SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Prostin E2 Sterile Solution 1 mg/ml.

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

Each ml contains 1 mg dinoprostone.

3    PHARMACEUTICAL FORM

Colourless, sterile solution, which after appropriate dilution is intended for intravenous administration to human beings.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

The induction of labour by the intravenous route.

4.2    Posology and method of administration

Adults: Ampoule contents must be diluted before use and full instructions on method of dilution and dosage are given on the package insert which should be consulted prior to initiation of therapy. The following is a guide to dosage:

Dilute with normal saline or 5% dextrose according to the package insert to produce a 1.5 micrograms/ml solution. The 1.5 micrograms/ml solution is infused at 0.25 micrograms/minute for 30 minutes and then maintained or increased. Cases of fetal death in utero may require higher doses. An initial rate of 0.5 micrograms/minute may be used with stepwise increases, at intervals of not less than one hour.

Elderly: Not applicable

Children: Not applicable.

4.3 Contraindications

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:

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 fetal malpresentation is present;

Cases where there is clinical suspicion or definite evidence of preexisting fetal distress;

Cases in which there is a history of difficult labour and/or traumatic delivery;

Grand multiparae with over five previous term pregnancies.

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

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

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

4.4 Special warnings and precautions for use

Use caution in handling this product to prevent contact with skin. Wash hands thoroughly with soap and water after administration.

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:

(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 Sterile Solution 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 Sterile Solution. 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 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. 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.

Interaction with other medicinal products and other forms of interaction

Since it has been found that prostaglandins potentiate the effect of oxytocin, it is not recommended that 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 Sterile Solution 1 mg/ml 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

Immune system disorders: Hypersensitivity reactions such as anaphylactoid reactions and anaphylactic reactions including anaphylactic shock.

Cardiac disorders: Cardiac arrest

Vascular disorders: Hypertension

Gastrointestinal disorders: Diarrhoea, nausea, vomiting

General disorders and administration site conditions: Fever, local tissue

irritation / erythema (injection site)

Immune system disorders: Hypersensitivity reactions such as anaphylactoid reactions and anaphylactic reactions including anaphylactic shock. Investigations: Elevated WBC

Musculoskeletal and connective tissue disorders: Back pain

Nervous system disorders: Transient vasovagal symptoms (flushing, shivering, headache, dizziness)

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 Respiratory, thoracic and mediastinal disorders: Asthma, bronchospasm

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 with actions on smooth muscle. It induces contraction of uterine muscle    at any stage of pregnancy.

5.2    Pharmacokinetic properties

General characteristics of active substance

Dinoprostone is rapidly metabolised in the body. Intravenous administration results in very rapid distribution and metabolism, with only 3% of unchanged drug remaining in the blood after 15 minutes. At least nine prostaglandin E2 metabolites have been identified in human blood and urine.

Characteristics in Patients

No special characteristics. See "Special Warnings and 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    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Dehydrated alcohol.

Incompatibilities

None known.

6.3    Shelf life

24 months.

6.4    Special precautions for storage

Store in a refrigerator at 4°C. The product after dilution should be stored in a refrigerator at 4°C and should not be kept for more than 24 hours.

6.5    Nature and contents of container

Ph. Eur. Type I glass ampoule, containing 0.75 ml sterile solution, packed in a carton.

6.6    Special precautions for disposal

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

CT139NJ UK

8 MARKETING AUTHORISATION NUMBER(S)

PL 00057/1028

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

28/10/2004

10 DATE OF REVISION OF THE TEXT

18/05/2014