Prepidil^® (Gel) Instructions for Use

Marketing Authorization Holder

Pfizer, Inc. (USA)

Manufactured By

Pfizer Manufacturing Belgium, NV (Belgium)

Contact Information

PFIZER INNOVATIONS LLC (Russia)

ATC Code

G02AD02 (Dinoprostone)

Active Substance

Dinoprostone (Rec.INN registered by WHO)

Dosage Form

Prepidil®

Intracervical gel 500 mcg/3 g: syringe in a set with a catheter

Dosage Form, Packaging, and Composition

Intracervical gel translucent, viscous.

Excipients: colloidal anhydrous silicon dioxide, triacetin (triacetin).

3 g – disposable polyethylene syringes (1) in a set with a catheter – plastic contour cell packaging (1) – cardboard packs.

Clinical-Pharmacological Group

Prostaglandin preparation that increases the tone and contractile activity of the myometrium

Pharmacotherapeutic Group

Labor stimulant – PGF2 preparation

Pharmacological Action

Labor stimulant. Dinoprostone (prostaglandin E₂) is one of the representatives of unsaturated fatty acids synthesized under physiological conditions. The specific mechanism of action during intracervical application has not been fully elucidated. It is believed that Dinoprostone enhances the blood supply to the cervix, accelerating its maturation (softening, effacement, and dilation), which corresponds to the changes characteristic of normal labor, leading to a decrease in cervical resistance, a simultaneous increase in myometrial contractile activity, and delivery.

Dinoprostone can also have a stimulating effect on the smooth muscle of the human gastrointestinal tract, which can sometimes cause nausea and/or vomiting when the drug is prescribed for cervical ripening.

In high doses, Dinoprostone can cause a decrease in blood pressure (possibly due to an effect on the smooth muscle of blood vessels), as well as an increase in body temperature; however, these effects are not observed when using dinoprostone in the doses recommended for cervical ripening.

Pharmacokinetics

Absorption

After intracervical administration at a dose of 500 mcg, the C_max of dinoprostone in plasma is reached after 30-45 minutes and then quickly decreases to the initial level, regardless of the level of uterine contractile activity.

Distribution

The binding of dinoprostone to human plasma albumin is 73%. Dinoprostone is distributed in various biological fluids and tissues of the mother’s body.

Metabolism

Dinoprostone is rapidly metabolized to form 13,14-dihydro-15-keto-prostaglandin E₂, which is then converted to 13,14-dihydro-15-keto-prostaglandin A₂. Dinoprostone is completely metabolized in the human body: largely in the lungs, and then in the liver and kidneys. At least 9 metabolites of prostaglandin E₂ are detected in human blood and urine.

Excretion

Dinoprostone and its metabolites are excreted mainly by the kidneys, in small amounts – through the intestines.

Indications

• Stimulation of cervical ripening in the presence of medical indications for labor induction.

ICD codes

Dosage Regimen

The initial dose is the entire contents of the syringe (500 mcg of dinoprostone in 3 g of gel) administered into the cervical canal just below the level of the internal os using the supplied catheter. After administration of the drug, the patient should lie on her back for 10-15 minutes to minimize leakage of the gel.

If the response to the initial dose of the drug is not achieved, the drug is administered again. The recommended repeat dose is 500 mcg, and the interval from the previous administration is at least 6 hours. The need for additional administration is determined based on the clinical situation. The maximum recommended cumulative dose over 24 hours is 1.5 mg.

Instructions for syringe assembly

Remove the sterile syringe and catheter from the packaging.

1. Remove the protective cap from the syringe tip.
2. Insert the cap into the syringe to use it as a plunger.
3. Firmly attach the catheter to the syringe tip (until it clicks) and administer the contents of the syringe to the patient.

Adverse Reactions

From the mother: tetanic uterine contractions (increase in frequency, uterine tone, or duration of contractions), uterine rupture, nausea, vomiting, diarrhea, increased body temperature, back pain, feeling of warmth in the vagina, hypersensitivity reactions.

From the fetus: fetal distress/changes in fetal heart rate, stillbirth, decrease in the newborn’s Apgar score below 7 points (noted only with the use of dinoprostone in oral and injectable forms).

Post-marketing observations

From the blood coagulation system: increased risk (less than 1 case per 1000 deliveries) of postpartum disseminated intravascular coagulation in patients after childbirth stimulated by the use of dinoprostone or oxytocin.

Contraindications

Conditions in which prolonged uterine contractions are contraindicated:

• Multiple pregnancy;
• 6 or more full-term pregnancies in history;
• If the fetal head has not engaged;
• Cesarean section or major surgical interventions on the uterus (in history);
• Difficult and/or traumatic childbirth (in history);
• Previous fetal distress;
• Disproportion between the size of the pelvis and the fetal head;
• Fetal heart rhythm disturbances;
• An obstetric situation where surgical intervention is preferable;
• Vaginal bleeding of unknown origin during pregnancy;
• Infections of the lower genital tract;
• Abnormal fetal presentation.

Hypersensitivity to the components of the drug.

Use with caution in cardiovascular diseases, arterial hypertension, impaired liver and/or kidney function, bronchial asthma, glaucoma or ocular hypertension, with ruptured amniotic membranes.

Use in Pregnancy and Lactation

Any dose of the drug that causes a prolonged increase in uterine tone poses a certain risk to the embryo or fetus.

In experimental studies on animals, prostaglandin E₂ causes an increase in skeletal abnormalities in rats and rabbits, and embryotoxicity of dinoprostone has also been identified in rats and rabbits.

Prostaglandins are excreted in breast milk in very small amounts, regardless of the timing of delivery.

Special Precautions

The drug is intended for use in a hospital setting only.

Before prescribing the drug, it is necessary to assess the correspondence between the size of the fetal head and the woman’s pelvis.

When using the drug, care should be taken to avoid introducing the gel above the level of the internal os into the extra-amniotic space (possible uterine hyperstimulation).

During the use of the drug, the process of cervical ripening and dilation should be monitored, and continuous monitoring of uterine contractile activity and fetal condition should be carried out. If there is a history of hypertonic or tetanic uterine contractions, monitoring of uterine contractile activity and fetal condition is necessary throughout the entire period of induced labor. If uterine hypertonus develops or if uterine contractions intensify and become more frequent, as well as if changes in fetal heart rate occur, measures should be taken to ensure the safety of the fetus and mother. The possibility of uterine rupture should be kept in mind.

In women over 35 years of age with complications that arose during pregnancy, as well as with a gestational age of more than 40 weeks, there is an increased risk of postpartum disseminated intravascular coagulation, so Dinoprostone should be used with caution in such patients. It is necessary to determine as early as possible after childbirth whether the patient is at risk of developing fibrinolysis.

Overdose

Symptoms uterine hypertonus, intensification and increased frequency of uterine contractions, fetal distress. The appearance of overdose symptoms indicates increased individual sensitivity to the drug, since a true overdose is unlikely due to the fact that the syringe with the drug contains a single dose.

Treatment is symptomatic. The drug is removed from the vagina by placing the patient in a semi-recumbent position on her side. If simple withdrawal of the drug is not sufficient to stop uterine hyperstimulation and/or fetal distress, intravenous beta-adrenergic agonists are administered. Oxygen administration is indicated. If ineffective – rapid delivery.

Drug Interactions

Dinoprostone enhances the effect of oxytocin on the uterus, so it is not recommended to use the drug simultaneously with other agents that stimulate labor. Oxytocin can be used only 6 hours after the administration of dinoprostone.

Storage Conditions

The drug should be stored out of the reach of children, in a refrigerator at a temperature from 2°C (35.6°F) to 8°C (46.4°F).

Shelf Life

Shelf life – 2 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.