Carbetocin-pharmak

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Carbetocin-Farmak (Carbetocin-Farmak)

Composition:

Active substance: carbetocin;

1 ml of injection solution contains carbetocin 0.1 mg;

Excipients: mannitol, succinic acid, methionine, sodium hydroxide, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: transparent, colorless liquid.

Pharmacotherapeutic group. Hormones for systemic use (excluding sex hormones and insulin). Pituitary, hypothalamic hormones and their analogues. Posterior pituitary hormones. Oxytocin and its derivatives. ATC code H01B B03.

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 ongoing contractions, and enhancing uterine muscle tone.

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

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

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 form 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.

• Pregnancy and labor period prior to delivery of the baby.
• Should not be used to stimulate uterine contractions during labor.
• Hypersensitivity to carbetocin or oxytocin or to any excipient contained in the formulation.
• Hepatic or renal disease.
• History of pre-eclampsia or eclampsia.
• Severe cardiovascular disorders.
• Epilepsy.

Special precautions.

Carbetocin should be administered only in well-equipped obstetric facilities with trained and qualified personnel continuously present.

Carbetocin-Farmak is intended for intravenous use only. Only clear solutions free from particulate matter should be used.

Any unused product should be disposed of according to local waste disposal regulations.

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 characteristic of oxytocin cannot be excluded.

Severe hypertension has been reported after administration of oxytocin 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 have been shown to potentiate the effects of oxytocin, a similar effect may be possible with carbetocin. Therefore, simultaneous administration of prostaglandins and carbetocin is not recommended. If co-administration is necessary, careful patient monitoring is required.

Certain inhalational anesthetics, such as halothane and cyclopropane, may enhance the hypotensive effect and reduce the uterine response to 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 is a significant difference compared to oxytocin, whose effect ceases rapidly after infusion is stopped.

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, or coagulopathy.

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

There are currently no data on repeated administration of carbetocin, or on its use after oxytocin in cases of persistent uterine atony.

Animal experimental studies have shown that carbetocin has minimal antidiuretic activity (vasopressin activity < 25 IU/vial), thus the possibility of hyponatremia cannot be excluded, particularly in patients receiving intensive intravenous fluid therapy. To prevent the development of convulsive syndrome or coma, early signs such as drowsiness, lethargy, and headache should be closely monitored.

Carbetocin should be used with caution in patients with a history of migraine, bronchial asthma, or cardiovascular disorders, as well as in any condition where a sudden increase in extracellular fluid volume may occur, potentially affecting an already compromised cardiovascular system. In such special cases, the decision to administer carbetocin should be made by a 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 the drug during pregnancy in patients with diabetes mellitus are currently unavailable. The efficacy of carbetocin in normal labour has not been studied.

This medicinal product contains less than 0.012 mmol (0.276 mg)/dose of sodium, i.e. it is practically sodium-free.

Use during pregnancy or breastfeeding.

Pregnancy.

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

Breastfeeding period.

Clinical studies have not shown any significant effect on lactation.

It has been shown 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 should not 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 assessed due to the clinical context being inappropriate.

Method of Administration and Dosage

Carbetocin-Farmak is administered intravenously only 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-Farmak should be administered immediately after childbirth, preferably before placental separation. Repeated administration is not required.

Children

Not applicable to children.

Overdose

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

Hyperactivity characterized by strong (tonic) or prolonged (tetanic) contractions due to oxytocin overdose may result in uterine rupture and postpartum hemorrhage.

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

Treatment: symptomatic and supportive therapy. If symptoms of overdose occur, 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 the clinical trials of carbetocin, the frequency and nature of adverse effects corresponded to those observed with oxytocin use.

*Refers to adverse reactions reported during the use of oxytocin (structurally similar to carbetocin).

During clinical trials, isolated cases of increased sweating were observed.

Suspected adverse reactions reporting.

Reporting of suspected adverse reactions after marketing authorization of the medicinal product is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Do not use the medicinal product after the expiry date stated on the packaging.

Storage conditions.

Store in the original cardboard package to protect from light. Store at a temperature not exceeding 25 °C. Do not freeze. Keep out of reach of children.

Incompatibility.

Due to the lack of compatibility studies, this medicinal product must not be mixed with other medicinal products.

Packaging. 1 ml in ampoules. 5 ampoules per blister. 1 blister per carton.

Or 1 ml in vials. 1 vial per carton.

Or 1 ml in pre-filled syringes. 1 syringe with needle in a blister. 1 blister per carton.

Or 2 syringes without needles in a blister. 3 blisters per carton.

Prescription status. Prescription only.

Manufacturer. JSC "Farmak".

Manufacturer's address and location of its business activity.

74, Kyrylivska Street, Kyiv, 04080, Ukraine.