PHYSICIAN LEAFLET

Prostin® E2 Sterile Solution 1mg/ml

(dinoprostone)

II III

PAA068840

583

For intravenous use only.

Presentation

This pack contains one ampoule containing

0.75 ml of a colourless, sterile solution of 1 mg/ml dinoprostone (prostaglandin E₂) in ethanol.

Uses

Oxytocic agent. Prostin E2 Sterile Solution 1 mg/ml is indicated for the induction of labour by the intravenous route.

Dosage and administration

Directions for the Preparation of a Dilute Solution: For use by IV. drip (a drip set delivering 60 drops per ml must be used) or constant rate infusion pump. Withdraw 0.75 ml from the ampoule using an aseptic technique and add to 500 ml sterile normal saline or 5% dextrose. Shake to ensure uniformity.

After dilution attach label provided. Use dilute solution within 24 hours of preparation and store in a refrigerator at 2-8°C.

The dose of Prostin E2 used, normally depends not only upon the indication, but also on patient response.

The following is a guide to dosage:

Dilute with normal saline or 5% dextrose as above 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.

The appearance of fetal distress or uterine hypertonus requires cessation of therapy until the state returns to normal. The situation should be re-assessed and, if necessary, the infusion can be recommenced but at lower dosage rates, 50% of the last dose level used.

If no response is seen within the first 12-24 hours of treatment, the medication should be discontinued.

Children and elderly patients: Not applicable.

Contra-indications, warnings etc.

Contra-indications: Prostin E2 Sterile Solution 1 mg/ml 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 in which there is cephalopelvic disproportion;

Cases in which fetal malpresentation is present; Cases in which 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 six or more 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 with unexplained vaginal bleeding during this pregnancy.

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

Interactions with other medicaments 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.

Effects on ability to drive and to use machines:

Not applicable.

Other undesirable effects:

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, Puerperium and Perinatal 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, 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. The frequency of this adverse event, however, appears to be rare (<1 per 1,000 labours).

Post-marketing surveillance:

Use in pregnancy and lactation: 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.

Other special warnings and precautions:

Warnings: This product is available only 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.

It is advised that Prostin E2 Sterile Solution should not be administered by the intramyometrial route, as there have been reports of a possible association between this route of administration and cardiac arrest in severely ill patients.

Precautions: Caution should be exercised in the administration of prostaglandins to 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, prostaglandins should be used with caution in patients with compromised (scarred) uteri.

In labour induction, cephalopelvic relationships should be carefully evaluated before use of prostaglandins. 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.

PATIENT INFORMATION LEAFLET Prostin® E2 Sterile Solution 1 mg/ml

Read all of this leaflet carefully before you are given this medicine.

Keep this leaflet. You may need to read it again. If you have any further questions, ask your doctor or midwife.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or midwife.

In this leaflet:

1.    What Prostin E2 Sterile Solution is and what it is used for

2.    Before you are given Prostin E2 Sterile Solution

3.    How Prostin E2 Sterile Solution is given to you

4.    Possible side effects

5.    How to store Prostin E2 Sterile Solution

6.    Further information

1.    What Prostin E2 Sterile Solution is and what it is used for

Prostin E2 Sterile Solution contains the prostaglandin dinoprostone and is used to “induce” labour. This means that the medicine will help your uterus (womb) to start contracting and you will go into labour. It is an infusion which will be given into your blood through a vein (intravenous). Dinoprostone is similar to the natural ‘E2', type of prostaglandins which are made in your body when labour starts. It will only be given to you in a hospital or clinic.

2.    Before you are given Prostin E2 Sterile Solution

Most women can be treated with Prostin E2.

Some women may need extra checks during treatment and for some women a different treatment may be better. Your doctor or midwife will ask you questions before giving you Prostin E2 to make sure it is safe for you. If you do not understand any of the questions, ask your doctor or midwife to explain.

Do not use Prostin E2 Sterile Solution:

•    If you have had an allergic reaction (e.g. wheezing, breathlessness, swelling of the hands, face, itchy rash or redness of the skin) to dinoprostone or any other prostaglandin or any of the other ingredients in the infusion, which are listed in Section 6 below.

•    If you have current heart, lung, kidney or liver disease Your doctor or midwife will not use Prostin E2 to start or strengthen your labour in certain circumstances if:

•    you have had a Caesarean section or any major surgery to your womb

•    you have been told that your baby is too big for your pelvis, is lying awkwardly or may be physically stressed

•    your baby is not lying with his or her head down

•    there has been or there is suspected foetal distress (your baby is short of oxygen).

•    you had a difficult labour or traumatic delivery in a previous pregnancy

•    you have already had six or more full-term pregnancies

•    you had any abnormal contractions of your womb that were too strong or went on for too long during a previous labour

•    you have an infection of your womb, ovaries or tubes (pelvic inflammatory disease) unless you are receiving treatment for these, or if you have ever had such an infection in the past.

•    you have been told that you have or might have placenta praevia (where the placenta lies across the entrance to the womb, rather than being high up and out of the way during birth). This causes bleeding from the vagina during pregnancy and may require that your baby is delivered by Caesarean section.

•    during your pregnancy you have had bleeding from the vagina or spotting at any time during months four to nine (second and third trimester) of your pregnancy

•    you have any infection or irritation in your cervix (the neck of the womb) or in your vagina, for example you might notice an unusual discharge or an unpleasant smell.

Take special care with Prostin E2 Sterile Solution:

Tell your doctor or midwife if you have or have had in the past any of the following conditions as they may want to monitor you more closely.

•    heart, lung, kidney or liver disease

•    glaucoma (raised pressure in the eye)

•    epilepsy

•    suffered from asthma

•    hypertension (high blood pressure) at any time, including during this or any previous pregnancy

•    been told you had abnormally strong contractions of your womb during a previous labour

•    scarring of your womb from a previous operation

•    Are you 35 years or older?

•    Is your pregnancy over 40 weeks?

•    Do you have any complications related to this pregnancy?

Your doctor or midwife will ask you questions before giving you Prostin E2 to make sure it is safe for you. If you do not understand any of the questions, ask your doctor or midwife to explain.

Taking other medicines:

Prostin E2 Sterile Solution can make you more sensitive to another medicine called oxytocin which is used to strengthen contractions. Medical staff will normally try not to use this medicine at the same time as Prostin E2 Sterile Solution. If used with this medicine in sequence, your doctor or midwife will watch over the womb contractions very carefully.

Your doctor may give you antibiotics before you start this prostaglandin treatment.

Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Pregnancy and breastfeeding

Prostin E2 will only be given to you in the late stages of pregnancy to induce labour.

Although prostaglandins are present in breast milk they will not harm your baby and you may breast-feed as normal after delivery.

Driving and using machinery

No effect on your ability to drive or use machinery is expected after being given Prostin E2.

3. How Prostin E2 Sterile Solution is given to you

Prostin E2 Sterile Solution is given by an intravenous drip, into a vein. It is always diluted before use with a saline (salt) or dextrose (sugar) solution. Your doctor or midwife will adjust the dose to suit you.

The mixture is made up to contain 1.5 micrograms per ml of Prostin E2 Sterile Solution and the drip is set to deliver 0.25 micrograms per minute (a microgram is a millionth of a gram - a very small unit of measurement) for 30 minutes. This dose is then either kept the same or increased. (If the baby has died (a 'still birth'), a higher dose may be needed so the drip may be set to deliver 0.5 micrograms per minute and this may be adjusted hourly).

Your doctor or midwife will be keeping a very close eye on you during your treatment. They should be able to act quickly if you have side-effects. If your baby becomes distressed or the muscles of your womb become very tense (uterine hypertonus), or your contractions become very strong and painful your doctor or midwife will stop your treatment temporarily. When the muscles of your womb have relaxed and your baby is not distressed any more your doctor or midwife may start your treatment again with half the last dose used. If your doctor or midwife stops your treatment temporarily and your condition does not return to normal then he or she may deliver your baby by Caesarean section.

If labour does not start within the first 12 to 24 hours of your being given prostaglandin E2, your doctor or midwife will stop treatment.

Your doctor or midwife will do internal checks to make sure that your cervix is opening enough. They will also check your contractions (to make sure that they are not too strong) and your baby (to make sure he or she does not get distressed).

4. Possible side effects

Like all medicines Prostin E2 Sterile Solution can cause side effects, although not everybody gets them.

If you have asthma, Prostin E2 could cause you to have an asthmatic attack by causing a narrowing of your airways (bronchospasm). You must tell your doctor or midwife if you suffer from asthma or if you start having difficulty in breathing.

Rare side effects

Rare but serious side effects which can sometimes happen include the following:

•    tearing or bursting of the wall of your womb (uterine rupture)

•    heart attack

•    allergic / anaphylactic reactions, including anaphylactic shock (serious allergic reactions which can include skin rash, itching, wheezing, shortness of breath, swollen face, lips, hands, fingers, neck and throat, sudden drop in blood pressure, abdominal pain and collapse ).

If you get any of these symptoms please tell your doctor or midwife straight away.

code	guidelines	dimensions	1 date	country
PAA068840	TSE-I134B	330x297/37	24-Nov-15 EA	ENGLAND