ANGUSTA

Posology The recommended dosing regimen for Angusta is 25 micrograms orally every two hours or 50 micrograms orally every four hours according to hospital practice. The maximum dose is 200 micrograms over a period of 24 hours. There may be a synergistic/additive effect of misoprostol and oxytocin.

2. 5). Due to the lack of clinical data, the use of Angusta is recommended from 37th week of pregnancy when the cervix is unfavourable (Bishop score <7). 2). Paediatric population The safety and efficacy of Angusta in pregnant women aged less than 18 years has not been established in clinical trials.

No data are available. Method of administration • Angusta should only be administered by trained obstetric personnel in a hospital setting where facilities for continuous fetal and uterine monitoring is available. • The cervix should be assessed carefully before Angusta is administered.

• Angusta should be taken orally with a glass of water.

The undesirable effects listed in the table below have been reported in 41 trials where a total of 3,152 women were exposed to oral misoprostol at doses of 20-25 μg every 2 hours or 50 μg every 4 hours. In addition, adverse events reported in a compassionate use program, where approximately 29,000 women have been exposed to Angusta for induction of labour are also listed.

System Organ Class Very common (≥ 1/10) Common (≥ 1/100 to < 1/10) Uncommon (≥ 1/1,000 to < 1/100) Not known (cannot be estimated from the available data) 1) Nervous system disorders Dizziness Convulsion neonatal* Respiratory, thoracic and mediastinal disorders Neonatal asphyxia* Cyanosis neonatal* Gastrointestinal disorders With 50 μg, 4- hourly: Nausea2) Vomiting3) Diarrhoea With 25 μg, 2- hourly: Nausea2) Vomiting3) System Organ Class Very common (≥ 1/10) Common (≥ 1/100 to < 1/10) Uncommon (≥ 1/1,000 to < 1/100) Not known (cannot be estimated from the available data) 1) Skin and subcutaneous tissue disorders Rash pruritic Pregnancy, puerperium and perinatal conditions Meconium stain With 25 μg, 2- hourly: Postpartum haemorrhage5) Uterine hyperstimulation4) With 50 μg, 4- hourly: Postpartum haemorrhage5) Foetal acidosis* Premature separation of placenta Uterine rupture General disorders and administration site conditions Chills Pyrexia Investigations With 50 μg, 4- hourly: Apgar score low*6) Foetal heart rate abnormal*7) With 25 μg, 2- hourly: Apgar score low*6) Foetal heart rate abnormal*7) * Neonatal adverse reaction 1) ADRs which were reported from the compassionate use programme including birth hospitals in Denmark, Norway and Finland, where approximately 29,000 women have been exposed to Angusta for induction of labour.

2) Nausea was common with 25 μg every 2 hours and very common with 50 μg every 4 hours. 3) Vomiting was common with 25 μg every 2 hours and very common with 50 μg every 4 hours. 4) Uterine hyperstimulation was reported both with and without foetal heart rate changes.

Angusta should only be administered by trained obstetric personnel in a hospital setting where facilities for continuous fetal and uterine monitoring is available and the cervix should be assessed carefully before product use. Angusta can cause excessive uterine stimulation.

If uterine contractions are prolonged or excessive, or there is a clinical concern for the mother or baby, additional Angusta tablets should not be administered. If excessive uterine contractions continue, treatment according to local guidelines should be started.

3). There are no or limited clinical data with misoprostol in pregnant women with severe pre-eclampsia marked by Haemolytic anaemia; Elevated Liver enzymes; Low Platelet count (HELLP) syndrome, other end organ affliction or CNS findings other than mild headache.

Chorioamnionitis may necessitate fast delivery. Decisions regarding antibiotic treatment, induced labour or caesarean section will be at the physician’s discretion. There are no or limited clinical data with misoprostol in women whose membranes have been ruptured for more than 48 hours prior to administration of misoprostol.

There may be synergistic/additive effects of misoprostol and oxytocin. Concomitant administration of oxytocin is contraindicated. 3. Angusta is eliminated after 4 hours. 2. 5). There are no or limited clinical data with misoprostol in multiple pregnancies.

There are no or limited clinical data with misoprostol in grand multiparity. 6). Angusta should be used only when induction of labour is clinically indicated. There are no or limited clinical data with misoprostol in pregnant women with Bishop score (mBS) >6.

An increased risk of post-partum disseminated intravascular coagulation has been described in patients whose labour has been induced by any physiological or pharmacological method. 2). This medicinal product contains 0,874 mg sodium per tablet that is to say essentially ‘sodium- free’.

g. g. 73 m2).