Carbetocin

Pharmacologic Category

Oxytocic Agent

Dosing: Adult

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

Dosing: Renal Impairment: Adult

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

Dosing: Hepatic Impairment: Adult

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

Use: Labeled Indications

Note: Not approved in the US

Prevention of uterine atony and postpartum hemorrhage: Prevention of uterine atony and postpartum hemorrhage following cesarean section under anesthesia (epidural or spinal)

Administration: IM

IM administration may also be used (Leduc 2018; WHO 2018).

Administration: IV

Administer as bolus IV injection over 1 minute only after delivery of infant has been completed by cesarean section. May administer before or after delivery of placenta.

Storage/Stability

Store at 15°C to 30°C (59°F to 86°F). Use immediately after opening.

Medication Safety Issues

High alert medication:

Contraindications

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

Warnings/Precautions

Concerns related to adverse effects:

• 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 Considerations

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).

Breast-Feeding Considerations

Carbetocin is present in breast milk.

Carbetocin was 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 breastfeeding women after receiving a carbetocin 70 mcg dose by the intramuscular route.

Adverse Reactions

≥10%:

Cardiovascular: Flushing, hypotension

Central nervous system: Headache

Dermatologic: Pruritus

Gastrointestinal: Abdominal pain, nausea, vomiting

Neuromuscular & skeletal: Tremor

Miscellaneous: Feeling of warmth

1% to 5%:

Cardiovascular: Chest pain, tachycardia

Central nervous system: Anxiety, chills, dizziness

Gastrointestinal: Metallic taste

Hematologic: Anemia

Neuromuscular & skeletal: Back pain

Respiratory: Dyspnea

Miscellaneous: Diaphoresis

Metabolism/Transport Effects

None known.

Drug Interactions Open Interactions

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Risk D: Consider therapy modification

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. Risk X: Avoid combination

Carboprost Tromethamine: May enhance the adverse/toxic effect of Oxytocic Agents. Specifically, oxytocic effects may be enhanced. Risk X: Avoid combination

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Dinoprostone: May enhance the adverse/toxic effect of Carbetocin. Specifically, Carbetocin oxytocic effects may be enhanced. Risk X: Avoid combination

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

MiSOPROStol: May enhance the adverse/toxic effect of Carbetocin. Specifically, Carbetocin oxytocic effects may be enhanced. Risk X: Avoid combination

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Monitoring Parameters

Persistent postpartum bleeding; blood pressure

Product Availability

Not available in the US

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Duratocin Injection: 100 mcg/mL (1 mL)

Generic: 100 mcg/mL (1 mL)

Anatomic Therapeutic Chemical (ATC) Classification

• H01BB03

Generic Available (US)

Yes

Mechanism of Action

Binds oxytocin receptors located in uterine smooth muscle producing rhythmic uterine contractions characteristic to deliver, as well as increasing both the frequency of existing contractions and uterine tone. Enhances uterine involution early in postpartum.

Pharmacodynamics/Kinetics

Onset of action: IV: 1.2 ± 0.5 minutes.

Duration: IV: ~60 minutes; IM: ~120 minutes (WHO 2018; Sweeney 1990).

Half-life elimination: ~40 minutes.

Excretion: Urine (<1%, as unchanged drug).

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

No significant effects or complications reported

Effects on Bleeding

No information available to require special precautions

References

Borruto F, Treisser A, and Comparetto C, “Utilization of Carbetocin for Prevention of Postpartum Hemorrhage After Cesarean Section: A Randomized Clinical Trial,” Arch Gynecol Obstet, 2009, 280(5):707-12.[PubMed 19229549]

Dansereau J, Joshi AK, Helewa ME, et al, “Double-Blind Comparison of Carbetocin Versus Oxytocin in Prevention of Uterine Atony After Cesarean Section,” Am J Obstet Gynecol, 1999, 180(3 Pt 1):670-6.[PubMed 10076146]

Duratocin (carbetocin) [product monograph]. North York, Ontario, Canada: Ferring Inc; February 2018.

Leduc D, Senikas V, Lalonde AB. No. 235-Active Management of the Third Stage of Labour: Prevention and Treatment of Postpartum Hemorrhage. J Obstet Gynaecol Can. 2018;40(12):e841-e855. doi: 10.1016/j.jogc.2018.09.024[PubMed 30527079]

Silcox J, Schulz P, Horbay GL, et al, “Transfer of Carbetocin Into Human Breast Milk,” Obstet Gynecol, 1993, 82(3):456-9.[PubMed 8355953]

Sweeney G, Holbrook AM, Levine M, et. al. Pharmacokinetics of carbetocin, a long-acting oxytocin analogue, in nonpregnant women. Current Therapeutic Research - Clinical and Experimental. 1990;47(3):528-540.

World Health Organization (WHO) recommendations. Uterotonics for the prevention of postpartum haemorrhage. Published 2018. https://apps.who.int/iris/bitstream/handle/10665/277276/9789241550420-eng.pdf?ua=1.

Brand Names: International

Arbecin IV (BD); Duratobal (ES); Duratocin (AR, AU, BD, CL, CN, CZ, EC, HK, IT, KR, MY, NZ, PE, SG, TH, UY); Lonactene (CR, DO, GT, HN, NI, PA, SV); Pabal (AE, AT, BE, BH, CH, DE, DK, EE, EG, FI, FR, GB, GR, IE, IL, JO, KW, LB, LT, LU, NL, NO, PL, PT, QA, RO, SA, SE, SK)

Last Updated 2/12/20