition)
• Click here for the Obstetrics Chapter (Standard Treatment Guidelines And Essential Medicines List For South Africa, Hospital Level, Adults, 2023 Edition)
• Click here for the Obstetrics & Gynaecology Chapter (Standard Treatment Guidelines And Essential Medicines List For South Africa, Primary Healthcare Level, 2023 Edition)

South African registered indications and dosages

Prevention of gastric ulcers, haemorrhagic lesions, and erosions induced by non-steroidal anti-inflammatory drugs (NSAIDs)

• Oral (tab): 200μg, twice daily with food (co-administered with the prescribed NSAID); May be increased to: 200μg, 3-4 times daily based on clinical condition, or to corresponding NSAID administration schedule; Max: 800μg/24hrs

Prevention of duodenal ulcers induced by non-steroidal anti-inflammatory drugs (NSAIDs)

• Oral (tab): 800μg/day in divided doses, with food

Antacids containing aluminium may be administered as needed for pain relief

To minimize the risk of diarrhoea, misoprostol should be taken with food, and magnesium-containing antacids should be avoided

Not established for use in children below 18 years

Pregnancy

South African recommendations

• Contraindicated
• Misoprostol is contraindicated in women who are pregnant because it induces uterine contractions and is associated with abortion, premature birth and foetal death and birth defects
• Women of childbearing potential should not be started on misoprostol until pregnancy is excluded and should be fully counselled on the importance of adequate contraception while undergoing treatment

Recommendations in other jurisdictions

• Contraindicated
• Misoprostol induces uterine contractions and is associated with abortion, premature birth, foetal death and foetal malformations
• Approximately a 3-fold increased risk of malformations was reported in pregnancies exposed to misoprostol during the first trimester, compared to a control group incidence of 2%. In particular, prenatal exposure to misoprostol has been associated with Moebius syndrome (congenital facial paralysis leading to hypomimia, troubles of suckling and deglutition and eye movements, with or without limb defects); amniotic band syndrome (limb deformities/ amputations, especially clubfoot, acheiria, olygodactyly, cleft palate inter alia) and central nervous system anomalies (cerebral and cranial anomalies as anencephaly, hydrocephaly, cerebellar hypoplasia, neural tube defects). Other defects including arthrogryposis have been observed
• Consequently, women should be informed of the risk of teratogenicity. Should the patient wish to continue with her pregnancy after exposure of misoprostol in utero, a careful ultrasound scan monitoring of the pregnancy, with special attention to the limbs and head must be carried out
• The risk of uterine rupture increases with advancing gestational age and with prior uterine surgery, including caesarean delivery. Grand multiparity also appears to be a risk factor for uterine rupture
• Women of childbearing potential must be informed about the risk of teratogenicity prior to treatment with misoprostol. 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

Breastfeeding

South African recommendations

• Contraindicated
• Misoprostol should not be administered to breastfeeding mothers because the potential excretion of misoprostol acid could cause diarrhoea in nursing infants

Recommendations in other jurisdictions

• Caution; not recommended
• 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 breastfeeding mothers because the excretion of misoprostol acid could cause undesirable effects such as diarrhoea in breastfeeding  infants

South African recommendations

• Mild: No dose adjustment recommended
• Moderate to severe: Contraindicated

Recommendations in other jurisdictions

• No dose adjustment recommended

• No dose adjustment recommended

• No dose adjustment recommended

Central Nervous System Disorders

• Dizziness
• Headache

Gastrointestinal Disorders

• Diarrhoea
• Abdominal pain 
• Constipation
• Dyspepsia
• Flatulence
• Nausea and vomiting

Genitourinary Disorders

• Vaginal haemorrhage (including postmenopausal bleeding) 
• Intermenstrual bleeding
• Menstrual disorder
• Uterine cramping
• Menorrhagia
• Dysmenorrhoea 
• Uterine haemorrhage
• Abnormal uterine contractions
• Uterine rupture
• Uterine perforation
• Amniotic fluid embolism
• Fetal death
• Incomplete abortion
• Premature birth
• Retained placenta
• Birth defects 

Skin and Subcutaneous Tissue Disorders

• Rash

Immune, Blood and Lymphatic System Disorders

• Anaphylactic reaction 
• Fever
• Chills

• Non-steroidal anti-inflammatory drugs
• Magnesium-containing antacids

None routine. Specific cases may require

• Fetal monitoring

Misoprostol, an analogue of naturally occurring prostaglandin E1, protects the gastroduodenal mucosa by inhibiting basal, stimulated and nocturnal acid secretion. It also acts by reducing the volume of gastric secretions and the proteolytic activity of the gastric fluid and increasing bicarbonate and mucus secretion. It has also been shown to induce uterine contractions.

Tablet 200μg

• Cytotec (Pfizer) originator

COMBINATION PREPARATIONS

Diclofenac/ Misoprostol

Tablet 50mg/200μg

• Arthrotec 50 (Pfizer) originator

Tablet 75mg/200μg

• Arthrotec 75 (Pfizer) originator