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

Drotaverine is an isoquinoline derivative, in chemical structure and pharmacological properties close to papaverine, but has a more pronounced and prolonged act. Drotaverine has a pronounced antispasmodic effect on smooth muscle by the inhibition of phosphodiesterase-4 (PDE-4). PDE-4 hydrolyzes 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 the calcium-calmodulin complex, as a result of which the inactivated form of KLMC supports muscular relaxation of cAMP, in addition it affects the cytosolic calcium concentration by stimulating calcium transport into the extracellular space and the sarcoplasmic reticulum.

In vitro drotaverin inhibits the isoenzyme PDE-4 without inhibiting the isoenzymes PDE-3 and PDE-5, therefore the effectiveness of drotaverin depends on the activity of PDE-4, the content of which in different tissues is different. High content of PDE-4 is noted in the bile and urinary tract, uterus, gastrointestinal tract (GIT). The hydrolysis of cAMP in the myocardium and smooth muscles of blood vessels is mainly due to PDE-3, therefore drotaverine less affects the cardiovascular system.

Drotaverine is effective in spasms of smooth muscles of both neurogenic and muscular origin.

Pharmacokinetics:

With parenteral administration drotaverine quickly absorbed. Bioavailability is 100%. The maximum concentration in the blood plasma is reached after 30-40 minutes.

Drotaverin and / or its metabolites can penetrate insignificantly through the placental barrier.

The association with blood plasma proteins is 95-97%, mainly with albumin, gamma and beta globulins, and high-density lipoprotein (HDL).

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

The half-life period (T1 / 2) is 8-10 hours. For 72 hours it is almost completely eliminated from the body, more than 50% by the kidneys (mainly in the form of metabolites) and about 30% through the intestine. Unchanged drotaverine in the urine is not found.

Indications:

- spasms of smooth muscles associated with diseases of the biliary tract: cholecystolithiasis, cholangiolithiasis, cholecystitis, pericholecystitis, cholangitis, papillitis.

- spasms of smooth muscles of the urinary tract: nephrolithiasis, urethrolithiasis, pyelitis, cystitis, bladder tenesmus.

As an aid (when the dosage form: tablets can not be applied):

- with spasms of smooth muscles of gastrointestinal origin: peptic ulcer of stomach and duodenum, gastritis, spasms of cardia and pylorus, enteritis, colitis;

- with gynecological diseases: dysmenorrhea, severe labor contractions.

Contraindications:

- Hypersensitivity to the active substance or to any of the excipients of the drug.

- Hypersensitivity to sodium disulfite (see section "Special instructions").

- Severe hepatic and renal insufficiency.

- Severe chronic heart failure.

- Children under 18 years.

- Lactation period.

Carefully:

With arterial hypotension (risk of collapse), pregnancy.

Pregnancy and lactation:

As reproductive studies in animals and clinical studies have shown, the use of drotaverine during pregnancy had neither teratogenic nor embryotoxic effects.

In pregnant women, the drug Drotaverine It is possible only in cases where the potential benefit to the mother exceeds the potential risk to the fetus.

In connection with the lack of the necessary clinical data, during the lactation the drug is not recommended.

Dosing and Administration:

The dose is set individually. Adults usually use the drug intramuscularly, 2-4 ml (40-80 mg) 1-3 times a day.

To remove hepatic or renal colic, it is recommended to administer intravenously, slowly 40-80 mg.

Side effects:

Frequency: 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 - more 1/10000, including individual messages.

From the central nervous system: infrequently - headache, dizziness, insomnia.

From the cardiovascular system: infrequently - tachycardia, decrease arterial pressure, collapse (with intravenous administration).

From the digestive system: infrequently - nausea, constipation.

Allergic reactions: infrequently - angioedema, urticaria, skin rash, itching.

Overdose:

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:

Levodopa

Phosphodiesterase inhibitors like papaverine weaken the antiparkinsonian effect of levodopa (increased rigidity and tremor).

Papaverine, benzazole and other antispasmodics (including m-cholinolytics)

Drotaverin enhances the spasmolytic effect of papaverine, bendazole and other antispasmodics, including m-holinoblokatory.

Tricyclic antidepressants, quinidine and procainamide

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

Morphine

Reduces the spasmogenic activity of morphine.

Phenobarbital

Phenobarbital enhances the spasmolytic effect of drotaverine.

Special instructions:

When intravenously administered Drotaverina patient must be in a horizontal position (risk of collapse).

The drug contains disulfite, 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 disulfite, parenteral administration of the drug should be avoided (see "Contraindications").

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

During the treatment period, it is necessary to refrain from driving and other potentially hazardous activities,requiring an increased concentration of attention and speed of psychomotor reactions (within 1 h after parenteral, especially intravenous administration).

Form release / dosage:

Solution for intravenous and intramuscular 20 mg / ml.

Packaging:

By 2 ml or 4 ml of the drug in ampoules of light-protective, neutral glass.

5 ampoules are placed in a contour plastic package (tray) made of a polyvinylchloride film or a polyethylene terephthalate film.

Five ampoules are placed in a contour mesh box made of a polyvinylchloride film or a polyethylene terephthalate film and aluminum foil of a printed lacquered or packaging material.

2, 5 contour plastic packages (pallets) or contour mesh packages with ampoules of the preparation of 2 ml together with the instruction for use are placed in a pack of cardboard.

1, 2, 5 contour plastic packages (pallets) or contour mesh packages with ampoules of the preparation of 4 ml together with the instruction for use are placed in a pack of cardboard.

5, 10, 25 ampoules, together with the instruction for use, are placed in a pack with a separating cardboard insert.

Packing for hospitals

50, 100 contour plastic packages (pallets) or contour mesh packages together with instructions for use are placed in a box.

Storage conditions:

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

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-000608

Date of registration:21.09.2011

The owner of the registration certificate:BINERGIYA, CJSC BINERGIYA, CJSC Russia

Manufacturer: & nbsp

ALTAIR, LLC Russia

Information update date: & nbsp25.12.2015

Illustrated instructions

Instructions

Drotaverine (Drotaverine)