Primigyn Gel

Indications

• Induction of labor
• Cervical ripening before labor
• Management of incomplete or missed miscarriage

Dosage

Children: Dinoprostone is not typically used in the pediatric population for any licensed indications. For specific pediatric dosing, refer to the BNF for Children.

Adults: For cervical ripening or induction of labor, the recommended dosage is 0.5 mg to 1 mg administered intravaginally every 6 hours, up to a maximum of 3 doses. For the treatment of missed miscarriage, a dose of 800 micrograms can be given intravaginally.

Mechanism of action

Dinoprostone acts by stimulating the myometrium of the gravid uterus to contract, mimicking the contractions observed during labor. This is achieved through direct stimulation of myometrial tissue, although the precise mechanism remains unclear. It may also influence cellular calcium transport and cyclic adenosine monophosphate concentrations. Furthermore, dinoprostone induces cervical effects such as softening and dilation, potentially through collagen degradation facilitated by collagenase enzymes.

Pharmacodynamics

Dinoprostone is recognized for its ability to stimulate uterine contractions, thus promoting labor and facilitating pregnancy termination. Its actions extend to smooth muscle stimulation in the gastrointestinal tract, which may lead to side effects such as vomiting or diarrhea, especially when used for pregnancy termination.

Pharmacokinetics

The pharmacokinetics of dinoprostone involve its rapid metabolism and clearance. After administration, it is absorbed quickly, with peak serum concentrations occurring shortly thereafter. The half-life of dinoprostone is relatively short, necessitating careful dosing and monitoring during use, particularly in intravenous applications. The drug is primarily metabolized in the liver and excreted via the urine.

Contra-indications

• Any condition where spontaneous labor is inadvisable
• Any condition where vaginal delivery is inadvisable
• Avoid intravenous injection during labor

Adverse effects

• Angioedema
• Electrolyte imbalance
• Flushing
• Uterine hyperstimulation
• Fetal distress
• Asphyxia
• Death
• Hypertonicity
• Tetanic contractions
• Soft-tissue damage
• Uterine rupture
• Disseminated intravascular coagulation
• Water intoxication with hyponatraemia

Precautions

• Careful monitoring of fetal heart rate and uterine motility is essential for dose titration
• Monitoring for disseminated intravascular coagulation after intravenous injection is necessary
• Use electrolyte-containing diluent when administering at high doses
• Prolonged intravenous administration at high doses may cause water intoxication with hyponatraemia

Pregnancy

Dinoprostone is indicated for use during pregnancy for the induction of labor and for the termination of pregnancy.

Breast-feeding

The amount present in breast milk is too small to be harmful, but large doses may suppress lactation.

Storage

Store at room temperature, away from light and moisture. Do not freeze.

Formulations

• Intravenous infusion
• Solution for injection
• Intravaginal gel

Mechanism of action

Dinoprostone administered intravaginally stimulates the myometrium of the gravid uterus to contract in a manner that is similar to the contractions seen in the term uterus during labor, resulting in the evacuation of the products of conception from the uterus. It is believed that dinoprostone exerts its uterine effects via direct myometrial stimulation, but the exact mechanism of action is unkown. Other suggested mechanisms include the regulation of cellular membrane calcium transport and of intracellular concentrations of cyclic 3',5'-adenosine monophosphate. Dinoprostone also appears to produce local cervical effects including softening, effacement, and dilation. The exact mechanism of action for this effect is also unknown, but it has been suggested that this effect may be associated with collagen degradation caused by secretion of the enzyme collagenase as a partial response to locally administered dinoprostone.

Pharmacodynamics

Dinoprostone is equivalent to prostaglandin E2 (PGE2). It stimulates labor and delivery by stimulating the uterine, and thus terminates pregnancy. Dinoprostone is also capable of stimulating the smooth muscle of the gastrointestinal tract of man. This activity may be responsible for the vomiting and/or diarrhea that is not uncommon when dinoprostone is used to terminate pregnancy.