Dinoprostone

Mechanism

Mechanism of Action

Dinoprostone is the endogenous prostaglandin E2 (PGE2). It acts as a natural agonist ligand for EP1, EP2, EP3 and EP4 receptors. In the cervical stroma, its predominant action is through the EP2 and EP4 subtypes, mediating the relaxation of collagen and stimulating the release of interleukin-8, which attracts neutrophils and induces the maturation of the cervix.

Pharmacokinetics

Pharmacokinetics

• Routes of administration: Vaginal, via controlled release device (10 mg insert in polymer matrix) or intracervical gel (0.5 mg).
• Absorption: The vaginal device releases dinoprostone at a constant rate of approximately 0.3 mg/hour for 24 hours. Provides controlled and local tissue exposure.
• Metabolism: Ultra-rapid metabolism in the lung in its first vascular pass (~90% is inactivated by the enzyme 15-hydroxyprostaglandin dehydrogenase in a single circulatory pass).
• Half-life (t_1/2): Less than 1 minute in free plasma.
• Excretion: Renal in the form of inactive dicarboxylic metabolites.

Indicators and dose

Indications

• Initiation or facilitation of cervical ripening in full-term pregnant women with an unfavorable neck (Bishop < 6) who present a medical indication for induction of labor.

Dosage and Administration

• Vaginal insert (Propess): A 10 mg insert placed in the posterior vaginal fornix, removed after 24 hours or immediately after the onset of the active phase of labor (or if tachysystole or suspected loss of fetal well-being occurs).
• Intracervical gel (Prepidil): 0.5 mg injected with syringe into the cervical canal (just below the internal cervical os). It can be repeated after 6 hours (maximum 1.5 mg in 24 hours).

Pregnancy and Breastfeeding

Indicated only for use in cervical ripening at term. It is not excreted in significant quantities in breast milk.

Security

Contraindications

• Hypersensitivity to dinoprostone.
• Uterine scar of any type (increased risk of rupture).
• Suspected or obvious acute fetal distress.
• Cephalopelvic disproportion or dynamic dystocias.
• Severe multiparity (more than 5 previous births).
• Concomitant use of oxytocin (requires insert removal at least 30 minutes before starting oxytocin).

Adverse Effects (ADR)

• Uterine tachysystole with or without fetal heart rate decelerations: Occurs in 3 to 5% of cases. It is solved immediately by removing the vaginal insert by pulling on the recovery tape.
• Uterine hypertonia: Persistent contractions lasting more than 2 minutes.
• Transient fever and nausea.