PABAL Solution for injection

Active ingredients: Carbetocin

Contraindications

  • During pregnancy and labour before delivery of the infant.
  • Carbetocin must not be used for the induction of labour.
  • Hypersensitivity to carbetocin, oxytocin or to any of the excipients listed in section 6.1.
  • Hepatic or renal disease.
  • Serious cardiovascular disorders.
  • Epilepsy.

Special warnings and precautions for use

Carbetocin is intended for use only at well-equipped specialist obstetrics units with experienced and qualified staff available at all times.

The use of carbetocin at any stage before delivery of the infant is not appropriate because its uterotonic activity persists for several hours. This is in marked contrast to the rapid reduction of effect observed after discontinuation of an oxytocin infusion.

In case of persistent vaginal or uterine bleeding after administration of carbetocin the cause must be determined. Consideration should be given to causes such as retained placental fragments, perineal, vaginal and cervix lacerations, inadequate repair of the uterus, or disorders of blood coagulation.

Carbetocin is intended for single administration only, intramuscular or intravenous. In case of intravenous administration, it must be administered slowly over 1 minute. In case of persisting uterine hypotonia or atonia and the consequent excessive bleeding, additional therapy with another uterotonic should be considered. There are no data on additional doses of carbetocin or on the use of carbetocin following persisting uterine atony after oxytocin.

Animal studies have shown carbetocin to possess some antidiuretic activity (vasopressin activity: <0,025 IU/vial) and therefore the possibility of hyponatraemia cannot be excluded, particularly in patients also receiving large volumes of intravenous fluids. The early signs of drowsiness, listlessness and headache should be recognised to prevent convulsions and coma.

In general, carbetocin should be used cautiously in the presence of migraine, asthma and cardiovascular disease or any state in which a rapid addition to extracellular water may produce hazard for an already overburdened system. The decision of administering carbetocin can be made by the physician after carefully weighing the potential benefit carbetocin may provide in these particular cases.

No data is available on the use of carbetocin in patients with eclampsia. Patients with eclampsia and pre-eclampsia should be carefully monitored.

Specific studies have not been undertaken in gestational diabetes mellitus.

Interaction with other medicinal products and other forms of interaction

During clinical trials, carbetocin has been administered in association with a number of analgesics, spasmolytics and agents used for epidural or spinal anaesthesia, 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 anaesthesia.

During combination with ergot-alkaloids, such as methylergometrine, oxytocin and carbetocin may enhance the blood pressure enhancing 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 and lactation

Pregnancy

Carbetocin is contraindicated during pregnancy and must not be used for the induction of labour (see section 4.3).

Breastfeeding

No significant effects on milk let-down have been reported during clinical trials. Small amounts of carbetocin have been shown to pass from plasma into breast milk of nursing women (see section 5.2). The small amounts transferred into colostrum or breast milk after a single injection of carbetocin, and subsequently ingested by the infant are assumed to be degraded by enzymes in the gut.

Breast-feeding does not need to be restricted after the use of carbetocin.

Effects on ability to drive and use machines

Not relevant.

Undesirable effects

The adverse events observed with carbetocin during the clinical trials were of the same type and frequency as the adverse events observed with oxytocin.

Intravenous administration* – Tabulated summary of adverse reactions:

Very common ≥1/10
Common ≥1/100 and <1/10
Not known (cannot be estimated from the available data)

Blood and lymphatic system disorders

Common: Anaemia

Nervous system disorders

Very common: Headache, tremor

Common: Dizziness

Cardiac disorders

Not known: Tachycardia, bradycardia***, arrhythmia***, myocardial ischaemia***, and QT prolongation***

Vascular disorders

Very common: Hypotension, flushing

Respiratory, thoracic and mediastinal disorders

Common: Chest pain, dyspnoea

Gastrointestinal disorders

Very common: Nausea, abdominal pain

Common: Metallic taste, vomiting

Skin and subcutaneous tissue disorders

Very common: Pruritus

Musculoskeletal and connective tissue disorders

Common: Back pain

General disorders and administration site conditions

Very common: Feeling of warmth

Common: Chills, pain

* Based on studies in caesarean section
*** Reported with oxytocin (closely related in structure to carbetocin)

In the clinical trials sweating was reported as sporadic cases.

Intramuscular administration** – Tabulated summary of adverse reactions:

Uncommon ≥1/1,000 and <1/100
Rare ≥1/10,000 and <1/1,000
Not known (cannot be estimated from the available data)

Blood and lymphatic system disorders

Uncommon: Anaemia

Nervous system disorders

Uncommon: Headache, dizziness

Rare: Tremor

Cardiac disorders

Uncommon: Tachycardia

Not known: Bradycardia***, arrhythmia***, myocardial ischaemia***, and QT prolongation***

Vascular disorders

Uncommon: Hypotension

Rare: Flushing

Respiratory, thoracic and mediastinal disorders

Uncommon: Chest pain

Rare: Dyspnoea

Gastrointestinal disorders

Uncommon: Nausea, abdominal pain, vomiting

Skin and subcutaneous tissue disorders

Rare: Pruritus

Musculoskeletal and connective tissue disorders

Uncommon: Back pain, muscular weakness

Renal and urinary disorders

Rare: Urinary retention

General disorders and administration site conditions

Uncommon: Chills, pyrexia, pain

** Based on studies in vaginal delivery
*** Reported with oxytocin (closely related in structure to carbetocin)

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme, website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.