This recommendation applies to women giving birth vaginally or via caesarean section. Heat-stable carbetocin must be administered by skilled health personnel trained in the use of injectable uterotonics, while misoprostol can be administered by skilled, community or lay health workers.

• In the 2018 WHO recommendations on uterotonics for the prevention of PPH, additional injectable uterotonic options – ergometrine/methylergometrine and the fixed-dose combination of oxytocin and ergometrine – were included for use in settings where oxytocin is unavailable (or its quality cannot be guaranteed). In this updated recommendation, the GDG placed greater emphasis on the safety profile of uterotonics and the availability of safer and comparably or more effective alternatives. Consequently, these previously recommended options are no longer included; only heat-stable carbetocin or misoprostol is now recommended in settings where the oxytocin cold chain cannot be reliably maintained.
• “Where oxytocin cold chain cannot be consistently maintained” refers to settings where continuous refrigeration (typically 2–8 °C) during storage, transport and handling of oxytocin cannot be reliably ensured because of infrastructure limitations, unstable electricity supply or lack of temperature-monitoring systems. Many low- and middle-income countries, particularly their rural and remote areas, fall into this category.
• Both heat-stable carbetocin and misoprostol are most effective when administered immediately after the birth of the baby or babies, preferably within 1 minute. Administration for PPH prevention does not preclude delayed cord clamping.
• This recommendation applies only to the use of heat-stable carbetocin for the prevention of PPH. The heatstable and non-heat-stable formulations of carbetocin are not currently recommended for other obstetric indications (such as labour induction, labour augmentation or treatment of PPH).
• The heat-stable formulation differs from the non-heat-stable formulation only in its excipientsa , and not the active pharmaceutical ingredients (46). It does not require refrigeration; therefore, it eliminates the costs and logistic constraints associated with cold-chain storage and transport for non-heat-stable uterotonics.
• Clinical trials of carbetocin have used both intramuscular and intravenous routes of administration, including a WHO multi-country trial of nearly 30 000 women that used a regimen of 100 µg intramuscular heat-stable carbetocin in a range of high-, middle- and low-income settings. Thus, the available evidence supports the recommendation of either intramuscular or intravenous route of administration for heatstable carbetocin, depending on the clinical setting and available expertise.
• Although existing trials of carbetocin have been conducted exclusively in hospital settings, the GDG agreed that there are no biological or pharmacological reasons to expect different effectiveness in community settings, provided carbetocin is administered under conditions similar to other injectable uterotonics.