Prostin® E2 Sterile Solution 10mg/ml

Dinoprostone

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8R3750

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PHYSICIAN LEAFLET

Prostin® E2 Sterile Solution 10 mg/ml

Dinoprostone

For extra-amniotic use only.

Presentation

This pack contains one ampoule containing 0.5 ml of a colourless, sterile solution of 10 mg/ml dinoprostone (prostaglandin E₂) in ethanol together with one vial containing 50 ml of sterile bacteriostatic saline.

Each ampoule contains 5 mg dinopostone in ethanol.

Each vial contains sodium chloride, benzyl alcohol and water. When mixed, each ml of the resulting solution will contain 0.1 mg (100 micrograms) dinoprostone.

Uses

Oxytocic agent. Prostin E2 Sterile Solution 10 mg/ml is indicated for therapeutic termination of pregnancy, by the extra-amniotic route.

Dosage and administration

Directions for the Preparation of a Dilute Solution: Withdraw 0.5 ml from the ampoule, using an aseptic technique and add to contents of the vial of diluent (50 ml) provided. Shake to ensure uniformity.

After dilution, attach label provided. Use dilute solution within 48 hours of preparation. Store in a refrigerator at 2-8°C.

The following is a guide to dosage:

A solution containing 100 micrograms per ml dinoprostone should be prepared using the diluent provided as described earlier in this leaflet. This should be installed into the extra-ovular space via a 12-14 French gauge Foley catheter with self-retaining balloon (a fine polyethene catheter may also be used). After filling the catheter system dead space with a predetermined quantity of dilute drug solution, the initial installation should be 1 ml. Subsequent installations will vary between 1 and 2 ml (usually 2 ml) in accordance with uterine response. Two hours should usually elapse between each installation and never less than 1 hour.

The appearance of 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.

In all cases the dosage should be adapted to the patient’s response. Continuous administration of the drug for more than two days is not recommended.

Children and elderly patients: Not applicable

Contra-indications, warnings etc.

Contra-indications: Prostin E2 Sterile Solution 10 mg/ml should not be used where the patient is sensitive to prostaglandins.

Prostin E2 Sterile Solution 10 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 where there is evidence of a potential for obstructed labour.

2.    In patients with a past history of, or existing, pelvic inflammatory disease, unless adequate prior treatment has been instituted.

3.    In patients with cervictis or vaginal infections.

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), temporary pyrexia, local infections

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 and puerperium conditions

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PATIENT INFORMATION

Prostin® E2 Sterile Solution 10 mg/ml

Dinoprostone

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 nurse.

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 nurse.

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 which will end the pregnancy. This is also called termination of pregnancy or an abortion. 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. It is given to you as an infusion, directly into the womb.

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 nurse 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 nurse to explain.

If you are having a pregnancy termination (abortion), it is very important for it to be complete. This is because prostaglandins given at this stage in pregnancy may cause abnormalities in the foetus. If your doctor thinks that the abortion has not worked completely, you will need another treatment, probably an operation.

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 nurse 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 in the past

•    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 will have an obstructed labour

Take special care with Prostin E2 Sterile Solution:

Tell your doctor or nurse 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 nurse 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 nurse 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 nurse 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. Prostin E2 is only used during pregnancy for the therapeutic termination of pregnancy.

Although prostaglandins are present in breast milk, you are not expected to be breast-feeding as this medicine is used to terminate the pregnancy.

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

This product can only be used in hospitals and clinics with specialised units for pregnancy and childbirth (obstetric units). Medical staff will be available at all times.

Prostin E2 Sterile Solution is diluted before use with the 50 ml of diluent supplied, to make a solution containing 100 micrograms/ml. The 100 micrograms/ml solution is instilled (placed drop by drop) into the womb, using a fine tube that is passed up into the womb through your vagina and cervix (neck of the womb). Medical staff will adjust the dose to suit you. At first 1 ml of solution is given. Then depending on how your womb responds, another 1 ml or 2 ml may be given at two-hourly intervals. The doctor or nurse will want to make sure that the contractions do not become too strong.

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Maternal-related conditions: uterine hypertonus, uterine rupture, abruptio placenta, pulmonary amniotic fluid embolism, rapid cervical dilatation

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).

Use in pregnancy and lactation: Prostin E2 Sterile Solution 10 mg/ml is only used during pregnancy for therapeutic termination of pregnancy. There has been some evidence in animals of a low order of teratogenic activity, therefore, if abortion does not occur or is suspected to be incomplete as a result of prostaglandin therapy, (as in spontaneous abortion, where the process is sometimes incomplete), the appropriate treatment for complete evacuation of the pregnant uterus should be instituted in all instances.

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.

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.

Overdosage (symptoms, emergency procedures, antidotes): Overdosage may be expressed by uterine hypercontractility and uterine hypertonus. During use, uterine activity and the progression of cervical dilation should be carefully monitored

to detect possible evidence of undesired responses, e.g. hypertonus or sustained uterine contractions. Because of the transient nature of PGE2-induced myometrial hyperstimulation, non-specific, conservative management should be used (rate of infusion should be decreased or discontinued, maternal position change and administration of oxygen). If conservative management is not effective, a tocolytic agent may be used in appropriate patients as a treatment of hyperstimulation following administration of PGE2 or appropriate measures should be considered. Incompatibilities: None known.

Pharmaceutical precautions

Prostin E2 Sterile Solution 10 mg/ml has a shelf-life of 24 months when stored under refrigeration at 4°C. It should be diluted before use only with the diluent provided. Diluted solutions should be used within 48 hours and stored in a refrigerator at 2-8°C.

Manufacturer

The product is manufactured by Pfizer Manufacturing Belgium NV, Rijksweg 12, B-2870 Puurs, Belgium and distributed in the United Kingdom by Pfizer Limited, Ramsgate Road, Sandwich, Kent, CT13 9NJ, UK.

Marketing Authorisation Holder

Pfizer Limited, Ramsgate Road, Sandwich, Kent,

CT13 9NJ, UK.

Further information

Oral Prostin E2 Tablets, Prostin E2 Vaginal Tablets and Prostin E2 Vaginal Gel are also available for the induction of labour.

Product authorisation number

PL 00057/1030

Date of preparation or last review

02/2014

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