Ginipral solution instructions for use. Ginipral during pregnancy: instructions for use, side effects, analogues. Application instruction of Ginipral in tablets
Ginipral is a drug that reduces contractile activity and muscle tone of the uterus.
Release form and composition
Ginipral tablets are made containing the active substance - hexoprenaline sulfate - 500 μg, as well as excipients: lactose hydrate, corn starch, disodium edetate dihydrate, copovidone, magnesium stearate, glycerol palmitate stearate, talc. In blisters of 10 pieces.
Ginipral solution for intravenous administration is prepared, containing 10 μg of hexoprenaline sulfate in 1 ampoule, as well as additional substances: water for injection, sodium chloride, sodium pyrosulfite, disodium edetate dihydrate, sulfuric acid 2N. In ampoules of 2 ml, 5 pieces in a box.
Ginipral is prepared for the preparation of a solution for infusion, containing 25 μg of hexoprenaline sulfate in 1 ml, as well as auxiliary components: deionized water, sodium chloride, sodium pyrosulfate, sulfuric acid, disodium edetate dihydrate. In packs of 5 ampoules.
Indications for use
According to the instructions, Ginipral solution and concentrate for the preparation of the solution are indicated for use in the following cases:
- Acute tocolysis: slowing labor pains during childbirth due to acute intrauterine asphyxia, prolapse of the umbilical cord, before turning the fetus from a transverse position, before caesarean section, complication of labor;
- Premature birth (as an emergency measure before taking the patient to the hospital);
- Massive tocolysis: suspension of premature labor if the woman in labor has a smoothed cervix and opening of the cervix of the uterus;
- Prolonged tocolysis: frequent and intensified contractions without opening the cervix and smoothing the cervix (for the prevention of premature birth), immobilization of the uterus before, during and after cervical cerclage;
Ginipral tablets are prescribed for the threat of premature birth (mainly as a continuation of infusion treatment).
Contraindications
According to the instructions, Ginipral should not be taken in the following cases:
- Cardiac ischemia;
- Myocarditis;
- thyrotoxicosis;
- Aortic stenosis, mitral valve disease;
- tachyarrhythmias;
- Premature placental abruption, uterine bleeding;
- First trimester of pregnancy;
- Severe impairment of kidney and / or liver function;
- High blood pressure;
- Angle-closure glaucoma;
- The period of breastfeeding;
- Intrauterine infections;
- Hypersensitivity to the active or auxiliary components of the drug.
Method of application and dosage
The dose of the Ginpral solution is selected individually. The contents of the ampoule should be administered slowly intravenously over 5-10 minutes - after dilution with isotonic NaCl solution.
In acute tocolysis, 1 ampoule (2 ml) of the drug is prescribed. If necessary, treatment is continued with infusions;
With massive tocolysis, treatment with a solution is prescribed in the amount of 1 ampoule, followed by an infusion of Ginipral at a rate of 0.3 μg per minute.
With prolonged tocolysis, the drug is prescribed as a continuous drip infusion at a rate of 0.075 μg per minute.
If the resumption of contractions does not occur within two days, the patient is transferred to taking Ginipral tablets.
Before use, the concentrate for preparing the Ginipral solution should be diluted in 5 ml of distilled water so that the total concentration of the active substance is 5 μg in 1 ml of the solution.
The finished solution is used parenterally, in the form of intravenous injections and infusions. The dosage of parenteral administration of Ginipral is set individually, depending on the clinical symptoms.
Ginipral tablets are taken orally with a sufficient amount of liquid.
With the threat of premature birth, 1 tablet of Ginipral is prescribed 1-2 hours before the end of the infusion.
The medicine is taken 1 tablet every three hours, then - 1 tablet every 4-6 hours. The daily dose of Ginipral should not exceed 4-8 tablets.
Side effects
The use of Ginipral can cause the following side effects:
- Cardiovascular system: lowering blood pressure, maternal tachycardia, heart rhythm disturbances, cardialgia;
- Central and peripheral nervous systems: anxiety, dizziness, finger tremor, headache;
- Digestive system: intestinal obstruction, nausea and vomiting, deterioration of intestinal motility, a temporary increase in hepatic transaminases;
- Laboratory indicators: hypocalcemia, hypokalemia, increased plasma glucose levels;
- Allergies: bronchospasm, difficulty breathing, impaired consciousness, anaphylactic shock;
- Side effects of Ginipral in newborns: acidosis, hypoglycemia.
special instructions
During treatment with Ginipral, patients should monitor the functions of the cardiovascular system of the mother and fetus.
With increased sensitivity to sympathomimetics, it is recommended to prescribe Ginipral from small doses and under constant medical supervision.
If the mother has a pronounced increase in heart rate (more than 130 beats per minute) or a significant decrease in blood pressure, the dose of Ginipral should be reduced.
In the event of signs of heart failure, pain in the region of the heart, difficulty breathing, the use of Ginipral should be stopped immediately.
In women with diabetes, carbohydrate metabolism should be monitored during therapy with Ginipral, since the use of the drug may cause an increase in plasma glucose levels.
In some cases, the simultaneous use of Ginipral and glucocorticosteroids can cause pulmonary edema, especially with impaired renal function. Therefore, the patient during treatment should be under regular medical supervision.
Analogues
Structural analogues of Ginipral are Ipradol and Hexoprenaline.
Drugs that have a similar pharmacological effect are: Partusisten, Salbutamol, Fenoterol, Magnesia.
Terms and conditions of storage
According to the instructions, Ginipral is stored in a dark, dry place out of the reach of children. The shelf life of the solution and concentrate is 3 years, tablets - 5 years.
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Ginipral is a drug used to treat diseases of the urogenital organs.
Release form and composition
Ginipral is produced in the form of biconvex white round tablets, in blisters of 10 pcs. One tablet contains 500 mcg of hexoprenaline sulfate and excipients - magnesium stearate, lactose hydrate, copovidone, corn starch, glycerol palmitate stearate, disodium edetate dihydrate and talc.
Ginipral is also produced in the form of a colorless, transparent solution, in 2 ml ampoules. Each of them contains 10 mcg of hexoprenaline sulfate and excipients such as:
- Disodium edetate dihydrate;
- Sodium pyrosulfite;
- Sulfuric acid 2N;
- Sodium chloride;
- Water for injection.
Indications for use
Ginipral solution, according to the instructions, is used for acute, massive and prolonged tocolysis.
The drug in the form of tablets is prescribed in cases of threatened premature birth.
Contraindications
The use of Ginipral is contraindicated in myocarditis, thyrotoxicosis, arterial hypertension, angle-closure glaucoma, tachyarrhythmia, intrauterine infections, premature placental abruption, as well as in cases of hypersensitivity to the components that make up the drug.
Also, the drug is contraindicated in coronary heart disease, mitral valve disease, aortic stenosis, uterine bleeding, severe liver and kidney disease.
Ginipral is not prescribed in the first trimester of pregnancy, as well as during the period of breastfeeding.
Method of application and dosage
The drug in the form of a solution is administered intravenously slowly over 5-10 minutes using conventional infusion systems or automatically dosing infusion pumps. Before use, the agent is diluted in isotonic sodium chloride solution to 10 ml. The dosage of Ginipral in acute and massive tocolysis is 1 ampoule.
If contractions do not resume within 2 days, therapy is continued with Ginipral tablets, which are taken orally with a small amount of water. In cases of threatened preterm labor, patients take 1 tablet 1-2 hours before stopping the infusion of Ginipral.
Side effects
The instructions for Ginipral indicate that the drug can cause side effects from some body systems, namely:
- Intestinal obstruction, nausea, vomiting and a temporary increase in the level of transaminases (digestive system);
- Dizziness, slight tremor of the fingers, headache and anxiety (central and peripheral nervous system);
- Tachycardia in the mother, rhythm disturbance and cardialgia (cardiovascular system).
Ginipral can cause oliguria, increased sweating, edema, increased plasma glucose levels, hypocalcemia and hypokalemia at the beginning of therapy, as well as allergic reactions - bronchospasm, anaphylactic shock, difficulty breathing and impaired consciousness up to coma.
In newborns, the drug causes acidosis and hypoglycemia.
Symptoms of an overdose of Ginipral are headaches, severe tachycardia in the mother, increased sweating, arrhythmia, shortness of breath, anxiety, finger tremor, decreased blood pressure and cardialgia. In such cases, the appointment of non-selective beta-blockers is required.
special instructions
During the period of drug therapy, it is important to carefully monitor the functions of the cardiovascular system of the mother and fetus. It is recommended to record an ECG before and during treatment. The dose of Ginipral should be reduced if there is a marked decrease in blood pressure or a significant increase in heart rate in the mother.
If it is necessary to use Ginipral in patients with hypersensitivity to sympathomimetics, the dose of the drug should be minimal and selected individually, and therapy should be carried out under medical supervision.
Therapy with the drug should be stopped immediately in cases where the patient develops pain in the heart, difficulty breathing or signs of heart failure.
In mothers with diabetes at the beginning of treatment, it is necessary to monitor carbohydrate metabolism, since the use of Ginipral in most cases causes an increase in plasma glucose.
In cases where childbirth occurs after a course of treatment with the drug, it should be borne in mind that the newborn may develop acidosis and hypoglycemia associated with transplacental penetration of ketone and lactic acids.
It should be borne in mind that against the background of the use of Ginipral, diuresis may decrease, and therefore it is recommended to pay special attention to the appearance of symptoms indicating fluid retention in the body.
Analogues
Synonyms of the drug are not released. The analogue of Ginipral is the drug Partusisten.
Terms and conditions of storage
Ginipral, according to the instructions, should be stored in a well-ventilated, dry place, out of the reach of children and protected from light, at a temperature varying between 18-25 ° C.
From pharmacies, the drug is dispensed by prescription. The shelf life of the solution is three years, tablets - five years. After the expiration date, Ginipral must be disposed of.
INSTRUCTIONS
on the medical use of the drug
Ginipral
(GYNIPRAL)
Compound:
active ingredient: hexoprenaline;
1 tablet contains 0.5 mg hexoprenaline sulfate;
Excipients: lactose, corn starch, previously latinized starch, copovidone, Trilon B (Trilon B), talc, glycerol distearate, magnesium stearate.
Dosage form. Pills.
Pharmacotherapeutic group.
Means for use in gynecology. Sympathomimetics that suppress the contractile activity of the uterus. ATC code G02C A 05.
Indications.
The threat of premature birth (primarily as a continuation of other fusion therapy).
Contraindications.
Hypersensitivity to the components of the drug, hypersensitivity to sulfites; thyrotoxicosis; cardiovascular diseases, ischemic heart disease, arterial hypertension, cardiac arrhythmias occurring with tachycardia, myocarditis, mitral valve disease and idiopathic hypertrophic subaortic stenosis; severe liver and kidney disease; closed angle glaucoma; uterine bleeding, premature exfoliation of the placenta; internal uterine infections.
Dosage and administration
Apply orally. The tablets are swallowed whole with water.
1-2 hours before stopping the infusion of Ginipral, start taking the tablets.
Take first 1 tablet every 3 hours, then every 4-6 hours
(From 4 to 8 tablets of Ginipral per day).
Adverse reactions
Ginipral is usually well tolerated by patients.
While taking Ginipral, headache, anxiety, slight tremor of the fingers, sweating, palpitation, tachycardia, dizziness, and in rare cases, nausea, vomiting may develop.
Sometimes there may be redness of the skin.
Perhaps a slight increase in heart rate (HR), a decrease in blood pressure, especially diastolic.
Isolated cases of cardiac arrhythmia (ventricular extrasystole) and complaints of pain behind the sternum were recorded. These symptoms quickly disappear after discontinuation of the drug.
The level of sugar in the blood, especially in diabetes, increases due to the glycogenlytic action of the drug.
Diuresis decreases, especially at the beginning of treatment. Sometimes there was a temporary decrease in the level of potassium (at the beginning of treatment) and an increase in the concentration of transaminases in the blood serum.
During treatment with Ginipral, the intensity of intestinal motility may decrease. In rare cases, atony of the intestine was observed (it is necessary to control the regularity of the stool).
Newborns may experience hypoglycemia and acidosis, bronchospasm, anaphylactic shock.
Overdose.
Symptoms: severe tachycardia, tremor, headache, dizziness, increased sweating, arrhythmia, anxiety, cardialgia, lowering blood pressure, shortness of breath.
Treatment. Usually, to eliminate side effects, it is enough to reduce the dosage of the drug. To eliminate severe symptoms, the use of non-selective beta-blockers is recommended, which completely neutralize the effect of Ginipral.
Use during pregnancy or lactation.
Ginipral is prescribed for use during pregnancy (see section "Indications").
The drug is not prescribed for use during breastfeeding.
Children. The drug is not used in children.
Application features. During treatment, blood pressure, pulse, cardiac activity, and fetal heart rate should be constantly monitored.
Patients with hypersensitivity to sympathomimetics should use Ginipral in small doses, prescribed individually, under constant medical supervision.
With a significant increase in the heart rate in the mother (more than 130 beats / min) or / and a significant decrease in blood pressure, the dose should be reduced, if there are complaints of shortness of breath, pain in the heart area and if there are signs of heart failure, the drug should be discontinued.
In the treatment of patients with diabetes mellitus, it is necessary to monitor the metabolism of carbohydrates, since the use of Ginipral, especially at the initial stage of treatment, can cause an increase in blood sugar.
If childbirth occurs immediately after a course of treatment with Ginipral, it is necessary to take into account the possibility of hypoglycemia and acidosis in newborns due to the penetration of acidic metabolic products (milk and ketone compounds).
When using the drug, diuresis decreases, so it is necessary to control vata for symptoms associated with fluid retention in the body.
In some cases, the simultaneous use of corticosteroids with infusions of the drug can cause pulmonary edema. This is especially important in combined treatment with corticosteroids in patients with concomitant diseases that lead to fluid retention (kidney disease, early toxicosis of pregnant women).
Before starting tocolytic therapy, it is necessary to take potassium preparations, since with hypokalemia the effect of sympathomimetics on the myocardium is enhanced.
Simultaneous use of certain narcotic drugs (for example, halothane) and sympathomimetics can lead to cardiac arrhythmias; co-administration with these drugs should be avoided.
With prolonged tocolytic therapy, it is necessary to control the state of the fetoplacental complex and make sure that there is no placental abruption. Clinical symptoms of placental abruption can be smoothed against the background of tocolytic therapy.
With a rupture of the fetal bladder and with the opening of the cervix by more than 2-3 cm, the effectiveness of tocolytic therapy is low.
During tocolytic treatment with the use of beta-agonists, the symptoms of concomitant dystrophic myotonia may increase. In such cases, the use of diphenylhydantoin (phenytoin) preparations is recommended.
Patients with rare hereditary galactose intolerance, lactase deficiency or malabsorption of glucose-galactose should not use the drug.
In the process of tocolytic treatment, it is necessary to control the vata release of the intestines.
Coffee and tea can increase the side effects of Ginipral.
The ability to influence the reaction rate when driving vehicles or other mechanisms.
Some adverse reactions from the central nervous system in individual cases may affect the ability to drive vehicles or work with mechanisms.
Interaction with other drugs and other types of interactions.
Non-selective beta-blockers weaken or neutralize the effect of Ginipral.
Methylxanthine (for example, theophylline) enhances the effect of Ginipral.
The intensity of the accumulation of glycogen in the liver, caused by the use of corticosteroids, is reduced by the action of Ginipral.
The effect of oral hypoglycemic agents against the background of Ginipral therapy is weakened.
Co-treatment with certain sympathomimetic tics (cardiovascular and anti-asthma drugs) should not be carried out, as the effect of drugs on the cardiovascular system is enhanced and the risk of adverse reactions due to overdose increases.
Ginipral should not be used in conjunction with drugs containing ergot alkaloids, as well as with drugs containing calcium, vitamin D, dihydrotachysterol and mineral corticoids, as well as with MAO inhibitors, tricyclic antidepressants.
Means for general anesthesia (halothane) and adrenostimulants increase side effects from the cardiovascular system.
pharmacological properties.
Pharmacological
Ginipral is a selective beta-2 sympathomimetic that relaxes the muscles of the uterus. Under the influence of Ginipral, the frequency and intensity of uterine contractions decreases. The drug suppresses spontaneous, as well as oxytocin-induced labor pains. During childbirth, it normalizes very strong or irregular contractions. Under the influence of Ginipral, premature contractions in most cases stop, which allows you to extend the pregnancy until the normal term of delivery. Inhibition of labor pains is observed immediately after intravenous administration of the drug and lasts approximately 20 minutes. The effect of the drug is prolonged after the subsequent drip of the drug. Due to its beta-2 selectivity, Ginipral has little effect on the cardiac activity and blood flow of the pregnant woman and fetus.
Pharmacokinetics
The drug consists of two catecholamine groups, which in the human body undergo the process of methylation due to catecholamine-O-methyltransferase. If the action of isoprenaline is almost completely stopped by the introduction of one methyl group, hexoprenaline becomes biologically inactive only if both of its catecholamine groups are methylated. This property, as well as the high ability of Ginipral to adhere to the surface, is considered the reason for its long-term action.
When using hexoprenaline, during the first 4 hours, 80% of the active substances are excreted in the urine unchanged, that is, in the form of free hexoprenaline and monomethyl derivative. After this, the excretion of dimethyl derivative and related compounds (glucuronide and sulfate) increases. A small part is excreted in the bile in the form of complex metabolites.
pharmaceutical characteristics.
Basic physical and chemical properties: white, round, biconvex.
Best before date. 5 years.
Storage conditions. Store at a temperature not exceeding 25 º C, protected from light and out of the reach of children.
Package. 10 tablets in a blister. 2 blisters in a cardboard box.
Compound
Each 2 ml ampoule contains:
Active substance: hexoprenaline sulfate 0.01 mg.
Excipients: sodium metabisulfite (sodium disulfite) 0.04 mg, disodium edetate dihydrate 0.05 mg, sodium chloride 18.00 mg, sulfuric acid 1 M solution as needed to bring to pH 3.0, water for injection up to 2.00 ml Description: Clear, colorless solution.
Pharmacotherapeutic group: tocolytic agent - selective beta-adrenergic agonist.
ATC Code: G02 CA
Pharmacological properties
Pharmacodynamics
Selectively stimulates beta-adrenergic receptors, activates adenylate cyclase, followed by an increase in the formation of cyclic adenosine monophosphate (cAMP), which stimulates the calcium pump that redistributes calcium ions (Ca2+) in myocytes, resulting in a decrease in the concentration of the latter in myofibrils. Expands the bronchi, blood vessels, reduces the contractile activity and tone of the myometrium, thereby contributing to the improvement of uteroplacental blood flow. Stimulates glycogenolysis. Due to its beta-selectivity, Ginipral® has little effect on the cardiac activity and blood flow of the pregnant woman and the fetus.
Under the influence of the drug Ginipral®, the tone of the uterus decreases, the frequency and intensity of uterine contractions decrease, up to their complete cessation, which allows you to prolong the pregnancy, incl. before the start of timely (term) delivery. Ginipral®, when administered intravenously, inhibits spontaneous, as well as oxytocin-induced labor pains; normalizes excessively strong or irregular contractions during childbirth.
The tocolytic effect of Ginipral® begins immediately after intravenous injection and lasts approximately 20 minutes. The action of the drug is maintained by subsequent long-term intravenous infusion.
Pharmacokinetics
Distribution
There are no data on the distribution of hexoprenaline in the human body. In animal studies with intravenous administration, a significant concentration of hexoprenaline was observed in the liver, kidneys and skeletal muscles, to a lesser extent in the brain and myocardium. Metabolism
Hexoprenaline is metabolized by catechol-O-methyl-transferase into mono-3-O-methyl-hexoprenalip and di-3-O-methyl-hexoprenaline.
breeding
With intravenous administration, the half-life (T1 / 2) is about 25 minutes. Within 24 hours, about 44% of the dose of hexoprenaline is excreted by the kidneys and 5% through the intestines, within 8 days 54% and 15.5%, respectively. In the initial stage, free hexoprenaline and both methylated metabolites, as well as their corresponding sulfates and conjugates with glucuronic acid, are excreted by the kidneys. After 48 hours, only di-3-O-methyl-hexoprenaline is found in the urine. About 10% of the dose is excreted in the bile, mainly in the form of conjugates of O-methylated metabolites. Some reabsorption takes place in the intestine as less substance is excreted in the feces than is found in the bile.
Indications for use
For short-term treatment of uncomplicated preterm birth:
Stopping labor activity at a period of 22 to 37 weeks of pregnancy in patients without medical or gynecological contraindications to tocolytic therapy.
External turn (fetus) on the head. Use in emergencies with premature uterine contractions outside the hospital before transport to the hospital.
Dosage and administration
Instructions for using ampoules with a break point:
Position the tip of the ampoule point up! Gently tapping with your finger and shaking the ampoule, allow the solution to flow down from the tip of the ampoule.
Position the tip of the ampoule point up! Break off the tip in a downward direction, as shown in the figure.
Treatment with hexoprenaline should only be carried out by obstetricians/physicians experienced in the use of tocolytic drugs. It should be carried out in facilities adequately equipped to provide continuous monitoring of maternal and fetal health.
Hexoprenaline should be administered immediately after diagnosing preterm labor and examining the patient to determine the presence of contraindications to the use of hexoprenaline.
This procedure should include an adequate assessment of the state of the patient's cardiovascular system, with the control of cardiorespiratory function, checked using an electrocardiogram (ECG) during the entire period of treatment.
Dosage
in the short-term treatment of premature contractions with contraction and / or opening of the cervix:Initial dose: Start with a bolus of hexoprenaline 10 mcg IV over 5 to 10 minutes. A bolus can be obtained by adding the contents of 1 ampoule (10 µg hexoprenaline) to isotonic saline or glucose solution to a total volume of 10 ml. The initial dose should be followed by a continuous infusion of 0.3 micrograms of hexoprenaline per minute (see below). In addition, infusion therapy can be started without an initial bolus dose.
Long-term dose: begins with an infusion of 0.3 micrograms of hexoprenaline per minute. The rate of infusion should be doubled every 10 minutes until any signs of uterine contractions have disappeared for at least 24 hours, or until the mother's pulse reaches a frequency of 120 beats per minute.
Calculation of the rate of drip infusion at a dosage of 0.3 mcg / min.: 20 drops = 1 ml. A solution for long-term treatment may be prepared by adding the contents of 1 or more ampoules (25 μg hexoprenaline) to isotonic saline or glucose solution to a total volume of 500 ml.
The daily dose of hexoprenaline 430 mcg was exceeded only in isolated cases.
in the short-term treatment of preterm uncomplicated labor in the absence of contraction and/or dilatation of the cervix:The recommended maintenance dose is 0.075 micrograms of hexoprenaline per minute. Calculation of the rate of drip infusion at a dosage of 0.075 mcg / min.: 20 drops = 1 ml. A solution for long-term treatment may be prepared by adding the contents of 1 or more ampoules (25 μg hexoprenaline) to isotonic saline or glucose solution to a total volume of 500 ml.
Amount of hexoprenaline Total drops/min. ml/min.
25 mcg (1 ampoule) 500 ml 30 drops/min. 1.5 ml/min.
50 mcg (2 ampoules) 500 ml 15 drops/min. 1.5 ml/min.
external rotation (of the fetus) on the head / as an emergency measure for premature strong labor pains in a patient out of hospital before transport to the hospital:The initial dose is a bolus of 10 micrograms of hexoprenaline intravenously over 5 to 10 minutes. A bolus can be obtained by adding the contents of 1 ampoule (10 µg hexoprenaline) to isotonic saline or glucose solution to a total volume of 10 ml. If necessary, start a continuous dose with an infusion of 0.3 micrograms of hexoprenaline per minute (see Dosage for short-term treatment of preterm contractions with contraction and/or dilatation of the cervix).
The infusion should be increased by 0.05 mcg/min. every 10 minutes and titrated against uterine contractions and maternal pulse to achieve satisfactory tocolysis and maintain maternal heart rate below 120 beats/min.
Duration of treatment
According to the data, should not exceed 48 hours, since the main effect of tocolytic therapy is to delay labor up to 48 hours; no statistically significant effect on perinatal mortality or morbidity was observed in randomized controlled trials. This short delay can be used to implement other interventions designed to improve perinatal health.
Special precautions forinfusions
The dose must be selected on an individual basis, taking into account the suppression of contractions, increased heart rate and changes in blood pressure, which are limiting factors. During treatment, these parameters should be carefully checked. The maximum heart rate of the mother should not exceed 120 beats per minute. Careful control of hydration levels is very important to avoid the risk of maternal pulmonary edema. The volume of liquid in which the drug is administered should be kept to a minimum. You also need to use
infusion control device, preferably a syringe pump:
Contraindications
Hexoprenaline is contraindicated in the following cases:
Hypersensitivity to hexoprenaline or any of the excipients any condition less than 22 weeks gestation as a tocolytic agent in patients with pre-existing coronary artery disease or in patients with significant risk factors for development
ischemic heart disease.
Threatened abortion during the 1st and 2nd trimester any maternal or fetal condition in which prolongation of the pregnancy is dangerous, such as severe toxemia, intrauterine infection, vaginal bleeding from placenta previa, eclampsia or severe preeclampsia, placental abruption, or umbilical cord clamping intrauterine fetal death, known fatal congenital or chromosomal anomaly leading to death, severe liver and kidney disease, glaucoma.
Hexoprenaline is contraindicated in any pre-existing medical conditions with which a beta-mimetic would have an undesirable effect, such as pulmonary hypertension and heart disease such as hypertrophic obstructive cardiomyopathy or any other type of left ventricular outflow tract obstruction such as aortic stenosis .
Special instructions and special precautions for use
Treatment should be carried out in facilities that are adequately equipped to conduct continuous monitoring of the health of the mother and fetus.
If the membranes rupture or the cervical dilation is greater than 4 cm, tocolysis with beta-agonists is not recommended. In the case of tocolysis, hexoprenaline should be used with caution, and cardiorespiratory function and ECG monitoring should be monitored during the entire treatment.
The following control measures should be taken continuously for the mother and, when possible/appropriate, for the fetus:
Blood pressure and heart rate - ECG Electrolyte and fluid balance - to monitor pulmonary edema Glucose and lactate levels - with special attention to patients with diabetes mellitus Potassium levels - beta-agonists associated with a decrease in serum potassium, which increase the risk of developing arrhythmias ( see section 4.5).
Treatment should be discontinued if signs of myocardial ischemia develop (such as chest pain or ECG changes).
Hexoprenaline should not be used as a tocolytic in patients with significant risk factors or suspected pre-existing cardiac disease (eg, tachyarrhythmia, heart failure, or valvular heart disease). In preterm labor in patients with known or suspected heart disease, the cardiologist should evaluate the use of hexoprenaline prior to its intravenous infusion.
Pulmonary edema
Since pulmonary edema and myocardial ischemia have been reported during or after treatment of preterm labor with beta-agonists, fluid balance and cardiorespiratory function require special attention. Patients with predisposing factors, including multiple pregnancies, fluid retention, infection, and maternal preeclampsia, may be at increased risk of developing pulmonary edema.
Administration with a syringe pump, as opposed to intravenous infusion, will limit the risk of excess fluid. If signs of pulmonary edema or myocardial ischemia develop, the option of discontinuing treatment should be considered. This is especially
concerns combination therapy with the use of corticosteroids and in the presence of concomitant diseases (renal diseases, edema, proteinuria, hypertension-preeclampsia).
Blood pressure and frequency palpitations
Infusion of beta-agonists is usually accompanied by an increase in cardiac rhythm mother about 20 to 50 beats per minute. The mother's pulse should be monitored and the need to control this increase by dose reduction or discontinuation of the drug should be assessed on a case-by-case basis. In general, the mother's pulse should not exceed a steady rate of 120 beats per minute.
The patient's blood pressure may drop slightly during the infusion; it will affect diastolic pressure more than systolic. The decrease in diastolic pressure occurs, as a rule, in the range from 10 to 20 mm Hg. Art. The effect of the infusion on the fetal heart rate is less noticeable, but there may also be an increase to 20 beats per minute. To minimize the risk of hypotension associated with tocolytic therapy, pay particular attention to avoid compressing the vein during the infusion process by keeping the patient in the right or left lateral supine position.
Beta-agonists have been associated with an increase in blood glucose levels. Therefore, in diabetic mothers, blood glucose and lactate levels should be monitored and diabetes management adjusted accordingly to meet the needs of the diabetic mother during tocolysis.
If delivery occurs shortly after treatment with hexoprenaline, the newborn baby should be checked for signs of hypoglycemia, since hexoprenaline can lead to an increase in glucose and insulin in the mother's blood, as well as for possible hyperacidity due to the potential passage of acid metabolites through the placenta (lactate , ketone acids).
Hyperthyroidism
Hexoprenaline should be used with extreme caution in patients suffering from thyrotoxicosis and only after a careful assessment of the benefits and risks of treatment.
Hypersensitivity to sympathomimetics
During tocolytic therapy with beta-adrenergic agents, the intensity of signs of pre-existing dystrophic myotonia may increase.
In selected patients with hypersensitivity to sympathomimetics, hexoprenaline can only be used in low, individually selected doses, and with particularly careful medical supervision.
The pyrosulfite contained in the hexoprenaline solution for injection or its concentrate for solution for infusion rarely causes serious hypersensitivity reactions, as well as bronchospasm.
Interaction with other drugs and other forms of interaction
Halogenated anesthetics
Due to the additional antihypertensive effect, sluggish contraction of the uterus can lead to bleeding; in addition, when interacting with halogenated anesthetics, serious ventricular arrhythmias were reported due to an increase in cardiac reactivity.
If possible, 6 hours before any planned anesthesia with halogenated anesthetics, treatment should be stopped.
Corticosteroids
Systemic corticosteroids are often given during preterm labor to promote fetal lung development. There have been cases of pulmonary edema in women taking beta-agonists and corticosteroids at the same time.
Corticosteroids are known to increase blood glucose levels and can lead to a decrease in serum potassium levels, so co-administration should be carried out carefully, and due to the increased risk of hyperglycemia and hypokalemia, the patient's condition should be carefully monitored.
Antidiabetic drugs
The use of beta-agonists is associated with an increase in blood glucose levels, which can; be interpreted as a weakening of the antidiabetic therapy, but this may require adjustment of individual antidiabetic therapy.
Potassium excretion agents
Due to the hypokalemic effect of beta-agonists, it is known that the co-administration of potassium excreting agents increases the risk of hypokalemia, therefore, drugs such as diuretics, digoxin, methylxanthines and corticosteroids should be taken only after a careful assessment of the benefits and risks, taking into account the increased risk of cardiac arrhythmias resulting from hypokalemia.
Other forms of interaction
Non-selective P-blockers reduce the effectiveness or completely neutralize the beta2 agonist effect of hexoprenaline.
Sodium lysulfite is a highly active component, therefore it is not recommended to mix Ginipral® with other solutions, except for 0.9% sodium chloride solution or 5% glucose (dextrose) solution.
Use during pregnancy and breastfeeding
The drug Ginipral® is not prescribed until the 20th week and after the 37th week of pregnancy, as well as during lactation (breastfeeding). Within the indicated terms, the drug is used according to indications (see section "Indications for use").
Influence on the ability to drive vehicles and control mechanisms
During the period of treatment, care should be taken when driving vehicles and during classes in potentially hazardous activities that require an increased concentration of attention and speed of psychomotor reactions.
Side effect
Classification of adverse adverse reactions (ADRs) according to the frequency of development:
Very often (>1/10); often (>1/100,<1/10); нечасто (>1/1000, <1/100); редко (>1/10000, <1/1000); очень редко (<1/10000); частота неизвестна (невозможно оценить на основе имеющихся данных).
The most common side effects of hexoprenaline are associated with the pharmacological activity of beta-mimetics and can be limited or avoided by careful monitoring of hemodynamic parameters such as blood pressure and heart rate, as well as the necessary dose adjustment. As a rule, after cessation of therapy, they disappear.
Endocrine Disorders
Frequency unknown: lipolysis;
Metabolic and nutritional disorders
Frequency unknown: * hypokalemia ; ,
Rare: *hyperglycemia.
Nervous System Disorders
Very common: muscle tremor;
Heart disorders
Very often: * tachycardia;
Often: *increased heartbeat, *decrease in diastolic blood pressure;
Rarely: *cardiac arrhythmias, for example, atrial fibrillation, myocardial ischemia; Frequency unknown: increased cardiac output, increased systolic pressure, slight changes in fetal heart rate, complaints of angina pectoris.
From the side cardiovascular systems
Common: *hypotension
Rare: *peripheral vasodilation.
Respiratory, thoracic and mediastinal disorders Frequency unknown: *pulmonary edema.
Gastrointestinal disorders
Rare: nausea.
Skin and subcutaneous tissue disorders
Often: sweating;
Frequency unknown: reddening of the skin.
Other drugs for the treatment of gynecological diseases. Tocolytic drugs - sympathomimetics.
ATX code G02CA
Pharmacological properties
Pharmacokinetics
Ginipral® consists of two catecholamine groups, which in the human body undergo a methylation process via catecholamine-O-methyltransferase. While the action of isoprenaline is almost completely stopped by the introduction of one methyl group, hexoprenaline becomes biologically inactive only if both of its catecholamine groups are methylated. This property, as well as the high ability of Ginipral® to adhere to the surface, are considered the reasons for its long-term action.
After intravenous administration, after 4 hours, 80% of unchanged hexoprenaline and its monomethyl derivative are excreted in the urine. In a smaller volume and somewhat later, the excretion of dimethyl derivative and conjugated compounds (glucuronide and sulfate) occurs. A small part is excreted in the bile in the form of complex metabolites. After oral administration, part of the dose is excreted in the urine as a dimethylated metabolite.
Pharmacodynamics
Ginipral is a b2 - adrenomimetic that relaxes the muscles of the uterus. Reduces the frequency and intensity of uterine contractions. The drug inhibits spontaneous, as well as labor pains caused by oxytocin; normalizes excessively strong or irregular contractions during childbirth. Under the influence of Ginipral, premature contractions in most cases stop, which allows you to keep the pregnancy until the normal term of delivery. Due to its b2-selectivity, Ginipral® has little effect on cardiac activity and blood flow, both in the pregnant woman and the fetus.
Indications for use
Short-term inhibition of uncomplicated preterm labor:
Inhibition of labor pains between 22 and 37 weeks of gestation in patients without medical or obstetric contraindications to tocolytic therapy.
Before turning the fetus from the transverse position
Emergency measures for premature birth outside the hospital, before taking the pregnant woman to the hospital
Dosage and administration
The doses indicated below can only be considered as recommendations, as tocolysis requires individual adaptation to the specific needs of the patient.
Acute tocolysis
10 μg of Ginipral, diluted in 10 ml of isotonic sodium chloride solution or 5% glucose solution, is administered slowly intravenously over 5-10 minutes. If necessary, continue administration by intravenous infusion at a rate of 0.3 μg / min (see massive tocolysis).
If cramping pain persists, the infusion rate should be increased by 0.05 mcg / min every 10 minutes until satisfactory tocolysis is achieved, while the heart rate of a pregnant woman should not exceed 130 / min.
Massive tocolysis
The starting dose of Ginipral is 10 mcg, administered slowly intravenously, followed by intravenous infusion at a rate of 0.3 mcg / min. You can administer the drug at a rate of 0.3 μg / min and without prior intravenous injection.
If cramping pain persists, the infusion rate should be doubled every 10 minutes until satisfactory tocolysis is achieved, while the heart rate of a pregnant woman should not exceed 120 / min.
When administered using standard infusion systems, the drug is diluted in 500 ml of isotonic sodium chloride solution or 5% glucose solution. The solution is administered intravenously, 20 drops = 1 ml.
Dose calculation of 0.3 µg/min corresponds to:
The maximum daily dose is 430 mcg / day (exceeding the dose is possible only in exceptional cases).
When administered using standard infusion systems, the drug is diluted with isotonic sodium chloride solution or 5% glucose solution. The solution is injected intravenously, 20 drops = 1 ml, the infusion rate is 0.075 μg / min.
A dose calculation of 0.075 µg/min corresponds to:
If within 48 hours there is no resumption of contractions, Ginipral® can be administered orally in the form of tablets, a single dose of 0.5 mg.
A solution of the drug Ginipral® in isotonic sodium chloride solution or 5% glucose solution is prepared immediately before the use of infusion therapy.
During the period of tocolytic therapy, the volume of fluid entering the body (including ingestion) should not exceed 1500 ml per day.
Side effects
The frequency of side effects of the drug is regarded as follows: very frequent: (³ 1/10); frequent: (³ 1/100,< 1/10); нечастые: (³ 1/1000, < 1/100); редкие: (³ 1/10 000, < 1/1000); очень редкие: (< 1/10 000), не известно (оценка не может быть проведена по имеющимся данным)
Disorders from the endocrine system
Not Known: Lipolysis
Metabolic disorders
Common: *Hypokalemia
Uncommon: *Hyperglycemia (more pronounced in patients with existing diabetes mellitus)
Disorders from the nervous system
Very common: Involuntary muscle contractions
Not Known: Headache, dizziness, nervous agitation
Disorders from the cardiac system
Very common: *Tachycardia
Common: *Palpitations, decreased diastolic blood pressure
Rare: *Cardiac arrhythmias, eg atrial fibrillation, myocardial ischemia
Not known: Increased cardiac output, increased systolic blood pressure, small fluctuations in fetal heart rate, angina pectoris
Disorders from the vascular system
Common: *Hypotension
Rare: *Peripheral vasodilation
Respiratory system disorders
Uncommon: *Pulmonary edema
Gastrointestinal disorders
Rare: Nausea
Not known: Vomiting, intestinal inhibition, intestinal atony
Hepatobiliary system disorders
Not known: (transient) increase in serum transaminases
Skin and subcutaneous tissue disorders
Common: Excessive sweating
Not known: Skin redness
Urinary excretion system disorders
Not known: Decreased urine output (especially in the initial phase of treatment).
*These reactions have been reported in association with the use of short-acting beta-antagonists for obstetric indications and are considered class effects.
Allergic reactions may occur in connection with the sulfite content, especially in patients with asthma, which may manifest as nausea, diarrhea, shortness of breath, acute asthma attacks, confusion or shock. The course of such reactions can vary greatly from person to person and can even lead to life-threatening consequences.
Reporting possible adverse reactions. Reporting possible adverse reactions after registration of a medicinal product is very important. This will allow continued monitoring of the benefit/risk assessment of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions using the national reporting system
Contraindications
Hypersensitivity to the active substance or to any of the components of the drug
Any condition up to 22 weeks gestation
Ischemic heart disease or risk of coronary heart disease
1st and 2nd trimester of pregnancy
Any condition of the mother or fetus in which prolongation of pregnancy is hazardous to health
o severe toxemia, intrauterine infection, uterine bleeding due to placenta previa, eclampsia or severe preeclampsia, placental abruption or cord clamping
Intrauterine fetal death, proven lethal congenital or chromosomal defect incompatible with life
Patients with asthma associated with hypersensitivity to sulfites
Cardiac arrhythmias, myocarditis, mitral valve stenosis/insufficiency, aortic stenosis
Hyperthyroidism
Severe liver and kidney disease
Angle-closure glaucoma
Ginipral is also contraindicated when b-agonists have a negative effect on pulmonary hypertension and cardiovascular disease - in hypertrophic obstructive cardiomyopathy or any type of left ventricular outflow tract obstruction, such as aortic stenosis
Drug Interactions
Incompatibility
Sodium pyrosulfite is a highly active component, therefore it is not recommended to mix Ginipral with other solutions (with the exception of isotonic sodium chloride solution or 5% glucose solution).
Halogenated anesthetics
Due to the additional antihypertensive effect, there is an increased risk of uterine bleeding. There is a risk of ventricular arrhythmia due to an increase in cardiac reactivity when interacting with halogenated anesthetics. Treatment with Ginipral should be discontinued 6 hours before the planned anesthesia with halogenated anesthetics (halothane)
Corticosteroids
Cases of pulmonary edema have been reported in women with concomitant use of β-antagonists and corticosteroids. Corticosteroids are known to increase blood glucose levels and can lead to depletion of serum potassium levels, so concomitant use should be done with caution and continuous monitoring of the patient due to an increased risk of hyperglycemia and hypokalemia
Antidiabetic drugs
The introduction of b-blockers is associated with an increase in blood glucose levels, which can lead to both a weakening of anti-diabetic therapy; Therefore, adjustment in individualized antidiabetic therapy may be required.
Potassium Degrading Agents
Due to the potassium-destroying effect of β-blockers, the concomitant use of potassium-depleting drugs that increase the risk of hypokalemia, such as diuretics, digoxins, methylxanthines, and corticosteroids, should be used cautiously after careful assessment of the benefits and risks in patients with an increased risk of cardiac arrhythmias resulting from hypokalemia
Other interactions
Non-selective β-blockers weaken the effect of Ginipral or neutralize it. An increase in the store of glycogen in the liver due to the intake of glucocorticoids reduces the hypoglycemic effect of Ginipral
Simultaneous use of Ginipral with sympathomimetics used to treat bronchial asthma (Berotek, Salbutamol, Beclazon and others) or sympathomimetics for systemic use (Ephedrine, Isoprenaline and others) should be avoided, as this can cause increased cardiac activity and lead to overdose. With the simultaneous use of sympathomimetics and halothane, the development of cardiac arrhythmias is possible.
Ginipral® should not be used in combination with ergot alkaloids.
Ginipral® should not be used in conjunction with products containing calcium and vitamin D, or with dihydrotachysterol and mineralocorticosteroids.
special instructions
The decision to start treatment with Ginipral should be made after careful consideration of the risks and benefits of treatment.
Treatment should be carried out in clinics that are properly equipped and allow continuous monitoring of the mother and fetus. Tocolysis with the use of b-adrenergic agonists is not recommended for rupture of the fetal bladder and for the opening of the cervix by more than 4 cm.
When using Ginipral, you should monitor the blood pressure and pulse of the mother, as well as the heartbeat of the fetus. Monitoring of ECG and cardiac function is recommended before and during treatment.
Treatment should be discontinued if there are signs of myocardial ischemia (for example, chest pain or ECG changes). Ginipral® should not be used for tocolysis in patients with pre-existing heart disease and risk factors.
Pulmonary edema
Patients with risk factors including multiple pregnancies, fluid retention, infections, pre-eclampsia may be at increased risk of developing pulmonary edema. Syringe administration, as opposed to infusion, will limit the risk of fluid overload. If signs of fluid retention and symptoms of pulmonary edema appear, the drug should be discontinued. This is especially true in the case of combination therapy with corticosteroids and the presence of concomitant diseases (kidney disease, preeclampsia). You should also limit your dietary salt intake.
Blood pressure and heart rate
An increase in maternal heart rate of the order of 20 to 50 beats per minute usually accompanies the administration of beta-agonists. The mother's pulse should be monitored during drug administration, dose reduction and withdrawal.
As a rule, the maternal pulse should not exceed a steady rate of 120 beats per minute. Blood pressure may decrease during the administration of the drug; The effect of the drug is greater on diastolic pressure than systolic. Diastolic pressure falls, usually in the range of 10 to 20 mm Hg. The effect on fetal heart rate is less pronounced, but increases up to 20 beats per minute may occur.