Consumer medicine information

What is in this leaflet

This leaflet answers some common questions about Syntometrine.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

The information in this leaflet was last updated on the date listed on the final page. Some more recent information on the medicine may be available.

You should ensure that you speak to your pharmacist or doctor to obtain the most up to date information on the medicine. You can also download the most up to date leaflet from www.phebra.com. Those updates may contain important information about the medicine and its use of which you should be aware.

All medicines have risks and benefits. Your doctor has weighed the risks of you having Syntometrine against the benefits they expect it will provide.

If you have any concerns about this medicine, ask your doctor or pharmacist.

Keep this leaflet. You may need to read it again.

What Syntometrine is used for

Syntometrine can be used during and immediately after delivery of a baby to help the birth and to prevent or treat excessive bleeding.

Syntometrine works by stimulating the muscles of the uterus (womb) to produce rhythmic contractions.

Ask your doctor if you have any questions about why Syntometrine has been prescribed for you. Your doctor may have prescribed it for another purpose.

Syntometrine is only available with a doctor's prescription.

It is not addictive.

Before you are given Syntometrine

When you must not be given it

You must not be given Syntometrine if you are allergic to:

• oxytocin
• ergometrine
• any of the other ingredients listed at the end of this leaflet.

Symptoms of an allergic reaction may include:

• shortness of breath, wheezing or difficulty breathing
• swelling of the face, lips, tongue or other parts of the body
• rash, itching or hives on the skin.

If you think you may be allergic to Syntometrine, ask your doctor for advice.

You must not have Syntometrine if you are pregnant or are in labour but the baby's shoulder has not yet been delivered. You must not have Syntometrine if you:

• have severe high blood pressure
• have severe heart, liver or kidney problems
• have high blood pressure, protein in the urine and swelling (pre-eclampsia) with convulsions or coma (eclampsia) during pregnancy or after giving birth
• have a narrowing or blockage of blood vessels
• have a severe infection.

The doctor or nurse will check to ensure the medicine is not past its expiry date and has not been tampered with.

Before you are given it

Tell your doctor if you have any of the following:

• allergy to latex. Syntometrine may cause a severe allergic reaction (anaphylaxis) in patients with latex allergy.
• mild or moderate high blood pressure
• an abnormal electrical signal of the heart called "prolongation of the QT interval"
• mild or moderate heart, liver or kidney problems
• any other conditions that affect the heart.
• problems with your lungs
• poor circulation which makes the toes and fingers numb and pale caused by Raynaud's phenomenon
• you are anaemic (have low iron levels in your blood)
• you have had toxaemia during pregnancy.

If you are not sure about any of the above, your doctor can advise you.

Tell your doctor if you are allergic to any other medicines, foods, dyes or preservatives. Your doctor will want to know if you are prone to allergies.

Taking other medicines

Tell your doctor if you are taking any medicines that may affect your heart, or any other medicines, including medicines that you buy without a prescription from a pharmacy, supermarket or health food shop.

Some medicines may interfere with Syntometrine. These may include:

• medicines used to start labour or to treat stomach ulcers known as prostaglandins
• medicines used to narrow the blood vessels and decrease the flow of blood such as vasoconstrictors
• sympathomimetic medicines, which are used in the treatment of asthma, nasal congestion and low blood pressure in emergency situations. This includes where these types of medicines are part of a local anaesthetic.
• medicines used to treat or prevent angina, e.g. glyceryl trinitrate
• beta-blocker medicines such as propranolol, which are used to prevent migraine, treat high blood pressure, irregular heartbeat, and other heart conditions
• inhalation anaesthetics
• medicines for infections, including ketoconazole, itraconazole, fluconazole, clotrimazole, erythromycin, clarithromycin
• medicines used for ulcers and heartburn such as cimetidine
• medicines used to treat HIV/AIDS, including ritonavir, indinavir, nelfinavir
• ergot alkaloids and derivatives, such as methysergide, bromocriptine, and ergometrine
• medicines used to treat migraine such as sumatriptan, and zolmitriptan.

If you have not told your doctor about any of these things, tell him/her before you are given Syntometrine.

Tell your doctor if you have recently had any grapefruit juice. It is recommended that you do not drink grapefruit juice around the same time as your treatment with Syntometrine as these may interact.

Tell your doctor if you plan to breast-feed after being given Syntometrine. Ergometrine derivatives are excreted in breast milk in unknown amounts. Its effects on breast fed newborn are unknown.

The ergometrine in Syntometrine may affect the amount of breast milk produced.

Your doctor will discuss the potential risks and benefits involved.

How Syntometrine is given

How much is given

Your doctor will decide the dose of Syntometrine that you will receive.

How it is given

An injection of Syntometrine is given intramuscularly (into a muscle) following delivery of the baby's shoulder or immediately after delivery is over.

For prevention or treatment of excessive bleeding, Syntometrine is given after the placenta has been delivered or when bleeding occurs. If needed, the dose can be repeated after 2 hours.

If you are given too much Syntometrine (Overdose)

It is unlikely that you will receive an overdose as this medicine is usually administered in a hospital, under the supervision of a doctor.

Some of the symptoms of an overdose include nausea, vomiting, dizziness, light headedness, or shallow breathing.

If you experience severe side effects and think that you or anyone else may have been given too much Syntometrine, tell your doctor or nurse immediately, or telephone the Poisons Information Centre (telephone number 131 126), or go to Accident and Emergency at your nearest hospital. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Keep the telephone numbers for these places handy.

While you are being given Syntometrine

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you have been given Syntometrine.

Tell any other doctors, dentists, and pharmacists who treat you that you have been given this medicine.

If you are going to have surgery, tell the surgeon or anaesthetist that you have been given this medicine. It may affect other medicines used during surgery.

Keep all of your doctor’s appointments so that your progress can be checked.

Things to be careful of

Be careful driving or operating machinery until you know how Syntometrine affects you. This medicine may cause dizziness, light-headedness and blurred vision in some people. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Taking Syntometrine can start labour. Women having contractions should not drive or use machines.

If you feel light-headed, dizzy or faint when getting out of bed or standing up, get up slowly. Standing up slowly, especially when you get up from bed or chairs, will help your body get used to the change in position and blood pressure. If this problem continues or gets worse, talk to your doctor.

Side effects

Tell your doctor or nurse as soon as possible if you do not feel well while you are having Syntometrine. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Tell your doctor or nurse immediately if you notice any of the following symptoms:

• rash, itching or hives on the skin
• swelling of the face, lips, tongue or other parts of the body
• shortness of breath, wheezing or troubled breathing
• nausea (feeling sick) or vomiting
• pain in the abdomen that is different from labour pains
• headache
• dizziness, light headedness or faintness
• slow or irregular heart beat
• chest pain.

The above symptoms may be signs of allergy or signs of too much fluid associated with high doses or long infusions.

Tell your doctor if you notice anything else that is making you feel unwell. Other side effects not listed above may happen in some people.

After using Syntometrine

Storage

Store Syntometrine in a refrigerator (at 2°C - 8°C).

Do not freeze it.

Protect Syntometrine from sunlight by keeping the ampoules in the original pack until it is time for it to be given. Exposure to light may change the solution appearance and product attributes.

Keep the medicine where children cannot reach it.

Once an ampoule is opened, the contents should be used immediately.

Product description

What it looks like

Syntometrine is available in an uncoloured glass ampoule with blue colour-code rings, containing 1 mL of a clear, colourless solution; 5 ampoules in a cardboard carton.

Ingredients

Each ampoule contains 5 IU (International Units) of oxytocin and 0.5 mg of ergometrine maleate. It also contains:

• acetic acid
• chlorobutanol hemihydrate
• maleic acid
• sodium acetate trihydrate
• sodium chloride
• water for injections

Sponsor

Syntometrine is supplied in Australia by:

Phebra Pty Ltd,
19 Orion Road, Lane Cove West,
NSW 2066, Australia
Telephone: 1800 720 020

Australian Registration Number:
Syntometrine AUST R 13396

This leaflet was prepared in 23 May 2019.

Phebra and the Phi symbol are trademarks of Phebra Pty Ltd, 19 Orion Road, Lane Cove West, NSW 2066, Australia.

Syntometrine, Alliance and associated devices are registered trademarks of Alliance Pharmaceuticals Limited, Avonbridge House, Bath Road, Chippenham, SN15 2BB, UK. ®= Registered Trademark

Published by MIMS July 2019

1 Name of Medicine

Oxytocin, ergometrine maleate.

2 Qualitative and Quantitative Composition

Syntometrine injection contains synthetic oxytocin 5 IU/mL and ergometrine maleate 500 microgram/mL.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution for injection.
Syntometrine injection is a sterile, clear, colourless solution, faintly bluish fluorescent solution.
It is buffered to pH 3.2.

4 Clinical Particulars

4.1 Therapeutic Indications

Active management of the third stage of labour.
Prevention and treatment of post-partum haemorrhage associated with uterine atony.

4.2 Dose and Method of Administration

Active management of third stage of labour.

Prevention and treatment of post-partum haemorrhage.

4.3 Contraindications

Hypersensitivity to oxytocin, ergometrine or to any of the components in the formulation.
Pregnancy, labour (except in second stage of labour following the delivery of the anterior shoulder) (see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy).
Severe hypertension, pre-eclampsia or eclampsia.
Severe cardiac disorders.
Severe hepatic or renal impairment.
Occlusive vascular disease.
Sepsis.

4.4 Special Warnings and Precautions for Use

In breech presentation and other abnormal presentations, Syntometrine should not be given until after delivery of the child is completed. When Syntometrine is used for the management of the third stage of labour the possibility of multiple pregnancy must be assessed; Syntometrine should not be given until the last child has been delivered. (See Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy.)
Ergometrine derivatives are excreted in breast milk but in unknown amounts. When mothers are administered with multiple doses of Syntometrine, a higher amount of the drug may be excreted through breast milk. The effects of Syntometrine on breast fed newborns are unknown (see Section 4.6 Fertility, Pregnancy and Lactation, Use in lactation).
Syntometrine should only be administered under hospital conditions and with qualified medical supervision. Active management of the third stage of labour requires expert obstetric supervision.
In post-partum haemorrhage, if bleeding is not arrested by the injection of Syntometrine, the possibility of retained placental fragments, of soft tissue injury (cervical or vaginal laceration) or of a clotting defect should be considered and appropriate measures taken before a further injection is given.
Ergot alkaloids are substrates of CYP3A4. The concomitant use of Syntometrine with strong CYP3A4 inhibitors such as macrolide antibiotics (e.g. troleandomycin, erythromycin, clarithromycin), HIV protease or reverse transcriptase inhibitors (e.g. ritonavir, indinavir, nelfinavir, delavirdine), or azole antifungals (e.g. ketoconazole, itraconazole, voriconazole) should be avoided, since this can result in an elevated exposure to methylergometrine and ergot toxicity (vasospasm and ischemia of the extremities and other tissues). Caution should be exercised when Syntometrine is used concurrently with other vasoconstrictors or other ergot alkaloids. Concurrent use of vasoconstrictors and Syntometrine after delivery during anaesthesia may lead to severe postpartum hypertension. Methylergometrine may enhance the vasoconstrictor/ vasopressor effects of other drugs such as triptans (5HT_1B/1D receptor agonists), sympathomimetics (including those in local anaesthetics), betablockers or other ergot alkaloids (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Caution is required when using Syntometrine alone or in combination with prostaglandins and their analogues in the treatment of postpartum atonic uterine haemorrhage (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Caution is required in patients with mild or moderate hypertension, cardiac disorders, or hepatic or renal impairment. Severe forms are contraindicated (see Section 4.3 Contraindications; Section 5 Pharmacological Properties). Patients with coronary artery disease may be more susceptible to myocardial ischemia and infarction caused by ergometrine-induced vasospasm (see Section 4.8 Adverse Effects (Undesirable Effects)). Caution is also required in patients with respiratory disease, chronic anaemia and toxaemia of pregnancy.
Oxytocin should be considered as potentially arrhythmogenic. Caution is required when using Syntometrine in patients with other risk factors for torsades de pointes such as drugs which prolong the QT interval or in patients with a history of long QT syndrome (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Ergometrine can cause vasoconstriction and should therefore be used with caution in patients with Raynaud's phenomenon. Treatment should be stopped if signs of vasoconstriction develop.
Accidental administration to the newborn infant has been reported. Treatment should be symptomatic; in most cases respiratory and cardiovascular support has been required (see Section 4.9 Overdose).
For oxytocin specific precautions, see Syntocinon product information.

Anaphylaxis in women with latex allergy.

Use in hepatic impairment.

Use in renal impairment.

Use in the elderly.

Paediatric use.

Effects on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Interactions related to both oxytocin and ergometrine administration.

Vasoconstrictors/ sympathomimetics.

Prostaglandins and their analogues.

Inhalation anaesthetics.

Interactions related to oxytocin administration.

Drugs prolonging the QT interval.

Interactions related to ergometrine administration.

CYP3A4 inhibitors.

Ergot alkaloids/ ergot derivatives.

Triptans.

Beta-blockers.

Glyceryl trinitrate and other antianginal drugs.

CYP3A4 inducers.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

4.7 Effects on Ability to Drive and Use Machines

Taking Syntometrine can start labour. Women having contractions should not drive or use machines.
Adverse effects of Syntometrine include dizziness and low blood pressure (symptoms of which are lightheadedness and blurred vision). If affected, you should not drive or use machinery until symptoms have subsided.

4.8 Adverse Effects (Undesirable Effects)

The following adverse drug reactions have been reported during postapproval use of Syntometrine via spontaneous case reports and literature cases. Because these reactions are reported voluntarily from a population of uncertain size and subject to confounding factors, it is not possible to reliably estimate their frequency which is therefore quoted as not known. Adverse drug reactions are listed according to system organ classes in MedDRA. Within each system class organ class, ADRs are presented in order of decreasing seriousness. See Table 1.
Syntometrine may cause uterine hypertonicity associated with abdominal pain.

Reporting suspected adverse effects.

4.9 Overdose

For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).
Accidental administration to the newborn infant has been reported and has proved fatal. In these accidental neonatal overdosage cases, symptoms such as respiratory depression, convulsions, cyanosis, oliguria, hypertonia, and arrhythmia have been reported. Treatment should be symptomatic; in most cases respiratory and cardiovascular support has been required.

Symptoms.

Treatment.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Ergot alkaloids and oxytocin incl. analogues, in combination; ATC code: G02AC.

Mechanism of action.

Clinical trials.

5.2 Pharmacokinetic Properties

Absorption.

5.3 Preclinical Safety Data

Genotoxicity.

Carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

Syntometrine Injection contains acetic acid, chlorobutanol hemihydrate, maleic acid, sodium acetate trihydrate, sodium chloride and water for injections.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG)¹. The expiry date can be found on the packaging.
¹ AUST R 13396.

6.4 Special Precautions for Storage

Store at 2° to 8°C. Refrigerate. Do not freeze. Protect from light. Keep out of the reach of children.

6.5 Nature and Contents of Container

Syntometrine Injection is supplied in 1 mL one-point-cut uncoloured glass ampoules with blue colour-code rings.
It is available in packs of 5 x 1 mL ampoules.
Phebra product code - INJ182.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Oxytocin.

Ergometrine maleate.

Chemical structure.

CAS number.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes