Gynipral^® (Tablets, Solution) Instructions for Use

ATC Code

G02CA (Adrenomimetics, tocolytic agents)

Active Substance

Hexoprenaline (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Drug reducing the tone and contractile activity of the myometrium

Pharmacotherapeutic Group

Tocolytic agent – selective beta2-adrenomimetic

Pharmacological Action

An agent that reduces the tone and contractile activity of the myometrium, a beta₂-sympathomimetic. Reduces the frequency and intensity of uterine contractions. Inhibits both spontaneous and oxytocin-induced labor contractions. During childbirth, it normalizes excessively strong or irregular contractions.

Under the action of hexoprenaline, premature contractions in most cases cease, which allows the pregnancy to be prolonged to the normal term of delivery. Due to its selectivity for β₂-adrenergic receptors, Hexoprenaline has a slight effect on the cardiac activity and blood flow of the pregnant woman and the fetus.

Pharmacokinetics

Hexoprenaline is well absorbed after oral administration. The molecule of the active substance consists of two catecholamine groups, which undergo methylation via COMT. Hexoprenaline becomes biologically inactive only in the case of methylation of both catecholamine groups.

It is excreted mainly in the urine unchanged and in the form of metabolites. Within the first 4 hours after administration, 80% of the administered dose is excreted in the urine as free hexoprenaline and a monomethyl metabolite. Then, the excretion of the dimethyl metabolite and conjugated compounds (glucuronide and sulfate) increases. A small part is excreted in the bile in the form of complex metabolites.

Indications

For parenteral administration: acute tocolysis – inhibition of labor contractions during childbirth in acute intrauterine asphyxia, immobilization of the uterus before caesarean section, before turning the fetus from a transverse position, with prolapse of the umbilical cord, with complicated labor, as an emergency measure for premature birth before delivery of the pregnant woman to the hospital; massive tocolysis – inhibition of premature labor contractions in the presence of a smoothed cervix and/or dilation of the uterine os; long-term tocolysis – prevention of premature birth with intensified or frequent contractions without smoothing of the cervix or dilation of the uterine os, immobilization of the uterus before, during and after Cerclage surgery.

For oral administration: threat of premature birth (primarily as a continuation of infusion therapy).

ICD codes

Dosage Regimen

For parenteral administration (intravenous injections and infusions), determine the dose individually based on the clinical situation.

For acute tocolysis, administer an initial intravenous infusion of 3 mcg/min. Titrate the infusion rate gradually to achieve the desired therapeutic effect.

For massive tocolysis, administer via controlled intravenous infusion. Adjust the rate to suppress uterine contractions effectively.

For long-term tocolysis, initiate therapy with an intravenous infusion. Continuously monitor uterine activity and adjust the dosage as required.

For oral administration, use a single dose of 500 mcg. Determine the frequency of administration and the total duration of therapy based on the individual patient’s clinical response and treatment goals.

When switching from intravenous to oral therapy, initiate oral tablets promptly after discontinuing the infusion to maintain tocolytic efficacy.

Adverse Reactions

From the central nervous system headache, anxiety, tremor, dizziness.

From the cardiovascular system slight tachycardia, decreased blood pressure (especially diastolic); rarely – ventricular extrasystoles, pain in the heart area (these symptoms disappear quickly after discontinuation of hexoprenaline).

From the digestive system inhibition of intestinal peristalsis, temporary increase in the activity of transaminases in the blood serum; rarely – nausea, vomiting, intestinal atony.

Other decreased diuresis (especially at the beginning of treatment), increased blood glucose levels (this effect is more pronounced in diabetes mellitus), increased sweating; in the first days of treatment – a decrease in the concentration of potassium in the blood (with further treatment – normalization).

The fetal heart rate in most cases remains unchanged or changes slightly.

Contraindications

Hyperthyroidism, cardiovascular diseases (heart rhythm disorders occurring with tachycardia, myocarditis, mitral valve disease, aortic stenosis), severe liver disease, severe kidney disease, angle-closure glaucoma, uterine bleeding (premature placental abruption), intrauterine infections, lactation (breastfeeding), hypersensitivity to hexoprenaline.

Use in Pregnancy and Lactation

Used for tocolytic therapy during pregnancy and childbirth.

Contraindicated during breastfeeding.

Use in Hepatic Impairment

Contraindicated in severe liver diseases.

Use in Renal Impairment

Contraindicated in severe kidney diseases.

Pediatric Use

Not applicable.

Geriatric Use

Not applicable.

Special Precautions

When using hexoprenaline, the mother’s pulse and blood pressure, as well as the fetal heartbeat, should be monitored. ECG monitoring before and during treatment is recommended.

In patients with increased sensitivity to sympathomimetics, Hexoprenaline should be used in low doses, selected individually, under constant medical supervision.

With a significant increase in the mother’s heart rate (more than 130 beats/min) and/or a pronounced decrease in blood pressure, the dose should be reduced; if there are complaints of difficulty breathing, pain in the heart area and if signs of heart failure appear, the use of hexoprenaline should be stopped immediately.

Before starting tocolytic therapy, it is necessary to prescribe potassium preparations, because in case of hypokalemia, the effect of sympathomimetics on the myocardium is enhanced.

Against the background of the use of hexoprenaline, the consumption of table salt with food should be limited.

When conducting tocolytic therapy, it is necessary to monitor the regularity of stool.

In pregnant women with diabetes mellitus, blood glucose concentration should be monitored, since the use of hexoprenaline, especially at the beginning of treatment, can cause an increase in glycemia levels.

If childbirth occurs directly after a course of treatment with hexoprenaline, it is necessary to take into account the possibility of hypoglycemia and acidosis in newborns due to the transplacental penetration of acidic metabolic products (lactic and ketone acids).

In some cases, with the use of corticosteroids during the administration of hexoprenaline, the development of pulmonary edema is possible. Therefore, during infusion therapy, constant careful clinical monitoring of patients is necessary. This is especially important when it is necessary to carry out combined therapy with corticosteroids and hexoprenaline in patients with concomitant diseases accompanied by fluid retention in the body (including kidney diseases).

Since there is a risk of developing pulmonary edema when administering hexoprenaline, the volume of fluid administered during infusion should, if possible, be limited; in addition, it is preferable to use solutions that do not contain electrolytes to dilute the drug.

During prolonged tocolytic therapy, it is necessary to ensure the absence of placental abruption. Clinical symptoms of premature placental abruption may be smoothed out against the background of tocolytic therapy. With rupture of the fetal bladder and with dilation of the cervix more than 2-3 cm, the effectiveness of tocolytic therapy is low.

Drug Interactions

When conducting tocolytic therapy using beta-adrenergic agonists, an increase in the symptoms of concomitant dystrophic myotonia is possible. In such cases, the use of diphenylhydantoin derivatives (phenytoin) is recommended.

Hexoprenaline is not recommended to be used simultaneously with ergot alkaloids, as well as with preparations containing calcium and vitamin D, dihydrotachysterol or mineralocorticoids.

The intensity of glycogen accumulation in the liver caused by the use of corticosteroids is reduced under the action of hexoprenaline.

With simultaneous use, non-selective beta-blockers weaken the effect of hexoprenaline or neutralize it.

With simultaneous use, methylxanthines, including theophylline, enhance the effect of hexoprenaline.

With simultaneous use, Hexoprenaline reduces the hypoglycemic effect of hypoglycemic agents.

With simultaneous use of hexoprenaline with other sympathomimetics (agents for normalizing blood circulation, anti-asthmatic agents), an increase in the stimulating effect on the cardiovascular system and the appearance of overdose symptoms are possible (combinations should be avoided).

With simultaneous use of sympathomimetics and halothane, the development of cardiac arrhythmias is possible.

Before using halothane, Hexoprenaline should be discontinued.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.