Prostin E2 Vaginal Tablets 3mg
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Prostin E2 Vaginal Tablets 3mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Dinoprostone HSE 3 mg
3 PHARMACEUTICAL FORM
Tablet for vaginal administration
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Oxytocic. Prostin E2 Vaginal Tablets 3mg are indicated for the induction of labour, especially in patients with favourable induction features, when there are no fetal or maternal contra-indications.
4.2 Posology and method of administration
Method of administration: Vaginal tablets are administered by insertion high into the posterior fornix.
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.
Children: Not applicable
Elderly: Not applicable
4.3 Contraindications
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:
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 pre-existing 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. 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 caution in handling this product to prevent contact with skin. Wash hands thoroughly with soap and water after administration.
Caution should be exercised in the administration of Prostin E2 Vaginal Tablets 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 Tablets 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 Tablets. 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.
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 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
Prostin E2 Vaginal Tablets are 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.
5.1 Pharmacodynamic properties
Dinoprostone is a prostaglandin of the E series with actions on smooth muscle; the endogenous substance is termed prostaglandin E2 (PGE2). It induces contraction of uterine muscle at any stage of pregnancy and is reported to act predominantly as a vasodilator on blood vessels and as a bronchodilator on bronchial muscle. It is postulated that vaginal absorption of PGE2 stimulates endogenous PGE2 and PGF2a production, similar to that which is seen in spontaneous labour.
5.2 Pharmacokinetic properties
Following insertion of the tablet, PGE2 absorption (as measured by the presence of PGE2 metabolites) increases to reach a peak at about 40 minutes. PGE2 is rapidly metabolised to 13, 14-dihydro, 15-keto PGE2 which is converted to 13, 14-dihydro, 15-keto PGA2 which binds covalently to albumen.
There has been found to be inter-patient variability regarding systemic absorption of PGE2. This can be attributed to different conditions of the vaginal mucosa between patients
5.3 Preclinical safety data
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 Ej during prolonged treatment. There is no evidence that short-term administration of prostaglandin E2 can cause similar bone effects.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose
Microcrystalline Cellulose Colloidal Silicon Dioxide Maize Starch Magnesium Stearate
6.2 Incompatibilities
None known
6.3 Shelf life
24 months.
6.4 Special precautions for storage
Store in a refrigerator.
Where the tablets are pack in a bottle, the tablets should be used within one month of opening the bottle.
6.5 Nature and contents of container
Amber glass bottle with screw cap and tac seal. Each bottle contains a desiccant capsule and 4 tablets.
Aluminium foil strip of 4 tablets, each box containing 4 or 8 tablets.
6.6 Special precautions for disposal
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 00057/1516
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
15/03/1982 / 28/10/2004
DATE OF REVISION OF THE TEXT
15/11/2014