Drotaverine 20 mg/ml solution for intravenous and intramuscular injection

• spasms of smooth muscle in diseases of the biliary tract: cholecystolithiasis, cholangiolithiasis, cholecystitis, pericholecystitis, cholangitis, papillitis;

• spasms of smooth muscle in the urinary tract: urolithiasis (including nephrolithiasis, ureterolithiasis), pyelitis, cystitis, tenesmus of the bladder; as an adjunct therapy (when the tablet form cannot be used):

• for spasms of smooth muscle in the gastrointestinal tract: peptic ulcer disease of the stomach and duodenum, gastritis, spasm of the cardia and pylorus, enteritis, colitis, irritable bowel syndrome;

• in gynecological diseases: dysmenorrhea;

• during certain instrumental studies, including cholecystography

Method of Administration and Dosage

Administer intramuscularly 2-4 ml (40-80 mg) 1-3 times a day. The course of treatment is 1-2 weeks. If prolonged treatment is necessary, switch to oral administration of the drug in tablet form.
In cases of acute colic (renal or biliary colic) - 2-4 ml (40-80 mg) in 10-20 ml of 0.9% sodium chloride solution or 5% dextrose solution intravenously slowly (duration of administration about 30 seconds).
Do not mix in the same syringe with aminophylline solution.

Section: Composition

Active ingredient: drotaverine hydrochloride – 20.0 mg.
Excipients: sodium disulfite (sodium metabisulfite), ethanol 95%, disodium edetate, water for injections.

A clear or slightly opalescent liquid ranging from light yellow to yellow or yellowish-green in color.

• hypersensitivity to the active substance or any of the excipients of the drug;

• hypersensitivity to sodium disulfite (see "Special Instructions");

• severe liver or kidney failure;

• severe chronic heart failure;

• AV block of grade II-III;

• childhood (the use of drotaverine in children has not been studied in clinical trials);

• the period of labor;

• the breastfeeding period.

With caution

• in case of arterial hypotension (risk of collapse, see "Special Instructions");

• in case of pronounced atherosclerosis of the coronary arteries;

• in case of prostate adenoma;

• in case of glaucoma;

• during pregnancy (see "Use during pregnancy and breastfeeding").

Special Instructions

The preparation contains sodium disulfite (sodium metabisulfite), which may cause allergic reactions, including anaphylactic symptoms and bronchospasm in sensitive individuals, especially in those with a history of asthma or allergic diseases. In case of increased sensitivity to sodium disulfite, parenteral use of the preparation should be avoided (see "Contraindications").
When administering drotaverine intravenously, patients with low blood pressure should be in a horizontal position due to the risk of collapse.

Section: Side Effects

From the immune system: allergic reactions (angioedema, urticaria, rash, itching, anaphylactic shock) (see "Contraindications").
From the nervous system: headache, dizziness, insomnia.
From the heart and blood vessels: tachycardia, decreased blood pressure, arrhythmia, collapse (with intravenous administration).
From the gastrointestinal tract: nausea, vomiting, constipation.
General disorders and conditions at the injection site: reactions at the injection site, feeling of heat, sweating.

Section: Overdose

In case of overdose, an increase in dose-dependent side effects is possible.
Symptoms: atrioventricular block, cardiac arrest, paralysis of the respiratory center.
Treatment: in the event of an overdose, patients should be under careful medical supervision and should receive symptomatic therapy and treatment aimed at maintaining the body's vital functions.

Interaction

With levodopa
Phosphodiesterase inhibitors, such as papaverine, weaken the antiparkinsonian effect of levodopa. When drotaverine is prescribed simultaneously with levodopa, there may be an increase in rigidity and tremor.
With papaverine, bendazole, and other antispasmodics (including m-cholinolytics)
Drotaverine enhances the antispasmodic effect of papaverine, bendazole, and other antispasmodics, including m-cholinoblockers.
With tricyclic antidepressants, quinidine, and procainamide
Increases hypotension caused by tricyclic antidepressants, quinidine, and procainamide.
With morphine
Reduces the spasmogenic activity of morphine.
With phenobarbital
Phenobarbital enhances the antispasmodic effect of drotaverine.

Pharmacodynamics

The pharmacological properties are similar to papaverine, but with a more pronounced and prolonged effect. Drotaverine has a pronounced spasmolytic effect on smooth muscles due to the inhibition of the enzyme phosphodiesterase-4 (PDE-4). The enzyme PDE-4 is necessary for the hydrolysis of cyclic adenosine monophosphate (cAMP) to adenosine monophosphate (AMP). Inhibition of the PDE-4 enzyme leads to an increase in cAMP concentration, which triggers the following cascade reaction: high concentrations of cAMP activate cAMP-dependent phosphorylation of myosin light chain kinase (MLCK). Phosphorylation of MLCK leads to a decrease in its affinity for calcium ions - calmodulin complex, resulting in the inactivated form of MLCK maintaining muscle relaxation. In addition, cAMP affects the cytosolic concentration of calcium ions by stimulating the transport of calcium ions into the extracellular space and the sarcoplasmic reticulum. This calcium-lowering effect of drotaverine through cAMP explains the antagonistic effect of drotaverine on calcium ions. In vitro, drotaverine inhibits the isoenzyme PDE-4 without inhibiting the isoenzymes PDE-3 and PDE-5, therefore the effectiveness of drotaverine depends on the concentrations of PDE-4 in tissues, the content of which varies in different tissues. High content is noted in the bile and urinary tracts, uterus, and gastrointestinal tract. PDE-4 is most important for suppressing the contractile activity of smooth muscle, which is why selective inhibition of PDE-4 may be useful for treating hyperkinetic dyskinesias and various diseases accompanied by spastic conditions of the gastrointestinal tract (GIT). The hydrolysis of cAMP in the myocardium and smooth muscles of blood vessels occurs mainly through PDE-3, which explains the fact that despite high spasmolytic activity, drotaverine has no serious side effects on the heart and blood vessels and pronounced effects on the cardiovascular system. Drotaverine is effective in spasms of smooth muscles of both neurogenic and muscular origin. Regardless of the type of autonomic innervation, drotaverine relaxes the smooth muscles of the GIT, bile ducts, and urogenital system.

Section: Pharmacokinetics

Bioavailability 100%. Drotaverine and its metabolites can cross the placental barrier. It does not cross the blood-brain barrier. Plasma protein binding is 95-97%. It is almost completely eliminated from the body within 72 hours.
When administered parenterally, the effect of the drug manifests within 2-4 minutes. The maximum effect occurs after 30 minutes. It is gradually released from binding to plasma proteins, providing a prolonged effect. The half-life is 2-4 hours.
Metabolism occurs in the liver, with the majority of metabolites excreted by the kidneys. Drotaverine is almost completely metabolized by O-desethylation. Its metabolites quickly conjugate with glucuronic acid. The main metabolite is 4'-desethyldrotaverine, in addition to which 6-desethyldrotaverine and 4'-desethyldrotaveraldine have been identified.