Consumer medicine information

Syntocinon

Oxytocin

BRAND INFORMATION

Brand name

Syntocinon

Active ingredient

Oxytocin

Schedule

SUMMARY CMI

SYNTOCINON^®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I given SYNTOCINON?

SYNTOCINON contains the active ingredient synthetic oxytocin. SYNTOCINON is used to bring on (induce) labour. It can also be used during and immediately after delivery to help the birth and to prevent or treat excessive bleeding.

For more information, see Section 1. Why am I using SYNTOCINON? in the full CMI.

2. What should I know before I am given SYNTOCINON?

Do not use if you have ever had an allergic reaction to SYNTOCINON or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions or take any other medicines.

For more information, see Section 2. What should I know before I use SYNTOCINON? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with SYNTOCINON and affect how it works.

For more information, see Section 3. What if I am taking other medicines? in the full CMI.

4. How is SYNTOCINON given?

SYNTOCINON must only be given by a doctor or nurse.

More instructions can be found in Section 4. How do I use SYNTOCINON? in the full CMI.

5. Are there any 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, throat, or other parts of the body, shortness of breath, wheezing or troubled breathing, headache, nausea (feeling sick) or vomiting, feeling drowsy and lethargic, pain in the abdomen that is different from labour pains, dizziness, light headedness or faintness, flushing of the face, chest pain, fast, slow or irregular heartbeat, excessive or continuous contractions, abnormal clotting or bleeding.

For more information, including what to do if you have any side effects, see Section 5. Are there any side effects? in the full CMI.

FULL CMI

SYNTOCINON^®

Active ingredient(s): synthetic oxytocin

Consumer Medicine Information (CMI)

This leaflet provides important information about using SYNTOCINON. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using SYNTOCINON.

Where to find information in this leaflet:

1. Why am I given SYNTOCINON?
2. What should I know before I am given SYNTOCINON?
3. What if I am taking other medicines?
4. How is SYNTOCINON given?
5. Are there any side effects?
6. Product details

1. Why am I using SYNTOCINON?

SYNTOCINON contains the active ingredient synthetic oxytocin. SYNTOCINON is a man-made chemical that is identical to a natural hormone called oxytocin. It works by stimulating the muscles of the uterus (womb) to produce rhythmic contractions.

SYNTOCINON is used to bring on (induce) labour. It can also be used during and immediately after delivery to help the birth and to prevent or treat excessive bleeding.

SYNTOCINON is not suitable in all situations - for example, if the baby or placenta are in the wrong position or if you have had a previous caesarean section or other surgery involving the uterus. Your doctor can give you more information on the suitability of SYNTOCINON in your particular case.

Ask your doctor if you have any questions about why SYNTOCINON has been prescribed for you.

Your doctor may have prescribed it for another purpose.

SYNTOCINON is only available with a doctor's prescription. It is not addictive.

2. What should I know before I use SYNTOCINON?

Warnings

You must not have SYNTOCINON if:

you are allergic to oxytocin (the active ingredient), latex or any of the 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.
Always check the ingredients to make sure you can use this medicine.
your doctor thinks that inducing or enhancing contractions for normal labour and vaginal delivery would be unsuitable for you or your baby
there are maternal or foetal reasons for caesarean delivery
you have been given medicines called prostaglandins within the past 6 hours

Check with your doctor if you:

have high blood pressure or any heart or kidney problems.
Your doctor may want to take extra precautions. For example, the amount of fluid you will be given may need to be reduced if you have a problem with your heart or kidneys.
are allergic to any other medicines, foods, dyes or preservatives.
Your doctor will want to know if you are prone to allergies.
have, or have ever had, any of the following problems:
- an abnormal electrical signal called "prolongation of the QT interval"
- any other conditions that affect the heart
- kidney problems
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.
have been given anaesthetics or medicines called prostaglandins.

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

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 5. Are there any side effects?

3. What if I am taking other medicines?

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

4. How SYNTOCINON is given?

To bring on (induce) or maintain labour, SYNTOCINON is given by intravenous infusion (drip). The speed of the infusion is set to maintain a pattern of contractions similar to normal labour. During the infusion, both you and your baby will be closely monitored to prevent complications.

If SYNTOCINON is needed at delivery or to prevent excessive bleeding, it can also be given intramuscularly (into a muscle) or by slow intravenous injection directly into a vein.

5. Are there any side effects?

Tell your doctor or nurse as soon as possible if you do not feel well while you are having SYNTOCINON.

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or nurse if you have any further questions about side effects.

Side effects

Side effects

What to do

rash, itching or hives on the skin
swelling of the face, lips, tongue, throat, or other parts of the body (possible signs of a reaction called angioedema)
shortness of breath, wheezing or troubled breathing
headache
nausea (feeling sick) or vomiting
feeling drowsy and lethargic
pain in the abdomen that is different from labour pains
dizziness, light headedness or faintness
flushing of the face
chest pain
fast, slow or irregular heartbeat
excessive or continuous contractions
abnormal clotting or bleeding
low level of salt in the blood (shown in a blood test)

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

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

Tell your doctor if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

6. Product details

This medicine is only available with a doctor's prescription.

What SYNTOCINON contains

Active ingredient

(main ingredient)

Each ampoule contains 5 or 10 International Units (IU) of oxytocin.

Other ingredients

(inactive ingredients)

sodium acetate trihydrate
glacial acetic acid
chlorobutanol hemihydrate
ethanol
water for injections

Potential allergens

N/A

Do not take this medicine if you are allergic to any of these ingredients.

What SYNTOCINON looks like

SYNTOCINON 5 IU or 10 IU is available in a glass ampoule containing 1 mL of a clear, colourless solution; 5 ampoules in a cardboard carton. (AUST R 13395; 13383)

Who distributes SYNTOCINON

Viatris Pty Ltd
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.viatris.com.au
Phone: 1800 274 276

SYNTOCINON^® is a Viatris company trade mark

This leaflet was prepared in July 2022.

SYNTOCINON_cmi\Jul22/00

Published by MIMS September 2022

BRAND INFORMATION

Brand name

Syntocinon

Active ingredient

Oxytocin

Schedule

1 Name of Medicine

Oxytocin.

2 Qualitative and Quantitative Composition

Oxytocin injection is a sterile aqueous solution containing synthetic oxytocin.
Syntocinon is available in ampoules containing 5 IU in 1 mL and 10 IU in 1 mL.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Oxytocin injection solution is clear and colourless.

4 Clinical Particulars

4.1 Therapeutic Indications

Induction of labour; inadequate uterine effort; management of third stage of labour; post-partum haemorrhage.

4.2 Dose and Method of Administration

Dosage regimens.

Induction or augmentation of labour.

Syntocinon should only be administered as an intravenous infusion, preferably by means of a variable speed infusion pump, or by drip infusion. It should not be administered by subcutaneous, intramuscular or intravenous bolus injection.
The initial infusion rate should be set at 1-4 milliunits/min. This rate may be gradually increased at intervals of not shorter than 20 min and increments of not more than 1-2 milliunits/minute, until a contraction pattern similar to that of normal labour is established. In pregnancy near term, this can often be achieved with an infusion of less than 10 milliunits/min. The recommended maximum rate is 20 milliunits/min. The increments in infusion rate should not be as high once contractions have been established as those used to initiate contractions. Once an adequate level of uterine activity is attained, the infusion rate can often be reduced.
The frequency and duration of contractions and foetal heart rate must be carefully monitored during oxytocin administration, the latter preferably by electronic means, and the infusion must be discontinued immediately in the event of uterine hyperactivity, foetal distress or foetal heart abnormalities.
If regular contractions are not established after the infusion of 5 IU oxytocin, the attempt to induce labour should be terminated. It can generally be repeated on the following day, starting again from a rate of 1-4 milliunits/min.
In general, the dose of Syntocinon required for the augmentation of labour is less than that required for induction. Therefore, the initial infusion rate should be at the lower end of the recommended range.

Third stage of labour and puerperium (haemorrhage, subinvolution of the uterus).

5-10 IU by intramuscular injection or 5 IU by slow bolus intravenous injection. In patients given Syntocinon by drip to induce or stimulate labour, the infusion should be continued during the third stage.

Caesarean section.

5 IU by intravenous infusion or slow bolus intravenous injection after delivery of the foetus.

Instructions for use and handling.

Infusion fluids.

Compatibility of Syntocinon has been demonstrated with 0.9% saline and 5% dextrose solutions. Syntocinon is not compatible with solutions containing bisulphites and metabisulphites as preservatives.
Due attention should be paid to the choice of infusion fluid in individual patients. Generally, Syntocinon should be administered in a combination of dextrose and an electrolyte solution, (such as 4% dextrose in N/5 saline), or in an isotonic electrolyte solution. The use of 5% dextrose in water is not recommended.
Due to the absence of compatibility studies, Syntocinon must not be mixed with other medicinal products.

Preparation of infusion solution.

For drip infusion, the preparation of a solution containing 10 IU Syntocinon per 1 litre infusion fluid is recommended. To ensure even mixing of the drip solution, the bottle or bag must be turned upside down several times before use. Using this concentration, the recommended initial infusion rate of 1-4 mU/min corresponds to 0.1-0.4 mL/min, and the recommended maximum rate of 20 mU/min is reached at a rate of 2 mL/min.
When using a mechanical infusion pump which delivers smaller volumes than those given by drip infusion, a more concentrated oxytocin solution will be required. The concentration suitable for infusions within the recommended dosage range (1-20 mU/min) must be calculated according to the specification of the pump used.

4.3 Contraindications

Foetal distress.
Any condition in which, for foetal or maternal reasons, spontaneous labour is inadvisable and/or vaginal delivery is contraindicated, e.g. cephalopelvic disproportion, abnormal presentation, cord presentation or prolapse, excessive distension or impaired resistance of the uterus to rupture (e.g. multiple pregnancy, polyhydramnios), parity greater than 4, elderly multiparae, grand multiparity and in the presence of uterine scar resulting from major surgery including previous caesarean section or other surgery involving the uterus.
Severe toxaemia, predisposition to amniotic fluid embolism (foetal death in utero, abruptio placentae), hypertonic contractions, placenta praevia and vasa praevia, placental abruption.
Hypersensitivity to oxytocin or to any of the excipients in the formulation.
Syntocinon must not be administered within 6 hours after vaginal prostaglandins have been given.

4.4 Special Warnings and Precautions for Use

Syntocinon should not be used for prolonged periods in patients with oxytocin resistant uterine inertia, severe pre-eclamptic toxaemia or severe cardiovascular disorders.

Induction or augmentation of labour.

The induction of labour by means of oxytocic agents should be attempted only when strictly indicated for medical reasons rather than for convenience. Administration should only be under hospital conditions, and all patients receiving intravenous oxytocin must be under continuous observation by trained personnel with a thorough knowledge of the drug and qualified to identify complications. A physician qualified to manage any complications must be immediately available.
When Syntocinon is given for the induction and augmentation of labour, it must only be administered as an intravenous infusion, preferably by means of a motor driven variable speed infusion pump, and not by subcutaneous, intramuscular or intravenous bolus injection as it may cause an acute short lasting hypotension accompanied by flushing and reflex tachycardia.

Foetal distress and foetal death.

Administration of oxytocin at excessive doses results in uterine overstimulation which may cause foetal distress, asphyxia and death, or may lead to hypertonicity, tetanic contractions or rupture of the uterus. Careful monitoring is essential (foetal heart rate, uterine response by tocometry if possible, blood pressure) so that dosage may be titrated to individual response.
When Syntocinon is used for the induction of labour, there is a chance that infants with unanticipated prematurity may be delivered. To reduce this risk, it is recommended that, in women with uncertain obstetric dating, the maturity of the foetus be assessed by ultrasonic measurement of foetal biparietal diameter.

Third stage of labour and puerperium.

When Syntocinon is used for prevention or treatment of uterine haemorrhage, rapid intravenous bolus injection of oxytocin at high doses should be avoided, as it may cause acute short lasting hypotension accompanied by flushing and reflex tachycardia. These rapid haemodynamic changes may result in myocardial ischemia, particularly in patients with pre-existing cardiovascular disease. Rapid i.v. bolus injection of oxytocin at doses amounting to several IU may also lead to QTc prolongation.
When Syntocinon is used for the management of the third stage of labour, multiple pregnancy must be excluded before the drug is injected.

Use caution in the following circumstances.

Particular caution is required in the presence of borderline cephalopelvic disproportion, secondary uterine inertia, mild or moderate degrees of pregnancy induced hypertension or cardiac disease and in patients above 35 years of age (note: use is contraindicated in elderly multiparae), or with a history of lower uterine segment caesarean section.

Intrauterine death.

In the case of foetal death in utero and/or in the presence of meconium stained amniotic fluid, tumultuous labour must be avoided, as it may cause amniotic fluid embolism (see Section 4.3 Contraindications).
Syntocinon should not be used for prolonged periods in patients with oxytocin resistant uterine inertia or severe cardiovascular disorders. In patients with cardiovascular disorders the infusion volume should be kept low by using a more concentrated solution.

Cardiovascular disorders.

Syntocinon should be used with caution in patients who have a predisposition to myocardial ischemia due to pre-existing cardiovascular disease (such as hypertrophic cardiomyopathy, valvular heart disease and/or ischemic heart disease including coronary artery vasospasm), to avoid significant changes in blood pressure and heart rate in these patients.

QT syndrome.

Syntocinon should be given with caution to patients with known 'long QT syndrome' or related symptoms and to patients taking drugs that are known to prolong the QTc interval.
In situations where more prolonged periods of administration may be required, such as in the treatment of inevitable or missed abortion, in the management of postpartum haemorrhage, or earlier in gestation when the uterus is less sensitive to Syntocinon, special precautions must be taken to avoid water intoxication.

Water intoxication.

Water intoxication associated with maternal and neonatal hyponatraemia, which is potentially fatal, has been reported in cases where high doses of oxytocin have been administered together with large amounts of electrolyte free fluid over a prolonged period of time. The weak anti-diuretic activity of oxytocin, acting to increase water reabsorption from the glomerular filtrate, may be a contributing factor, but the major cause is the use of large amounts of electrolyte free fluids. The combined antidiuretic effect of oxytocin and the intravenous fluid administration may also cause fluid overload leading to a haemodynamic form of acute pulmonary oedema without hyponatraemia.
Renal impairment: caution should be exercised in patients with severe renal impairment because of possible water retention and possible accumulation of oxytocin.
The symptoms and signs of water intoxication are:
1. Headache, anorexia, nausea, vomiting and abdominal pain.
2. Lethargy, drowsiness, unconsciousness and grand mal type seizures.
3. Low blood electrolyte concentration including maternal and neonatal hyponatraemia.
4. Possible acute pulmonary oedema without hyponatraemia.
Therefore, if high doses or a more prolonged period of administration is expected, the following precautions must be observed:
1. A strict fluid balance chart must be kept.
2. Low-sodium infusion fluids should be avoided.
3. Syntocinon should be infused in small volumes of isotonic diluent (not dextrose), using higher concentrations than recommended for the induction and augmentation of labour at term in non-complicated cases.
4. Fluid intake by mouth must be restricted.
5. Maternal serum electrolytes should be measured at regular intervals, e.g. 8-12 hourly.
Treatment of water intoxication:
1. Discontinue oxytocin.
2. Restrict fluid intake.
3. Promote diuresis.
4. Correct electrolyte imbalance.
5. Control convulsions, e.g. with judicious use of diazepam.
6. If coma is present, maintain a free airway and carry out the routine measures for care of an unconscious patient.

Disseminated intravascular coagulation.

In rare circumstances, (i.e. incidence rate < 0.0006) the pharmacological induction of labour using uterotonic agents, including dinoprostone or oxytocin, increases the risk of postpartum disseminated intravascular coagulation (DIC). The pharmacological induction itself and not a particular agent is linked to such risk. This risk is increased in particular if the woman has other risk factors for DIC such as 35 years of age or over, complications during the pregnancy and gestational age more than 40 weeks. In these women, Syntocinon or any other alternative drug should be used with care, and the practitioner should be alerted by signs of DIC (fibrinolysis).

Anaphylaxis in women with latex allergy.

There have been reports of anaphylaxis following administration of oxytocin in women with a known latex allergy. Latex allergy/intolerance may be an important predisposing risk factor for anaphylaxis following oxytocin administration.

Use in hepatic impairment.

No studies have been performed in hepatically-impaired patients. See Section 5.2 Pharmacokinetic Properties, Hepatic impairment.

Use in renal impairment.

No studies have been performed in renally-impaired patients. See Section 5.2 Pharmacokinetic Properties, Renal impairment.

Use in the elderly.

No studies have been performed in elderly patients (65 years and over).

Paediatric use.

No studies have been performed in paediatric patients.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Prostaglandins and their analogues.

Prostaglandins and their analogues facilitate contraction of the myometrium hence may potentiate the uterotonic effect of oxytocin and vice versa. Very careful monitoring is, therefore, recommended in cases of concomitant administration.

Inhalation anaesthetics.

Some inhalation anaesthetics, e.g. cyclopropane, enflurane, halothane, sevoflurane, desflurane or isoflurane, have a relaxing effect on the uterus and produce a notable inhibition of uterine tone and thereby may enhance the hypotensive effect of oxytocin and reduce its oxytocic action. Their concurrent use with oxytocin has also been reported to cause cardiac rhythm disturbances.

Drugs prolonging QT interval.

Oxytocin should be considered as potentially arrhythmogenic, particularly in patients with other risk factors for torsades de pointes such as drugs which prolong the QT interval or in patients with history of long QT syndrome (see Section 4.4 Special Warnings and Precautions for Use). Oxytocin should be given with caution in patients taking drugs that are known to prolong the QTc interval.

Vasoconstrictors/sympathomimetics.

Oxytocin may enhance the vasopressor effects of vasoconstrictors and sympathomimetics, even those contained in local anaesthetics.

Caudal anaesthetics.

When given during or after caudal block anaesthesia, oxytocin may potentiate the pressor effect of sympathomimetic vasoconstrictor agents.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There are no studies on the potential effect of oxytocin on fertility.
(Category A)
Use of oxytocin has contributed significantly to the safety of parturition. However, there have been instances of idiosyncratic sensitivity of the uterus resulting in foetal anoxia.
Based on the wide experience with this drug and its chemical structure and pharmacological properties, it is not expected to present a risk of foetal abnormalities when used as indicated.
Treatment of rats with oxytocin early in pregnancy, in doses approximately three thousand times the dose used to induce labour in humans, caused embryonic foetal loss in one study. No standard embryofoetal development studies with oxytocin are available.
Endogenous oxytocin may be found in small quantities in mother's breast milk. However, oxytocin is not expected to cause harmful effects in the newborn because it passes into the alimentary tract where it undergoes rapid inactivation.

4.7 Effects on Ability to Drive and Use Machines

Syntocinon can induce uterine contractions and, therefore, caution should be exercised when driving or operating machines. Women with uterine contractions should not drive or use machines.

4.8 Adverse Effects (Undesirable Effects)

Adverse reactions from clinical trials (Table 1) are ranked using the following convention: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, < 1/1,000) very rare (< 1/10,000), including isolated reports.

Post-marketing experience.

The adverse drug reactions derived from post-marketing experience with Syntocinon are via spontaneous case reports and literature cases. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency which is therefore categorised as 'not known'. Adverse drug reactions are listed according to system organ classes in MedDRA. Within each system organ class, adverse reactions are presented in order of decreasing seriousness in Tables 2 and 3.

Other adverse events that have been reported include ECG changes following intravenous administration of concentrated solutions, hypertension, neonatal jaundice, neonatal convulsions, oedema, cardiovascular spasm and collapse.
Water intoxication associated with maternal and neonatal hyponatraemia, which is potentially fatal, can result from high doses or prolonged periods of infusion of oxytocin in electrolyte free fluids. The combined antidiuretic effect of oxytocin and the intravenous fluid administration may also cause fluid overload leading to a haemodynamic form of acute pulmonary oedema without hyponatraemia (see Section 4.4 Special Warnings and Precautions for Use).
When oxytocin is used by intravenous infusion for the induction or augmentation of labour, its administration at excessive doses results in uterine overstimulation which may cause foetal distress, asphyxia and death, or may lead to hypertonicity, tetanic contractions or rupture of the uterus.
Rapid intravenous bolus injection of oxytocin at doses as little as 2 IU may result in acute short lasting hypotension accompanied by flushing and reflex tachycardia (see Section 4.4 Special Warnings and Precautions for Use). These rapid haemodynamic changes may result in myocardial ischaemia, particularly in patients with pre-existing cardiovascular disease. Rapid intravenous bolus injection of oxytocin at these doses may also lead to QTc prolongation.
Amniotic fluid embolism (in association with predisposing factors, e.g. tumultuous labour, foetal death in utero, meconium stained amniotic fluid) has been reported.
Increases in postpartum bleeding have been observed rarely in conjunction with oxytocin. This effect probably relates more to abnormality of uterine action rather than to side effects of the drug.
There are rare reports of postpartum disseminated intravascular coagulation following the induction of labour using oxytocin (see Section 4.4 Special Warnings and Precautions for Use).

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Symptoms.

Overdosage may give rise to the following complications:
foetal distress (foetal bradycardia, meconium staining of the amniotic fluid, foetal asphyxia);
uterine hypertonicity, tetanic contraction or rupture;
placental abruption;
amniotic fluid embolism;
water intoxication (see Section 4.4 Special Warnings and Precautions for Use).

Treatment.

For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).
When signs or symptoms of overdosage occur during continuous intravenous administration of Syntocinon, the infusion must be discontinued at once and oxygen should be given to the mother. In the event of water intoxication, it is essential to restrict fluid intake, promote diuresis, correct electrolyte imbalance and control possible convulsions by judicious use of diazepam (see Section 4.4 Special Warnings and Precautions for Use, Water intoxication).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

The active substance of Syntocinon is a synthetic nonapeptide identical with oxytocin, a hormone released by the posterior lobe of the pituitary. Being wholly synthetic, it does not contain vasopressin and has a constant and reliable effect.
Oxytocin stimulates the smooth muscle of the uterus, producing rhythmic contractions, particularly towards the end of pregnancy, during labour, after delivery and in the puerperium, i.e. at times when the number of specific oxytocin receptors in the myometrium is increased. When given by low dose intravenous infusion, Syntocinon elicits rhythmic uterine contractions that are indistinguishable in frequency, force and duration from those observed during spontaneous labour. At higher infusion dosages, or when given by single injection, the drug is capable of causing sustained tetanic uterine contractions. Upon discontinuation of the infusion or following a substantial reduction in the infusion rate (e.g. in the event of overstimulation), uterine activity declines rapidly but may continue at an adequate lower level.
Oxytocin also causes contraction of the myoepithelial cells surrounding the mammary alveoli. It therefore facilitates lactation in women experiencing difficulty in breastfeeding. Synthetic oxytocin has only very slight pressor and antidiuretic activity (absence of vasopressin).
Another pharmacological effect observed with high doses of oxytocin, particularly when administered by rapid intravenous bolus injection, is a transient direct relaxing effect on vascular smooth muscle, resulting in brief hypotension, flushing and reflex tachycardia (see Section 4.4 Special Warnings and Precautions for Use).
Oxytocin, being a polypeptide, is largely inactivated in the alimentary tract and therefore virtually ineffective when ingested.

Clinical trials.

Not available.

5.2 Pharmacokinetic Properties

Plasma levels and onset/duration of effect.

Intravenous infusion.

When Syntocinon is given by continuous intravenous infusion at doses appropriate for induction or augmentation of labour, the uterine response sets in gradually and usually reaches a steady state within 20 to 40 minutes. The corresponding plasma levels of oxytocin are comparable to those measured during spontaneous first stage labour. For example, oxytocin plasma levels in 10 pregnant women at term, receiving an intravenous infusion at a rate of 4 milliunits/minute, were 2 to 5 microunits/mL.

Intravenous injection and intramuscular injection.

When administered by intravenous or intramuscular injection for prevention or treatment of postpartum haemorrhage, Syntocinon acts rapidly, with a latency period of less than 1 minute by intravenous injection and of 2 to 4 minutes by intramuscular injection. The oxytocic response lasts for 30 to 60 minutes after intramuscular administration and possibly less after intravenous injection.

Distribution.

Oxytocin distributes throughout the extracellular fluid, with minimal amounts reaching the foetus. The steady-state distribution volume determined in 6 healthy men after intravenous injection was 12.2 L or 0.17 L/kg. Plasma protein binding is very low. Oxytocin may be found in small quantities in mother's breast milk.

Biotransformation.

A glycoprotein aminopeptidase, oxytocinase, is produced during pregnancy and appears in the plasma. It is capable of degrading oxytocin. It is produced from both the mother and the fetus. Liver and kidney play a major role in metabolising and clearing oxytocin from the plasma. Thus liver, kidney and systemic circulation contribute to the biotransformation of oxytocin.

Elimination.

The relative ease with which the rate and force of uterine contractions can be regulated by the intravenous infusion of Syntocinon is due to the short half-life of oxytocin. Values reported by various investigators range from 3 to 20 minutes. Removal of oxytocin from plasma is accomplished mainly by the liver and the kidneys. The metabolic clearance rate amounts to about 20 mL/kg/min in men as well as in pregnant women. Less than 1% of a given dose is excreted unchanged in the urine.

Renal impairment.

No studies have been performed in renally impaired patients. However, considering the excretion of oxytocin and its reduced urinary excretion because of anti-diuretic properties, the possible accumulation of oxytocin can result in prolonged action (see Section 4.4 Special Warnings and Precautions for Use).

Hepatic impairment.

No studies have been performed in hepatically impaired patients. Pharmacokinetic alteration in patients with impaired hepatic function is unlikely since metabolising enzyme, oxytocinase, is not confined to liver alone and the oxytocinase levels in placenta during the term has significantly increased. Therefore, biotransformation of oxytocin in impaired hepatic function may not result in substantial changes in metabolic clearance of oxytocin (see Section 4.4 Special Warnings and Precautions for Use).

5.3 Preclinical Safety Data

Genotoxicity.

Oxytocin did not induce chromosomal aberration and sister chromatid exchange in human peripheral lymphocytes in vitro.

Carcinogenicity.

No carcinogenicity studies with oxytocin are available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sodium acetate trihydrate, glacial acetic acid, chlorobutanol hemihydrate, ethanol, water for injections.

6.2 Incompatibilities

See Section 4.2 Dose and Method of Administration, Instructions for use and handling.

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). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store at 2° to 8°C. Refrigerate. Do not freeze.
Keep out of the reach and sight of children.

6.5 Nature and Contents of Container

The 5 IU and 10 IU injections are supplied in clear Type 1 glass 1 mL ampoules in packs of 5 ampoules per carton. Some strengths, pack sizes and/or pack types may not be marketed.

Australian register of therapeutic goods (ARTG).

AUST R 13395 - Syntocinon oxytocin 5 IU/1 mL injection ampoule.
AUST R 13383 - Syntocinon oxytocin 10 IU/1 mL injection ampoule.

6.6 Special Precautions for Disposal

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

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