Propess 10mg Vaginal Delivery System
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
PROPESS 10mg vaginal delivery system
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each vaginal delivery system consists of a non-biodegradable polymeric drug delivery device containing 10mg dinoprostone (Prostaglandin E2) dispersed throughout its matrix.
For a full list of excipients, see 6.1
3 PHARMACEUTICAL FORM
Vaginal delivery system
PROPESS is presented as a thin, flat semi-opaque polymeric vaginal delivery system which is rectangular in shape with radiused corners contained within a knitted polyester retrieval system.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Initiation of cervical ripening in patients, at term (from 38th week of gestation).
4.2 Posology and method of administration
One vaginal delivery system is administered high into the posterior vaginal fornix.
If there has been insufficient cervical ripening in 24 hours, the vaginal delivery system should be removed.
A dosing interval of at least 30 minutes is recommended for the sequential use of oxytocin following the removal of the vaginal delivery system.
PROPESS should be removed from the freezer in direct connection with the insertion.
The vaginal delivery system should be inserted high into the posterior vaginal fornix using only small amounts of water soluble lubricants to aid insertion. After the vaginal delivery system has been inserted, the withdrawal tape may be cut with scissors always ensuring there is sufficient tape outside the vagina to allow removal. No attempt should be made to tuck the end of the tape into the vagina as this may make retrieval more difficult.
The patient should be recumbent for 20 minutes to 30 minutes after insertion. As dinoprostone will be released continuously over a period of 24 hours, it is important to monitor uterine contractions and fetal condition at frequent regular intervals.
Removal
The vaginal delivery system can be removed quickly and easily by gentle traction on the retrieval tape.
It is necessary to remove the vaginal delivery system to terminate drug administration when cervical ripening is judged to be complete or for any of the reasons listed below.
1. Onset of labour. For the purposes of induction of labour with PROPESS, the onset of labour is defined as the presence of regular painful uterine contractions occurring every 3 minutes irrespective of any cervical change. There are two important points to note:
(i) Once regular, painful contractions have been established with PROPESS they will not reduce in frequency or intensity as long as PROPESS remains in situ because dinoprostone is still being administered.
(ii) Patients, particularly multigravidae, may develop regular painful contractions without any apparent cervical change. Effacement and dilatation of the cervix may not occur until uterine activity is established. Because of this, once regular painful uterine activity is established with PROPESS in-situ, the vaginal delivery system should be removed irrespective of cervical state to avoid the risk of uterine hyperstimulation.
2. Spontaneous rupture of the membranes or amniotomy.
3. Any suggestion of uterine hyperstimulation or hypertonic uterine contractions.
4. Evidence of fetal distress.
5. Evidence of maternal systemic adverse dinoprostone effects such as nausea,
vomiting, hypotension or tachycardia.
6. At least 30 minutes prior to starting an intravenous infusion of oxytocin.
The opening on one side of the retrieval device is present only to allow the manufacturer to enclose the vaginal delivery system into the retrieval device during manufacture. The vaginal delivery system should NEVER be removed from the retrieval device.
On removal of the product from the vagina, the vaginal delivery system will have swollen to 2-3 times its original size and be pliable.
4.3 Contraindications
PROPESS should not be used or left in place:
1. When labour has started.
2. When oxytocic drugs are being given.
3. When strong prolonged uterine contractions would be inappropriate such as in patients:
a. who have had previous major uterine surgery, e.g. caesarean section, myomectomy etc (see sections 4.4 and 4.8)
b. with cephalopelvic disproportion
c. with fetal malpresentation
d. with suspicion or evidence of fetal distress
e. who have had more than three full term deliveries
f. previous surgery or rupture of the cervix
4. When there is current pelvic inflammatory disease, unless adequate prior treatment has been instituted.
5. When there is hypersensitivity to dinoprostone or to any of the excipients.
6. When there is placenta previa or unexplained vaginal bleeding during the current pregnancy.
4.4 Special warnings and precautions for use
The condition of the cervix should be assessed carefully before PROPESS is used. After insertion, uterine activity and fetal condition must be monitored regularly. PROPESS must only be used if facilities for continuous fetal and uterine monitoring are available. If there is any suggestion of maternal or fetal complications or if adverse effects occur, the vaginal delivery system should be removed from the vagina.
The experience of PROPESS in patients with ruptured membranes is limited. Therefore, PROPESS should be used with caution in those patients. Since the release of dinoprostone from the insert can be affected in the presence of amniotic fluid, special attention should be given to uterine activity and fetal condition.
PROPESS should be used with caution in patients with a previous history of uterine hypertony, glaucoma or asthma.
Medication with non-steroidal anti-inflammatory drugs, including acetylsalicylic acid, should be stopped before administration of dinoprostone.
If uterine contractions are prolonged or excessive, there is possibility of uterine hypertonus or rupture and the vaginal delivery system should be removed immediately.
Uterine rupture has been reported in association with the use of PROPESS, mainly in patients with contra-indicated conditions (see section 4.3). Therefore, PROPESS should not be administered to patients with a history of previous caesarean section or uterine surgery given the potential risk for uterine rupture and associated obstetrical complications.
PROPESS should be used with caution when there is a multiple pregnancy. No studies in multiple pregnancy have been performed.
A second dose of PROPESS is not recommended, as the effects of a second dose have not been studied.
The use of the product in patients with diseases which could affect the metabolism or excretion of dinoprostone, e.g. lung, liver or renal disease, has not been specifically studied. The use of the product in such patients is not recommended.
Women aged 35 and over, women with complications during pregnancy, such as gestational diabetes, arterial hypertension and hypothyroidism, and women at gestational age above 40 weeks have a higher post partum risk for developing disseminated intravascular coagulation (DIC). These factors may additionally enhance the risk of disseminated intravascular coagulation in women with pharmacologically induced labour (see section 4.8). Therefore, dinoprostone and oxytocin should be used with caution in these women. In the immediate post-partum phase the physician should look out carefully for early signs of a developing DIC (e.g fibrinolysis).
4.5 Interaction with other medicinal products and other forms of interaction
Prostaglandins potentiate the uterotonic effect of oxytocic drugs. Therefore, PROPESS should not be used concurrently with the use of oxytocic drugs.
The product is for the initiation of cervical ripening in pregnant patients at term only where labour induction is indicated.
PROPESS is not indicated for use during early or other phases of pregnancy or during lactation.
4.7 Effects on ability to drive and use machines
Not relevant.
4.8 Undesirable effects
The occasional effects seen have been those normally associated with intravaginal dinoprostone administration.
CTG changes and unspecified fetal distress have been reported during and after administration of intravaginal dinoprostone. Increased uterine activity with hypertonic contractions with or without fetal distress has been reported. There is a much greater risk of hyperstimulation if the dinoprostone source is not removed before administration of oxytocin because prostaglandins are known to potentiate the uterotonic effects of oxytocic drugs.
|
Frequency |
MedDRA System Organ Class |
Adverse Events (MedDRA Preferred Term) |
|
Common (>1/100, <1/10) |
Pregnancy, puerperium and perinatal conditions |
Abnormal labour affecting fetus Fetal heart rate disorder Fetal distress syndrome Uterine hypertonus |
|
Uncommon (>1/1,000, <1/100) |
Gastro-intestinal disorders |
Nausea, vomiting, diarrhoea |
|
Rare (>1/10,000, <1/1,000) |
Blood and lymphatic system disorders Pregnancy, puerperium and perinatal conditions |
Disseminated intravascular coagulation Uterine rupture |
|
Very rare (<1/10,000) including |
Immune system disorders Reproductive |
Anaphylactic reaction |
In the pivotal efficacy study, five (4.9%) of 102 patients had hyperstimulation. Of these, three cases were associated with fetal distress. Of the five cases, uterine hypertonus was resolved in four after removal of the insert.
In post-marketing experience reports, uterine rupture has been reported rarely in association with the use of PROPESS (see sections 4.3 and 4.4).
An increased risk of post-partum disseminated intravascular coagulation has been reported in patients whose labour was induced by pharmacological means, either with dinoprostone or oxytocin (see section 4.4).
PGE2 is known to be responsible for the patency of the ductus arteriosus in pregnancy but there have been no reports of "blue babies" in the neonatal period after the use of
PROPESS.
isolated
reports
system and breast disorders
Genital oedema
4.9 Overdose
Overdosage or hypersensitivity may lead to hyperstimulation of the uterine muscle or fetal distress. The PROPESS vaginal delivery system should be removed immediately and the patient should be managed in accordance with local protocol.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: oxytocics, ATC-code: G02AD02
Prostaglandin E2 (PGE2) is a naturally occurring compound found in low concentrations in most tissues of the body. It functions as a local hormone.
Prostaglandin E2 plays an important role in the complex set of biochemical and structural alterations involved in cervical ripening. Cervical ripening involves a marked relaxation of the cervical smooth muscle fibres of the uterine cervix which
must be transformed from a rigid structure to a soft, dilated configuration to allow passage of the fetus through the birth canal. This process involves activation of the enzyme collagenase which is responsible for the breakdown of the collagen.
Local administration of dinoprostone to the cervix results in cervical ripening which then induces the subsequent events which complete labour.
5.2 Pharmacokinetic properties
PGE2 is rapidly metabolised primarily in the tissue of synthesis. Any which escapes local inactivation is rapidly cleared from the circulation with a half-life generally estimated as 1-3 minutes.
No correlation could be established between PGE2 release and plasma concentrations of its metabolite, PGEm. The relative contributions of endogenously and exogenously released PGE2 to the plasma levels of the metabolite PGEm could not be determined.
The reservoir of 10 mg dinoprostone serves to maintain a controlled and constant release. The release rate is approximately 0.3 mg per hour over 24 hours in women with intact membranes whereas release is higher and more variable in women with premature rupture of membranes. PROPESS releases dinoprostone to the cervical tissue continuously at a rate which allows cervical ripening to progress until complete, and with the facility to remove the dinoprostone source when the clinician decides that cervical ripening is complete or labour has started, at which point no further dinoprostone is required.
5.3 Preclinical safety data
Preclinical studies have demonstrated that dinoprostone is a locally acting substance which is rapidly inactivated and thus it has no significant systemic toxicity.
The hydrogel and polyester polymers are inert compounds with good local tolerability.
Reproduction toxicity, genotoxic or carcinogenic effects of the polymers have not been investigated but systemic exposure is negligible.
6 PHARMACEUTICAL PARTICULARS
6.1
List of excipients
Hydrogel Polymer.
6.2 Incompatibilities
Not applicable
6.3 Shelf life
3 years
6.4 Special precautions for storage
Store in a freezer. Store in the original container in order to protect from moisture.
6.5 Nature and contents of container
PROPESS vaginal delivery systems are presented in individual, sealed aluminium/polyethylene laminate sachets in packs of 5 vaginal delivery systems.
6.6 Special precautions for disposal
PROPESS should be removed from the freezer in direct connection with the insertion.
After usage, the whole product should be disposed of as clinical waste.
7 MARKETING AUTHORISATION HOLDER
Ferring Pharmaceuticals Ltd. Drayton Hall Church Road West Drayton UB7 7PS (UK)
MARKETING AUTHORISATION NUMBER(S)
PL 03194/0084
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DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
13/12/2006
DATE OF REVISION OF THE TEXT
13/12/2011