PABAL® RTS is indicated for the prevention of postpartum haemorrhage due to uterine atony.

Posology
Caesarean section under epidural or spinal anaesthesia:
Withdraw 1 ml of PABAL® RTS containing 100 mcg carbetocin and administer only by intravenous injection, under adequate
medical supervision in a hospital.

Vaginal delivery:
Withdraw 1 ml of PABAL® RTS containing 100 mcg carbetocin and administer by intravenous injection or intramuscular injection, under adequate medical supervision in a hospital.

Method of Administration
For intravenous or intramuscular administration.Carbetocin must only be administered after delivery of the infant, and as soon as possible after delivery, preferably before the delivery of the placenta. For intravenous administration carbetocin must be administered slowly, over 1 minute.
PABAL® RTS is intended for single use only. No further doses of carbetocin should be administered.

Pediatric population
There is no relevant use of carbetocin in children below 12 years of age. The safety and efficacy of carbetocin in adolescents has not yet been established. Currently available data are described in Pharmacodynamic Properties but no recommendation on a posology can be made.

- During pregnancy and labour before delivery of the infant. - Carbetocin must not be used for the induction of labour. - Hypersensitivity to carbetocin or oxytocin or to any of the excipients of the product. - Hepatic or renal disease. - Serious cardiovascular disorders - Epilepsy

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 (vasopressor 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 recognized 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 preeclampsia should be carefully monitored.Specific studies have not been undertaken in gestational diabetes mellitus.

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
Carbetocin is contraindicated during pregnancy and must not be used for the induction of labour.
Breast-feeding
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.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.

Not relevant.

The adverse events observed with carbetocin during the clinical
trials were of the same type and frequency as the adverse
events observed with oxytocin.
The frequency of adverse reactions listed below is defined
using the following convention: Very common (≥1/10); Common (≥1/100 to <1/10); Uncommon (≥ 1/1000 and <1/100); Rare (≥ 1/10000 and < 1/1000) Not known (cannot be estimated from the available data).

Intravenous administration*

Blood and lymphatic system disorders:
Common: Anaemia.
Nervous system disorders:
Very Common: Headache, tremor.
Common: Dizziness.
Cardiac Disorders:
Not known: Tachycardia, Bradycardia***, arrhythmia***,
Myocardial ischemia***, 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 to structure to
Carbetocin).
In the clinical trials, sweating was reported as sporadic cases.

Intramuscular administration**
Blood and lymphatic system disorders:
Uncommon: Anaemia
Nervous system disorders:
Uncommon: Headache, Dizziness.
Rare: tremor
Cardiac disorders
Uncommon: Tachycardia
Not known: Bradycardia***, arrhythmia***, Myocardial
ischemia***, 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 to structure to Carbetocin).

Overdosage of carbetocin may produce uterine hyperactivity whether or not due to hypersensitivity to this agent.Hyperstimulation with strong (hypertonic) or prolonged (tetanic) contractions resulting from oxytocin overdose can lead to uterine rupture or postpartum haemorrhage.
Overdosage of oxytocin may lead to hyponatraemia and water intoxication in severe cases, especially when associated with excessive concomitant fluid intake. As carbetocin is an analogue of oxytocin, the possibility of a similar event cannot be excluded.Treatment of overdosage of carbetocin consists of symptomatic and supportive therapy. When signs or symptoms of overdosage occur oxygen should be given to the mother. In
cases of water intoxication it is essential to restrict fluid intake, promote diuresis, correct electrolyte imbalance, and control convulsions that may eventually occur.

Pharmacotherapeutic group: Oxytocin and analogues.
ATC code: H01BB03.
The pharmacological and clinical properties of carbetocin are those of a long acting oxytocin agonist.
Like oxytocin, carbetocin selectively binds to oxytocin receptors in the smooth muscle of the uterus, stimulates rhythmic contractions
of the uterus, increases the frequency of existing contractions, and raises the tone of the uterus musculature. On the postpartum
uterus, carbetocin is capable of increasing the rate and force of spontaneous uterine contractions. The onset of uterine contraction
following carbetocin is rapid, with a firm contraction being obtained within 2 minutes. A single 100 micrograms intravenous dose of
carbetocin administered after the delivery of the infant is sufficient to maintain adequate uterine contraction that prevents uterine
atony and excessive bleeding comparable with an oxytocin infusion lasting for several hours.

Clinical efficacy and safety
The efficacy of carbetocin in the prevention of postpartum haemorrhage due to uterine atony following Caesarean section was established in a randomised, active controlled,double‑blind, double dummy, parallel group trial designed to establish the efficacy and safety of carbetocin compared to oxytocin 25 IU. Six hundred fifty‑nine healthy pregnant women undergoing elective Caesarean section under epidural anaesthesia received either carbetocin 100 mcg/ml as an IV bolus dose or oxytocin 25 IU as an 8 h IV infusion.The results of analysis of the primary endpoint, the need for additional oxytocic intervention, showed that additional oxytocic intervention was required in 15 (5%) of the subjects receiving carbetocin 100 mcg IV compared with 32 (10%) of the subjects in the oxytocin 25 IU group (p=0.031).
The efficacy of carbetocin in the prevention of postpartum haemorrhage following vaginal delivery was established in one randomised, active controlled, double‑blind trial. In total 29645 subjects were randomised to receive a single intramuscular dose of either carbetocin 100 mcg or oxytocin 10 IU.
For the primary endpoint of blood loss of ≥500 mL or use of additional uterotonics, similar rates were obtained in both treatment groups (carbetocin: 2135 subjects, 14.47%; oxytocin:2122 subjects, 14.38%; relative risk [RR] 1.01; 95% CI: 0.95 to 1.06), demonstrating noninferiority of carbetocin compared with oxytocin with regard to the primary endpoint.
Paediatric population
In the clinical development of carbetocin for prevention of postpartum haemorrhage following vaginal delivery 151 women between 12 and 18 years of age received carbetocin at the recommended dosage of 100 mcg and 162 received oxytocin 10 IU. Efficacy and safety was similar for the two treatment arms in these patients.

The pharmacokinetics of carbetocin have been investigated in healthy female subjects.Carbetocin shows biphasic elimination after intravenous administration with linear pharmacokinetics in the dose range of 400 to 800 mcg. The median terminal elimination half‑life is 33 minutes after intravenous administration and 55 minutes after intramuscular administration. After intramuscular administration, peak concentrations are reached after 30 minutes and the mean bioavailability is 77%. The mean volume of distribution at pseudo-equilibrium (Vz) is 22 L.Renal clearance of the unchanged form is low, with <1% of the injected dose excreted unchanged by the kidney.After intramuscular administration of 70 μg carbetocin in
5 healthy nursing mothers, carbetocin concentrations were detectable in milk samples. Mean peak concentrations in milk were below 20 pg/ml, which was approximately 56 times lower than in plasma at 120 min.

N/A

L-methionine (1.00 mg), Succinic acid (1.19 mg), Mannitol (47.0 mg), Sodium hydroxide 2M (q.s to pH 5.5), Water for injection
(q.s to 1ml).

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

See outer pack. Shelf life after first opening the container: After first opening the vial the solution should be used immediately. From a microbiological point of view, unless the method of opening/reconstitution/dilution precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in‑use storage times and conditions are the responsibility of the user.

Keep vials in the outer carton, in order to protect from light. Store below 30°C. Do not freeze.

Type I glass vial (2R) with type 1 bromobutyle stoppers with aluminium crimp cap containing 1ml of solution for injection.
Pack of 5 vials.

PABAL® RTS is for intravenous and intramuscular use only. Only clear solutions practically free from particles should be used.
Any unused product or waste material should be disposed of in accordance with local requirements.