By: Dr. Azuka Ezeike, MBBS, FWACS (Obstetrics and Gynaecology), MSc (Public Health), Freelance Medical Writer. Medical review by: Chinedu Akpa, B. Pharm.
Carbetocin
Carbetocin is a long-acting uterotonic that is closely related to oxytocin. [1] It is derived from oxytocin by changing some components in the parent drug. Unlike oxytocin, which is natural, carbetocin is synthetic. It acts the same way as oxytocin by causing the contraction of the muscles of the womb thereby preventing bleeding.
Carbetocin is used for the prevention of postpartum haemorrhage (PPH) [2]
Carbetocin is administered as a single dose of 100 mcg.
It is either given
It is available as a clear, colourless 1ml solution in glass vials.
Carbetocin works by attaching itself to the peripheral oxytocin receptors in the smooth muscles of the womb (uterus). By so doing, carbetocin causes:
The onset of action is within two minutes and the duration of action is up to an hour. See Table 1.
.
It has a longer half-life (the time it takes for the concentration to reduce to half in the body) of about 40 minutes, compared with oxytocin which has a half-life of 4-10 minutes. [3, 4] Therefore, the duration of action is longer than that of oxytocin, leading to a prolonged duration of action on the womb muscles. [5] This reduces the need for additional uterotonics.
Click on image to enlarge.
About 80% of the drug is available in the blood after intramuscular administration. [1]. Less than 1% of the drug is excreted through the kidneys, [6] and an insignificant amount is secreted into the breast milk. [7]
Carbetocin can cause water retention in the body.
This manifests as
If not recognised on time, the adverse effects could progress to uncontrolled jerky muscle movements (convulsion) and loss of consciousness (coma).
Some of additional adverse effects of carbetocin that have been observed in different systems of the body during the use of carbetocin in clinical trials include:
Carbetocin should be avoided in women with the following conditions
It should be used with caution in patients with migraine and asthma.
No drug interaction studies have been done with carbetocin.
Since carbetocin is related to oxytocin, some of the drug interactions associated with oxytocin may also occur with the use of carbetocin.
It is not known to interact with any type of food.
Overdose of Carbetocin leads to:
The management of carbetocin overdose is by;
It was formulated by adding excipients to carbetocin. An excipient is a substance other than the active pharmaceutical ingredient that is incorporated into a drug for various purposes, including long-term stabilisation.
Heat-stable carbetocin came to the limelight in the year 2018 after a landmark study that compared it with oxytocin. The advantage of this new formulation over oxytocin and carbetocin is that it maintains its stability for years even at a temperature of up to 30 degrees centigrade. [8] This is unlike oxytocin which must be stored at a temperature of 2 to 8 degrees centigrade, or else it loses its potency.
The stability at room temperature makes it a viable alternative in low-resource settings where the cold chain needed to preserve oxytocin may not be maintained due to a lack of stable electricity.
The Champion Trial was conducted between 2015 and 2018 to compare the effect of oxytocin and carbetocin in preventing postpartum haemorrhage (bleeding after birth). The study was funded by the non-profit, MSD for Mothers and was done in collaboration with the World Health Organization (WHO). The study involved 29,645 women and was conducted in 23 sites in 10 countries. The results showed that carbetocin was as good as oxytocin in preventing blood loss of at least 500 mls following vaginal delivery. [8]
The heat-stable carbetocin has been added to the WHO model list of essential medicines. [2] Heat-stable carbetocin is marketed under the brand names Pabal®, Duratocin®, and Carbetocin Ferring.
Even though carbetocin has obvious advantages over oxytocin because it can be stored at room temperature, the use of carbetocin has been limited due to the high cost as it is considerably more expensive than oxytocin.
To address the challenge, the WHO signed a memorandum of understanding (MOU) with the manufacturer of carbetocin to make it available in public sector facilities of low-income and low-middle-income countries at an affordable and sustainable price.[2] The effect of the MOU is yet to be seen as the drug is still comparatively more costly in most local
The WHO however recommends carbetocin for the prevention of PPH for all births in contexts where the cost is comparable to other effective uterotonics. [2] It is not recommended for the treatment of PPH.
Carbetocin, particularly the heat-stable formulation, is a valuable addition to the drugs used for preventing postpartum haemorrhage. It is known for its safety and stability at room temperature, and its longer duration of action makes it an attractive option in low-resource settings. However, the high cost remains a barrier to its widespread use. It is hoped that the cost will decrease over time, enabling broader utilisation in Africa.
1. PubChem. Carbetocin [Internet, n.d.]. Cited 2024 Jun 29. Available from here.
2. World Health Organization (WHO). WHO recommendations: Uterotonics for the prevention of postpartum haemorrhage [Internet. 2018 Dec. 20]. Cited 2024 Jun 29. Available from here.
3. Moertl M, Friedrich S, Kraschl J, Wadsack C, Lang U, Schlembach D. Haemodynamic effects of carbetocin and oxytocin given asintravenous bolus on women undergoing caesarean delivery: a randomised trial. BJOG 2011;118:1349–1356. Doi: 10.1111/j.1471-0528.2011.03022.x. Cited 2024 Jun 29. Available from here.
4. Holleboom CA, van Eyck J, Koenen SV, Kreuwel IA, Bergwerff F, Creutzberg EC, Bruinse HW. Carbetocin in comparison with oxytocin in several dosing regimens for the prevention of uterine atony after elective caesarean section in the Netherlands. Arch Gynecol Obstet. 2013 Jun;287(6):1111-7. doi: 10.1007/s00404-012-2693-8. Cited 2024 Jun 29. Available from here.
5. Sciencedirect. Carbetocin - an overview [Internet, n.d.]. Cited 2024 Jun 29. Available from here.
6. Musaba MW, Dey T, Wandabwa JN and Weeks AD. Carbetocin for the Management of Postpartum Hemorrhage; In: A comprehensive textbook of postpartum haemorrhage. 2nd edition, Chapter 44. Available from here.
7. MedEx. Carbetocin. [Internet, n.d.]. Cited 2024 Jul 1. Available from here.
8. Widmer M, Piaggio G, Nguyen TMH, Osoti A, Owa OO, Misra S, Coomarasamy A. Heat-stable carbetocin versus oxytocin to prevent haemorrhage after vaginal birth. N Engl J Med [Internet]. 2018 Aug 23, 379(8):743–52. Available from here.
Published: July 2, 2024
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