Usage
Dinoprostone is prescribed for the following medical conditions:
- Cervical ripening: To soften and dilate the cervix before labor induction.
- Labor induction: To initiate uterine contractions in pregnant women at or near term when there is a medical or obstetrical indication.
- Second-trimester abortion: To terminate pregnancy in the second trimester.
Pharmacological classification: Prostaglandin E2 analog, oxytocic.
Mechanism of Action: Dinoprostone binds to prostaglandin E2 receptors in the myometrium and cervix, stimulating uterine contractions and cervical ripening.
Alternate Names
Brand Names: Cervidil, Prepidil, Prostin E2.
How It Works
Pharmacodynamics: Dinoprostone mimics the effects of endogenous prostaglandin E2, causing cervical softening, effacement (thinning), and dilation, along with myometrial contractions.
Pharmacokinetics:
- Absorption: Vaginal absorption varies depending on the formulation.
- Metabolism: Rapidly metabolized in the lungs, liver, kidney, and spleen.
- Elimination: Primarily through renal excretion.
Mode of Action: Dinoprostone binds to G protein-coupled prostaglandin E2 (EP) receptors, specifically EP1, EP2, and EP3 subtypes, in the cervix and myometrium. This leads to increased intracellular calcium levels, activating myosin light chain kinase, resulting in smooth muscle contraction.
Receptor Binding: Binds to EP1, EP2, and EP3 receptors.
Elimination Pathways: Primarily renal excretion of metabolites. Hepatic metabolism also plays a role.
Dosage
Standard Dosage
Adults:
Dosage depends on the indication and formulation. Please refer to below section on clinical use-cases.
Children:
Not typically used in children outside of neonatal intensive care for ductal patency. The dose is 5-10 nanograms/kg/min intravenously via syringe pump. The solution can be titrated upwards in increments of 5 nanograms/kg/min to a maximum of 100 nanograms/kg/min as per consultant’s advice. Facilities for intubation and ventilation must be readily available.
Special Cases:
- Elderly Patients: Not applicable for labor induction or abortion. Dose adjustments may be needed for other uses if applicable.
- Patients with Renal Impairment: Caution advised; dose adjustments may be necessary.
- Patients with Hepatic Dysfunction: Caution advised; dose adjustments may be necessary.
- Patients with Comorbid Conditions: Use with caution in patients with asthma, glaucoma, hypertension, cardiovascular disease.
Clinical Use Cases
- Cervical Ripening:
- Gel: 0.5 mg endocervically. May repeat after 6 hours if needed.
- Vaginal Insert: 10 mg (releases 0.3 mg/hour over 12 hours).
- Labor Induction:
- Gel: 1 mg (or 2 mg in primigravida with unfavorable induction features) intravaginally. May repeat 1-2 mg after 6 hours if needed.
- Vaginal Tablets: 3 mg intravaginally. May repeat 3 mg after 6-8 hours if needed. Maximum 6 mg per course.
- Second-Trimester Abortion:
- Vaginal Suppositories: 20 mg intravaginally. May repeat every 3-5 hours for up to 2 days.
- Neonatal Ductus Arteriosus Patency: 5-10 nanograms/kg/min intravenously, titrated up to 100 nanograms/kg/min if necessary.
Dosage Adjustments
Dose adjustments may be needed based on patient response, uterine activity, and fetal heart rate. For renal or hepatic dysfunction, consider lower initial doses and monitor closely.
Side Effects
Common Side Effects
Nausea, vomiting, diarrhea, fever, back pain, uterine hyperstimulation (strong or frequent contractions).
Rare but Serious Side Effects
Uterine rupture, amniotic fluid embolism, severe allergic reactions (anaphylaxis), fetal distress. Disseminated intravascular coagulation, particularly in women over 35, with pregnancy complications, or gestational age over 40 weeks.
Long-Term Effects
Not applicable for indications like labor induction or abortion.
Adverse Drug Reactions (ADR)
Uterine tachysystole, uterine hyperstimulation, fetal bradycardia, uterine rupture.
Contraindications
- Hypersensitivity to dinoprostone or other prostaglandins.
- Previous cesarean section or major uterine surgery.
- Cephalopelvic disproportion.
- Fetal distress.
- Placenta previa or unexplained vaginal bleeding.
- Active pelvic inflammatory disease.
- Multifetal pregnancy (except for ductus arteriosus patency).
- Non-vertex fetal presentation (except for ductus arteriosus patency).
Drug Interactions
Oxytocin (increased risk of uterine hyperstimulation). Misoprostol should not be co-administered.
Pregnancy and Breastfeeding
Pregnancy: Indicated for use in term or near-term pregnancies for labor induction and cervical ripening. Contraindicated in the first and second trimesters except for medically indicated termination of pregnancy.
Breastfeeding: Limited information; exercise caution.
Drug Profile Summary
- Mechanism of Action: Prostaglandin E2 analog, stimulates uterine contractions and cervical ripening.
- Side Effects: Nausea, vomiting, diarrhea, fever, back pain, uterine hyperstimulation, rarely uterine rupture.
- Contraindications: Hypersensitivity, previous cesarean section, cephalopelvic disproportion, fetal distress.
- Drug Interactions: Oxytocin, misoprostol.
- Pregnancy & Breastfeeding: Use cautiously.
- Dosage: Varies by indication and formulation.
- Monitoring Parameters: Uterine activity, fetal heart rate, maternal vital signs.
Popular Combinations
Often used sequentially with oxytocin for labor induction after cervical ripening.
Precautions
- Careful monitoring of uterine activity and fetal heart rate is essential.
- Use cautiously in patients with asthma, glaucoma, hypertension, or cardiovascular disease.
- Discontinue if uterine hyperstimulation or fetal distress occurs.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Dinoprostone?
A: The dosage varies depending on indication and formulation. See the Dosage section above.
Q2: How is Dinoprostone administered?
A: Administered vaginally (gel, insert, tablets, suppositories) by a qualified healthcare professional. Intravenous administration is reserved for neonatal ductus arteriosus patency and should only be done under the care of a neonatologist.
Q3: What are the common side effects?
A: Nausea, vomiting, diarrhea, fever, back pain, and uterine hyperstimulation are common.
Q4: What are the serious side effects?
A: Uterine rupture, amniotic fluid embolism, and fetal distress are rare but serious side effects.
Q5: Can Dinoprostone be used in patients with previous cesarean sections?
A: No, it is contraindicated due to the risk of uterine rupture.
Q6: What are the drug interactions?
A: Concomitant administration of oxytocin can increase the risk of uterine hyperstimulation, therefore, use with caution. Misoprostol is also contraindicated.
Q7: Is Dinoprostone safe during pregnancy?
A: It is indicated for cervical ripening and labor induction in term or near-term pregnancies. Contraindicated in other stages of pregnancy except for medically indicated termination of pregnancy in the second trimester.
Q8: Is Dinoprostone safe during breastfeeding?
A: Limited information is available. Exercise caution if use is necessary.
Q9: How should uterine hyperstimulation be managed?
A: Discontinue dinoprostone immediately, administer a tocolytic if necessary, and monitor the patient and fetus closely.
Q10: What is the role of Dinoprostone in neonates?
A: Dinoprostone, specifically an intravenous infusion, can be used in the neonatal intensive care unit to maintain the patency of the ductus arteriosus in neonates with specific congenital cardiac defects until corrective or palliative surgery can be performed. This is an off-label use, and the decision to use it must be made after consultation with a consultant paediatric cardiologist or paediatric intensivist.
