Drotaverin - instructions for use, dose, side effects, contraindications

Drotaverin is a myotropic antispasmodic. The isoquinoline derivative, in chemical structure and pharmacological properties, is close to papaverine, but has a more pronounced and prolonged effect.

Drotaverine reduces the intake of calcium ions in the smooth muscle cells and has a powerful spasmolytic effect on smooth muscles due to selective inhibition of the enzyme phosphodiesterase type 4 (PDE-4) and intracellular accumulation of cAMP.

The enzyme PDE-4 hydrolyses cyclic adenosine monophosphate (cAMP) to adenosine monophosphate (AMP). Inhibition of PDE-4 leads to an increase in the concentration of cAMP, which activates cAMP-dependent phosphorylation of myosin light chain kinase (CMLC). Phosphorylation of CMLC leads to a decrease in its affinity for Ca²⁺-kalmodulin complex, as a result of which the inactivated form of CLCM supports muscular relaxation.

In addition, cAMP affects the cytosolic concentration of Ca²⁺ due to the stimulation of transport of Ca²⁺ in the extracellular space and sarcoplasmic reticulum. This effect of drotaverin on lowering the cytosolic concentration of Ca²⁺ through cAMP, explains the antagonistic effect of drotaverine in relation to Ca²⁺.

In vitro drotaverin 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 differs in different tissues. High content of PDE-4 is noted in the bile and urinary tract, gastrointestinal tract (GIT), uterus.

PDE-4 is most important for suppressing the contractile activity of smooth muscles,in connection with which selective inhibition of PDE-4 is useful for the treatment of hyperkinetic dyskinesias and various diseases accompanied by a spastic condition of the gastrointestinal tract.

The hydrolysis of cAMP in the myocardium and smooth musculature of the vessels occurs mainly with the help of the isoenzyme PDE-3, which explains the fact that with high spasmolytic activity, drotaverin has no pronounced therapeutic effects and adverse reactions to the cardiovascular system.

Drotaverin effectively eliminates spasms of smooth muscles of neurogenic and muscular etiology. Regardless of the type of autonomic innervation drotaverine relaxes the smooth muscles of the gastrointestinal tract, biliary tract, urogenital system.

Pharmacokinetics:

When parenteral administration is rapidly absorbed. Bioavailability is 100%. The onset of the drug - in 2-4 minutes. The maximum concentration in the blood plasma is reached after 30-40 minutes.

Drotaverin and / or its metabolites can penetrate the placental barrier. Does not penetrate the blood-brain barrier.

The connection with blood plasma proteins is 95-97%, mainly with albumin, gamma and beta globulins, as well as high density lipoproteins.

Almost completely metabolized in the liver by O-de-ethylation. Metabolites are rapidly conjugated with glucuronic acid. The main metabolite - 4-dezetildrotaverin other metabolites - 6-dezetildrotaverin and 4'-dezetildrotaveraldin.

Half-life (T_1/2) . - For 8-10 h 72 h almost completely excreted over 50% kidney (primarily as metabolites) and about 30% through the intestine. Unchanged drotaverine in the urine is not found.

Indications:

- Spasms of smooth muscle in diseases of the biliary tract: cholecystitis, cholecystolithiasis, cholangiolithiasis, pericholecystitis, cholangitis, an inflammation of duodenal papilla (papillitis).

- Spasms of smooth muscle in diseases of the urinary tract: nefrourolitiaz, uretrolitiaz, pyelitis, cystitis, bladder spasm.

- As an aid (When the dosage form is a tablet can not be used): spasm of smooth muscles of the gastrointestinal tract (stomach and duodenal ulcer disease, gastritis, spasms of cardia and pylorus, enteritis, colitis, irritable bowel syndrome with constipation and irritable bowel syndrome with bloating); with gynecologicaldiseases (dysmenorrhea).

- In carrying out some instrumental studies, including cholecystography.

Contraindications:

- Hypersensitivity to the active substance or to any of the components of the drug; hypersensitivity to sodium metabisulphite (see section "Special instructions").

- Severe hepatic and / or renal failure.

- Severe chronic heart failure.

- AV-blockade II-III degree.

- Period of delivery.

- Breastfeeding period.

- Children under 18 years.

Carefully:

With severe atherosclerosis of the coronary arteries, prostate adenoma, glaucoma, arterial hypotension (risk of collapse), pregnancy.

Pregnancy and lactation:

The use of the drug during pregnancy is possible only in cases where the potential benefit to the mother exceeds the potential risk to the fetus.

The drug should not be used during labor (the potential risk of postpartum atonic bleeding).

If you need to use the drug during lactation, you must stop breastfeeding.

Dosing and Administration:

Intravenous and intramuscular.

Adults: the average daily dose is 40-240 mg drotaverina hydrochloride (2-12 ml solution), divided into 1-3 doses per day, intramuscularly.

In acute colic (renal or cholelithiasis) - 40-80 mg (2-4 ml of solution) is intravenously striated slowly (duration of administration is approximately 30 seconds).

Side effects:

The frequency of unfavorable adverse reactions is given in accordance with the WHO classification: very often more than 1/10, often more than 1/100 and less than 1/10, infrequently more than 1/1000 and less than 1/100, rarely more than 1/10000 and less than 1/1000, very rarely - less than 1/10000, including individual messages.

From the central nervous system:

rarely - headache, dizziness, insomnia.

From the side of the cardiovascular system:

rarely - arrhythmia, tachycardia, lowering blood pressure, collapse (with intravenous administration).

From the digestive system:

rarely - nausea, vomiting, constipation.

Allergic reactions:

rarely - angioedema, urticaria, rash, itching; individual reports - anaphylactic shock.

Local Reactions:

rarely - reactions at the injection site.

Overdose:

In case of an overdose, dose-dependent side effects may be increased.Overdose of drotaverine can lead to heart rhythm and conduction disorders, including a complete blockade of the bundle's legs and cardiac arrest, which can be fatal.

In case of an overdose, patients should be under close medical supervision and should be given symptomatic therapy and treatment aimed at maintaining the basic functions of the body.

Interaction:

The drug weakens the antiparkinsonian effect of levodopa (increased rigidity and tremor).

Enhances the spasmolytic effect of papaverine, bendazole and other antispasmodics, including m-holinoblokatory (atropine, platyphylline, scopolamine, pirenzepine, trihexyphenidyl).

Increases the risk of arterial hypotension caused by tricyclic antidepressants, quinidine and procainamide (novocaineamide).

Reduces the spasmogenic activity of morphine.

Phenobarbital enhances the spasmolytic effect of drotaverine.

Special instructions:

With intravenous administration of the drug, the patient should be in a horizontal position in connection with the risk of developing a collapse.

The drug contains metabisulphite, which can cause allergic reactions,including anaphylactic symptoms and bronchospasm in predisposed patients, especially in patients with bronchial asthma or a history of allergic anamnesis. In case of hypersensitivity to metabisulphite, parenteral administration of the drug should be avoided (see the section "Contraindications").

Effect on the ability to drive transp. cf. and fur:

During the period of treatment, it is necessary to refrain from driving vehicles and practicing other potentially hazardous activities that require an increased concentration of attention and speed of psychomotor reactions (within 1 hour after parenteral administration, especially intravenously).

Form release / dosage:Solution for intravenous and intramuscular injection, 20 mg / ml.

Packaging:

For 2 ml, 4 ml of the drug into the ampoules of the light-protective glass.

10 ampoules are placed in a box of cardboard.

5 ampoules are placed in a contour mesh box made of polyvinyl chloride film and aluminum foil printed lacquered, or without foil.

1 or 2 contour mesh packages are placed in a pack of cardboard.

In each pack, the box is attached instructions for use, the ampullar scarifier.

Ampoule scapper does not invest in case of using ampoules with a kink ring or with an incision and a point.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 of the year.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003415

Date of registration:18.01.2016

Expiration Date:18.01.2021

The owner of the registration certificate:SYNTHESIS, OJSC SYNTHESIS, OJSC Russia

Manufacturer: & nbsp

SYNTHESIS, OJSC Russia

Representation: & nbspSYNTHESIS JSC Joint-Stock Kurgan Society of Medical Preparations and Products SYNTHESIS JSC Joint-Stock Kurgan Society of Medical Preparations and Products Russia

Information update date: & nbsp04.08.2016

Illustrated instructions

Instructions

Drotaverine (Drotaverine )