Carbetocin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT CARBETOCIN

Composition:

Active substance: carbetocin;

1 ml of solution contains carbetocin 100 mcg;

Excipients: sodium chloride, glacial acetic acid, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: colorless clear solution, free from visible particles.

Pharmacotherapeutic group. Pituitary, hypothalamic hormones and their analogues. Posterior pituitary hormones. Oxytocin and analogues.

ATC code H01BB03.

Pharmacological properties.

Pharmacodynamics.

Carbetocin is a long-acting oxytocin agonist.

Like oxytocin, carbetocin selectively binds to oxytocin receptors on the smooth muscle cells of the myometrium, stimulating rhythmic contractions of the uterus, increasing the frequency of contractions already initiated, and enhancing uterine muscle tone.

In the postnatal period, carbetocin is capable of increasing the frequency and strength of spontaneous uterine contractions. After administration, an intense onset of contractile activity with strong contractions is achieved within 2 minutes.

A single intravenous dose of 100 mcg carbetocin administered after delivery of the baby is sufficient to maintain adequate uterine contractility, thereby preventing uterine atony and excessive blood loss, compared to oxytocin infusion over several hours.

Pharmacokinetics.

Carbetocin exhibits a biphasic elimination pattern after intravenous administration, with linear pharmacokinetics within the dose range of 400 to 800 mcg. The elimination half-life is approximately 40 minutes. Renal clearance of the unchanged drug is low, with less than 1% of the administered dose excreted unchanged in the urine.

In 5 healthy breastfeeding mothers, carbetocin plasma concentrations were detectable within 15 minutes, reaching a maximum level of 1035±218 pg/mL within 60 minutes. At 120 minutes, the maximum concentration in breast milk was approximately 56 times lower than in plasma.

Clinical characteristics.

Indications.

For the prevention of uterine atony following cesarean section performed under spinal or epidural anesthesia.

Contraindications.

• Hypersensitivity to carbetocin or oxytocin, or to any excipient contained in the formulation.
• Pregnancy and labor period prior to delivery of the baby.
• Should not be used for stimulation of labor.
• Liver and kidney disease.
• Episodes of pre-eclampsia and eclampsia.
• Severe cardiovascular disorders.
• Epilepsy.

Special precautions.

Carbetocin should be administered only in well-equipped obstetric units with trained and qualified personnel constantly available.

Carbetocin is intended for intravenous use only. Only a clear solution free from particulate matter should be used.

Any unused medicinal product should be disposed of in accordance with local requirements for waste disposal.

Interaction with other medicinal products and other forms of interaction.

No evidence of any drug interaction has been observed when carbetocin was used concomitantly with various analgesics, spasmolytics, or agents used for spinal and epidural anesthesia.

Since carbetocin is chemically similar to oxytocin, interactions similar to those of oxytocin cannot be excluded.

Severe hypertension has been observed after administration of oxytocin within 3–4 hours following prophylactic use of vasoconstrictors for spinal anesthesia.

Oxytocin and carbetocin, when used concomitantly with ergot alkaloids such as methylergometrine, may increase blood pressure, thereby enhancing the effects of these agents. The risk of cumulative effects increases if oxytocin or methylergometrine is administered after carbetocin.

Since prostaglandins are known to potentiate the effect of oxytocin, a similar effect may be possible with carbetocin. Therefore, concomitant administration of prostaglandins and carbetocin is not recommended. If simultaneous administration is necessary, careful patient monitoring is required.

Some inhalational anesthetics, such as halothane and cyclopropane, may enhance the hypotensive effect and reduce the uterine effect of carbetocin. Cases of arrhythmia have been reported with concomitant use of oxytocin.

Special precautions for use.

Carbetocin should not be used at any stage of labour, as its uterotonic effect lasts for several hours. This property represents a significant difference compared to the rapid termination of oxytocin's effect following discontinuation of infusion.

If uterine bleeding persists after administration of carbetocin, the underlying cause should be identified. Possible causes include incomplete placental separation, inadequate uterine curettage or suturing, and coagulopathy.

In case of persistent hypotonia or uterine atony and, consequently, prolonged uterine bleeding, the possibility of administering an additional uterotonic agent should be considered.

Currently, there are no data on repeat administration of carbetocin, nor on its use after oxytocin in cases of persistent uterine atony.

Experimental animal studies have shown that carbetocin has minimal antidiuretic activity (vasopressin activity < 25 IU/vial); therefore, development of hyponatremia cannot be excluded, especially in patients receiving intensive intravenous fluid therapy. To prevent the onset of convulsive syndrome or coma, patients should be monitored for early signs such as drowsiness, lethargy, and headache.

Carbetocin should generally be used with caution in patients with a history of migraine, bronchial asthma, or cardiovascular disorders, as well as in any conditions where a rapid increase in extracellular fluid volume may occur, potentially overloading the already compromised cardiovascular system. In such special cases, the decision to administer carbetocin should be made by the physician after careful assessment of the potential benefits.

Studies on the use of carbetocin in patients with eclampsia are lacking.

Studies on the use of carbetocin during pregnancy in patients with diabetes mellitus are currently unavailable. The efficacy of oxytocin in normal labour has not been studied.

Use during pregnancy or breastfeeding.

Pregnancy.

Carbetocin is contraindicated during pregnancy and should not be used to stimulate uterine contractions.

Breastfeeding period.

Clinical studies have not shown any significant impact on lactation.

It has been found that a small amount of carbetocin passes into breast milk.

It is assumed that after a single injection, a negligible amount of carbetocin is transferred to the infant via colostrum or breast milk and is subsequently degraded by enzymes in the infant's gastrointestinal tract.

Breastfeeding does not need to be restricted after administration of carbetocin.

Ability to affect reaction speed when driving or operating machinery.

The effect on the ability to drive or operate machinery has not been evaluated due to the clinical context being inappropriate.

Dosage and Administration.

Carbetocin should only be administered intravenously under appropriate medical supervision in a hospital setting.

The drug should be administered as a single dose of 1 mL slowly over 1 minute, only after cesarean section and delivery of the baby. Carbetocin should be administered immediately after childbirth, preferably before placental separation. Further administration of the drug is not recommended.

Children.

Not to be used in children.

Overdose.

Exceeding the dose of carbetocin may lead to increased uterine activity.

Hyperactivity, manifested by strong (tonic) or prolonged (tetanic) contractions caused by carbetocin overdose, may result in uterine rupture and postpartum hemorrhage.

In severe cases of overdose, oxytocin may cause hyponatremia and water intoxication, especially when associated with simultaneous administration of excessive amounts of fluid. Since carbetocin is an oxytocin analogue, similar effects cannot be excluded.

Treatment: symptomatic and supportive therapy. If symptoms of overdose are present, oxygen therapy should be initiated in the patient. In cases of water intoxication, restriction of fluid intake is essential, along with stimulation of diuresis, correction of electrolyte imbalances, and control of possible seizure activity.

Adverse reactions.

During clinical trials, the frequency and nature of adverse effects with carboprost were consistent with those observed with oxytocin administration.

*** Reported with oxytocin (structurally very similar to carbetocin)

During clinical trials, isolated cases of tachycardia and increased sweating were reported.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature between 20 and 80 °C. Do not freeze.

Keep out of reach of children.

Incompatibility.

Due to lack of compatibility studies, this medicinal product should not be mixed with other drugs.

Packaging.

1 ml in a vial, 4 or 5 vials in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

LLC "Farmideya", Latvia.

Manufacturer's address and location of business operations.

4 Rupnīcu Street, Olaine, Olaine district, LV-2114, Latvia.