SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Prostin E2 Vaginal Gel 1mg.

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 3g gel (2.5 ml) contains 1 mg dinoprostone.

3 PHARMACEUTICAL FORM

Translucent, thixotropic gel.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Oxytocic. Prostin E2 Vaginal Gel is indicated for the induction of labour, when there are no foetal or maternal contra-indications.

4.2 Posology and method of administration

Adults: In primigravida patients with unfavourable induction features (Bishop score of 4 or less), an initial dose of 2 mg should be administered vaginally. In other patients an initial dose of 1 mg should be administered vaginally.

In both groups of patients, a second dose of 1 mg or 2 mg may be administered after 6 hours as follows:

1    mg should be used where uterine activity is insufficient for satisfactory progress of labour.

2    mg may be used where response to the initial dose has been minimal.

Maximum dose 4 mg in unfavourable primigravida patients or 3 mg in other patients (see "Precautions").

The gel should be inserted high into the posterior fornix avoiding administration into the cervical canal. The patient should be instructed to remain recumbent for at least 30 minutes.

Elderly: Not applicable. Children: Not applicable.

4.3 Contraindications

Prostin E2 Vaginal Gel should not be used where the patient is sensitive to prostaglandins or other constituents of the gel.

Prostin E2 Vaginal Gel is not recommended in the following circumstances:

1.    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; Grand multiparae with over five previous term pregnancies.

2.    Patients with ruptured membranes

3.    In patients with a past history of, or existing, pelvic inflammatory disease, unless adequate prior treatment has been instituted.

4.    In patients where there is clinical suspicion or definite evidence of placenta praevia or unexplained vaginal bleeding during this pregnancy.

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

4.4 Special warnings and precautions for use

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 the total contents of the syringe for one patient only. Discard after use. Use caution in handling the product to prevent contact with skin. Wash hands thoroughly with soap and water after administration.

Prostin E2 Vaginal Gel and Prostin E2 Vaginal Tablets are not bioequivalent.

Caution should be exercised in the administration of Prostin E2 Vaginal Gel for the induction of labour in patients with:

(i)    asthma or a history of asthma;

(ii)    epilepsy or a history of epilepsy;

(iii)    glaucoma or raised intra-ocular pressure;

(iv)    compromised cardiovascular, hepatic, or renal function;

(v) hypertension

As with any oxytocic agent, Prostin E2 Vaginal Gel should be used with caution in patients with compromised (scarred) uteri.

In labour induction, cephalopelvic relationships should be carefully evaluated before use of Prostin E2 Vaginal Gel. During use, uterine activity, fetal status and the progression of cervical dilation should be carefully monitored to detect possible evidence of undesired responses, e.g. hypertonus, sustained uterine contractions, or fetal 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 fetus (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.

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 E

during prolonged treatment. There is no evidence that short-term administration of prostaglandin E can cause similar bone effects.

The Clinician should be alert that the intracervical placement of dinoprostone gel may result in inadvertent disruption and subsequent embolization of antigenic tissue causing in rare circumstances the development of Anaphylactoid Syndrome of Pregnancy (Amniotic Fluid Embolism).

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. In addition, these factors may further increase the risk associated with labour induction (see section 4.8 Undesirable Effects). Therefore, in these women, use of dinoprostone should be undertaken with caution. Measures should be applied to detect as soon as possible an evolving fibrinolysis in the immediate post-partum phase.

4.5 Interaction with other medicinal products and other forms of interaction

Since it has been found that prostaglandins potentiate the effect of oxytocin, it is recommended that if these drugs are used together. If used in sequence, the patient's uterine activity should be carefully monitored.

4.6 Fertility, Pregnancy and lactation

Pregnancy Code A

Prostin E2 Vaginal Gel is only used during pregnancy, to induce labour.

Prostaglandins are excreted in breast milk. This is not expected to be a hazard given the circumstances in which the product is used.

4.7 Effects on ability to drive and use machines

Not applicable.

4.8 Undesirable effects

Cardiac disorders: Cardiac arrest

Vascular disorders: Hypertension

Gastrointestinal disorders: Diarrhoea, nausea, vomiting

General disorders and administration site conditions: Fever

Immune system disorders: Hypersensitivity reactions such as anaphylactoid

reactions and anaphylactic reactions including anaphylactic shock.

Musculoskeletal and connective tissue disorders: Back pain

Pregnancy andpuerperium conditions:

Maternal-related conditions: uterine hypertonus, uterine rupture, abruptio placenta, pulmonary amniotic fluid embolism, rapid cervical dilatation

Foetus-related conditions: uterine hypercontractility with/without fetal bradycardia fetal distress/altered fetal heart rate (FHR)

Neonatal conditions: neonatal distress

Pregnancy and perinatal conditions:

Neonatal conditions: neonatal death, stillbirths, low Apgar score

Reproductive system and breast disorders: Warm feeling in vagina, irritation, pain

Respiratory, thoracic and mediastinal disorders: Asthma, bronchospasm Skin and subcutaneous tissue disorders: Rash

Blood and lymphatic system disorders: An increased risk of post-partum disseminated intravascular coagulation has been described in patients whose labour was induced by pharmacological means, either with dinoprostone or oxytocin (see section 4.4 Special Warnings and Special Precautions for Use). The frequency of this adverse event, however, appears to be rare (<1 per

1,000 labours).

4.9 Overdose

Overdosage may be expressed by uterine hypercontractility and uterine hypertonus. During use, uterine activity, fetal status and the progression of

cervical dilation should be carefully monitored to detect possible evidence of undesired responses, e.g. hypertonus, sustained uterine contractions, or fetal distress. Because of the transient nature of PGE2-induced myometrial hyperstimulation, non-specific, conservative management was found to be effective in the vast majority of cases: i.e. maternal position change and administration of oxygen to the mother. If conservative management is not effective, B-adrenergic drugs may be used as a treatment of hyperstimulation following administration of PGE2 for cervical ripening, in appropriate patients.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Dinoprostone is a prostaglandin of the E series, which induces myometrial contractions and promotes cervical ripening.

5.2 Pharmacokinetic properties

General characteristics of active substance

When given vaginally, PGE2 is rapidly absorbed. Plasma levels of 15-keto PGE2 equivalents peak at 1.5 hours after administration of a 5 mg dose. In vitro work indicates that PGE2 is 73% bound to human plasma albumin. It is rapidly metabolised in the lungs, kidneys, spleen and liver, with a single pass of the circulatory system converting 90% of an injected PGE2 dose to metabolites.

Characteristics in patients

No special characteristics. See "Special warnings and special precautions for use" for further information.

5.3 Preclinical safety data

There are no pre-clinical data of relevance which are additional to that already included in other sections of the SPC.

6.1 List of excipients

Triacetin and colloidal silicon dioxide.

6.2 Incompatibilities

None known.

6.3 Shelf life

Prostin E2 Vaginal Gel has a shelf-life of 24 months when stored in a refrigerator at 2-8°C.

6.4 Special precautions for storage

Store in a refrigerator at 2 - 8°C.

6.5 Nature and contents of container

Polyethylene syringe containing 3 g or 2.5 ml of gel.

6.6 Special precautions for disposal

Use the total contents of the syringe for one patient only. Discard alter use. Use caution in handling this product to prevent contact with skin. Wash hands thoroughly with soap and water after administration.

7    MARKETING AUTHORISATION HOLDER

Pfizer Limited Ramsgate Road Sandwich Kent CT13 9NJ United Kingdom

8    MARKETING AUTHORISATION NUMBER(S)

PL 00057/1029

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

30/04/1986 / 28/10/2004

10    DATE OF REVISION OF THE TEXT

24/04/2014