Duratocin Injection - Product Information
|Form:||Liquid solution, Intramuscular (IM), Intravenous (IV)|
|Ingredients:||Carbetocin, methionine, succinic acid, mannitol, sodium hydroxide, water for injections.|
Actions and Clinical Pharmacology
DURATOCIN (carbetocin injection) is a long-acting synthetic nonapeptide analogue of oxytocin with agonist properties. It can be administered intravenously as a single dose immediately following delivery by cesarean section under epidural or spinal anesthesia, to prevent uterine atony and postpartum hemorrhage.
The clinical and pharmacological properties of carbetocin are similar to those of naturally occurring oxytocin, another posterior pituitary hormone. Like oxytocin, carbetocin binds to oxytocin receptors present on the smooth musculature of the uterus, resulting in rhythmic contractions of the uterus, increased frequency of existing contractions, and increased uterine tone. The oxytocin receptor content of the uterus is very low in the non-pregnant state, and increases during pregnancy, reaching a peak at the time of delivery. Therefore carbetocin has no effect on the non-pregnant uterus, and has a potent uterotonic effect on the pregnant and immediate postpartum uterus.
The onset of uterine contraction following carbetocin administration by either the intravenous or intramuscular route is rapid, with a firm contraction being obtained within 2 minutes. The total duration of action of a single intravenous injection of carbetocin on uterine activity is about one hour suggesting that carbetocin may act long enough to prevent postpartum hemorrhage in the immediate postpartum period. In comparison to oxytocin, carbetocin induces a prolonged uterine response when administered postpartum, in terms of both amplitude and frequency of contractions.
Carbetocin, when administered immediately postpartum as a single intravenous bolus injection of 100 μg to women delivered by cesarean section under epidural or spinal anesthesia, was found to be significantly more effective than placebo in preventing uterine atony and minimizing uterine bleeding.
Carbetocin administration also appears to enhance uterine involution in the early postpartum period.
Indications and Clinical Use
DURATOCIN (carbetocin injection) is indicated for the prevention of uterine atony and postpartum hemorrhage following elective cesarean section under epidural or spinal anesthesia.
DURATOCIN has not been studied in cases involving emergency cesarean section, classical cesarean section, anesthesia other than epidural or spinal, or in patients presenting significant heart disease, history of hypertension, known coagulopathy or evidence of liver, renal or endocrine disease (excluding gestational diabetes). Appropriate studies have not been undertaken and doses have not been established in women following labour or vaginal delivery.
Because of its long duration of action relative to oxytocin, uterine contractions produced by carbetocin cannot be stopped by simply discontinuing the medication. Therefore carbetocin should not be administered prior to delivery of the infant for any reason, including elective or medical induction of labour. Inappropriate use of carbetocin during pregnancy could theoretically mimic the symptoms of oxytocin over dosage, including hyperstimulation of the uterus with strong (hypertonic) or prolonged (tetanic) contractions, tumultuous labour, uterine rupture, cervical and vaginal lacerations, postpartum hemorrhage, utero-placental hypoperfusion and variable deceleration of fetal heart, fetal hypoxia, hypercapnia, or death.
Carbetocin should not be used in patients with a history of hypersensitivity to oxytocin or carbetocin.
Carbetocin should not be used in patients with vascular disease, especially coronary artery disease, except with extreme caution.
Carbetocin is not intended for use in children.
Some patients may not have an adequate uterine contraction after a single injection of DURATOCIN (carbetocin injection). In these patients, administration of DURATOCIN should not be repeated and more aggressive treatment with additional doses of other available uterotonic drugs like oxytocin or ergometrine is warranted. In cases of persistent bleeding, the presence of retained placental fragments, coagulopathy, or trauma to the genital tract should be ruled out.
Although no cases of partial retention or trapping of the placenta have been reported, this remains a theoretical possibility if the drug is administered before delivery of the placenta.
DURATOCIN (carbetocin injection) use during pregnancy, prior to the delivery of the infant, is contraindicated (see CONTRAINDICATIONS).
See WARNING section regarding potential requirement for further oxytocin therapy.
DURATOCIN is not recommended for use in elderly patients.
Small amounts of carbetocin have been shown to cross over from plasma into the breast milk of nursing women who were given a 70 μg dose intramuscularly, between 7 and 14 weeks postpartum. The mean peak concentration in breast milk was approximately 50 times lower than in plasma, and the ratio of the milk to plasma area under the concentration versus time curves (M/PAUC) was only 2-3%. The small amount of carbetocin transferred into breast milk or colostrum after a single injection, and subsequently ingested by a breast feeding infant, would not be expected to present a significant safety concern. This is due to the fact that carbetocin would be rapidly degraded by peptidases in the infant gastrointestinal tract.
Oxytocin is known to cause contraction of the myoepithelial cells surrounding the mammary alveoli, thereby stimulating milk let-down. There is no sufficient evidence to determine whether carbetocin can also stimulate milk let-down. However, milk let-down was found to occur normally in 5 nursing women after receiving a 70 μg carbetocin dose by the intramuscular route.
No specific drug interactions have been reported with carbetocin. However, since carbetocin is closely related in structure to oxytocin, it is possible that some of the same drug interactions could occur. Severe hypertension has been reported when oxytocin was given 3-4 hours following prophylactic administration of a vasoconstrictor in conjunction with caudal block anesthesia. Cyclopropane anesthesia may modify oxytocin=s cardiovascular effects, so as to produce unexpected results such as hypotension. Maternal sinus bradycardia with abnormal atrioventricular rhythms has also been noted when oxytocin was used concomitantly with cyclopropane anesthesia.
The adverse events observed with carbetocin during the clinical trials were of the same type and frequency as the adverse events observed with oxytocin when administered after cesarean section under epidural or spinal anesthesia.
Intravenous carbetocin was frequently (10-40% of patients) associated with nausea, abdominal pain, pruritis, flushing, vomiting, feeling of warmth, hypotension, headache and tremor.
Infrequent adverse events (1-5% of patients) included back pain, dizziness, metallic taste, anaemia, sweating, chest pain, dyspnea, chills, tachycardia and anxiety.
Symptoms and Treatment of Over Dosage
Over dosage of carbetocin can be expected to produce enhanced pharmacological effects.
Therefore, when carbetocin is administered postpartum, over dosage may be associated with uterine hyperactivity and pain. Treatment consists of symptomatic and supportive management.
Dosage and Administration
A single intravenous dose of 100 μg (1 mL) of DURATOCIN (carbetocin injection) is administered by bolus injection, slowly over 1 minute, only when delivery of the infant has been completed by cesarean section under epidural or spinal anesthesia. DURATOCIN can be administered either before or after delivery of the placenta.