Drotaverine-darnitsa

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DROTAVERIN-DARNITSA (DROTAVERINE-DARNITSA)

Composition:

Active substance: drotaverine;

1 ml of solution contains 20 mg of drotaverine hydrochloride;

Excipients: ethanol (96%), sodium metabisulfite (E 223), water for injections.

Pharmaceutical form. Injection solution.

Main physicochemical properties: clear greenish-yellow or yellow liquid.

Pharmacotherapeutic group. Drugs used in functional gastrointestinal disorders. ATC code A03AD02.

Pharmacological properties.

Pharmacodynamics.

Drotaverine is an isoquinoline derivative that exerts a spasmolytic effect on smooth muscle by inhibiting the enzyme phosphodiesterase IV (PDE IV), leading to increased intracellular cAMP concentration. This results in inactivation of myosin light chain kinase (MLCK), thereby causing relaxation of smooth muscles.

In vitro, drotaverine inhibits the activity of PDE IV and also inhibits isoenzymes phosphodiesterase III (PDE III) and phosphodiesterase V (PDE V). PDE IV plays a significant functional role in reducing contractile activity of smooth muscles; therefore, selective inhibitors of this enzyme may be beneficial in treating diseases associated with hypermotility, as well as various disorders accompanied by gastrointestinal tract spasms.

In smooth muscle cells of the myocardium and blood vessels, cAMP is predominantly hydrolyzed by the isoenzyme PDE III. Thus, drotaverine acts as an effective spasmolytic agent without causing significant adverse effects on the cardiovascular system or exerting strong therapeutic effects on this system.

Drotaverine is effective against smooth muscle spasms of both neural and myogenic origin. It acts on the smooth musculature of the gastrointestinal, biliary, genitourinary, and vascular systems independently of their type of autonomic innervation. The drug enhances tissue blood flow due to its vasodilatory properties.

The effect of drotaverine is stronger than that of papaverine, with faster and more complete absorption, and it binds less extensively to plasma proteins. An additional advantage of drotaverine is that, unlike papaverine, it does not cause respiratory stimulation as a side effect following parenteral administration.

Pharmacokinetics.

Drotaverine is rapidly and completely absorbed and is highly bound (95–98%) to plasma proteins, particularly albumin, gamma-, and beta-globulins. After first-pass metabolism, 65% of the administered dose reaches systemic circulation unchanged. It is metabolized in the liver. The elimination half-life is 8–10 hours. Within 72 hours, drotaverine is almost completely eliminated from the body: more than 50% is excreted via urine and approximately 30% via feces. Drotaverine is mainly excreted in the form of metabolites; the unchanged compound is not detected in urine.

Clinical characteristics.

Indications.

Spasms of smooth musculature associated with biliary tract diseases such as cholelithiasis, choledocholithiasis, cholecystitis, pericholecystitis, cholangitis, papillitis;

Spasms of smooth musculature in urinary tract disorders: nephrolithiasis, ureterolithiasis, pyelitis, cystitis, urinary bladder tenesmus.

As an adjunctive treatment (when administration of the medicinal product in tablet form is not possible):

• in spasms of gastrointestinal tract smooth musculature: gastric and duodenal ulcers, gastritis, cardio- and/or pylorospasm, enteritis, colitis;
• in gynecological disorders (dysmenorrhea).

Contraindications.

Hypersensitivity to drotaverine or to any of the excipients of the medicinal product (particularly to sodium metabisulfite). Hypersensitivity to sodium disulfite. Severe hepatic, renal or cardiac insufficiency (low cardiac output syndrome).

Interaction with other medicinal products and other forms of interaction.

Concomitant use of the medicinal product with levodopa may reduce the antiparkinsonian effect of the latter. This combination should be used with caution, as the antiparkinsonian effect of levodopa decreases, while rigidity and tremor intensify.

Special precautions for use

When administering the medicinal product intravenously, the patient must be in a horizontal position due to the risk of collapse.

DROTAVÉRIN-DARNYTSIA should be used with caution in patients with arterial hypotension.

Caution should be exercised when administering the drug parenterally to pregnant women (see section "Use during pregnancy or breastfeeding").

DROTAVÉRIN-DARNYTSIA contains metabisulfite, which may cause allergic-type reactions, including anaphylactic shock and bronchospasm, in sensitive individuals, particularly those with a history of asthma or allergy.

In case of hypersensitivity to sodium metabisulfite, parenteral administration of the drug should be avoided.

Use during pregnancy or breastfeeding

Animal studies have shown no evidence of teratogenic or embryotoxic effects following oral administration of the drug. The medicinal product should be used during pregnancy only with caution. Drotaverine should not be used during labor.

Due to lack of adequate studies during breastfeeding, the use of the drug is not recommended.

Ability to influence reaction rate while driving or operating machinery

Patients should refrain from driving or operating machinery requiring high concentration during treatment (especially during intravenous administration) with the drug.

Dosage and method of administration.

DROTAVERIN-DARNYTSIA should be administered to adults by intramuscular injection at a daily dose of 40–240 mg given in 1–3 doses.

For acute colic, the medicinal product should be administered to adults by slow intravenous injection at a dose of 40–80 mg.

Children.

DROTAVERIN-DARNYTSIA must not be used in children.

Overdose.

Symptoms: overdose with drotaverine has been associated with cardiac arrhythmias and conduction disturbances, including complete bundle branch block of the His bundle and cardiac arrest, which may result in fatal outcomes.

Treatment: symptomatic and supportive therapy. In case of overdose, the patient must be under close medical supervision.

Adverse reactions.

Cardiovascular system: arterial hypotension, tachycardia, arrhythmia, atrioventricular block.

Nervous system: headache, dizziness, insomnia.

Gastrointestinal tract: nausea, vomiting, constipation.

Immune system: hypersensitivity reactions, including urticaria, skin rashes, dermatosis, pruritus, hyperemia, flushing, chills, increased body temperature, weakness, angioneurotic edema, bronchospasm, particularly in patients with sensitivity to metabisulfite. Cases of anaphylactic shock, with fatal and non-fatal outcomes, have been reported with the use of the injectable form.

DROTAVIRIN-DARNYTSIA contains metabisulfite, which may cause allergic-type reactions, including anaphylactic shock symptoms and bronchospasm in sensitive individuals, especially those with a history of asthma or allergy.

General disorders: hypersensitivity reactions at the injection site.

Shelf life.

3 years.

Storage conditions.

Store in the original packaging, protected from light, in a place inaccessible to children, at a temperature not exceeding 25 °C. Do not freeze.

Packaging.

2 ml in an ampoule; 5 or 10 ampoules in a blister pack; 1 blister pack in a carton.

Prescription status.

Prescription only.

Manufacturer.

JSC "Pharmaceutical Company "Darnitsya".

Manufacturer's address.

13, Borispilska Street, Kyiv, 02093, Ukraine.