PROPESS 10MG VAGINAL DELIVERY SYSTEM

Active substance: DINOPROSTONE

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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.

Administration
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.
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.

4.4

When labour has started.

When there is placenta previa or unexplained vaginal bleeding during the
current pregnancy.

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.

4.6

Pregnancy and lactation
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

Common
(>1/100,
<1/10)

Adverse Events (MedDRA Preferred
Term)
Abnormal labour affecting fetus

Pregnancy,
puerperium and
perinatal conditions

Fetal heart rate disorder
Fetal distress syndrome
Uterine hypertonus

Uncommon
(>1/1,000,
<1/100)

Gastro-intestinal
disorders

Nausea, vomiting, diarrhoea

Rare

Blood and lymphatic Disseminated intravascular coagulation
(>1/10,000, system disorders
<1/1,000)
Pregnancy,
Uterine rupture
puerperium and
perinatal conditions
Very rare

Immune system
(<1/10,000) disorders
including
Reproductive

Anaphylactic reaction

isolated
reports

system and breast
disorders

Genital oedema

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.

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)

8

MARKETING AUTHORISATION NUMBER(S)
PL 03194/0084

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
13/12/2006

10

DATE OF REVISION OF THE TEXT
13/12/2011

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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