Consumer medicine information

Oxytocin GH

Oxytocin

BRAND INFORMATION

Brand name

Oxytocin GH

Active ingredient

Oxytocin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Oxytocin GH.

What is in this leaflet

This leaflet answers some common questions about Oxytocin GH.

It does not contain all the available information. It does not take the place of talking with 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. 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 your treatment using Oxytocin GH against the benefits they expect it will have for you.

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

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

What Oxytocin GH is used for

Oxytocin GH 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 GH 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.

Oxytocin GH 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 Oxytocin GH in your particular case.

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

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

Before you are given Oxytocin GH

When you must not use it

You must not have Oxytocin GH if:

  • 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.
  • You are allergic to oxytocin (the active ingredient) or any of the other ingredients listed at the end of this leaflet.
  • You are allergic to latex.

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.

Before you are given it

Tell 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.

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.

Tell your doctor if you 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;
  • liver problems.

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.

Tell your doctor if you 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 Oxytocin GH.

How Oxytocin GH is given

To bring on (induce) or maintain labour, Oxytocin GH 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 GH 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.

Side effects

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

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

After using Oxytocin GH

Storage

Store unopened Oxytocin GH ampoules in a refrigerator, where the temperature stays between 2°C to 8°C. Protect from light and do not freeze.

The unopened product may be stored for up to three (3) months at or below 25°C. Once removed from the refrigerator the product must be discarded if not used. It must not be returned to the refrigerator.

Oxytocin GH will be kept in a locked cupboard in the hospital pharmacy or operating theatre.

Oxytocin GH should not be used after the date (month and year) printed after "EXP". The anaesthetist will inspect Oxytocin GH before use to determine that it is still within its use by date.

Disposal

The hospital staff looking after you will dispose of any remaining Oxytocin GH appropriately.

Product description

What it looks like

Oxytocin GH is a clear, colourless solution.

A carton of Oxytocin GH contains 1, 5 or 10 ampoules.

Not all pack sizes may be marketed.

Ingredients

Active ingredient

Oxytocin GH is available in 1 mL glass ampoules containing either 8.3 microgram (5 IU) or 16.7 micrograms (10 IU) of oxytocin.

Other ingredients

  • glacial acetic acid;
  • sodium acetate;
  • sodium chloride;
  • water for injections.

Australian Registration Numbers

Oxytocin GH 5 IU/1 mL:
AUST R 207985

Oxytocin GH 10 IU/1 mL:
AUST R 207986

Sponsor

Generic Health Pty Ltd
Suite 2, Level 2
19-23 Prospect Street
Box Hill, VIC, 3128
Australia

E-mail: [email protected]
Telephone: +61 3 9809 7900
Website: www.generichealth.com.au

This leaflet was prepared in October 2021.

Published by MIMS December 2021

BRAND INFORMATION

Brand name

Oxytocin GH

Active ingredient

Oxytocin

Schedule

S4

 

1 Name of Medicine

Oxytocin.

2 Qualitative and Quantitative Composition

Oxytocin GH injection is available in ampoules containing 5 IU in 1 mL or 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 GH injection is a sterile aqueous solution containing synthetic oxytocin. The solution is clear and colourless.

4 Clinical Particulars

4.1 Therapeutic Indications

Induction of labour; inadequate uterine effort; management of third stage of labour; postpartum haemorrhage.

4.2 Dose and Method of Administration

Dosage regimens.

Induction or augmentation of labour.

Oxytocin GH injection 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/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 GH 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 GH injection 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.

Method of administration.

Use in one patient on one occasion only. Contains no antimicrobial preservative. Discard any residue.

Instructions for use and handling.

Infusion fluids.

Compatibility of Oxytocin GH injection has been demonstrated with 0.9% saline and 5% dextrose solutions. Oxytocin GH 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 GH injection 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 GH injection 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.

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 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.

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 antidiuretic 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. 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 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, 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. 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

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.

Postmarketing experience.

The adverse drug reactions derived from postmarketing 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 categorized 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 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.

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 Poison Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

The active substance of Oxytocin GH injection 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, 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 myoepithelial cells surrounding the mammary alveoli. It therefore facilitates lactation in women experiencing difficulty in breast feeding. 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.

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 min. 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/min, 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, oxytocin acts rapidly, with a latency period of less than 1 min by intravenous injection and of 2 to 4 min by intramuscular injection. The oxytocic response lasts for 30 to 60 min 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. It is produced from both the mother and the foetus. 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.

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 min. 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 chloride, sodium acetate, glacial acetic acid and 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°C-8°C. Refrigerate. Do not freeze. Protect from light.
The unopened product may be stored for up to three (3) months at or below 25°C. Once removed from the refrigerator the product must be discarded if not used, it must not be returned to the refrigerator.

6.5 Nature and Contents of Container

Oxytocin GH injection 5 IU: Clear glass ampoules available in cartons of 1 mL x 1, 5 or 10 ampoules*.
Oxytocin GH injection 10 IU: Clear glass ampoules available in cartons of 1 mL x1, 5 or 10 ampoules*.
* Not all pack sizes may be marketed.

Australian registration number.

Oxytocin GH Solution for Injection 5 IU/1 mL ampoule - AUST R 207985.
Oxytocin GH Solution for Injection 10 IU/1 mL ampoule - AUST R 207986.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.


Molecular Formula: C43H66N12O12S2.
Molecular Weight: 1007.19.

CAS number.

50-56-6.

7 Medicine Schedule (Poisons Standard)

(S4) Prescription Only Medicine.

Summary Table of Changes