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 and uterine haemorrhage.

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. 5 ml from the ampoule using an aseptic technique and add to 1,000 ml of sterile normal saline or 5% dextrose. Shake to ensure uniformity.

After dilution, attach the infusion bag label provided. Use dilute solution within 24 hours of preparation and store in a refrigerator at 2-8°C. 0 micrograms per ml should be prepared in accordance with instructions given above. 5 micrograms per minute, and this rate should be maintained for at least the first 30 minutes.

If a satisfactory uterine contractility response is produced, this rate should be maintained; if not, the rate should be increased to 5 micrograms per minute. If satisfactory uterine activity is not produced after at least 4 hours at this rate of infusion, the rate may be increased up to 10 micrograms per minute, side-effects permitting, and maintained until abortion occurs or the treatment is considered a failure.

If significant side-effects occur, the rate of infusion should be decreased by 50% or discontinued. g. 15 micrograms per ml) may be required, dependent on the type of pump, but the dose rates (micrograms per minute) should remain as above.

The appearance of 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.

In all cases the dosage should be adapted to the patient's response. Continuous administration of the drug for more than two days is not recommended. 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 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 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) 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 and maternal status should be taken into consideration in order to minimise the risk of uterine hyperstimulation, uterine rupture and uterine haemorrhage.

Careful and regular monitoring of uterine activity should be conducted during use of dinoprostone. Patients who develop uterine hypertonus or hypercontractility should be managed in a manner that addresses the welfare of the 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 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. Animal studies lasting several weeks at high doses have shown that prostaglandins of the E and F series can induce proliferation of bone. Such effects have also been noted in newborn infants who received prostaglandin E1 during prolonged treatment.

There is no evidence that short-term administration of prostaglandin E2 can cause similar bone effects. Women aged 35 years or older, those with complications during pregnancy and those with a gestational age over 40 weeks have been shown to have an increased risk of post-partum disseminated intravascular coagulation.

1. Prostin E2 Sterile Solution should not be used where the patient is sensitive to prostaglandins. Prostin E2 Sterile Solution 10 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 evidence of a potential for obstructed labour. • In patients with a past history of, or existing, pelvic inflammatory disease, unless adequate prior treatment has been instituted. • Patients with active cardiac, pulmonary, renal or hepatic disease.