PROSTIN E2 STERILE

Usage is restricted to qualified health care professionals and to hospitals and clinics with specialised obstetric units with facilities for continuous monitoring. The recommended dose should not be exceeded, and the dosing interval should not be shortened as this increases the risk of uterine hyperstimulation, uterine rupture, uterine haemorrhage, foetal and neonatal death.

Posology Adults Directions for the Preparation of a Dilute Solution:

For use by IV drip (a drip set delivering 60 drops per ml must be used) or constant rate infusion pump. 75 ml from the ampoule using an aseptic technique and add to 500 ml sterile normal saline or 5% dextrose. Shake to ensure uniformity.

After dilution attach label provided. Use dilute solution within 24 hours of preparation and store in a refrigerator at 2-8°C. The dose of Prostin E2 Sterile Solution used normally depends not only upon the indication but also on patient response.

5 micrograms/ml solution. 25 micrograms/minute for 30 minutes and then maintained or increased. Cases of foetal death in utero may require higher doses. 5 micrograms/minute may be used with stepwise increases, at intervals of not less than one hour.

The appearance of foetal distress or uterine hypertonus requires cessation of therapy until the state returns to normal. The situation should be re-assessed and, if necessary, the infusion can be recommenced but at lower dosage rates, 50% of the last dose level used.

If no response is seen within the first 12-24 hours of treatment, the medication should be discontinued. Elderly Not applicable. Paediatric population Not applicable. Method of administration For intravenous administration only.

The table below lists the adverse reactions identified through clinical trial experience and post-marketing surveillance by system organ class and frequency. Adverse reactions identified from post-marketing experience are included in italics.

The frequency grouping is defined using the following convention:

Very common (≥1/10); Common (≥ 1/100 to <1/10); Uncommon (≥1/1 000 to <1/100); Rare (≥ 1/10 000 to <1/1 000); Very Rare (< 1/10 000); and Not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Table 1. Adverse Reactions System Organ Class Very Common ≥1/10 Common ≥1/100 to <1/10 Uncommon ≥1/1 000 to <1/100 Rare ≥1/10 000 to <1/1 000 Very Rare <1/10 000 Frequency Not Known (Cannot Be Estimated From Available Data) Blood and lymphatic system disorders Disseminated intravascular coagulation Immune system disorders Hypersensitivity, Anaphylactoid reaction, Anaphylactic reaction, Anaphylactic shock Nervous system disorders Vasovagal symptoms (flushing, shivering, headache, dizziness) Cardiac disorders Cardiac arrest Vascular disorders Hypertension Respiratory, thoracic and mediastinal disorders Bronchospasm Asthma Gastrointestinal disorders Diarrhoea, Nausea, Vomiting Musculoskeletal and connective tissue disorders Back pain System Organ Class Very Common ≥1/10 Common ≥1/100 to <1/10 Uncommon ≥1/1 000 to <1/100 Rare ≥1/10 000 to <1/1 000 Very Rare <1/10 000 Frequency Not Known (Cannot Be Estimated From Available Data) Pregnancy, Puerperium and Perinatal conditions Foetal distress syndrome, Uterine hypertonus, Uterine contractions abnormal Premature separation of placenta Uterine rupture, Anaphylactoid syndrome of pregnancy, Rapid cervical dilatation, Neonatal distress, Death neonatal, Stillbirth, Foetal death General disorders and administration site conditions Injection site irritation, Injection site erythema Pyrexia Local infections Investigations Apgar score low, Foetal heart rate abnormal White blood cell count increased Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

This product is only available to hospitals and clinics with specialised obstetric units and should only be used where 24-hour resident medical cover is provided. Use caution in handling this product to prevent contact with skin. Wash hands thoroughly with soap and water after administration.

As with any oxytocic agent, the risk of uterine rupture should be considered. Concomitant medication, maternal and foetal status should be taken into consideration in order to minimise the risk of uterine hyperstimulation, uterine rupture, uterine haemorrhage, foetal and neonatal death.

Careful and regular monitoring of uterine activity and foetal heart rate should be conducted during use of dinoprostone. Patients who develop uterine hypertonus or hypercontractility, or in whom unusual foetal heart rate patterns develop, should be managed in a manner that addresses the welfare of the foetus and mother.

It is advised that Prostin E2 Sterile Solution should not be administered by the intramyometrial route since there have been reports of a possible association between this route of administration and cardiac arrest in severely ill patients.

Caution should be exercised in the administration of Prostin E2 Sterile Solution 1 mg/ml for the induction of labour in patients with: • asthma or a history of asthma • epilepsy or a history of epilepsy • glaucoma or raised intra-ocular pressure • compromised cardiovascular, hepatic, or renal function • hypertension • ruptured chorioamniotic membranes.

Dinoprostone should be used with caution in patients with multiple pregnancy. In labour induction, cephalopelvic relationships should be carefully evaluated before use of Prostin E2 Sterile Solution. g. hypertonus, sustained uterine contractions, or foetal distress.

In cases where there is a known history of hypertonic uterine contractility or tetanic uterine contractions, it is recommended that uterine activity and the state of the foetus (where applicable) should be continuously monitored throughout labour.

1. Prostin E2 Sterile Solution should not be used where the patient is sensitive to prostaglandins. Prostin E2 Sterile Solution 1 mg/ml is not recommended in the following circumstances: • For patients in whom oxytocic drugs are generally contra-indicated or where prolonged contractions of the uterus are considered inappropriate such as: - Cases with a history of Caesarean section or major uterine surgery.

- Cases where there is cephalopelvic disproportion. - Cases in which foetal malpresentation is present. - Cases where there is clinical suspicion or definite evidence of pre-existing foetal distress. - Cases in which there is a history of difficult labour and/or traumatic delivery.

• In patients with a past history of, or existing, pelvic inflammatory disease, unless adequate prior treatment has been instituted. • In patients where there is clinical suspicion or definite evidence of placenta praevia or unexplained vaginal bleeding during this pregnancy.

• Patients with active cardiac, pulmonary, renal or hepatic disease.