Carbetocin (Duratocin) or (1-butanoic acid-2-(O-methy-L-tyrosine)-1-carbaoxytocin, is an oxytocic used in obstetrics to control postpartum hemorrhage and bleeding after giving birth, particularly following Cesarean section. It is an eight amino acids long analog of oxytocin (a nonapeptide) and has a similar mechanism of action. Carbetocin is an agonist at peripherally expressed oxytocin receptors. Carbetocin is a drug used to control postpartum hemorrhage, bleeding after giving birth. It is an analog of oxytocin, and its action is similar to that of oxytocin — it causes contraction of the uterus.

Mechanism of Action of Carbetocin

Carbetocin functions as an agonist at peripheral oxytocin receptors, particularly in the myometrium, with a lesser affinity for myoepithelial cells. Oxytocin receptors are G protein-coupled and their mechanism of action involves second messengers and the production of inositol phosphates. Carbetocin mimics this mechanism. Binding for carbetocin and other oxytocin agonists has been shown to be nonselective at the extracellular N-terminus and loops E2 and E3. While the oxytocin receptor shows an equal affinity for oxytocin and carbetocin, the biological effect of carbetocin is almost 50% that of endogenous or exogenous oxytocin. Carbetocin has a much longer-lasting effect than oxytocin, necessitating only a single dose. Carbetocin inhibits endogenous oxytocin release, interrupting the uterine feedback loop with the hypothalamus and decreasing both central and peripheral release of oxytocin. During pregnancy, the synthesis of oxytocin receptors in the uterus greatly increases, reaching a peak during labor and delivery. Consequently, the administration of carbetocin or another oxytocin analog during or immediately following birth will have increased uterotonic and contractile effect. The application of carbetocin does not affect a non-pregnant uterus with lower oxytocin receptor expression. Carbetocin also functions to thicken the blood, further preventing post-partum hemorrhage. Carbetocin should not be used to induce or augment labor since it could cause cardiac or respiratory distress to mother or infant.

Indications of Carbetocin

• Postpartum hemorrhage
• Uterine Atony
• Used to control postpartum hemorrhage and bleeding after giving birth.

Contra-Indications of Carbetocin

During pregnancy and labor before delivery of the infant.

• Carbetocin must not be used for the induction of labor.
• Hypersensitivity to carbetocin, oxytocin or to any of the excipients.
• Hepatic or renal disease
• contractions, tumultuous labor, uterine rupture,
• cervical and vaginal lacerations,
• postpartum hemorrhage,
• uteroplacental hypoperfusion and
• variable deceleration of fetal heart,
• fetal hypoxia, hypercapnia, or death.
• Cases of pre-eclampsia and eclampsia.
• Serious cardiovascular disorders.
• Epilepsy.

Dosage of Carbetocin

Prophylaxis of uterine atony and excessive bleeding after cesarean section

• 100 mcg as a single dose via bolus inj slowly over 1 min, given after delivery of the infant (preferably before removal of the placenta).
• A single intravenous dose of 100 μg (1 mL) of DURATOCIN (carbetocin injection) is administered by bolus injection, slowly over 1 minute, only when delivery of the infant has been completed by cesarean section under epidural or spinal anesthesia. It can be administered either before or after delivery of the placenta.
• Duration is a medicine that is used only in the hospital and should only be administered by qualified staff.
  Duration will be given to you by injection into one of your veins immediately after the delivery of your baby.

Side Effects of Carbetocin

The most common

• chest pain, irregular heartbeat, or shortness of breath
• rapid or irregular heartbeat or pulse
• heart palpitations
• increased appetite
• weight loss
• dizziness
• drowsiness
• dry mouth
• headache
• joint pain
• nausea and vomiting
• Severe stomach ache
• diarrhoea,
• anorexia,
• flatulence,
• headache,
•  fainting, fast or pounding heartbeats.

More common

• weight loss
• Syndrome of inappropriate secretion of antidiuretic hormone
• Fast or irregular heartbeat
• fever
• Back pain
• dizziness
• headache
• increased cough
• Acid or sour stomach
• decreased appetite
• Agitation
• chest congestion
• chest pain
• cold sweats
• confusion
• decreased sexual ability or desire
• diarrhea or loose stools
• heartburn
• sleepiness or unusual drowsiness
• stomach or abdominal cramps, gas, or pain
• trouble sleeping

Less common

• Abnormal dreams
• change in sense of taste
• congestion
• discouragement, feeling sad, or empty
• Acting on dangerous impulses
• Aggressive or violent behavior
• Thoughts about suicide or dying
• New or worse depression
• New or worse anxiety or panic attacks
• Agitation, restlessness, anger, or irritability
• Trouble sleeping
• An increase in activity or talking more than normal

Drug Interactions of Carbetocin

• During clinical trials, carbetocin has been administered in association with a number of analgesics, spasmolytics, and agents used for epidural or spinal anesthesia, and no drug interactions have been identified. Specific interaction studies have not been undertaken.
• Since carbetocin is closely related in structure to oxytocin, the occurrence of interactions known to be associated with oxytocin cannot be excluded:
• Severe hypertension has been reported when oxytocin was given 3 to 4 hours following prophylactic administration of a vasoconstrictor in conjunction with caudal block anesthesia.
• During combination with ergot-alkaloids, such as methylergometrine, oxytocin and carbetocin may enhance the blood pressure enhancing the effect of these agents. If oxytocin or methylergometrine are administered after carbetocin there may be a risk of cumulative exposure.
• Since it has been found that prostaglandins potentiate the effect of oxytocin, it is expected that this can also occur with carbetocin. Therefore, it is not recommended that prostaglandins and carbetocin be used together. If they are concomitantly administered, the patient should be carefully monitored.
• Some inhalation-anesthetics, such as halothane and cyclopropane may enhance the hypotensive effect and weaken the effect of carbetocin on the uterus. Arrhythmias have been reported for oxytocin during concomitant use

Pregnancy & Lactation of Carbetocin

FDA Pregnancy Risk Catagory – N( Not Categorized)

Pregnancy

• Carbetocin is not indicated during pregnancy, prior to the delivery of the infant. Use of carbetocin during pregnancy could result in hyperstimulation of the uterus with hypertonic or tetanic contractions, tumultuous labor, uterine rupture, cervical and vaginal lacerations, postpartum hemorrhage, uteroplacental hypoperfusion and deceleration of the fetal heart rate, fetal hypoxia, hypercapnia, or death.

Lactation

• Carbetocin, in small amounts, has been distributed in the breast milk. This small amount found in breast milk or colostrum after a single injection would not be expected to present a significant safety concern. There is insufficient evidence to determine whether carbetocin stimulates milk let-down. However, normal let-down occurred in five nursing mothers who received 70 mcg of carbetocin intramuscularly.No information is available on the relationship of age to the effects of carbetocin in pediatric patients. Safety and efficacy have not been established.

References