PROPESS® is indicated for initiation of cervical ripening in the late pregnancy (from 37 completed weeks of gestation)

Posology:

One vaginal delivery system is administered high into the posterior vaginal fornix. The vaginal delivery system should be removed after 24 hours irrespective of whether cervical ripening has been achieved. A dosing interval of at least 30 minutes is recommended for the sequential use of oxytocin following the removal of the vaginal delivery system.
Paediatric population: The safety and efficacy of PROPESS® in pregnant woman aged less than 18 years has not been established. No data are available.
Method of administration
Administration: PROPESS® should be removed from the freezer immediately before insertion.
No thawing is required prior to use.
There is a “tearmark” on side of the foil sachet. Open the package along the tear mark across the top of the sachet. Do not use scissors or other sharp objects which may cut the retrieval system. 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. The end of the tape should not be tuck into the vagina as this may make retrieval more difficult. The patient should be recumbent for 20 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 foetal 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 follows: the presence of regular painful uterine contractions occurring every 3 minutes irrespective of any cervical change.
There are two important points to note:
- 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.
- 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®, 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 a fetal distress situation.
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, as there is a much greater risk of hyperstimulation if the dinoprostone source is not removed before administration 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 duringmanufacture. 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 of its original size and be pliable.

PROPESS® must not be used or the administration must be discontinued if the following occurs: 1. When labour has started. 2. When oxytocic drugs and/or other labour induction agents 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… b. With cephalopelvic disproportion. c. With fetal malpresentation. d. With suspicion or evidence of fetal distress. e. Who have had previous major surgery (e.g. other than biopsies and cervical abrasion) or rupture of the uterine 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.

The condition of the cervix should be assessed carefully before PROPESS® is used. After insertion, uterine activity and foetal condition must be monitored regularly. PROPESS® must only be used if facilities for continuous foetal and uterine monitoring are available. If there is any suggestion of maternal or foetal 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 hypertonus, 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 then 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. 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. PROPESS® should be used with caution when the woman has had more than three full term deliveries. No studies in woman with more than three full term deliveries 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 PROPESS® 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 PROPESS® 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 intravasal coagulation in women with pharmacologically induced labour. Therefore, dinoprostone an 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). The clinician should be alert that, as with other labour induction methods, use of dinoprostone may result in inadvertent abruption of placenta and subsequent embolization of antigenic tissue causing in rare circumstances the development of Anaphylactoid
Syndrome of Pregnancy (Amniotic Fluid Embolism).

No dedicated interaction studies have been performed with PROPESS®.Prostaglandins potentiate the uterotonic effect of oxytocic drugs. Therefore,
PROPESS® should not be used concurrently with the use of oxytocic drugs.

Pregnancy: PROPESS® should not be used during pregnancy prior to 37 completed weeks of gestation.
Breast-feeding: No studies have been performed to investigate the amount
of dinoprostone in colostrum or breast milk following the use of PROPESS®.Dinoprostone may be excreted in colostrum and breast milk, but the level and duration is expected to be very limited and should not hinder breastfeeding. No effects on the breastfed new borns have been observed in the clinical studies conducted with PROPESS®.
Fertility: Not relevant

Not relevant.

Summary of safety profile: The most commonly
reported adverse drug reactions in placebo-controlled
and active comparator efficacy clinical trials (N=1116) were “foetal heart rate
disorder” (6.9%), “uterine contractions abnormal” (6.2%) and “abnormal labour
affecting foetus” (2.6 %). The ADRs below are distributed by system organ classes
(SOC) and frequency. Further, the ADRs seen during post-marketing experience
are mentioned with unknown frequency. Adverse reactions observed in clinical
studies are presented according to their incidence, post authorization reported
adverse reactions are presented under frequency unknown.
- Blood and lymphatic system disorders: Not known (frequency cannot be
estimated from the available data): Disseminated intravascular coagulation.
- Immune system disorders: Not known (frequency cannot be estimated from
the available data): Anaphylactic reaction, hypersensitivity.
- Nervous system disorders: Uncommon (≥ 1/1000 and ≤ 1/100): Headache
- Cardiac disorders: Common (≥ 1/100 and < 1/10): Foetal heart rate
disorder1*.
- Vascular disorders: Uncommon (≥ 1/1000 and ≤ 1/100): Hypotension.
- Respiratory, thoracic and mediastinal disorders: Uncommon (≥ 1/1000
and ≤ 1/100): Neonatal respiratory distress related conditions.
- Gastrointestinal disorders: Not known (frequency cannot be estimated from
the -available data): Abdominal pain, nausea, vomiting, diarrhoea.
- Hepatobiliary disorders:Uncommon (≥ 1/1000 and ≤ 1/100): Neonatal
hyperbilirubinaemia.
- Skin and subcutaneous tissue disorders: Uncommon (≥ 1/1000 and
≤ 1/100): Pruritus.
- Pregnancy, puerperium and perinatal conditions:
Common (≥ 1/100 and < 1/10): Abnormal labour affecting foetus 2*, uterine
contractions abnormal 4*, meconium in amniotic fluid.
Uncommon (≥ 1/1000 and ≤ 1/100): Postpartum haemorrhage, premature
separation of placenta, apgar score low, arrested labour, chorioamnionitis,
uterine atony.
Not known (frequency cannot be estimated from the available data):
Anaphylactoid syndrome of pregnancy, Foetal distress syndrome 3*.
- Reproductive system and breast disorders: Uncommon (≥ 1/1000 and
≤ 1/100): Vulvovaginal burning sensation. Not known (frequency cannot be
estimated from the available data): Genital oedema
- General disorders and administration site conditions: Uncommon (≥ 1/1000
and ≤ 1/100): Febrile disorders
- Injury, poisoning and procedural complications: Not known (frequency
cannot be estimated from the available data):
Uterine rupture 1*’’Foetal heart rate disorder’’ was in clinical studies
reported as ‘’foetal heart rate abnormalities’’, ‘’foetal bradycardia’’, ‘’foetal
tachycardia’’, ‘’unexplained absence of normal variability’’, ‘’foetal heart rate
decreased’’, ‘’foetal heart rate deceleration’’, ‘’early or late decelerations’’,
‘’variable decelerations’’, ‘’prolonged decelerations’’.
2* ‘’Abnormal labour affecting foetus’’ as expression for hyperstimulation
syndrome was in clinical studies reported as ‘’uterine tachysystole’’ combined
with ‘’late decelerations’’, ‘’foetal bradycardia’’, or ‘’prolonged decelerations’’
3* ‘’Foetal distress syndrome’’ was also reported as ‘’foetal acidosis’’ ,
‘’pathological CTG’’, ‘’foetal heart rate abnormalities’’,
‘’intrauterine hypoxia’’ or ‘’threatening asphyxia’’. The term itself is unspecific,
has a low positive predictive value and is often associated with an infant who
is in good condition at birth.
4* ‘’Uterine contractions abnormal’’ were reported as ‘’uterine
hyperstimulation’’ and ‘’uterine hypertonus’’.

Over dosage or hypersensitivity may lead to hyperstimulation of the uterine muscle with or without foetal distress. If foetal distress occurs, remove PROPESS® immediately and manage in accordance with local protocol.

Pharmacotherapeutic group: oxytocics, prostaglandins. ATC‑code: G02AD02.
Prostaglandin E2 (dinoprostone) 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 transformation 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.

Dinoprostone is rapidly metabolized 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 dinoprostone 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.

N/A

Hydrogel Polymer prepared with: Macrogol 8000,
Dicyclohexyl methane-4, 4’-diisocyanate 1,2,6-Hexanetriol, Ferric Chloride
Polyester retrieval system

Not applicable.

See outer carton

Store in a freezer (-15°C to -25°C). Store in the original container in order to protect from moisture.
No thawing is required prior to use.

PROPESS® vaginal delivery systems are presented in individual, sealed aluminium/ polyethylene laminate sachets in packs of 1 or 5 vaginal delivery systems. Not all pack sizes may be marketed in your country.

PROPESS® should be taken from the freezer only immediately before use. After usage, the whole product should be disposed of as clinical waste.