**2. Carbetocin: a therapy advance for the prevention of postpartum haemorrhage**

Carbetocin is a novel drug, developed as long-acting congener of oxytocin. It has shown similar pharmacologic traits as oxytocin, but around 10-times longer half-life than oxytocin. Carbetocin does not show variation in dose response, it lacks receptor desensitisation, and thus is an advance over oxytocin in this space [17].

As shown in **Figure 4**, the amino group and the disulfide bond, which were altered to create carbetocin, are indicated. The amino group was removed and the sulphur atom was replaced by a carba group.

Its long uterine activity is beneficial in the management of the third stage of labour. The side-effect profile of carbetocin is better than oxytocin and other uterotonics. Heat-stable carbetocin has demonstrated to maintain stability for 36 months at 30°C and 75% relative humidity [18].

#### **2.1 Pharmacological properties of carbetocin**

As a novel analogue of oxytocin, carbetocin has uterotonic activity by binding to oxytocin receptors on the myometrial cells. The main disadvantage of oxytocin is its short half-life (3–17 minutes) [19]. By modifying the oxytocin molecule, its half-life has been prolonged. Because of alterations, carbetocin has more pronounced pharmacological effects [20].

Carbetocin is a synthetic oxytocin analogue, with a potency of about one-tenth that of oxytocin [21]. Its plasma half-life is approximately 40 minutes, which is about 10 times longer than that of oxytocin [22]. It causes an increase in the intracellular concentration of calcium that promotes uterine contractility, via inositol phosphates signalling pathways [23].

*Oxytocin and Its Congeners in Obstetrics Practice: An Update on Carbetocin DOI: http://dx.doi.org/10.5772/intechopen.112223*

The onset of action is rapid, with a firm contraction being obtained within 2 minutes in around 90% of patients. The duration of action of a single iv injection is about 1 hour, and approximately 2 hours when given as an IM injection. Carbetocin induces a prolonged uterine response, in parameters like amplitude and frequency of contractions.

**Adverse reactions:** The adverse reactions are the same as those with the use of oxytocin. Carbetocin was associated with nausea, abdominal pain, pruritus, flushing, and tremor (11%) [24].

#### **2.2 Carbetocin to prevent haemorrhage after vaginal birth**

Widmer et al. enrolled women across 23 sites in a randomised trial comparing IM injections of heat-stable carbetocin with oxytocin after vaginal birth [25]. The endpoints included the proportion of patients with blood loss of 500 ml or the additional uterotonics use, and patients with blood loss of 1000 ml. The authors concluded that carbetocin was non-inferior to oxytocin.

#### **2.3 Carbetocin to prevent haemorrhage after caesarean delivery**

This study enrolled women at risk of PPH after Caesarean section [26]. More than 1200 women were included. Around 750 received oxytocin first and around 480 received carbetocin first. It was demonstrated that compared with oxytocin, carbetocin reduced the need for uterotonics or interventions in high-risk patients.

#### **2.4 Agents for in PPH prophylaxis meta-analysis**

The uterotonics use during the third stage of labour for preventing PPH were compared with a control groups. The study demonstrated that ergometrine plus oxytocin combination, carbetocin, and misoprostol plus oxytocin combination were most efficacious in evaluated parameters. Carbetocin showed the best side-effect profile among the studied groups [27, 28].

The WHO did not include carbetocin in its 2012 guideline for PPH [29]. But in its update published in 2018, it has included carbetocin to the Essential Medicines List [30]. Carbetocin is recommended for the prevention of bleeding after all births when oxytocin is unavailable or its quality cannot be assured. Carbetocin remains effective at warm temperatures [31], while oxytocin has to bestored and transported at 2°C–8°C.
