Yet Another Shortage? Alternatives to Oxytocin

InpharmD™ Clinical Literature Summaries — S4E2

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We’ve always had the occasional issue with medication shortages, and I don’t know about you… but ever since the pandemic started it seems like there’s a new shortage almost every week. We’ve been getting lots of questions on alternatives to oxytocin due to the ongoing shortage of this critical medication.

As you all know, oxytocin is the backbone of labor and delivery. It has a few uses in this setting… it can induce or augment labor, it can prevent postpartum hemorrhage, and it can treat postpartum hemorrhage as well. So this begs the question, what should we do if we just don’t have enough for everybody?

Well, this is a tough question and there probably isn’t a perfect answer. We did a deep dive on possible alternatives and here’s what we found.

Other countries have carbetocin, which is an oxytocin analogue, but this medication is not available in the United States, so we won’t dwell on it long. In the setting of postpartum hemorrhage prevention or treatment there’s also ergotamine derivatives, such as methylergonovine. This medication works to increase the tone of the uterus and thus prevent bleeding. While FIGO guidelines recommend oxytocin first line in the prevention of postpartum hemorrhage, they do state that if oxytocin is unavailable, methylergonovine is a reasonable alternative.

In the setting of active postpartum hemorrhage, tranexamic acid is recommended by the World Health Organization if diagnosis of bleeding is within 3 hours of delivery. This is not to say this is a replacement for oxytocin however, as it does not work by treating uterine atony... It’s really more of an adjunct in this setting. Methylergonovine can also be used per ACOG. And lets remember that in the setting of active bleeding due to uterine atony, sometimes multiple agents are needed to cause contraction of the uterus in addition to oxytocin.

And lets not forget about misoprostol. Many of you were probably waiting to talk about this agent. It can be used either orally or vaginally for labor induction and is recommended by the World Health Organization for this purpose. One important point is that both the World Health Organization and ACOG do not recommend its use in women who’ve had a prior C section due to increased risk of uterine rupture. There’s some debate about misoprostol vs oxytocin however. We know that misoprostol is useful for the ripening of an unfavorable cervix, but this is different than actually stimulating contractions of the uterus as oxytocin can do. Traditionally, when the cervix is favorable, oxytocin is given to induce labor. But, misoprostol can in fact induce labor and cause uterine contractions in addition to its effects on cervical ripening and can be used for this purpose per the World Health Organization.

In the setting of postpartum hemorrhage prevention and treatment, misoprostol can also be used if oxytocin is unavailable per FIGO guidelines, however a Cochrane review did conclude that oxytocin for the treatment of postpartum hemorrhage is probably more effective than misprostol with fewer side effects.

All this being said, we know everyone would like to use oxytocin when they want to use it. While probably not the silver bullet we’re all looking for, small things like using multi dose vials or not drawing up doses early may help reduce waste.

At the end of the day, this oxytocin shortage really puts a spotlight on how supply chain issues have affected all areas of healthcare. Unfortunately, there’s not a magical oxytocin replacement, but we hope this review shows that there are some alternatives and adjuncts that can be used in the right clinical setting.

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Other papers/resources used:

Arrowsmith S, Wray S. Oxytocin: its mechanism of action and receptor signalling in the myometrium. J Neuroendocrinol. 2014;26(6):356–369. doi:10.1111/jne.12154

Escobar MF, Nassar AH, Theron G, et al. FIGO recommendations on the management of postpartum hemorrhage 2022. Int J Gynaecol Obstet. 2022;157 Suppl 1(Suppl 1):3–50. doi:10.1002/ijgo.14116

Vogel JP, Oladapo OT, Dowswell T, Gülmezoglu AM. Updated WHO recommendation on intravenous tranexamic acid for the treatment of post-partum haemorrhage. Lancet Glob Health. 2018;6(1):e18-e19. doi:10.1016/S2214–109X(17)30428-X

ACOG Practice Bulletin №107: Induction of labor. Obstet Gynecol. 2009;114(2 Pt 1):386–397. doi:10.1097/AOG.0b013e3181b48ef5

Beigi A, Kabiri M, Zarrinkoub F. Cervical ripening with oral misoprostol at term. Int J Gynaecol Obstet. 2003;83(3):251–255. doi:10.1016/s0020–7292(03)00275–3

Parry Smith WR, Papadopoulou A, Thomas E, et al. Uterotonic agents for first-line treatment of postpartum haemorrhage: a network meta-analysis. Cochrane Database Syst Rev. 2020;11(11):CD012754. Published 2020 Nov 24. doi:10.1002/14651858.CD012754.pub2

WHO Recommendations for Induction of Labour. Geneva: World Health Organization; 2011

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