Ginipral in pregnancy: instructions for use, side effects, analogs

Pregnancy is a very sensitive and responsible period in the life of every woman. During this period, medications can harm the developing child. The doctor will not always patiently and clearly explain to the expectant mother the advisability of using this drug, which, moreover, has many impressive side effects. And doubts arise - is it worth using Ginipral during pregnancy?

This is a drug that inhibits contractile activity of the uterine muscle layer and thus prolongs the period of intrauterine development of the fetus. Its active ingredient (hexoprenaline sulfate) belongs to the group of selective β-2 sympathomimetics.

Currently, Ginipral is one of the most frequently used drugs for prolonging pregnancy. Its effects have been well studied and are quite predictable, and measures have been developed that doctors take in the event of adverse reactions from the body of the expectant mother.

Ideally, during a normal pregnancy, the uterine muscles are relaxed throughout the entire period. However, in reality, modern expectant mothers often experience stress, suffer from chronic diseases, and lead an unhealthy lifestyle. In the last months of pregnancy, increased tone appears in women with a large fetus or those carrying twins. There are many reasons why the uterine muscles begin to actively contract. Hypertonicity of the uterus can cause premature delivery, in addition, unfavorable conditions are created for the development of the fetus - hypoxia, insufficient nutrition, from which, first of all, the central nervous system and its main organ - the brain - suffer.

In order to protect the child and his mother from these dangerous consequences of increased activity of the uterine muscles, the above-mentioned medicine is used.

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Indications ginipral in pregnancy

1. Short-term emergency therapy involving inhibition of preterm labor contractions (gestation period more than three months):
   • for transporting a woman in labor to a hospital;
   • suppression of contractions in a woman in labor during labor in cases of acute antenatal oxygen deficiency of the fetus, prolapse of the umbilical cord loops, and in some other situations that complicate the course of labor;
   • ensuring immobility and rest of the myometrium before medical manipulations (caesarean section, performed manually by turning the fetus head down).
2. Massive inhibition of preterm delivery with symptoms of a ripe cervix (shortened, smoothed or slightly open - up to two to three centimeters).
3. Long-term tocolytic therapy to prevent premature delivery in case of prolonged or massive hypertonicity without signs of readiness of the cervix for labor, ensuring immobility and rest of the myometrium before, during the process of cervical closure (cerclage) and after the procedure.

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Release form

It is produced in the form of tablets with a dosage of 500 mcg of hexoprenaline sulfate and a solution in ampoules containing 25 mcg; 10 mcg of the active substance.

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Pharmacodynamics

The active component of the medicine effectively relaxes the myometrium, as well as the muscles of the bronchi and bronchioles, stopping their spasms. This ingredient suppresses not only spontaneous contractions, but also premature contractions caused by oxytocin, which threaten miscarriage. Basically, the muscles of the uterus respond to the action of the medicine by relaxing, which contributes to the full bearing of the child.

During labor, it can be used as a means of coordinating labor activity (stopping abnormally strong and arrhythmic contractions).

Additionally, the drug is able to eliminate bronchospasm. Long-term therapy leads to normalization of bronchial secretion, normalization of blood gas composition and external respiration parameters. In addition, the effect of the active ingredient on the work of the heart muscle and blood circulation of the mother and child has been practically not revealed.

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Pharmacokinetics

Distribution in human tissues has not been studied sufficiently. It is known that high concentrations of the active substance are determined in the tissues of the liver, kidneys and skeletal muscles, and less significant concentrations are found in the brain parenchyma and cardiac muscle during intravenous infusion.

The cleavage process is catalyzed by catechol-O-methyltransferase. As a result, two metabolites are formed - mono- and di-3-O-methyl-hexoprenaline.

After intravenous administration, approximately 44% of the active substance is eliminated via the urinary tract and only 5% via the intestines within 24 hours. Then, over the course of eight days, the remaining portion is excreted via the same route and in the same proportions, as well as via the gall bladder (approximately 10%) in the form of O-methylated cleavage product compounds. At the initial stage of excretion, the free active substance and its metabolites are not detected in the urine, and after two days, only di-3-O-methyl-hexoprenaline can be detected there. Considering that the intestines excrete less hexoprenaline sulfate than is excreted via the biliary tract, it is possible to assume reabsorption of some of the administered Ginipral.

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Dosing and administration

The dosage given below is approximate, since the doses of Ginipral during pregnancy are calculated individually for each patient, taking into account the complex of indicators of her health condition and the reason for its prescription.

Short-term tocolysis in cases of ensuring a calm state of the myometrium before turning the fetus head-on, as well as before transporting a woman in labor with symptoms of the initial stage of premature labor to the hospital.

The medicine is injected into a vein by jet and slowly (over five to ten minutes), after one two-milliliter ampoule (10 mcg hexoprenaline sulfate) is dissolved in 10 ml of injection solution of NaCl (0.9%) or dextrose (5%). If necessary, the patient continues to receive the medicine by infusion through a dropper at a rate of 0.3 mcg/min.

The same scheme is used for short-term prevention of premature delivery in case of strong contractions of the uterine muscles and/or small (up to 2-3 cm) opening of the uterine os. As an alternative, Ginipral IV drip is used during pregnancy (rate 0.3 mcg/min) without a preceding jet injection.

To correctly set up the infusion device, take into account the ratio: 1 ml equals 20 drops.

To ensure the rate of administration of hexoprenaline sulfate of 0.3 mcg/min, the required number of ampoules are diluted in 500 ml of NaCl solution (0.9%) or dextrose (5%):

• when diluting one ampoule of 5 ml (25 mcg), the infusion rate should be set at 120 drops (6 ml) per minute;
• when diluting two 5 ml (50 mcg) ampoules, the infusion rate should be set at 60 drops (3 ml) per minute;
• when diluting three 5 ml (75 mcg) ampoules, the infusion rate should be set at 40 drops (2 ml) per minute;
• When diluting 4 ampoules of 5 ml (100 mcg), the infusion rate should be set at 30 drops (1.5 ml) per minute.

Brief tocolysis of a patient with moderate symptoms is performed by continuous drip infusion of 0.075 mcg hexoprenaline sulfate per minute. To ensure the required infusion rate, the prescribed number of ampoules are added to 500 ml of NaCl (0.9%) or dextrose (5%) solution:

• when diluting one 5 ml ampoule (25 mcg of active component in 500 ml of any specified solution), the infusion rate is set at 30 drops (1.5 ml) per minute;
• When diluting two 5 ml (50 mcg) ampoules, the infusion rate is set at 15 drops (0.75 ml) per minute.

The duration of drip tocolysis is determined depending on the degree of probability of premature delivery (tendency to shorten the time interval between contractions, degree of maturation of the cervix) and manifestations of its undesirable effects (hypotension, arrhythmia, tachycardia).

If contractions do not resume within two days, treatment can be continued with a tablet form of the drug. They are swallowed with water in the required amount. A tablet (0.5 mg) is taken an hour or two before the end of the drip administration. At first, with an interval of every three hours, then it is increased to four to six hours. Two to four milligrams of hexoprenaline sulfate are taken per day. The withdrawal is done gradually, reducing the dose by half a tablet every three days.

During pregnancy, a doctor may prescribe Ginipral in tablets if there is a mild threat of miscarriage, although in this case other medications are more often chosen.

Side effects are relieved as follows:

• Prescribe two or three tablets of valerian extract simultaneously with a dropper or tablets;
• Verapamil, which slows the pulse, is prescribed by a doctor.

Unpleasant symptoms will not necessarily be completely eliminated, especially with intravenous infusions. If negative effects are pronounced and not relieved by the indicated means, it is recommended to cancel this drug and prescribe another one.

The drug is intended specifically for pregnant women; it is not used during other periods, in particular, lactation.

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Consequences for the child

The results of randomization showed no significant effect of Ganipral therapy on perinatal mortality or morbidity during this period. It was concluded that the prevention of premature birth allows the extended period of gestation due to the use of this drug to be used for measures improving the health of newborns. However, long-term and frequent tocolysis with Ginipral leads to the fact that newborns experience increased blood acidity and, occasionally, hypoglycemia. Sometimes, after infusion, the fetal pulse increases (by about 20 beats per minute).

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Contraindications

1. Sensitization to any ingredient of this medicinal product.
2. Toxic goiter, increased production of thyroid hormone.
3. Cardiovascular pathologies, including hypertension, arrhythmia, tachycardia, aortic stenosis, and others.
4. Bronchial asthma sensitized to sulfuric acid derivatives.
5. Ocular and pulmonary hypertension.
6. Insulin-dependent diabetes mellitus.
7. Severe hepatic and renal dysfunction.
8. The inadvisability or danger of prolonging pregnancy.
9. Fetal distress syndrome not associated with uterine hypertonicity.
10. The first three months of pregnancy, the breastfeeding stage.
11. Traces of blood in the vaginal discharge of a pregnant woman.

It is not advisable to carry out tocolytic therapy if the integrity of the membranes of the fertilized egg is compromised or if the diameter of the opening of the cervix exceeds two to three centimeters.

When prescribing this medication, it is necessary to carefully weigh all the pros and cons in order to assess the predominance of benefits from its use. Treatment measures are carried out under conditions of the possibility of constantly monitoring the condition of the pregnant woman and her unborn child:

• monitor the work of the heart muscle (including ECG, blood pressure, pulse) and respiratory functions;
• water-salt balance;
• serum glucose and potassium levels, blood acidity;
• regularity of bowel movements.

Patients with hypokalemia are prescribed potassium replacement therapy.

The occurrence of pain in the heart area or changes in the electrocardiogram is a signal to stop tocolysis.

The presence of factors increasing the likelihood of developing pulmonary edema (multiple pregnancy, preeclampsia, plethora, infection) suggests the use of jet administration of the drug instead of drip administration.

During therapy with Ginipral, it is recommended to limit salt intake.

The drug also affects the muscles of the arterial wall and has vasodilating properties, which is why the patient and her unborn child have an increased pulse rate and decreased blood pressure.

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Side effects ginipral in pregnancy

The use of this medication most often causes complaints of:

• the occurrence of headaches, anxiety, restlessness, dizziness up to loss of consciousness, tremors of the fingers, rapid heartbeat;
• chest pain that goes away after stopping the drug infusion;
• digestive disorders - nausea, vomiting, constipation;
• increased sweating, skin hyperemia;
• oliguria;
• swelling (especially in women with impaired renal function), very rarely – pulmonary edema.

The results of the examination during the tocolysis period showed hypotension, hypokalemia, stimulation of lipolysis, and an increase in the serum level of liver transaminases.

In isolated cases, sulfates contained in the drug caused a sensitization reaction, including the development of shock (especially in patients with bronchial asthma).

If tocolysis with Ginipral is carried out on women in labor with diabetes mellitus immediately before delivery, it is necessary to monitor the presence of symptoms of glucose deficiency in the newborn, as well as blood acidification due to acidic metabolites overcoming the placental barrier.

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Overdose

The antidote is non-selective β-blockers.

Exceeding the dose is manifested by severe tachycardia, finger tremors, headache, hyperhidrosis, hypotension, shortness of breath. As a rule, it is sufficient to reduce the dose of Ginipral to relieve the symptoms of overdose.

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Interactions with other drugs

The result of this medicine:

• significantly reduced or completely eliminated when combined with other β-blockers;
• is enhanced in combination with medications containing methyl derivatives of xanthine (caffeine, euphyllin, theobromine);
• mutually enhances in combination with other sympathomimetics and the narcotic drug fluorothane (symptoms of heart problems and signs of overdose may occur).

In combination with glucocorticosteroids, glycogen accumulation in the liver decreases.

The effect of hypoglycemic drugs (oral) is reduced when used concomitantly with hexaprinoline sulfate.

Due to incompatibility, it is not recommended to use simultaneously with

Tricyclic antidepressants, MAO inhibitors, ergot alkaloids, mineralocorticoids, dihydrotachysterol, medications and vitamin-mineral complexes containing vitamin D and calcium.

Since the solution packaged in ampoules contains sulfuric acid, their contents must be mixed only with the solutions recommended in the instructions (NaCl (0.9%) and glucose (5%)).

To reduce the side effects of Ginipral on the heart, Verapamil tablets are prescribed, in particular - to normalize the rhythm and heart rate. The attending physician should tell you how to take Ginipral and Verapamil during pregnancy. These drugs are dosed individually depending on the condition of the expectant mother. It is only necessary to take into account that it is recommended to swallow a Verapamil tablet during a meal, and an hour later you can take Ginipral. If we are talking about infusion tocolysis, then it is carried out under the supervision of specialists who will make the necessary appointments.

Store tablets and ampoules in the original packaging for no more than three years, observing the temperature regime up to 25℃. Keep out of reach of children. Use the prepared infusion solution immediately.

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Ginipral analogues during pregnancy

Therapy for uterine hypertonicity, which can lead to premature birth, is very individual. Medicines are prescribed, and sometimes combined, only by a doctor, based on the examination data and complaints of the woman. Therefore, which drug to prescribe, Ginipral or Metacin during pregnancy, should be decided by a specialist. Ginipral is a specific drug that acts mainly on the myometrium, and quite significantly. Metacin has a wider spectrum of action, it is used for spasms of any internal organs, more often for chronic gastritis with high acidity and gastroduodenal ulcers, since it reduces the secretion of the gastric, as well as salivary and bronchial glands. Metacin has also found wide application as a tocolytic. Contraindications and side effects also overlap, since both cause similar effects. Therefore, when prescribing a drug, the doctor will be guided by the characteristics of the patient's anamnesis.

Magnesium salt of sulfuric acid or Magnesia is a good alternative to Ginipral, although its effect on the myometrium is more moderate. Magnesia is prescribed when the threat of premature birth is not so significant. Magnesium sulfate in tablets (Magnesium B6) can also be prescribed in the first trimester of pregnancy with the threat of miscarriage, when Ginipral is useless, since the receptors on which it acts, relaxing the myometrium, appear by the end of the third month of pregnancy. Magnesia, unlike the previous drugs, is indicated for gestosis. Therefore, the doctor will choose Ginipral or Magnesia based on the characteristics of a particular case. Sometimes these drugs are prescribed in one treatment regimen: the patient is given an IV with Magnesia on one day, and with Ginipral on the next. And although Magnesia is currently considered a weak tocolytic compared to more modern drugs, a recent meta-analysis (2009) concluded that the use of this drug in cases of threatened premature birth leads to a decrease in the incidence of cerebral palsy and neonatal mortality. However, even with seemingly innocent Magnesia, caution is necessary. Its overdose can cause respiratory paralysis. Calcium preparations act as an antidote in this case.

The calcium channel blocker Nifedipine or Corinfar, as practice shows, is not inferior to other tocolytics in efficiency. Its ability to relax smooth muscles in general, including in the uterus, is used. However, in the instructions for use, this "heart" drug is contraindicated during pregnancy. It is used when there is a threat of premature birth, when other tocolytics do not help or the expectant mother does not tolerate them. Practical observations indicate that the use of Nifedipine helps to reduce neonatal mortality. The drug itself has a relatively small number of side effects, and also - they do not occur too often and their strength is not great. True, the long-term effects of the use of Nifedipine in tocolytic therapy have not yet been properly studied. However, doctors are interested in the new quality of the drug and consider it promising.

Nifedipine is started to be used in the first half of pregnancy, when Ginipral is not yet effective, and then Ginipral therapy is often stopped. However, the safety of Nifedipine for the expectant mother and her unborn baby has not yet been proven, it is not yet recognized as an official tocolytic. The instructions do not recommend taking this drug during pregnancy. In addition, various studies have shown that the drug exhibits teratogenicity, embryotoxicity and fetotoxicity. Therefore, it should not be considered safe, especially in the first half of pregnancy. And a study conducted by the American National Heart Institute found that oral use of Nifedipine by people with heart disease (whom it should theoretically treat) increases their risk of stroke, heart attack and, thus, increases the likelihood of mortality. Therefore, the choice between tocolytic agents, Ginipral or Nifedipine, is definitely up to the doctor. And no self-treatment is appropriate in this case.

There are no completely safe drugs, you just need to have a good idea of what the consequences of taking them can be for a pregnant patient. With the help of all the listed drugs, it was possible to delay labor and prevent miscarriage. Many women gave birth to healthy babies and are grateful to doctors for their intervention.

Doctors' reviews, as usual, are ambiguous. They have instructions and recommendations on how to act in case of pregnancy complications, they have experience working with expectant mothers and experience using medications. There are even "favorite" medications. Many patients notice that a particular doctor likes to prescribe a particular drug, which he considers the most effective and safe. And it is often worth listening to the doctor's opinion. In addition, each expectant mother feels her condition and, if doubts arise whether it is worth taking pills at all, then there are several options - consult with another doctor. Get more rest, be less nervous. There are cases when one suppository with Papaverine relieved the tone of the myometrium and this condition did not return.

Whether or not to take Ginipral during pregnancy will be determined by your well-being, especially since this drug is intended for hospital conditions. Discuss your doubts with your doctor, if there are any, ask questions - the answer is born in the dialogue. So think with your head, be guided by your feelings and healthy children for you!