PROSTIN E2 VAGINAL

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 One tablet to be inserted high into the posterior fornix. A second tablet may be inserted after six to eight hours if labour is not established. Maximum dose 6 mg. Elderly Not applicable. Paediatric population Not applicable.

Method of administration Vaginally. The tablets should be inserted high into the posterior fornix.

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 <1/1000 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, Anaphylactic reaction, Anaphylactic shock, Anaphylactoid reaction Cardiac disorders Cardiac arrest Vascular disorders Hypertension∗∗ Respiratory, thoracic and mediastinal disorders Asthma∗∗, Bronchospasm∗∗ Gastrointestinal disorders Vomiting Nausea Diarrhoea Skin and subcutaneous tissue disorders Rash 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 <1/1000 Very Rare <1/10 000 Frequency Not Known (Cannot Be Estimated From Available Data) Pregnancy, Puerperium and Perinatal conditions Uterine hypertonus, Foetal distress syndrome, Uterine contractions abnormal Uterine rupture, Premature separation of placenta, Anaphylactoid syndrome of pregnancy∗∗, Rapid cervical dilatation, Neonatal distress, Death neonatal††, Stillbirth†, Foetal death Reproductive system and breast disorders Vulvovaginal burning sensation Irritation, Pain General disorders and administration site conditions Pyrexia Investigations Foetal heart rate abnormal† Apgar score low * Reported during post marketing surveillance ∗∗ Maternal adverse events that have been reported only with use of the vaginal tablets.

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.

Caution should be exercised in the administration of Prostin E2 Vaginal Tablets 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 Vaginal Tablets. 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.

The possibility of uterine rupture should be borne in mind where high-tone uterine contractions are sustained. 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 Vaginal Tablets should not be used where the patient is sensitive to prostaglandins or other constituents of the tablet. Prostin E2 Vaginal Tablets are 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.