Consumer medicine information

Duratocin Injection

Carbetocin

BRAND INFORMATION

Brand name

Duratocin

Active ingredient

Carbetocin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Duratocin Injection.

SUMMARY CMI

DURATOCIN®

Consumer Medicine Information (CMI) summary

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

1. Why am I being given DURATOCIN?

DURATOCIN contains the active ingredient carbetocin. DURATOCIN is used after birth to minimise the risk of bleeding in women who have delivered their baby vaginally or by caesarean section.

For more information, see Section 1. Why am I being given DURATOCIN? in the full CMI.

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

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

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or breastfeeding.

For more information, see Section 2. What should I know before I am given DURATOCIN? in the full CMI.

3. What if I am taking other medicines?

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

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How will I be given DURATOCIN?

  • DURATOCIN is a medicine that is used only in hospital and will be given to you by a healthcare professional.
  • A single dose of 100 micrograms (1 mL) will either be injected into one of your muscles, or injected slowly over one minute into a vein.

More instructions can be found in Section 4. How will I be given DURATOCIN? in the full CMI.

5. What should I know while using DURATOCIN?

Looking after your medicine
  • DURATOCIN is usually stored at the hospital or at the pharmacy. Keep DURATOCIN in the original container until it is time for it to be given, in a place where the temperature stays below 30°C.

For more information, see Section 5. What should I know while using DURATOCIN? in the full CMI.

6. Are there any side effects?

Some common side effects of DURATOCIN are nausea (feeling sick) or vomiting, stomach pain, itching, flushing or feeling of warmth, feeling light headed, dizzy or faint (low blood pressure), headache, and tremor (shaking).

Serious side effects include hypersensitivity and severe allergic reactions, fast or abnormal heart beat, chest pain, cold clammy skin, and fainting or palpitations.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

DURATOCIN®

Active ingredient: carbetocin

Consumer Medicine Information (CMI)

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

Where to find information in this leaflet:

1. Why am I am I being given DURATOCIN?
2. What should I know before I am given DURATOCIN?
3. What if I am taking other medicines?
4. How will I be given DURATOCIN?
5. What should I know while using DURATOCIN?
6. Are there any side effects?
7. Product details

1. Why am I being given DURATOCIN?

DURATOCIN contains the active ingredient carbetocin. Carbetocin is a medicine that causes the womb (uterus) to contract. Such medicines are sometimes called oxytocic agents because they act in a similar manner to oxytocin.

In some women, following delivery, the womb fails to contract quickly enough which increases the risk of bleeding.

DURATOCIN is used after birth to minimise the risk of bleeding in women who have delivered their baby vaginally or by caesarean section.

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

Warnings

DURATOCIN must not be given to you if you:

  • are allergic to carbetocin, or any of the ingredients listed at the end of this leaflet.
    Always check the ingredients to make sure you can use this medicine.
  • are allergic to any medicine containing oxytocin.
  • have disorders of the heart and blood vessels.

You must not be given DURATOCIN during pregnancy or any time before delivery of the baby.

DURATOCIN must only be given after delivery of your baby.

DURATOCIN should not be given to children.

Check with your doctor if you have any other medical conditions such as:

  • severe heart disease
  • high blood pressure (including eclampsia and pre-eclampsia)
  • abnormalities of the placenta
  • liver or kidney problems
  • problems with blood clotting
  • disease of a gland (endocrine disorders)
  • gestational diabetes (diabetes that starts during pregnancy)
  • migraine
  • epilepsy
  • asthma.

Tell your doctor if you have previously given birth four or more times.

DURATOCIN is not recommended for use in elderly patients.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks. See additional information under Section 6. Are there any side effects?

Breastfeeding

Talk to your doctor if you are breastfeeding or intend to breastfeed.

3. What if I am taking other medicines?

Tell your doctor, pharmacist or midwife 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 will I be given DURATOCIN?

DURATOCIN is a medicine that is used only in hospital and will be given to you by a healthcare professional.

How much you will be given

  • A single dose of 100 micrograms (1 mL) will either be injected into one of your muscles, or injected slowly over one minute into a vein.

When you will be given DURATOCIN

  • DURATOCIN will be given to you immediately after the delivery of your baby.

5. What should I know while using DURATOCIN?

Looking after your medicine

DURATOCIN is usually stored at the hospital or at the pharmacy.

Keep DURATOCIN in the original container until it is time for it to be given, in a place where the temperature stays below 30°C.

Getting rid of any unwanted medicine

Any medicine that it is unused or out of date will be safely disposed of by the hospital.

6. Are there any side effects?

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 pharmacist if you have any further questions about side effects.

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

  • nausea (feeling sick) or vomiting
  • stomach pain
  • itching
  • flushing or feeling of warmth
  • feeling light headed, dizzy or faint (low blood pressure)
  • headache
  • tremor (shaking)
  • back pain
  • dizziness
  • metallic taste
  • signs of anaemia, such as tiredness, being short of breath and looking pale
  • sweating
  • chills
  • nervousness, feeling anxious.

Some side effects can be serious, for example:

  • hypersensitivity reaction and severe allergic reaction (anaphylactic reaction), which can include: rash, itching or hives on the skin, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or trouble breathing
  • fast, slow or abnormal heart beat
  • chest pain
  • cold clammy skin
  • fainting or palpitations.

These are very serious side effects, which can be life-threatening. They need urgent medical attention.

Tell your doctor, pharmacist or midwife 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.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

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

What DURATOCIN contains

Active ingredient
(main ingredient)		carbetocin
Other ingredients
(inactive ingredients)		mannitol
succinic acid
methionine
sodium hydroxide
water for injections

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

What DURATOCIN looks like

DURATOCIN is a clear colourless solution for injection in a 1 mL clear glass vial with a rubber stopper and aluminium cap, with a tear-off over cap.

Each 1 mL vial contains carbetocin 100 micrograms.

It is supplied in packs of 5 vials (AUST R 233671).

Who distributes DURATOCIN

DURATOCIN is distributed in Australia by:

Ferring Pharmaceuticals Pty Ltd
Suite 2, Level 1, Building 1
20 Bridge Street
Pymble NSW 2073

DURATOCIN® is a registered trademark of Ferring B.V.

This leaflet was prepared in December 2022.

DOCS#11524-v10

Published by MIMS March 2023

BRAND INFORMATION

Brand name

Duratocin

Active ingredient

Carbetocin

Schedule

S4

 

1 Name of Medicine

Carbetocin.

2 Qualitative and Quantitative Composition

Duratocin contains carbetocin 100 micrograms/mL.
Carbetocin is a white, fluffy lyophilized powder, soluble in water, ethanol, methanol and acetic acid. Carbetocin is insoluble in ether and petroleum ether.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution for injection.

4 Clinical Particulars

4.1 Therapeutic Indications

Duratocin is indicated for the prevention of uterine atony and excessive bleeding following delivery of the infant by caesarean section or vaginal delivery.
Duratocin must be administered after delivery of the infant.

4.2 Dose and Method of Administration

Duratocin should be administered as a single dose only, when delivery of the infant has been completed. There are no efficacy or safety data on repeat doses of Duratocin following delivery of the infant. The use of carbetocin should occur in the context of other measures to prevent PPH and associated morbidity, including uterine massage, detection and correction of coagulopathies (refer to local clinical guidelines). Other uterotonic agents should be administered if additional treatment is required to reduce excessive postpartum bleeding and increase uterine tone.

Caesarean section.

A single dose of 100 micrograms (1 mL) of Duratocin (carbetocin injection) should be administered intravenously as a bolus injection, slowly over 1 minute after delivery of the infant. Duratocin can be administered either before or after delivery of the placenta.

Vaginal delivery.

A single dose of 100 micrograms (1 mL) of Duratocin (carbetocin injection) should be administered after delivery of the infant for the active management of the third stage of labour as an intramuscular injection or intravenously as a bolus injection slowly over 1 minute.

4.3 Contraindications

Because of its long duration of action relative to oxytocin, uterine contractions produced by carbetocin cannot be stopped by simply discontinuing the medication. Therefore, carbetocin should not be administered prior to delivery of the infant for any reason, including elective or medical induction of labour. Inappropriate use of carbetocin during pregnancy could theoretically mimic the symptoms of oxytocin overdosage, including hyperstimulation of the uterus with strong (hypertonic) or prolonged (tetanic) contractions, tumultuous labour, uterine rupture, cervical and vaginal lacerations, postpartum haemorrhage, utero-placental hypoperfusion and variable deceleration of foetal heart, foetal hypoxia, hypercapnia, or death.
Carbetocin should not be used in patients with a history of hypersensitivity to oxytocin or carbetocin.
Carbetocin should not be used in patients with cardiovascular disease, especially coronary artery disease, valvular heart disease, cardiomyopathy and heart failure.
Carbetocin is not intended for use in children.

4.4 Special Warnings and Precautions for Use

General.

Some patients may not have an adequate uterine contraction after a single injection of Duratocin (carbetocin injection). In these patients, administration of Duratocin should not be repeated and more aggressive treatment with additional doses of other available uterotonic drugs like oxytocin or ergometrine is warranted. In cases of persistent bleeding, the presence of retained placental fragments, coagulopathy, or trauma to the genital tract should be ruled out.
Although no cases of partial retention or trapping of the placenta have been reported, this remains a theoretical possibility if the drug is administered before delivery of the placenta.
Patients with eclampsia and pre-eclampsia should be monitored for changes in blood pressure.
There is limited data on the use of carbetocin under general anaesthesia, in women with a history of coagulopathy, placental abnormalities, and in women at high risk of postpartum haemorrhage, for example with parity greater than 4, with hypertension, following labour especially prolonged labour, or with general anaesthesia.
Carbetocin should be used cautiously in any state in which a rapid addition to extracellular water may produce hazard for an already overburdened system.

Endocrine and metabolism.

There is limited data on the use of carbetocin in women with endocrine disorders (other than gestational diabetes).

Antidiuretic effect.

Significant antidiuretic effect is not anticipated and has not been demonstrated at the recommended dose but, as carbetocin is closely related in structure to oxytocin, hyponatraemia and water intoxication should be considered in relevant clinical situations.

Neurologic.

Carbetocin should be used cautiously in the presence of epilepsy and migraine.

Respiratory.

Carbetocin should be used cautiously in the presence of asthma.

Use in hepatic impairment.

There is limited data on the use of carbetocin in women with a history of liver disease.

Use in renal impairment.

There is limited data on the use of carbetocin in women with a history of renal disease.

Use in the elderly.

Duratocin is not recommended for use in elderly patients.

Paediatric use.

Carbetocin is not intended for use in children (see Section 4.3 Contraindications).

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No specific drug interactions have been reported with carbetocin. However, since carbetocin is closely related in structure to oxytocin, it is possible that some of the same drug interactions could occur. Severe hypertension has been reported when oxytocin was given 3-4 hours following prophylactic administration of a vasoconstrictor in conjunction with caudal block anaesthesia.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C)
Carbetocin induces uterine contraction and may cause premature or hypertonic labour. Therefore, Duratocin (carbetocin injection) use during pregnancy is contraindicated (see Section 4.3 Contraindications).
 Small amounts of carbetocin have been shown to cross over from plasma into the breast milk of nursing women who were given a 70 micrograms dose intramuscularly, between 7 and 14 weeks postpartum. The mean peak concentration in breast milk was approximately 50 times lower than in plasma, and the ratio of the milk to plasma area under the concentration versus time curves (M/PAUC) was only 2-3%. The small amount of carbetocin transferred into breast milk or colostrum after a single injection, and subsequently ingested by a breast feeding infant, would not be expected to present a significant safety concern. This is due to the fact that carbetocin would be rapidly degraded by peptidases in the infant gastrointestinal tract.
Oxytocin is known to cause contraction of the myoepithelial cells surrounding the mammary alveoli, thereby stimulating milk let-down. There is not sufficient evidence to determine whether carbetocin can also stimulate milk let-down.
However, milk let-down was found to occur normally in 5 nursing women after receiving a 70 micrograms carbetocin dose by the intramuscular route.
In a pilot postnatal development study, administration of IV doses ≥ 0.01 mg/kg/day (similar to the clinical dose based on body surface area) to lactating rats was associated with impaired pup growth. A no-effect dose was not determined.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Clinical trial data.

The adverse events observed with carbetocin during the clinical trials were of the same type and frequency as the adverse events observed with oxytocin when administered after caesarean section under epidural or spinal anaesthesia.
Intravenous carbetocin was frequently (10-40% of patients) associated with nausea, abdominal pain, pruritus, flushing, vomiting, feeling of warmth, hypotension, headache and tremor.
As most of these reactions also occurred in patients treated with placebo, it is likely that many were associated with caesarean section, spinal or epidural anaesthesia or drugs used during the procedure.
In a 122 patient placebo controlled study, the adverse events occurring in > 5% of women are presented in Table 1.
Infrequent adverse events (1-5% of patients) included back pain, dizziness, metallic taste, anaemia, sweating, chest pain, dyspnoea, chills, tachycardia and anxiety.
In the clinical trials pain was reported as common (≥ 1/100 and < 1/10) under system organ class general disorders and administration site conditions.

Published data.

Caesarean section.

The adverse event profile for patients receiving IV carbetocin was similar for patients undergoing either elective or emergency caesarean sections.
The adverse events experienced by women given carbetocin in comparison to oxytocin are similar, and include nausea, vomiting, flushing, headache, feeling of warmth, tremors, abdominal/back pain, metallic taste, sweating, and shortness of breath, tachycardia, hypotension, pruritus, chills and blurred vision.

Vaginal delivery.

The adverse event profile of carbetocin observed in trials with vaginal delivery is similar to that established in the clinical trials and during post-marketing elective caesarean section and is shown to be comparable to oxytocin infusion.
Carbetocin was also associated with a significantly improved tolerability profile in comparison to Syntometrine, with reduced incidence in gastrointestinal and cardiovascular adverse effects being reported.

Post marketing adverse effects.

There have been reports of hypersensitivity (including anaphylactic reaction) under system organ class immune system disorders (frequency not known).
There have been reports of hypersensitivity, including anaphylactic reactions and shock, cardiac arrhythmias, and cardiac arrest associated with the use of carbetocin IV in patients undergoing caesarean section.
Reactions of tachycardia, bradycardia*, arrhythmia*, myocardial ischaemia* and QT prolongation* have been reported under the SOC Cardiac disorders with frequency unknown.
*Reported with oxytocin (closely related in structure with carbetocin).

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 http://www.tga.gov.au/reporting-problems.

4.9 Overdose

Overdosage of carbetocin can be expected to produce enhanced pharmacological effects. Therefore, when carbetocin is administered postpartum, overdosage may be associated with uterine hyperactivity and pain. Treatment consists of symptomatic and supportive management.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Duratocin (carbetocin injection) is a long acting synthetic octapeptide analogue of oxytocin with agonist properties. It can be administered intravenously as a single dose immediately following delivery by caesarean section under epidural or spinal anaesthesia, to prevent uterine atony and postpartum haemorrhage.
The clinical and pharmacological properties of carbetocin are similar to those of naturally occurring oxytocin, another posterior pituitary hormone. In in vitro studies, carbetocin was shown to bind to the oxytocin receptor with similar affinity as the natural peptide. Carbetocin elicited similar uterotonic and galactogogic effects to oxytocin in animals and in vitro. Carbetocin was less potent than oxytocin, but its action was more prolonged. The oxytocin receptor content of the uterus is very low in the non-pregnant state, and increases during pregnancy, reaching a peak at the time of delivery. Therefore, carbetocin has no effect on the non-pregnant uterus, and has a potent uterotonic effect on the pregnant and immediate postpartum uterus.
The onset of uterine contraction following carbetocin administration by either the intravenous or intramuscular route is rapid, with a firm contraction being obtained within 2 minutes in around 90% of patients. The total duration of action of a single intravenous injection of carbetocin on uterine activity is about one hour, and approximately 2 hours when given as an intramuscular injection suggesting that carbetocin may act long enough to prevent postpartum haemorrhage in the immediate postpartum period. The time course for the onset and duration of action of carbetocin reflects its pharmacokinetic profile. In comparison to oxytocin, carbetocin induces a prolonged uterine response when administered postpartum, in terms of both amplitude and frequency of contractions. The prolonged effect can in part be attributed to the longer half-life of carbetocin.
Carbetocin, when administered immediately postpartum as a single intravenous bolus injection of 100 micrograms to women delivered by caesarean section under epidural or spinal anaesthesia, was found to be significantly more effective than placebo or oxytocin, as evidenced by the need for additional oxytocin therapy in the operating room.
Carbetocin administration also appears to enhance uterine involution in the early postpartum period, as evidenced by the repeated measurement of the uterine fundus.

Clinical trials.

Elective caesarean.

Two large double blind trials were conducted using carbetocin. See Tables 2 and 3.
The dose-response relationship of carbetocin and uterine contraction was evaluated in a clinical trial involving 18 patients. Here the intravenous dose of carbetocin required to produce sustained tetanic contraction after caesarean section was determined. Although 11 of 12 women responded with adequate uterine contraction to total doses of 30-90 micrograms carbetocin, none was considered to have adequate response to a starting dose less than 60 micrograms. All 6 women given 100 micrograms had an adequate uterine contraction although one did not satisfy the response criteria of the study. A single 100 micrograms intravenous injection was therefore selected for clinical use.
In a trial in 57 women undergoing elective caesarean section under epidural anaesthesia, carbetocin was compared to oxytocin for its ability to reduce intraoperative blood loss. A single 100 micrograms injection of carbetocin was compared to oxytocin (total dose 32.5 IU).
It was found that a single intravenous bolus injection of carbetocin was at least as effective as 16 hours of continuous oxytocin infusion, in terms of efficacy in maintaining uterine contraction after caesarean section, and in preventing excessive intraoperative blood loss following caesarean delivery. This study confirmed the ability of a 100 micrograms intravenous dose of carbetocin to maintain adequate uterine tone after caesarean section.
Carbetocin also appeared to accelerate the initial stages of uterine involution, associated with the return of the uterus to the non-pregnant size and position.

Emergency caesarean.

Three randomised, double blind clinical studies identified in the literature (Whigham et al 2016, El Behery et al 2016, Razali et al 2016) investigated the safety and efficacy of carbetocin compared to oxytocin in the prevention of postpartum haemorrhage in patients undergoing emergency caesarean delivery. A total of 849 patients were enrolled, with 425 receiving 100 micrograms of carbetocin by slow bolus intravenous injection, and 424 receiving between 5 and 20 IU of oxytocin via intravenous infusion. In these studies, administration of carbetocin was associated with comparable blood loss and incidence of postpartum haemorrhage and in two of these studies a statistically significant reduction in the need for additional uterotonics compared to patients receiving oxytocin. No significant differences in tolerability between the treatment groups were observed. These results are broadly consistent with the clinical trial data obtained in patients receiving carbetocin following delivery by elective caesarean section.

Vaginal delivery.

Seven randomised, double blind, placebo or active controlled studies were identified in the literature that investigated the safety and efficacy of carbetocin in woman delivering vaginally. Two studies (Maged et al 2016, Boucher et al 2004) containing a total of 360 patients, compared the performance of a carbetocin 100 microgram intramuscular injection to that of oxytocin 5 IU delivered either intramuscularly or 10 IU via intravenous infusion in the prevention of postpartum haemorrhage. Similar to the data reported following delivery via caesarean section, carbetocin was associated with a comparable incidence of postpartum haemorrhage and a reduced need for uterine massage and additional uterotonic treatment, versus oxytocin, with one study additionally reporting a reduction in blood loss. No differences in tolerability were reported. Five clinical studies (Samimi et al 2013, Askar et al 2011, Su et al 2009, Nirmala et al 2009, Leung et al 2006) in 1230 patients, compared the safety and efficacy of 100 micrograms intramuscular carbetocin (615 patients) with intramuscular administration of Syntometrine (oxytocin 5 IU+ 0.51 mg ergometrine, 615 patients). In these studies, the efficacy of carbetocin was reported to be at least as good as the combination of oxytocin and ergometrine, with the majority of studies also recording a statistically significant reduction in blood loss and fall in haemoglobin.

Meta-analyses of published studies.

The performance of carbetocin in the prevention of postpartum haemorrhage following caesarean and vaginal delivery was further assessed in two independent meta analyses (Su et al 2012, Jin et al 2015). These meta-analyses concluded that carbetocin was associated with a statistically significant benefit over oxytocin following caesarean delivery (mixed elective and emergency population). There was a 32% reduction in the need for additional uterotonic agents in the carbetocin group relative to the oxytocin group (RR= 0.68; [95% CI: 0.55, 0.84])2 and a 46% reduction in the need for uterine massage (RR= 0.54; [95% CI: 0.31, 0.96])2. Following vaginal delivery, carbetocin was associated with a statistically significant reduction in the need for uterine massage versus oxytocin (RR= 0.70; [95% CI 0.51, 0.94])3. When carbetocin was compared to Syntometrine, there was a statistically significant reduction in blood loss (delta = -48.84 mL; [95% CI: -94.82, -2.85]) and fall in haemoglobin (mean difference -0.10; [95% CI -0.17, -0.03]) as well as a significant reduction in gastrointestinal (e.g. nausea (RR = 0.24; [95% CI 0.15, 0.40]) and vomiting (RR = 0.21; [95% CI 0.11, 0.39]) and cardiovascular (e.g. hypertension (RR = 0.07; [95% CI 0.01, 0.49]) side effects3.
1 One study utilised a dose of 0.2 mg ergometrine.
2 Jin et al, 2016. Carbetocin for the prevention of postpartum hemorrhage: a systematic review and meta-analysis of randomized controlled trials. The Journal of Maternal-Fetal and Neonatal Medicine, 29(3), pp.400-407.
3 Su et al, 2012. Carbetocin for preventing postpartum haemorrhage. Cochrane Database Syst Rev, 4.

5.2 Pharmacokinetic Properties

The pharmacokinetics of carbetocin were evaluated in 25 non-pregnant healthy women after administration of 400 microgram and 800 microgram IV or IM (Study CLN 6.3.1). Clearance and the volume of distribution do not appear to be dose dependent, whereas Cmax and AUC0-∞ show dose proportionality indicating linear pharmacokinetics.

Absorption.

Following intramuscular administration of carbetocin, the peak concentration of carbetocin was achieved within 20-30 minutes and bioavailability was approximately 80%.

Distribution.

The IV pharmacokinetics follows a 2 compartment model with a distribution half-life of 5.5 ± 1.6 minutes after a 400 micrograms intravenous dose. Similar values were obtained after administration of the 800 micrograms dose.

Metabolism.

Approximately 0.7% of the carbetocin dose is eliminated in the unchanged form by the kidney, indicating that carbetocin, like oxytocin, is eliminated primarily by non-renal routes.

Excretion.

The clearance of carbetocin was 0.55-0.60 L/min and the terminal elimination half-life of carbetocin was 41 ± 11.9 minutes after a 400 micrograms intravenous dose. Similar values were obtained after administration of the 800 micrograms dose.

5.3 Preclinical Safety Data

Genotoxicity.

Carbetocin was not genotoxic in assays for gene mutation (in vitro bacterial and mouse lymphoma cell assays) and chromosomal damage (human lymphocytes in vitro and mouse micronucleus test in vivo).

Carcinogenicity.

No long-term studies in animals have been performed to evaluate the carcinogenic potential of carbetocin.

6 Pharmaceutical Particulars

6.1 List of Excipients

Methionine 1 mg, succinic acid 1.19 mg, mannitol 47.0 mg, sodium hydroxide 2 M to pH 5.5 and water for injections to 1 mL.

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

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 below 30°C. Once the vial has been opened, the product should be used immediately.

6.5 Nature and Contents of Container

Duratocin is a ready-for-use solution containing 100 micrograms carbetocin in a 1 mL clear glass vial with a bromobutyl rubber stopper and an aluminium crimp cap with a tear-off over cap. Each pack contains 5 vials.

6.6 Special Precautions for Disposal

Only particle free, clear solutions should be used.
In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.


Molecular formula: C45H69N11O12S.
Molecular weight: 988.1.
Synonyms: 2,1-desamino-4, 1-desthio-O4, 2-methyl 1 [1-homocysteine] oxytocin 1-desamino-1-monocarba-2-(0-methyl)- tyrosine-oxytocin(2-0-methyltyrosine)- 1-deaminocarba-1-oxytocin(6,1-β deaminocystathionine, 2-0-methyl-tyrosine)-oxytocin [Tyr(Me)2]-desamino-1-carba-oxytocin.

CAS number.

37025-55-1.

7 Medicine Schedule (Poisons Standard)

(S4) Prescription Only Medicine.

Summary Table of Changes