Usage
Atosiban is prescribed to delay imminent pre-term birth in pregnant women between 24 and 33 completed weeks of gestation experiencing regular uterine contractions (at least 4 contractions every 30 minutes, lasting at least 30 seconds each), cervical dilation of 1 to 3 cm (0-3 cm for nulliparas), cervical effacement of ≥ 50%, and a normal fetal heart rate.
It is classified as a tocolytic agent, specifically an oxytocin receptor antagonist.
Atosiban competes with oxytocin for binding to its receptors in the uterine myometrium. By blocking oxytocin’s action, Atosiban decreases the frequency and strength of uterine contractions, thus delaying preterm labor.
Alternate Names
Atosiban acetate is the generic name. Tractocile is a common brand name. There are no widely recognized international or regional variations of this name.
How It Works
Pharmacodynamics: Atosiban competitively binds to oxytocin receptors in the myometrium, inhibiting oxytocin-induced contractions and promoting uterine quiescence. Onset of uterine relaxation is typically rapid, with significant reduction in contractions within 10 minutes, leading to stable uterine quiescence (≤ 4 contractions/hour) for up to 12 hours.
Pharmacokinetics:
- Absorption: Atosiban is administered intravenously, ensuring complete bioavailability. Following intravenous infusion, steady-state plasma concentrations are achieved within an hour.
- Distribution: It has a volume of distribution of approximately 42 L and exhibits placental transfer, with a maternal/fetal concentration ratio of approximately 0.12 at a dose of 300 µg/min. Atosiban is 46-48% bound to plasma proteins.
- Metabolism: Atosiban is not extensively metabolized by CYP450 enzymes.
- Elimination: Primarily excreted unchanged in the urine. Small amounts are excreted in breast milk. The half-life is independent of the dose.
Mode of Action: Atosiban acts as a competitive antagonist at oxytocin receptors in the uterine myometrium.
Receptor Binding: Specifically targets and binds to oxytocin receptors, blocking the binding of endogenous oxytocin.
Enzyme Inhibition/Neurotransmitter Modulation: Atosiban’s primary mechanism is receptor antagonism. It does not significantly inhibit CYP450 enzymes or directly modulate neurotransmitters.
Elimination Pathways: Predominantly eliminated via renal excretion with minimal hepatic metabolism.
Dosage
Atosiban should be administered by a physician experienced in managing preterm labor.
Standard Dosage
Adults:
Atosiban is administered intravenously in three stages:
- Initial bolus: 6.75 mg over 1 minute.
- Loading infusion: 300 µg/min (24 ml/hour of a 75mg/100ml diluted solution, equivalent to 18 mg/hour) for 3 hours.
- Subsequent infusion: 100 µg/min (8 ml/hour of a 75mg/100ml diluted solution, equivalent to 6 mg/hour) for up to 45 hours.
The total duration of treatment should not exceed 48 hours, and the total dose should preferably not exceed 330.75 mg.
Children:
Atosiban is not indicated for use in children.
Special Cases:
- Elderly Patients: Not applicable, as Atosiban is used in pregnancy.
- Patients with Renal Impairment: Dose adjustment is unlikely to be necessary.
- Patients with Hepatic Dysfunction: Use with caution due to limited data.
- Patients with Comorbid Conditions: Use with caution in multiple pregnancies and/or with concomitant use of other tocolytic agents. Increased risk of pulmonary edema may be observed in these cases.
Clinical Use Cases
Atosiban’s use is specific to delaying preterm birth. It is not indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
No specific dosage adjustments are indicated based on renal or hepatic impairment. Monitor patients with multiple pregnancies or those on other tocolytics carefully for pulmonary edema.
Side Effects
Common Side Effects
Nausea, vomiting, headache, dizziness, hot flushes, tachycardia, hypotension, injection site reactions, hyperglycemia.
Rare but Serious Side Effects
Allergic reactions, pulmonary edema, postpartum hemorrhage.
Long-Term Effects
Limited data are available on long-term effects.
Adverse Drug Reactions (ADR)
Severe allergic reactions and pulmonary edema require immediate medical intervention.
Contraindications
- Gestational age <24 or >33 completed weeks.
- Premature rupture of membranes >30 weeks of gestation.
- Abnormal fetal heart rate.
- Antepartum uterine hemorrhage requiring immediate delivery.
- Eclampsia and severe pre-eclampsia requiring delivery.
- Intrauterine fetal death.
- Suspected intrauterine infection.
- Placenta previa.
- Abruptio placenta.
- Any maternal or fetal condition where continuing pregnancy is hazardous.
- Hypersensitivity to atosiban or any of its excipients.
Drug Interactions
Atosiban is not metabolized by CYP450 enzymes and does not inhibit CYP450 isoenzymes. No clinically significant interactions with betamethasone or labetalol have been observed. Data on interaction with antibiotics, ergot alkaloids and anti-hypertensive agents other than labetalol are limited.
Pregnancy and Breastfeeding
Atosiban is indicated for use during pregnancy specifically to delay preterm birth between 24 and 33 weeks of gestation. Breastfeeding should be discontinued during Atosiban treatment. Small amounts of Atosiban are excreted in breast milk.
Drug Profile Summary
- Mechanism of Action: Competitive oxytocin receptor antagonist in the myometrium.
- Side Effects: Nausea, vomiting, headache, dizziness, hot flushes, tachycardia, hypotension, injection site reactions, hyperglycemia. Rarely: allergic reactions, pulmonary edema, postpartum hemorrhage.
- Contraindications: See detailed list above.
- Drug Interactions: No clinically significant interactions with betamethasone or labetalol.
- Pregnancy & Breastfeeding: Indicated for use in pregnancy (24-33 weeks). Breastfeeding contraindicated.
- Dosage: See detailed dosage guidelines above.
- Monitoring Parameters: Uterine contractions, fetal heart rate, maternal blood pressure, signs of pulmonary edema.
Popular Combinations
Often co-administered with corticosteroids (e.g., betamethasone) to accelerate fetal lung maturity in anticipated preterm birth.
Precautions
Close monitoring is advised in patients with multiple pregnancies, intrauterine growth restriction, and those receiving other tocolytics. Monitor blood loss after delivery due to potential for uterine atony.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Atosiban?
A: See detailed dosage guidelines above.
Q2: How does Atosiban work?
A: Atosiban competitively inhibits the action of oxytocin at its receptors in the uterine myometrium, decreasing the frequency and intensity of uterine contractions.
Q3: What are the common side effects of Atosiban?
A: Common side effects include nausea, vomiting, headache, dizziness, hot flushes, tachycardia, and injection site reactions.
Q4: Is Atosiban safe to use in patients with renal impairment?
A: Dose adjustment is unlikely to be needed in patients with renal impairment, as only a small amount of atosiban is excreted in the urine.
Q5: Can Atosiban be used in patients with hepatic impairment?
A: Atosiban should be used with caution in patients with hepatic impairment due to limited experience.
Q6: What are the contraindications for using Atosiban?
A: Atosiban is contraindicated in several conditions, including gestational age <24 or >33 weeks, abnormal fetal heart rate, antepartum hemorrhage, eclampsia/severe pre-eclampsia, intrauterine fetal death, suspected intrauterine infection, placenta previa, abruptio placentae, and hypersensitivity to atosiban.
Q7: Are there any significant drug interactions with Atosiban?
A: Atosiban is not extensively metabolized by the CYP450 system. No clinically significant interactions with betamethasone or labetalol have been observed.
Q8: Can Atosiban be used during breastfeeding?
A: Breastfeeding should be discontinued during Atosiban treatment, as small amounts of the drug are excreted in breast milk.
Q9: What is the maximum duration of Atosiban treatment?
A: The maximum duration of Atosiban treatment should not exceed 48 hours.
Q10: Can Atosiban treatment be repeated if contractions resume?
A: Yes, retreatment with Atosiban is possible if contractions resume, with the same dosing regimen. Up to three retreatments are permissible.
