Carbetocin

H01B - Posterior pituitary lobe hormones ATC H01BB03 Protein Parenteral Natural product

JFDA label: Pabal RTS

Mechanism of Action

Agonist of Oxytocin receptor — Oxytocin receptor agonist

Target	Action	Gene / class
Oxytocin receptor efficacy	AGONIST	OXTR

Indications

Approved

Prevention of uterine atony and postpartum hemorrhage

Contraindications

Source: Lexicomp

Hypersensitivity to carbetocin, oxytocin, or any component of the formulation Absolute
administration prior to delivery of infant for any reason (including elective or medical induction of labor) Absolute
serious cardiovascular disorders Absolute
use in children Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (4)

Very Common Flushing · hypotension

Common Chest pain · tachycardia

Nervous system disorders (4)

Very Common Headache

Common Anxiety · chills · dizziness

Blood and lymphatic system disorders (1)

Common Anemia

Gastrointestinal disorders (4)

Very Common Abdominal pain · nausea · vomiting

Common Metallic taste

Skin and subcutaneous tissue disorders (1)

Very Common Pruritus

Musculoskeletal and connective tissue disorders (2)

Very Common Tremor

Common Back pain

General disorders and administration site conditions (2)

Very Common Feeling of warmth

Common Diaphoresis

Respiratory, thoracic and mediastinal disorders (1)

Common Dyspnea

Dosing

Source: Lexicomp

Prevention of uterine atony and postpartum hemorrhage: IV: 100 mcg (single dose only)

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Warnings & Precautions

Source: Lexicomp

Antidiuretic effect

May produce antidiuretic effect; risk of water intoxication cannot be excluded.

Bleeding

Persistent bleeding warrants further evaluation to rule out coagulopathy, genital tract trauma, or the presence of retained placental fragments. Disease-related concerns:

Asthma

Use with caution in patients with asthma.

Cardiovascular disease

Use has not been studied in patients with a history of hypertension, or known coagulopathy; use with extreme caution in patients with cardiovascular disease (contraindicated in serious cardiovascular disorders), especially coronary artery disease.

Epilepsy

Use with caution in patients with epilepsy.

Migraines

Use with caution in patients with migraines. Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Other warnings/precautions:

Appropriate use

Carbetocin induced contractions are of a longer duration than those observed with oxytocin and are not stopped by discontinuation of therapy. Improper use during pregnancy may produce symptoms similar to those observed with oxytocin overdosage (eg, hyperstimulation of uterus with strong or prolonged contractions, tumultuous labor, uterine rupture, cervical and vaginal lacerations, postpartum hemorrhage, utero-placental hypoperfusion and variable deceleration of fetal heart, fetal hypoxia, hypercapnia, or death). Therapy should not be repeated if response to initial dose is inadequate; aggressive therapy with alternative agents (eg, oxytocin, ergonovine) should be utilized. Safety of use in patients with eclampsia and pre-eclampsia has not been evaluated; monitor blood pressure. Appropriate doses have not been established in women following labor or vaginal delivery.

Pregnancy & Lactation

Pregnancy

Use in pregnancy prior to delivery is contraindicated. Carbetocin induced contractions are of a longer duration than those observed with oxytocin and are not stopped by discontinuation of therapy. Improper use during pregnancy may produce symptoms similar to those observed with oxytocin overdosage (eg, hyperstimulation of uterus, uterine rupture).

Lactation

Carbetocin is present in breast milk. Small amounts of carbetocin were detected in the breast milk of 5 healthy nursing women approximately 7 to 14 weeks postpartum though peak levels observed were 50 times lower than in plasma (Silcox 1993). Exposure to the breastfeeding infant is expected to be minimal and not expected to pose significant health risks as carbetocin in breast milk is rapidly degraded in the GI tract of a breastfeeding infant. Milk let-down was found to occur normally in 5 breas

Monitoring

Clinical pearl	Persistent postpartum bleeding; blood pressure

Chemistry & Properties

Formula	C45H69N11O12S
Molecular weight	988.18 g/mol
IUPAC name	(2S)-N-[(2S)-1-[(2-amino-2-oxoethyl)amino]-4-methyl-1-oxopentan-2-yl]-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-9-(3-amino-3-oxopropyl)-12-[(2S)-butan-2-yl]-15-[(4-methoxyphenyl)methyl]-5,8,11,14,17-pentaoxo-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]pyrrolidine-2-carboxamide
CAS	37025-55-1
PubChem CID	16681432
InChIKey	`NSTRIRCPWQHTIA-DTRKZRJBSA-N`
logP	-2.5 (XLogP -1.1)
Polar surface area	362.51 Å²
H-bond acceptors / donors	13 / 10
Drug-likeness (QED)	0.07
Lipinski violations	3

SMILES

CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(OC)cc2)NC(=O)CCCSC[C@@H](C(=O)N2CCC[C@H]2C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC1=O

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	1.37 h
Volume of distribution	0.326 L/kg
Protein binding	47.5%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2C19	Substrate	—

Receptor binding (top 1)

Target	Action	Affinity
OT receptor (OXTR)	Agonist	pEC50 8.0

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Registered Products (3)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
CARBETOCIN GP-PHARM 100 MICROGRAMS SOLUTION FOR INJECTION IN PREFILLED SYRINGE, 5 PFS /box	Injection 0.1 mg/1 ml	5 SYR/1 BOX	Almutanabbe Drug Store	—
Datocin 100mcg/ml solution for injection	Injection 0.1 mg/1 ml	4 vial	Al Rayah drug store	—
Pabal RTS	Vial 100 mcg/1 ml	5 vial	Petra Drug Store	—