Carbetocin: A Comprehensive Pharmacological and Clinical Monograph

Introduction

Carbetocin is a long-acting, synthetic nonapeptide analogue of the endogenous human hormone oxytocin, engineered to possess enhanced stability and a prolonged duration of action.[1] It has established a prominent position in modern obstetric practice as a critical uterotonic agent, a class of drugs that stimulates contraction of the myometrium.[1] The principal clinical indication for Carbetocin is the prevention of postpartum hemorrhage (PPH), a life-threatening complication of childbirth characterized by excessive bleeding.[5] Its use is particularly well-established following Cesarean section and is increasingly supported for the prevention of PPH after vaginal delivery.[8]

The primary pharmacological distinction and clinical advantage of Carbetocin over oxytocin, the conventional first-line uterotonic, lies in its significantly longer biological half-life and duration of action.[10] This superior pharmacokinetic profile, a direct result of specific structural modifications to the oxytocin peptide, allows for effective uterine tone to be achieved and maintained with a single bolus injection. This contrasts sharply with the short half-life of oxytocin, which often necessitates a prolonged intravenous infusion to prevent uterine atony, the most common cause of PPH.[10]

A landmark innovation in the drug's history has been the development and introduction of a heat-stable formulation of Carbetocin.[14] This advancement holds profound implications for improving global maternal health outcomes, particularly in low- and middle-income countries (LMICs). In these regions, the efficacy of oxytocin is frequently compromised by the logistical challenges of maintaining an unbroken "cold chain"—refrigerated transport and storage—from manufacturer to patient.[16] By remaining stable at ambient temperatures, heat-stable Carbetocin overcomes this critical barrier, offering a reliable and effective intervention to prevent PPH in resource-constrained settings.

Beyond its established role in obstetrics, the therapeutic potential of Carbetocin is being explored in other clinical areas. Most notably, an intranasal formulation, designated LV-101, is under active investigation for the treatment of hyperphagia and behavioral symptoms associated with Prader-Willi syndrome (PWS), a rare genetic neurodevelopmental disorder.[19] This emerging application highlights the drug's activity on central oxytocin pathways and showcases its potential to address unmet needs beyond maternal health.

This report provides an exhaustive, evidence-based monograph on Carbetocin. It synthesizes current knowledge on its chemistry and formulations, details its molecular pharmacology, critically evaluates its clinical efficacy and safety profile, outlines its regulatory status across key jurisdictions, and discusses future directions in its clinical development.

Section 1: Chemical Profile and Formulations

A comprehensive understanding of Carbetocin begins with its precise chemical identity, molecular structure, and the composition of its pharmaceutical preparations. These foundational characteristics dictate its stability, pharmacological behavior, and clinical utility.

1.1 Identification and Nomenclature

Carbetocin is classified as a small molecule, specifically a heterodetic cyclic peptide, reflecting its complex, ring-containing structure derived from amino acids.[4] For unambiguous scientific and regulatory communication, it is cataloged across numerous international databases with a consistent set of identifiers.

• [Generic Name:] Carbetocin [10]
• [DrugBank ID:] DB01282 [1]
• [CAS (Chemical Abstracts Service) Number:] 37025-55-1 [1]
• [Other Key Identifiers:] Additional identifiers ensure its unique traceability across different chemical and biological databases, including the European Community (EC) Number 253-312-6, the FDA's Unique Ingredient Identifier (UNII) 88TWF8015Y, the ChEBI (Chemical Entities of Biological Interest) ID CHEBI:59204, the ChEMBL ID CHEMBL3301668, and the KEGG (Kyoto Encyclopedia of Genes and genomes) ID D07229.[1]

The drug is recognized under various synonyms and systematic chemical names that describe its structure relative to oxytocin. These include systematic names such as 1-butanoic acid-2-(O-methyl-L-tyrosine)-1-carbaoxytocin and (2-O-Methyltyrosine)deamino-1-carbaoxytocin.[1] In medical literature, it is often indexed under Medical Subject Headings (MeSH) terms like

1-deamino-1-monocarba-2-(Tyr(OMe))-oxytocin and the abbreviation dcomot.[1] Its International Nonproprietary Names (INN) include

Carbetocina (Spanish) and Carbetocinum (Latin), reflecting its global use.[1]

1.2 Chemical Structure and Properties

Carbetocin's unique pharmacological properties are a direct consequence of its molecular architecture. Its chemical formula is C45​H69​N11​O12​S, and it has an average molecular weight of approximately 988.17 g/mol and a precise monoisotopic mass of 987.484787417 Da.[23]

Carbetocin is defined as a synthetic carba-analogue of oxytocin, meaning it is derived from the structure of the natural hormone but with specific, deliberate modifications designed to enhance its therapeutic characteristics.[1] These modifications are threefold:

1. [Deamination at Position 1:] The N-terminal amino group of the first amino acid residue (cysteine in oxytocin) is replaced with a hydrogen atom. This modification, known as deamination, protects the peptide from degradation by aminopeptidases, enzymes that cleave amino acids from the N-terminus.[4]
2. [Methylation at Position 2:] The tyrosine residue at the second position is O-methylated, meaning the hydrogen atom of its phenolic hydroxyl group is replaced by a methyl (CH3​) group. This creates a Tyr(Me) residue.[4]
3. [Carba-1 Substitution:] The disulfide bridge (S−S) that connects the cysteine residues at positions 1 and 6 in oxytocin, forming its characteristic cyclic structure, is replaced by a more chemically stable thioether bond (CH2​−S). This is achieved by replacing the sulfur atom of the cysteine at position 1 with a methylene group (CH2​). This "carba" modification makes the cyclic structure highly resistant to reduction and enzymatic cleavage, which is a primary pathway for oxytocin inactivation.[4]

The amino acid sequence of the active peptide is often represented as YIQNCPLG, with the understanding that this represents the core sequence subject to the aforementioned modifications.[5] A more descriptive representation is

But-Tyr(Me)-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH2, where But stands for butanoic acid (resulting from the deamination and modification at position 1) and the bracketed term indicates the stable carba bridge between the first and sixth positions.[28] For complete chemical definition, its IUPAC name, Canonical SMILES, and InChI strings are available in chemical databases.[1]

The relationship between these structural modifications and the drug's clinical advantages is a clear example of rational peptide drug design. The native oxytocin molecule is susceptible to rapid enzymatic breakdown in the body, which accounts for its very short half-life. The deamination at the N-terminus and, most critically, the replacement of the labile disulfide bond with a robust thioether bridge, render the Carbetocin molecule significantly more resistant to these degradation pathways. This enhanced chemical stability is the direct molecular basis for its prolonged pharmacokinetic profile, particularly its longer half-life. This extended duration of action allows a single administration to provide a sustained therapeutic effect, a key convenience and safety advantage over the continuous infusion required for oxytocin.

1.3 Physical Properties and Pharmaceutical Formulations

Carbetocin is supplied either as a white, fluffy lyophilized (freeze-dried) powder that is reconstituted before use or, more commonly, as a ready-to-use clear, colorless solution for injection.[3] It exhibits solubility in polar solvents such as water, ethanol, methanol, and acetic acid, but is insoluble in nonpolar organic solvents like ether and petroleum ether.[3] Two principal formulations exist, distinguished by their excipients and resulting storage requirements.

[Standard Refrigerated Formulation (e.g., Duratocin®)]

• [Composition:] This formulation contains 100 micrograms/mL of Carbetocin as the active ingredient. The excipients are simple and functional: sodium chloride is used to make the solution isotonic with bodily fluids, glacial acetic acid is used to adjust the pH to an acidic value of approximately 3.8, and water for injection serves as the solvent.[32]
• [Storage:] This formulation is heat-labile and must be stored under refrigeration at 2-8°C (36-46°F). It must be protected from freezing.[3]

[Heat-Stable Formulation (e.g., Carbetocin Ferring, Pabal® RTS)]

• [Composition:] This advanced formulation also contains 100 micrograms/mL of Carbetocin. However, its excipient composition is specifically engineered for thermal stability. It includes L-methionine, which acts as an antioxidant to prevent oxidative degradation of the peptide; succinic acid, which serves as a buffering agent; mannitol, which acts as a stabilizer and isotonicity agent; and sodium hydroxide for pH adjustment to a less acidic value of approximately 5.45. Water for injection is the solvent.[14]
• [Storage:] This formulation is stable for at least three years at temperatures up to 30°C (86°F) and 75% relative humidity. It should be kept in its outer carton to protect from light and must not be frozen.[14]

The development of the heat-stable formulation represents a significant advancement in pharmaceutical engineering aimed at solving a critical global health challenge. The "cold chain" required for the refrigerated formulation is a major logistical and economic barrier in many LMICs, leading to the use of sub-potent medication and contributing to preventable maternal deaths from PPH. By employing a sophisticated system of a specific buffer (succinate), a stabilizer (mannitol), and an antioxidant (L-methionine), the heat-stable formulation protects the peptide's integrity without refrigeration. This formulation engineering directly addresses the public health barrier, making a reliable uterotonic agent accessible in settings where it is needed most.

Both formulations are supplied in single-dose 1 mL glass vials or ampoules, intended for single use only, with any remaining solution to be discarded.[14]

[Table 1: Drug Identification and Chemical Properties of Carbetocin]

Parameter	Value	Source(s)
Generic Name	Carbetocin	23
DrugBank ID	DB01282	5
CAS Number	37025-55-1	1
Molecular Formula	C45​H69​N11​O12​S	23
Average Molecular Weight	988.17 g/mol	23
IUPAC Name	(2S)-N--4-methyl-1-oxopentan-2-yl]-1--15-[(4-methoxyphenyl)methyl]-5,8,11,14,17-pentaoxo-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]pyrrolidine-2-carboxamide	1
Key Synonyms	1-butanoic acid-2-(O-methyl-L-tyrosine)-1-carbaoxytocin; (2-O-Methyltyrosine)deamino-1-carbaoxytocin; Pabal; Duratocin	1
Structural Description	A synthetic analogue of oxytocin with three key modifications: deamination at position 1, O-methylation of tyrosine at position 2, and replacement of the disulfide bridge with a thioether (carba) bridge between positions 1 and 6.	1

Section 2: Comprehensive Pharmacology

The clinical effects of Carbetocin are governed by its pharmacodynamic interactions at the molecular level and its pharmacokinetic profile, which describes its journey through the body. A detailed analysis of these properties is essential to understand its therapeutic efficacy and safety.

2.1 Pharmacodynamics: Mechanism of Action

Carbetocin exerts its therapeutic effect by acting as a selective agonist at the oxytocin receptor (OXTR), its primary molecular target.[2] The OXTR is a member of the Class A G-protein coupled receptor (GPCR) family, predominantly expressed on the smooth muscle cells (myocytes) of the uterus.[10]

Receptor Binding and Signaling Cascade

Carbetocin binds to the OXTR with high affinity, with a reported dissociation constant (Ki​) of 7.1 nM.35 The binding interaction has been shown to be nonselective at the extracellular N-terminus and extracellular loops E2 and E3 of the receptor.10 Although some studies suggest its affinity for the OXTR may be slightly lower than that of native oxytocin, its structural modifications confer a much greater in-vivo stability, resulting in a potent and sustained biological effect.10

The binding of Carbetocin to the OXTR, which is coupled to Gq/11 proteins, initiates a well-defined downstream signaling cascade:

1. [G-Protein Activation:] Receptor activation triggers the dissociation of the Gq alpha subunit, which in turn activates the enzyme phospholipase C (PLC).[10]
2. [Second Messenger Production:] PLC catalyzes the hydrolysis of the membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2​) into two second messengers: inositol trisphosphate (IP3​) and diacylglycerol (DAG).[10]
3. [Calcium Release:] IP3​ diffuses through the cytoplasm and binds to specific IP3​ receptors on the membrane of the sarcoplasmic reticulum, the cell's intracellular calcium store. This binding opens calcium channels, leading to a rapid and significant release of stored calcium (Ca2+) into the cytosol.[12]
4. [Muscle Contraction:] The elevated intracellular Ca2+ concentration is the ultimate trigger for muscle contraction. Ca2+ binds to the protein calmodulin, and the resulting Ca2+-calmodulin complex activates myosin light-chain kinase (MLCK). MLCK then phosphorylates the light chains of myosin, the motor protein in muscle cells. This phosphorylation enables the cross-bridge cycling between myosin and actin filaments, causing the smooth muscle cell to contract.[12]

Physiological Effect on the Uterus

The physiological response to Carbetocin is highly dependent on the reproductive state of the uterus. In the non-pregnant state, the density of oxytocin receptors in the myometrium is very low, and consequently, Carbetocin has minimal uterotonic effect.1 During pregnancy, however, hormonal changes lead to a dramatic upregulation of OXTR expression, which reaches a peak at the time of labor and delivery.1

When administered in the immediate postpartum period, Carbetocin leverages this high receptor density to produce a powerful therapeutic effect. It stimulates the uterine smooth muscle, resulting in strong, rhythmic contractions, an increased frequency of any existing spontaneous contractions, and a significant increase in overall uterine tone.[1] This firm contraction of the uterus, known as uterine involution, constricts the spiral arteries that supplied the placenta, mechanically staunching blood flow and preventing PPH. The onset of this action is rapid and robust; a firm uterine contraction is typically observed within two minutes of either intravenous or intramuscular administration.[10]

Selectivity and Off-Target Effects

The molecular pharmacology of Carbetocin also informs its potential side effects. Due to its close structural homology with vasopressin (also known as antidiuretic hormone, ADH), Carbetocin can exhibit some cross-reactivity with vasopressin receptors (V1a, V1b, and V2), albeit with a much lower affinity than for the OXTR.10 This off-target activity is the basis for its weak antidiuretic effect, which has been quantified as having a vasopressin activity of less than 0.025 I.U. per vial.6 While this effect is not typically significant at the standard therapeutic dose, it creates a potential risk for water intoxication and hyponatremia (low blood sodium) if the patient is simultaneously receiving large volumes of intravenous fluids, a common scenario in obstetric care.6 This link between the drug's molecular selectivity and a specific clinical risk underscores the importance of careful fluid balance monitoring in patients receiving Carbetocin.

In vitro assays confirm this receptor profile, with EC50 values (a measure of agonist potency) for human V1a, V1b, and V2 receptors reported as 2.3 nM, 4.8 nM, and 170 nM, respectively, demonstrating significantly higher potency at V1 (vasoconstrictive) receptors compared to V2 (antidiuretic) receptors.[35]

2.2 Pharmacokinetics: Absorption, Distribution, Metabolism, and Excretion (ADME)

The pharmacokinetic profile of Carbetocin is the cornerstone of its clinical utility, defining its rapid onset and sustained duration of action, which set it apart from oxytocin.

[Absorption]

• [Intravenous (IV) Administration:] When injected directly into a vein, bioavailability is 100% by definition, and the drug immediately enters systemic circulation. The resulting pharmacokinetic profile is best described by a two-compartment model.[32]
• [Intramuscular (IM) Administration:] When injected into a muscle, Carbetocin is well-absorbed, with a high bioavailability reported to be between 77% and 80%.[23] Peak plasma concentrations ( Tmax​) are achieved approximately 30 minutes after injection.[30]

Distribution

The drug distributes from the plasma into the tissues, with a mean volume of distribution at pseudo-equilibrium (Vz​) calculated to be 22 liters.30 A notable aspect of its distribution is its transfer into breast milk. Studies have shown that small amounts of Carbetocin can cross from the maternal plasma into breast milk. However, the concentrations are very low; peak levels in milk have been measured to be approximately 56 times lower than corresponding plasma concentrations.30 This small amount, subsequently ingested by a nursing infant, is not considered a significant safety concern because, as a peptide, it is expected to be rapidly degraded by digestive enzymes in the infant's gastrointestinal tract and not absorbed systemically.3

Metabolism

Carbetocin is primarily eliminated from the body via metabolic degradation.10 Similar to oxytocin, it is broken down by endogenous enzymes called peptidases, which are found throughout the body, with the kidney being a significant site of this enzymatic activity.38 The structural modifications that define Carbetocin—the thioether bond and the deaminated N-terminus—make it far more resistant to these peptidases than the native oxytocin molecule. This inherent resistance to metabolism is the principal reason for its prolonged half-life and duration of action.12 Research has identified at least two metabolites of Carbetocin which appear to have an antagonistic (blocking) effect at the oxytocin receptor, though the clinical significance of these metabolites is not fully established.38

Excretion

The elimination of Carbetocin is predominantly non-renal.32 Direct renal clearance of the parent drug is minimal, with studies showing that less than 1% of an administered dose is excreted unchanged in the urine.10 This confirms that metabolism, not renal excretion, is the primary route of elimination.

Half-Life

The elimination half-life of Carbetocin is markedly longer than that of oxytocin, which is approximately 3.5 minutes.10 This difference is central to its clinical value.

• Following [IV administration], the elimination half-life is consistently reported to be in the range of 33 to 40 minutes.[1]
• Following [IM administration], the absorption phase prolongs the drug's presence in the body, resulting in a slightly longer apparent elimination half-life of approximately 55 minutes.[30]

This combination of a rapid onset of action (within 2 minutes) and a long half-life (40-55 minutes) forms the basis of Carbetocin's entire clinical use case. PPH is an acute emergency that demands immediate intervention, a need met by the drug's fast onset. The sustained risk of uterine atony in the hours following delivery, which would require a continuous and carefully monitored infusion of short-acting oxytocin, is effectively managed by the prolonged uterotonic effect from a single bolus of Carbetocin. This pharmacokinetic profile simplifies clinical management, reduces the potential for medication errors associated with complex infusions, and conserves valuable healthcare resources, representing a significant operational advantage in any obstetric setting.

[Table 2: Summary of Pharmacokinetic Parameters of Carbetocin]

Parameter	Intravenous (IV) Administration	Intramuscular (IM) Administration	Source(s)
Bioavailability	100% (by definition)	~77-80%	23
Tmax​ (Time to Peak Concentration)	Immediate	~30 minutes	30
Volume of Distribution (Vz​)	~22 L	Not Applicable	30
Elimination Half-life (t1/2​)	~33-40 minutes	~55 minutes	10
Primary Route of Metabolism	Enzymatic degradation by peptidases	Enzymatic degradation by peptidases	10
Renal Excretion (% unchanged)	< 1%	< 1%	10

Section 3: Clinical Efficacy in the Prevention of Postpartum Hemorrhage (PPH)

The clinical value of Carbetocin is substantiated by a large body of evidence from randomized controlled trials (RCTs) and meta-analyses. This section critically evaluates this evidence, examining the drug's efficacy in different delivery settings and comparing its performance against other standard-of-care uterotonic agents.

3.1 Efficacy Following Cesarean Section

Carbetocin was first approved and remains widely indicated for the prevention of uterine atony and PPH in women undergoing elective Cesarean section, particularly when performed under epidural or spinal anesthesia.[8] The rationale for its use in this context is strong, as the surgical incision of the uterus can impair its ability to contract effectively on its own post-delivery.[10]

A substantial volume of clinical trial evidence has established Carbetocin's efficacy in this patient population. Multiple RCTs and subsequent meta-analyses have consistently demonstrated that, when compared to a standard oxytocin regimen, a single dose of Carbetocin significantly reduces the need for additional therapeutic uterotonics to control bleeding and maintain uterine tone.[41] This finding suggests that Carbetocin provides a more reliable and sustained first-line uterotonic effect.

The clinical benefits extend beyond just reducing the need for additional drugs. A recent meta-analysis published in 2024, which included 17 RCTs and over 3,600 participants, found that for low-risk women undergoing Cesarean delivery, Carbetocin administration was associated with a nearly 50% reduction in the odds of requiring additional uterotonics (Odds Ratio 0.53). Furthermore, it was linked to a significantly smaller postoperative drop in hemoglobin levels and a lower requirement for blood transfusions (OR 0.57) compared to oxytocin.[43] The need for therapeutic uterine massage, another intervention for uterine atony, is also significantly reduced with Carbetocin use following Cesarean section.[9]

It is important to note that while Carbetocin reduces the need for these secondary interventions, most studies have not found a statistically significant difference in the primary incidence of PPH itself, whether defined as blood loss greater than 500 mL or the more severe threshold of 1000 mL.[42] This distinction is crucial. Carbetocin's superiority in the Cesarean section setting is not necessarily in preventing the initial bleed better than a perfectly administered oxytocin regimen, but rather in more effectively

maintaining uterine tone over the prolonged critical period, thereby preventing the clinical situation from deteriorating to the point where further, more invasive, and costly interventions are required. This improvement in the overall management and resource efficiency of the third stage of labor is a key element of its efficacy.

3.2 Efficacy Following Vaginal Delivery

The evidence base for Carbetocin's use following vaginal delivery has been significantly strengthened by the landmark World Health Organization (WHO)-led CHAMPION trial.[17] This large-scale, non-inferiority RCT enrolled nearly 30,000 women across 10 countries and was designed to assess whether heat-stable Carbetocin was at least as effective as the standard of care, oxytocin.[17]

In the trial, women were randomized to receive a single intramuscular injection of either 100 mcg of heat-stable Carbetocin or 10 IU of oxytocin immediately after vaginal birth. The primary composite outcome was blood loss of at least 500 mL or the use of additional uterotonic agents. The results showed that Carbetocin was non-inferior to oxytocin, with the primary outcome occurring in 14.5% of the Carbetocin group versus 14.4% of the oxytocin group.[17] For the secondary outcome of severe PPH (blood loss ≥1000 mL), the non-inferiority margin was not met, primarily due to low event rates in both arms (1.51% vs. 1.45%), which limited the statistical power for this specific endpoint.[45]

The findings of the CHAMPION trial have been corroborated by systematic reviews and meta-analyses. A 2019 meta-analysis incorporating data from five RCTs (including CHAMPION) confirmed that there was no significant difference between Carbetocin and oxytocin in the prevention of PPH (either ≥500 mL or ≥1000 mL), or in the need for additional uterotonics, blood transfusion, or uterine massage following vaginal delivery.[9] Other head-to-head studies have reported similar findings, concluding that Carbetocin is equally effective and safe as oxytocin in this patient population.[11]

A critical consideration when interpreting the CHAMPION trial results is the context in which it was conducted. The trial's rigorous protocol required that the oxytocin used as the comparator be stored and handled under ideal cold-chain conditions to ensure its full potency.[17] This was necessary for a scientifically valid non-inferiority comparison. However, the very rationale for developing heat-stable Carbetocin is the fact that in many real-world, low-resource settings, oxytocin is frequently exposed to heat, leading to degradation and reduced potency.[15] Therefore, the trial compared heat-stable Carbetocin to

perfect oxytocin, not the potentially sub-potent oxytocin that is often available in the settings where a heat-stable alternative is most needed. The finding of non-inferiority under these ideal conditions strongly suggests that in a real-world scenario where a significant fraction of oxytocin may be degraded, heat-stable Carbetocin would likely demonstrate superiority. This is a vital point for health policymakers in LMICs to consider when evaluating the evidence for adoption.

3.3 Comparative Analysis: Carbetocin versus Other Uterotonics

A complete assessment of Carbetocin's clinical role requires comparison not only with oxytocin but also with other uterotonic agents.

[Carbetocin vs. Oxytocin]

• [Efficacy:] As detailed above, Carbetocin's primary efficacy advantage is the reduction in the need for subsequent interventions (additional uterotonics, massage, transfusions), which is most pronounced after Cesarean section.[42] In vaginal delivery, overall efficacy is largely equivalent.[9]
• [Safety and Tolerability:] The side effect profiles of the two drugs are generally comparable, with similar types and frequencies of adverse events reported in large clinical trials.[6]
• [Administration and Logistics:] Carbetocin offers significant advantages. Its single-dose administration is a major improvement in convenience and safety over the continuous infusions required for oxytocin.[12] The heat-stable formulation completely removes the logistical burden and cost of maintaining a cold chain, a transformative benefit for health systems in LMICs.[16]

[Carbetocin vs. Syntometrine (a fixed-dose combination of Oxytocin and Ergometrine)]

• [Efficacy:] In women undergoing vaginal delivery, comparative studies have generally found no statistically significant difference between Carbetocin and syntometrine in the prevention of PPH or the need for additional uterotonics.[44] Some data have suggested a lower mean blood loss in women who received Carbetocin.[42]
• [Safety and Tolerability:] Carbetocin demonstrates a significantly superior safety and tolerability profile. Compared to syntometrine, Carbetocin is associated with a much lower risk of common and distressing side effects, particularly nausea and vomiting. Crucially, it is also associated with a significantly lower incidence of postpartum hypertension, a known risk with the ergometrine component of syntometrine.[42] This favorable side-effect profile makes Carbetocin a more attractive option, especially for routine prophylaxis.

[Table 3: Summary of Key Clinical Trials Comparing Carbetocin and Other Uterotonics]

Trial Name/Lead Author	Year	Comparison	Patient Population	Primary Endpoint(s)	Key Findings	Source(s)
CHAMPION Trial (Widmer et al.)	2018	Heat-Stable Carbetocin vs. Oxytocin	Vaginal Delivery (n≈30,000)	Blood loss ≥500 mL or use of additional uterotonics	Carbetocin was non-inferior to oxytocin.	17
Maged et al. (Meta-analysis)	2024	Carbetocin vs. Oxytocin	Cesarean Delivery (17 RCTs, n=3,667)	Need for additional uterotonics; PPH incidence; blood transfusion	Carbetocin reduced need for additional uterotonics and blood transfusions; no difference in PPH incidence.	43
Su et al. (Meta-analysis)	2019	Carbetocin vs. Oxytocin	Vaginal Delivery (5 RCTs, n=30,314)	Blood loss ≥500 mL	No significant difference between Carbetocin and oxytocin in preventing PPH.	9
Su et al. (Cochrane Review)	2012	Carbetocin vs. Oxytocin or Syntometrine	Cesarean & Vaginal Delivery (11 RCTs, n=2,635)	Need for additional uterotonics; adverse effects	Carbetocin reduced need for additional uterotonics vs. oxytocin (C-section). Carbetocin had fewer adverse effects than syntometrine (vaginal).	51
Attilakos et al.	2010	Carbetocin vs. Oxytocin	Cesarean Delivery (n=377)	Need for additional uterotonics	Carbetocin significantly reduced the need for additional uterotonic treatment compared to oxytocin.	50

Section 4: Safety, Tolerability, and Risk Management

While Carbetocin is an effective therapeutic agent, its safe use requires a thorough understanding of its potential adverse effects, contraindications, and drug interactions. The risk management framework for Carbetocin is fundamentally shaped by its potent and prolonged pharmacological action.

4.1 Adverse Drug Reactions (ADRs)

The overall safety profile of Carbetocin is well-characterized, with the type and frequency of most adverse drug reactions (ADRs) being similar to those observed with oxytocin.[3] The majority of side effects are mild in severity and transient in nature.[32]

[Common and Very Common ADRs (occurring in ≥1% of patients):]

• [Vascular Effects:] The most frequently reported ADRs are related to vasodilation. These include hypotension (low blood pressure), which can sometimes be significant, flushing (a sense of warmth and redness in the face and neck), and a general feeling of warmth.[50]
• [Gastrointestinal Effects:] Nausea and vomiting are very common, along with abdominal pain.[10]
• [Nervous System Effects:] Headache and tremor are very common, while dizziness is also frequently reported.[50]
• [Other Common Effects:] Pruritus (itching) and anemia (a decrease in red blood cell count, often related to blood loss during delivery) are also commonly observed.[10]

Less Common/Uncommon ADRs (occurring in <1% of patients):

A range of less frequent side effects have been documented, including back pain, chest pain, dyspnea (shortness of breath), chills, sweating, a metallic taste in the mouth, tachycardia (a rapid heart rate), and feelings of anxiety.10

Serious and Post-Marketing ADRs (frequency cannot be estimated from available data):

Long-term pharmacovigilance has identified rare but serious risks that were not apparent in initial clinical trials.

• [Cardiac Events:] Following reviews of post-marketing data, regulatory agencies such as the European Medicines Agency (EMA) have mandated warnings for serious cardiac events. These include [bradycardia (a slow heart rate) which can lead to cardiac arrest], and other cardiac arrhythmias.[6] This highlights that a drug's safety profile can evolve over time and underscores the need for continued monitoring.
• [Hypersensitivity Reactions:] There have been spontaneous post-marketing reports of hypersensitivity, including severe, life-threatening [anaphylactic reactions and anaphylactic shock].[6]
• [Water Intoxication:] As a consequence of its weak antidiuretic (vasopressin-like) effect, Carbetocin carries a risk of causing water intoxication and hyponatremia. This risk is exacerbated by overdosage or the co-administration of large volumes of intravenous fluids. Early warning signs include drowsiness, listlessness, and headache, which can progress to more severe neurological complications such as convulsions and coma if not recognized and managed promptly by restricting fluids and correcting electrolyte imbalances.[6]

4.2 Contraindications and High-Risk Populations

The use of Carbetocin is strictly prohibited in certain clinical situations where its potent and sustained action could cause significant harm.

[Absolute Contraindications:]

1. [Prior to Delivery of the Infant:] This is the most critical contraindication. Administering Carbetocin during pregnancy or labor, before the baby is delivered, is absolutely forbidden. Its long-lasting uterotonic effect, which cannot be easily reversed by discontinuing the drug, can lead to uterine hyperstimulation (prolonged, tetanic contractions), tumultuous labor, uterine rupture, cervical and vaginal lacerations, and severe fetal compromise (hypoxia, distress) or death.[3] This inextricable link between the drug's primary pharmacokinetic advantage (its long half-life) and its primary safety liability dictates that the timing of administration is the single most important factor for its safe use.
2. [Induction of Labor:] For the same reasons, Carbetocin must not be used to induce or augment labor.[6]
3. [Hypersensitivity:] A known history of hypersensitivity or allergic reaction to Carbetocin or to oxytocin is a contraindication.[6]
4. [Serious Cardiovascular Disorders:] Patients with serious pre-existing cardiovascular disease, particularly coronary artery disease, valvular heart disease, cardiomyopathy, and heart failure, should not receive Carbetocin.[6]
5. [Hepatic or Renal Disease:] The presence of significant liver or kidney disease is a contraindication.[30]
6. [Epilepsy:] Epilepsy is listed as a contraindication for use.[10]

Special Warnings and Precautions for Use:

In certain populations, Carbetocin should be used with caution and under careful monitoring.

• [Hypertensive Disorders of Pregnancy:] In patients with eclampsia or pre-eclampsia, blood pressure must be carefully monitored following administration.[6]
• [Other Medical Conditions:] Caution is advised in patients with migraine, asthma, or any condition where a rapid addition of extracellular water could be hazardous to an already overburdened system.[6]
• [High-Risk PPH Patients:] There is limited clinical trial data on the use of Carbetocin in patients with specific high-risk factors for PPH, such as grand multiparity (more than four previous births), prolonged labor, known coagulopathy, or placental abnormalities.[6]
• [Anesthesia:] Data on the use of Carbetocin in patients under general anesthesia is limited.[6]
• [Pediatric and Geriatric Use:] Carbetocin is not intended for use in children or the elderly.[6]

4.3 Drug-Drug and Other Interactions

While dedicated drug interaction studies for Carbetocin are limited, clinically significant interactions are inferred from the known profile of oxytocin due to their structural and pharmacological similarity.[3]

[Potentiation of Effects:]

• [Other Uterotonic Agents:] Co-administration of Carbetocin with other uterotonics, such as prostaglandins (e.g., misoprostol) or ergot alkaloids (e.g., methylergometrine), should be done with extreme caution, as their synergistic effects can lead to uterine hyperstimulation and excessive vasoconstriction. Carbetocin can specifically potentiate the hypertensive (blood pressure-raising) effect of ergot alkaloids.[10]
• [Vasoconstrictors:] A clinically significant interaction has been reported with oxytocin, where severe hypertension occurred when it was administered 3 to 4 hours after a prophylactic vasoconstrictor (e.g., in an epidural solution) was used with caudal block anesthesia. This risk is assumed to apply to Carbetocin as well.[3]

[Antagonism of Effects:]

• [Inhalation Anesthetics:] Certain volatile anesthetics, such as halothane and cyclopropane, may relax the uterine muscle, thereby weakening the uterotonic effect of Carbetocin. This combination can also increase the risk of hypotension and cardiac arrhythmias.[50]

Hypotensive Agents:

Given that hypotension is a common side effect of Carbetocin, its concurrent use with other drugs that lower blood pressure can lead to an additive or synergistic hypotensive effect. This includes a wide range of cardiovascular medications such as beta-blockers (e.g., atenolol, bisoprolol), calcium channel blockers (e.g., amlodipine), ACE inhibitors (e.g., enalapril), and many others, increasing the risk of clinically significant hypotension.23

[Table 4: Adverse Drug Reactions Associated with Carbetocin by System Organ Class and Frequency]

System Organ Class	Very Common (≥1/10)	Common (≥1/100 to <1/10)	Uncommon (≥1/1,000 to <1/100)	Not Known (cannot be estimated from data)
Immune System Disorders				Hypersensitivity (including anaphylactic reaction) 56
Blood and Lymphatic System Disorders		Anemia 50
Nervous System Disorders	Headache, Tremor 50	Dizziness, Anxiety 50
Cardiac Disorders		Tachycardia 10		Bradycardia which can lead to cardiac arrest 56
Vascular Disorders	Hypotension, Flushing, Feeling of warmth 50
Respiratory, Thoracic and Mediastinal Disorders		Dyspnea (Shortness of breath), Chest pain 50
Gastrointestinal Disorders	Nausea, Vomiting, Abdominal pain 50	Metallic taste 10
Skin and Subcutaneous Tissue Disorders	Pruritus (Itching) 50		Sweating 10
Musculoskeletal and Connective Tissue Disorders		Back pain 50
General Disorders and Administration Site Conditions		Chills, Pain 50

Section 5: Dosage, Administration, and Overdose Management

The correct dosage and method of administration are paramount for the safe and effective use of Carbetocin. The guidelines are specific and differ slightly based on the mode of delivery. The drug is intended for single-dose administration only in a hospital setting by qualified medical personnel.

5.1 Approved Dosage and Administration

The standard dose of Carbetocin for the prevention of PPH is a single 100 microgram dose, which corresponds to 1 mL of the 100 microgram/mL solution for injection.[10]

[Method of Administration:]

• [Timing:] Carbetocin must [only] be administered after the delivery of the infant has been completed.[6] It should be given as soon as possible after delivery, preferably before the delivery of the placenta, although administration after placental delivery is also acceptable.[8]
• [Route and Rate:]
• [Intravenous (IV) Administration:] For both Cesarean section and vaginal delivery, the 100 microgram (1 mL) dose should be administered as a slow bolus injection over a period of one minute.[29] A slower administration rate may help to minimize cardiovascular side effects such as hypotension and tachycardia.[60]
• [Intramuscular (IM) Administration:] For vaginal delivery, the 100 microgram (1 mL) dose can also be administered via the intramuscular route.[29] The IM route provides a longer duration of action compared to the IV route.[60]

[Delivery-Specific Guidelines:]

• [Cesarean Section:] A single 100 microgram IV dose, administered slowly over one minute, is the standard of care after delivery of the infant.[6]
• [Vaginal Delivery:] A single 100 microgram dose can be administered either intravenously (slowly over one minute) or intramuscularly after delivery of the infant.[6]

5.2 Management of Non-Response and Overdose

Management of Inadequate Uterine Response:

Carbetocin is intended for single administration only. Repeat doses of Carbetocin should not be given.6 If uterine atony or hypotonia persists and excessive bleeding continues after the initial dose, the patient is considered a non-responder. In such cases, the cause of the persistent bleeding must be thoroughly investigated to rule out factors like retained placental fragments, trauma to the genital tract, or an underlying coagulopathy.6 More aggressive treatment with additional doses of other, different uterotonic drugs, such as oxytocin or ergometrine, is warranted.6

Overdose Management:

Overdosage of Carbetocin can be expected to produce an exaggeration of its known pharmacological effects.31 The primary risks associated with overdose are uterine hyperactivity (hypertonic or tetanic contractions) and pain, as well as the potential for severe water intoxication and hyponatremia, especially if associated with excessive concomitant fluid administration.31

Treatment for overdose is symptomatic and supportive.[31] There is no specific antidote. Management strategies include:

• [Oxygen Administration:] Supplemental oxygen should be given to the patient.[38]
• [Fluid Restriction:] In the case of water intoxication, it is critical to restrict fluid intake.[29]
• [Diuresis:] Initiating diuresis can help to eliminate excess fluid.[29]
• [Electrolyte Correction:] Any electrolyte disturbances, particularly hyponatremia, must be carefully corrected.[29]
• [Seizure Control:] If convulsions occur as a result of severe water intoxication, they should be controlled with appropriate anticonvulsant therapy.[29]

In all cases of suspected overdose, consultation with a regional poisons information center is recommended.31

Section 6: Regulatory Status and Global Availability

The regulatory journey of Carbetocin reflects its established role in high-income countries and its growing importance as a key tool for global maternal health. Its approval status varies by jurisdiction and by formulation (injectable for PPH vs. investigational nasal spray for PWS).

6.1 Regulatory Approval in Major Jurisdictions

United States (FDA):

Carbetocin is not approved by the U.S. Food and Drug Administration (FDA) for its primary indication of preventing postpartum hemorrhage.10 However, an intranasal formulation of Carbetocin (LV-101) for the treatment of Prader-Willi syndrome has been granted Orphan Drug and Fast Track designations by the FDA.20 As of late 2021, a New Drug Application (NDA) for this indication was under Priority Review, but it has not yet received final approval.22

Europe (EMA and National Agencies):

Carbetocin is approved for medical use in numerous European countries. In 2015, the new room-temperature-stable (RTS) formulation of Pabal® (Carbetocin) for intravenous administration received approval through the EU Mutual Recognition Procedure, making it the first long-acting, room-temperature-stable oxytocic agent approved for PPH prevention after Cesarean section in Europe.63

The European Medicines Agency (EMA) continues to monitor the drug's safety through its Pharmacovigilance Risk Assessment Committee (PRAC). In 2022-2023, the PRAC and the Coordination Group for Mutual Recognition and Decentralised Procedures – human (CMDh) recommended updates to the product information for all Carbetocin-containing products across the EU to include warnings about rare but serious risks of bradycardia leading to cardiac arrest and hypersensitivity reactions, including anaphylaxis.[56] The EMA has also granted orphan designation for Carbetocin for the treatment of Prader-Willi syndrome.[19]

United Kingdom (MHRA):

Carbetocin was first approved for medical use in the UK in 1997.10 It is authorized for the prevention of PPH, and the patient information leaflet for Pabal® has been approved by the Medicines and Healthcare products Regulatory Agency (MHRA).39 Clinical trials, including the large multinational CHAMPION trial, have been conducted in the UK under MHRA oversight.64 However, its use within the National Health Service (NHS) has faced some barriers; in 2018, NHS Scotland did not recommend its routine use, citing that the economic analysis presented at the time was not sufficiently robust compared to less expensive options like oxytocin.10

Canada (Health Canada):

Carbetocin was approved for medical use in Canada in 1997.10 The approved indication, as per the product monograph for Duratocin®, is for the prevention of uterine atony and postpartum hemorrhage following delivery by Cesarean section under epidural or spinal anesthesia.3 The Society of Obstetricians and Gynaecologists of Canada (SOGC) has issued guidelines recommending a single 100 mcg dose of Carbetocin for this indication, and also considers its use for vaginal delivery in women with at least one PPH risk factor.41

Australia (TGA):

In Australia, Carbetocin is approved by the Therapeutic Goods Administration (TGA) for the prevention of uterine atony and excessive bleeding following both Cesarean section and vaginal delivery.6 It is available under brand names such as Duratocin® and Carbetocin Wockhardt®.32 The Australian product information provides detailed guidelines on its use, contraindications, and safety profile, consistent with international standards.31

6.2 World Health Organization (WHO) and Global Health Impact

The World Health Organization has played a pivotal role in establishing the global importance of Carbetocin, particularly its heat-stable formulation, as a tool to combat maternal mortality.

Postpartum hemorrhage is the leading cause of maternal death worldwide, and the efficacy of the standard treatment, oxytocin, is often compromised in LMICs due to failures in the cold-chain storage system.[15] Recognizing this challenge, the WHO co-sponsored the landmark CHAMPION trial, which demonstrated that heat-stable Carbetocin was non-inferior to quality-assured oxytocin for preventing PPH after vaginal birth.[17]

Based on this and other evidence, the WHO has taken several key steps:

• [Updated Guidelines:] In 2018, the WHO updated its recommendations on uterotonics for the prevention of PPH. The guidelines now recommend heat-stable Carbetocin as an option for the prevention of PPH for all births in settings where oxytocin is unavailable or its quality cannot be guaranteed, and where its cost is comparable to other effective uterotonics.[14]
• [Essential Medicines List (EML):] In 2019, heat-stable Carbetocin was added to the WHO Model List of Essential Medicines.[14] Inclusion on the EML is a powerful endorsement that signals to countries that a medicine is a priority for their health systems and helps to guide procurement and ensure availability.
• [PPH Roadmap:] In its 2023 "Roadmap to Combat Postpartum Haemorrhage," the WHO explicitly highlights the use of heat-stable uterotonics as a preferred option in environments where refrigeration cannot be assured.[15]

These actions by the WHO have solidified heat-stable Carbetocin's role as a vital alternative to oxytocin, with the potential to save thousands of lives by providing a reliable, effective, and logistically feasible intervention for PPH prevention in the world's most vulnerable settings.[17]

6.3 Brand Names and Availability

Carbetocin is marketed globally by several pharmaceutical companies under various brand names. The originator company is Ferring Pharmaceuticals.[68]

• [Common Brand Names:] Duratocin®, Pabal®, Lonactene®, and Carbetocin Ferring are the most widely recognized brand names.[10] Other names include Duratobal® and CARITEC®.[63]
• [Global Reach:] It is approved in over 80 countries worldwide.[67] Brand names vary by region; for example, Duratocin® is used in Canada, Australia, and China; Lonactene® in Mexico; and Pabal® across many European nations.[10]
• [Heat-Stable Formulations:] The heat-stable products are often marketed as Pabal® RTS (Room Temperature Stable), Duratocin® (heat-stable vial), or Carbetocin Ferring (heat-stable ampoule).[14] Ferring Pharmaceuticals has committed to providing Carbetocin Ferring at an affordable and sustainable price (approximately $0.31 per ampoule) for public sector use in LMICs to facilitate its adoption.[14]

Section 7: Emerging Applications and Future Directions

While Carbetocin's primary role is firmly established in obstetrics, its unique pharmacological properties have opened avenues for investigation into other therapeutic areas. The most significant emerging application is in the treatment of Prader-Willi syndrome, with other potential uses also being explored.

7.1 Prader-Willi Syndrome (PWS)

Prader-Willi syndrome is a rare and complex genetic neurodevelopmental disorder. It is characterized by a range of debilitating symptoms, including hypotonia (low muscle tone) in infancy, growth hormone deficiency, mild to moderate intellectual disability, anxiety, compulsive behaviors, and, most notably, life-threatening hyperphagia—an insatiable, uncontrollable hunger that leads to severe obesity if not strictly managed.[22]

Rationale for Carbetocin Use:

The rationale for using Carbetocin in PWS stems from the role of the oxytocin system in regulating social behavior, anxiety, and satiety. Oxytocin deficiency is thought to be a key contributing factor to the hyperphagia and behavioral symptoms seen in PWS.22 Carbetocin was selected for investigation due to its properties as a selective oxytocin receptor agonist. It was specifically designed to have a more favorable receptor binding profile than native oxytocin, with greater affinity and selectivity for the oxytocin receptor and lower affinity for the related vasopressin receptors, potentially leading to a more targeted effect with fewer side effects.22

Clinical Development and Trials:

An intranasal formulation of Carbetocin, known as LV-101 (and previously as ACP-101), has been developed to deliver the drug to the central nervous system, bypassing the blood-brain barrier.21 This formulation has been the subject of a dedicated clinical development program led by Levo Therapeutics and, more recently, Acadia Pharmaceuticals.21

• [Regulatory Status:] The FDA has granted LV-101 both [Orphan Drug designation] (for treating a rare disease) and [Fast Track designation] to facilitate its development and expedite its review.[22] The EMA has also granted orphan designation for this indication.[19]
• [Clinical Trials:] The development program has progressed through Phase 2 and Phase 3 clinical trials. The Phase 3 CARE-PWS study was a multi-center, randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy of intranasal Carbetocin in treating hyperphagia and behavioral distress in individuals with PWS.[22] Participants, aged 5-30 years, were randomized to receive either the drug or a placebo nasal spray three times daily before meals.[21] Top-line results from this study were announced in August 2020, and a New Drug Application was subsequently submitted to the FDA and granted Priority Review in July 2021.[22] Despite these promising steps, as of late 2021, LV-101 had not yet received final FDA approval.[22]

The investigation of Carbetocin for PWS represents a significant shift from its peripheral action on the uterus to a centrally-mediated effect on behavior and appetite, highlighting the versatility of targeting the oxytocin system for therapeutic benefit.

7.2 Other Potential and Investigational Uses

Beyond PPH and PWS, the uterotonic properties of Carbetocin suggest potential utility in other gynecological procedures where controlling uterine bleeding is important.

• [Hysteroscopic Myomectomy:] The NCI Thesaurus notes that Carbetocin may be used to decrease blood loss during hysteroscopic myomectomy, a minimally invasive surgical procedure to remove uterine fibroids.[1] By inducing uterine contraction, Carbetocin can help to constrict blood vessels within the uterine wall, thereby reducing intraoperative bleeding and improving the surgeon's field of view.
• [Surgical Blood Loss:] Clinical trials have explored the use of Carbetocin in the context of decreasing bleeding during open myomectomy, further supporting its potential role in managing surgical blood loss in gynecological surgery.[71]
• [Maternal Obesity:] A Phase 1/2 clinical trial has been completed to evaluate the efficacy of Carbetocin in preventing PPH specifically in obese women, a population known to be at higher risk for this complication.[72]

7.3 Future Research Directions

Future research on Carbetocin is likely to proceed along several key paths:

• [Treatment of PPH:] While Carbetocin is currently only indicated for the prevention of PPH, its potent uterotonic effects suggest it could also be effective for the treatment of established PPH. Unitaid is supporting clinical trials to evaluate the safety and efficacy of heat-stable Carbetocin for this indication, which, if successful, could further expand its role and simplify PPH management protocols, especially in LMICs.[16]
• [Optimization of Administration:] Research continues into the optimal method of administration. For example, a non-inferiority trial compared a slow IV bolus to a short infusion, finding that the short infusion did not compromise uterine tone and had a similar cardiovascular side-effect profile, offering an alternative administration strategy.[60]
• [Cost-Effectiveness Analysis:] A major barrier to the widespread adoption of Carbetocin, particularly in LMICs, has been its higher cost compared to oxytocin.[9] While Ferring's commitment to an affordable price for the heat-stable formulation helps to mitigate this, further robust, region-specific cost-effectiveness analyses are needed to provide policymakers with the economic evidence required to justify its inclusion in national guidelines and budgets.[15]
• [Central Nervous System Applications:] The ongoing development of Carbetocin for PWS may spur further investigation into its use for other conditions involving dysfunction of the oxytocin system, such as certain aspects of autism spectrum disorder or other social-behavioral conditions. Its improved pharmacokinetic and receptor selectivity profile compared to oxytocin makes it an attractive candidate for such research.

Conclusion

Carbetocin represents a significant and successful example of rational peptide drug design, transforming a transient natural hormone into a robust and clinically manageable therapeutic agent. Its primary identity is that of a long-acting oxytocin analogue, whose structural modifications confer a prolonged half-life and enhanced stability, allowing for a convenient and effective single-dose administration for the prevention of postpartum hemorrhage. This pharmacokinetic advantage simplifies clinical practice, reduces the need for subsequent interventions like additional uterotonics and blood transfusions, and improves the overall efficiency of care in the third stage of labor, particularly following Cesarean section.

The development of a heat-stable formulation has been a paradigm-shifting innovation. By overcoming the cold-chain requirement that limits the reliability of oxytocin in many parts of the world, heat-stable Carbetocin has emerged as a cornerstone of global efforts to reduce maternal mortality. Its inclusion on the WHO Model List of Essential Medicines and in international PPH prevention guidelines solidifies its role as a life-saving intervention, especially in low- and middle-income countries. Clinical evidence, anchored by the large-scale CHAMPION trial, has established its non-inferiority to quality-assured oxytocin, a finding that likely translates to real-world superiority in settings where oxytocin quality is compromised.

However, the clinical profile of Carbetocin is not without complexities. Its potent, long-lasting effect is also the source of its most significant safety risk; its use prior to the delivery of the infant is absolutely contraindicated due to the danger of irreversible uterine hyperstimulation. The safety profile, while generally comparable to oxytocin, includes rare but serious risks of cardiac events and anaphylaxis, necessitating continued pharmacovigilance and careful patient selection. Its use is restricted to well-equipped obstetric units where staff are trained in the precise timing of its administration.

Looking forward, the therapeutic landscape for Carbetocin continues to expand. The investigation of an intranasal formulation for Prader-Willi syndrome demonstrates its potential to modulate central nervous system pathways, opening a new frontier of research beyond obstetrics. Ongoing trials exploring its use for the treatment—not just prevention—of PPH may further enhance its utility. As a molecule, Carbetocin has proven its value. Its future impact will depend on continued research, successful navigation of regulatory pathways for new indications, and concerted global health efforts to ensure its cost-effective and equitable access for all women and patients who stand to benefit.

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