Consumer medicine information

Oxytocin APX Solution for Injection

Oxytocin

BRAND INFORMATION

Brand name

Oxytocin APX

Active ingredient

Oxytocin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Oxytocin APX Solution for Injection.

What is in this leaflet

This leaflet answers some common questions about oxytocin. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you using this medicine against the benefits they expect it will have for you.

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

Keep this leaflet with the medicine. You may need to read it again.

What this medicine is used for

Oxytocin can be 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.

Oxytocin 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 whether oxytocin is suitable for you.

How it works

Oxytocin 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.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed this medicine for another reason.

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

This medicine is not addictive.

This medicine should not be used in children.

Before are given this medicine

When you must not be given this medicine

Do not receive this medicine if you have an allergy to:

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

Some of the symptoms of an allergic reaction may include:

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

You should not receive this medicine if:

  • your doctor thinks that inducing or enhancing contractions for normal labour and vaginal delivery would be unsuitable for you and your baby
  • there are maternal or foetal reasons for caesarean delivery
  • you have been given medicines called prostaglandins within the past 6 hours.

Do not receive this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you are given this medicine

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have ever had any of the following medical conditions:

  • high blood pressure
  • abnormal heart electrical signals (QT interval prolongation)
  • any other heart conditions
  • kidney problems

If you have not told your doctor about any of the above, tell them before you start taking this medicine.

Taking other medicines

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

Some medicines may interact with oxytocin. These include:

  • prostaglandins and their analogues, used to help bring on contractions
  • inhalation or caudal anaesthetics
  • medicines affecting your heart
  • medicines that prolong the QT interval
  • vasoconstrictors/ sympathomimetics, which can act on blood vessels

These medicines may be affected by this medicine or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

How to this medicine is given

How much is given

Your doctor will decide what dose you will receive. This depends on your condition and other factors, such as your age and other medicines that are being given.

How it is given

To bring on (induce) or maintain labour, oxytocin 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 oxytocin 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.

If you receive too much (overdose)

As oxytocin is given to you in a hospital under the supervision of your doctor or medical staff, it is very unlikely that you will receive an overdose. You will be closely monitored while in the hospital so that any unwanted side effects can be treated. However, if you experience severe side effects tell your doctor and nurse immediately.

Side effects

Tell your doctor and nurse as soon as possible if you do not feel well while you are receiving oxytocin.

This medicine helps most people, but it may have unwanted side effects in a few people. All medicines can have side effects. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

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

  • 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 heart beat
  • excessive or continuous contractions
  • abnormal clotting or bleeding
  • shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue, throat or other parts of the body; rash, itching or hives on the skin (signs of a severe allergic reaction)

The above list includes some symptoms that may require urgent medical attention.

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

Storage and Disposal

Storage

This medicine will be stored in the pharmacy or on the ward. It is stored at 2-8°C (do not freeze).

Protect from light. Do not freeze.

Disposal

Oxytocin is used for one dose in one patient only. Any remaining contents should be discarded.

Product description

What it looks like

Clear and colourless sterile aqueous solution, with a characteristic odour.

Available in ampoules containing 10 IU in 1 mL.

Ingredients

Each ampoule contains 10 IU of synthetic oxytocin as the active ingredient.

It also contains the following:

  • glacial acetic acid
  • chlorobutanol hemihydrate
  • water for injections

This medicine does not contain gluten, lactose, sucrose, tartrazine or any other azo dyes.

Australian Registration Numbers

Oxytocin APX 10 IU in 1 mL glass ampoules: AUST R 225656.

Sponsor

Apotex Pty Ltd
16 Giffnock Avenue
Macquarie Park NSW 2113

This leaflet was prepared in December 2020.

Published by MIMS February 2021

BRAND INFORMATION

Brand name

Oxytocin APX

Active ingredient

Oxytocin

Schedule

S4

 

1 Name of Medicine

Oxytocin.

2 Qualitative and Quantitative Composition

Oxytocin is available in ampoules containing 10 IU in 1 mL.
For the full list of excipients see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution for Injection.
Oxytocin 10 IU/mL injections are sterile aqueous solutions containing synthetic oxytocin. The injection solutions are clear and colourless, with a characteristic odour.

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

Oxytocin APX Solution for Injection is intended for intravenous administration.

Dosage.

Induction or augmentation of labour.

Oxytocin 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, 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 oxytocin 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 oxytocin 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 oxytocin has been demonstrated with 0.9% saline and 5% dextrose solutions. Oxytocin 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, oxytocin 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, oxytocin must not be mixed with other medicinal products.

Preparation of infusion solution.

For drip infusion, the preparation of a solution containing 10 IU oxytocin 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 milliunits/min corresponds to 0.1-0.4 mL/min, and the recommended maximum rate of 20 milliunits/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 milliunits/min) must be calculated according to the specification of the pump used.
Single dose use in single patient only. Discard any residue. To reduce microbiological hazard, use as soon as practicable after dilution.

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. cephalo-pelvic 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.
Oxytocin must not be administered within 6 hours after vaginal prostaglandins have been given.

4.4 Special Warnings and Precautions for Use

Oxytocin 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 oxytocin 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 over-stimulation 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 oxytocin 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 oxytocin 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 oxytocin 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).
Oxytocin 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.

Oxytocin should be used with caution in patients who have a pre-disposition 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.

Oxytocin 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 oxytocin, 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.
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. Oxytocin 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 post-partum 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, oxytocin 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. Due to the existing structural homology between oxytocin and latex, 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.

Use in renal impairment.

No studies have been performed in renally-impaired patients.
Caution should be exercised in patients with severe renal impairment because of possible water retention and possible accumulation of oxytocin (see Water intoxication above).

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

Oxytocin 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 oxytocin 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. See 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 over stimulation 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 pre-disposing factors, e.g. tumultuous labour, foetal death-in utero. meconium-stained amniotic fluid) has been reported.
Increases in post-partum 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 post-partum 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 and contact Apotex Medical Information Enquiries/Adverse Drug Reaction Reporting on 1800 195 055.

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.

When signs or symptoms of overdosage occur during continuous intravenous administration of oxytocin, 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).
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

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, oxytocin 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 over stimulation), uterine activity declines rapidly but may continue at an adequate lower level. Oxytocin also causes contraction of the myo-epithelial cells surrounding the mammary alveoli. It therefore facilitates lactation in women experiencing difficulty in breast feeding. Synthetic oxytocin has only very slight pressor and anti-diuretic 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.

No data available.

5.2 Pharmacokinetic Properties

Plasma levels and onset/duration of effect.

Intravenous infusion.

When oxytocin 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 post-partum haemorrhage, oxytocin 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.

Metabolism.

A glycoprotein aminopeptidase, oxytocinase, is produced during pregnancy and appears in the plasma. It is capable of degrading oxytocin. Enzyme activity increases gradually until term approaches, at which time it rises steeply to high levels. Enzyme activity then declines after delivery. Enzyme activity in the placenta and in the uterine tissue is also high during this period. There is little or no degradation of oxytocin by plasma in men, non-pregnant women or cord blood.

Excretion.

The relative ease with which the rate and force of uterine contractions can be regulated by the intravenous infusion of oxytocin 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.

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

Glacial acetic acid, chlorobutanol hemihydrate, 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). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store at 2 - 8°C (Refrigerate. Do not freeze). Protect from light.

6.5 Nature and Contents of Container

Oxytocin APX Solution for Injection.

10 IU/mL solution for injection.

1 mL clear glass ampoules, packs of 5 (AUST R 225656).

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 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 is a white or almost white fluffy hygroscopic powder. Very soluble in water and in dilute solutions of acetic acid and of ethanol.

Chemical structure.


Chemical Name: L-Cysteinyl-L-tyrosyl-L -isoleucyl-L-glutaminyl-L -asparaginyl-L-cysteinyl-L -prolyl-L-leucylglycinamide cyclic (1→6)disulphide.
Molecular Formula: C43H66N12O12S2.
Molecular Weight: 1007.20.

CAS number.

50-56-6.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes