Pabal (Solution) Instructions for Use

Marketing Authorization Holder

Ferring, GmbH (Germany)

Manufactured By

Ferring, GmbH (Germany)

Or

Pharmstandard-UfaVITA OJSC (Russia)

Labeled By

FERRING INTERNATIONAL CENTER, S.A. (Switzerland)

Or

PHARMSTANDARD-UfaVITA, OJSC (Russia)

Quality Control Release

FERRING, GmbH (Germany)

Or

PHARMSTANDARD-UfaVITA, OJSC (Russia)

ATC Code

H01BB03 (Carbetocin)

Active Substance

Carbetocin (Rec.INN registered by WHO)

Dosage Form

Pabal

Solution for intravenous and intramuscular administration 100 mcg/1 ml: fl. 5 pcs.

Dosage Form, Packaging, and Composition

Solution for intravenous and intramuscular administration transparent, colorless.

Excipients : L-methionine – 1 mg, succinic acid – 1.19 mg, mannitol – 47 mg, 2M sodium hydroxide solution – to pH 5.5, water for injections – to 1 ml.

1 ml – vials of colorless glass (5) with first opening control – blister packs (1) – cardboard packs.

Clinical-Pharmacological Group

A drug that increases the tone and contractile activity of the myometrium

Pharmacotherapeutic Group

Hypothalamic and pituitary hormones and their analogues; posterior pituitary lobe hormones; oxytocin and its analogues

Pharmacological Action

Carbetocin (1-deamino-1-monocarbo-[2-O-methyltyrosine]-oxytocin) is a long-acting oxytocin agonist.

Similar to oxytocin, Carbetocin selectively binds to oxytocin receptors in the smooth muscle of the uterus, stimulates rhythmic uterine contractions, increases the frequency of existing contractions, and increases the tone of the uterine muscles.

In the postpartum uterus, Carbetocin increases the rate and strength of spontaneous uterine contractions. After administration of carbetocin, uterine contractions become more frequent, and a sharp contraction occurs after two minutes.

A single dose of carbetocin 100 mcg is sufficient to maintain adequate uterine contractions that prevent uterine atony and heavy bleeding, which can be compared to the administration of oxytocin acting for several hours.

Pharmacokinetics

Distribution

C_max in plasma is reached within 15 minutes after administration and is 1035±218 pg/ml within 60 minutes. Carbetocin penetrates into breast milk, with its C_max being approximately 56 times lower than in blood plasma after 120 minutes.

Metabolism

By analogy with oxytocin, Carbetocin is hydrolyzed by proteinases.

Elimination

The elimination of carbetocin is biphasic with linear pharmacokinetics in the dose range of 400-800 mcg. T_1/2 is about 40 minutes. Renal clearance of the unchanged form is low, less than 1% of the administered dose is excreted by the kidneys unchanged.

Indications

• Prevention of uterine atony after delivery of the baby during operative delivery by caesarean section;
• Prevention of uterine atony in parturient women with an increased risk of postpartum hemorrhage after vaginal delivery.

ICD codes

Dosage Regimen

Pabal is administered once intravenously or intramuscularly only after the birth of the child. The drug should not be used repeatedly. Pabal should not be mixed with other drugs in the same syringe. The drug should not be used if insoluble particles are observed in the solution or if the solution has changed color.

Unused drug must be destroyed.

During caesarean section, a single dose of Pabal (100 mcg/ml) is administered immediately after delivery of the baby, preferably before placental separation.

During vaginal delivery, 1 dose of Pabal (100 mcg/ml) is administered into the upper thigh immediately after delivery of the placenta.

Adverse Reactions

The nature and frequency of side effects with the use of carbetocin are comparable to the side effects of oxytocin

General disorders chills, pain at the injection site.

Contraindications

• Pregnancy and labor before the birth of the child;
• Impaired liver or kidney function;
• Serious disorders of the cardiovascular system (rhythm and conduction disturbances);
• Epilepsy;
• For induction of labor;
• Hypersensitivity to carbetocin, oxytocin or to any of the components of the drug.

With caution Carbetocin has a certain antidiuretic effect. Therefore, the possibility of developing hyponatremia when using Pabal should be taken into account, especially in patients receiving large volumes of intravenous infusions.

Attention should be paid to the first signs of hyponatremia (drowsiness, apathy, headache) to prevent seizures and coma.

Pabal should be used with caution in migraine, bronchial asthma and cardiovascular diseases, as well as in any conditions in which a rapid increase in the volume of extracellular fluid can provoke complications associated with overhydration. The decision to use Pabal should be made by the doctor taking into account the risk-benefit ratio in each specific case. Constant monitoring of blood pressure is necessary in patients with severe late gestosis, eclampsia and preeclampsia.

Use in Pregnancy and Lactation

The use of Pabal is contraindicated during pregnancy and labor until the moment of birth of the child.

A small amount of carbetocin may penetrate into the mother’s breast milk and then be broken down by the newborn’s enzymes.

Use in Hepatic Impairment

Contraindicated in impaired liver function.

Use in Renal Impairment

Contraindicated in impaired kidney function.

Special Precautions

Pabal is administered intramuscularly or intravenously only in specialized obstetric departments, appropriately equipped and staffed with qualified and experienced medical personnel.

The use of Pabal at any stage of labor before the birth of the child is prohibited, since the stimulating effect of carbetocin on the uterus after a single administration of 100 mcg/ml lasts for several hours, unlike the rapid decrease in the effect of oxytocin.

In case of persistent uterine bleeding after the use of Pabal, such causes as retained placental fragments and coagulation disorders should be excluded.

Pabal is administered only once. In case of uterine hypotension or atony accompanied by heavy bleeding, the possibility of using oxytocin and/or ergometrine should be considered.

Since Pabal has a certain antidiuretic effect, the first signs of hyponatremia (drowsiness, apathy and headache) should be identified to prevent seizures and coma.

Effect on ability to drive vehicles and operate machinery

Not applicable, considering the indications for use.

Overdose

Symptoms: cases of overdose with a single injection of the recommended dose of 100 mcg/ml are very rare. Administration of Pabal at a dose of 800 mcg/ml may cause tachycardia. Violation of the recommended dosage regimen may provoke myometrial hypertonicity regardless of the presence or absence of hypersensitivity to carbetocin or postpartum hemorrhage. In severe cases, an overdose of Pabal may lead to hyponatremia and overhydration, especially in combination with simultaneous large-volume intravenous infusion of solutions performed during delivery.

Treatment consists of symptomatic and supportive therapy. If signs or symptoms of overdose occur, the parturient woman should be provided with adequate oxygenation. In case of water intoxication, fluid intake should be restricted, diuresis should be stimulated, electrolyte disturbances should be corrected, and clinical signs of hyponatremia (drowsiness, apathy, headache) should be monitored to prevent seizures and coma.

Drug Interactions

No cases of drug interaction with analgesics, antispasmodics and agents used for epidural or spinal anesthesia have been observed. However, Pabal should not be mixed in the same syringe with other drugs.

Since Carbetocin is an analogue of oxytocin, cases of interaction characteristic of oxytocin may be observed. A sharp increase in blood pressure is possible when Pabal is administered 3-4 hours after the prophylactic use of vasoconstrictors, in combination with caudal-conduction anesthesia. An increase in blood pressure and enhancement of the effect of carbetocin is also possible with the combined use of Pabal with ergot preparations (methylergometrine).

It is not recommended to use Pabal simultaneously with prostaglandins due to the possible enhancement of the effect of carbetocin. If their simultaneous use is nevertheless necessary, the patient should be under constant observation.

Inhalation anesthetics (halothane, cyclopropane) may enhance the hypotensive effect and reduce the effect of Pabal on the uterus.

When Pabal is used simultaneously with oxytocin, arrhythmia may develop.

Storage Conditions

Store out of the reach of children at a temperature of 2-8°C (35.6-46.4°F). Do not freeze.

Shelf Life

Shelf life – 2 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.