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

Drotaverin is a derivative of isoquinoline, it is close in chemical structure and pharmacological properties to papaverine, but it has a more pronounced and prolonged effect. Drotaverine has a pronounced antispasmodic effect on smooth muscles due to inhibition of phosphodiesterase-4 (PDE-4).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 calcium ions - calmodulin complex, as a result of which the inactivated form of CLCAM supports muscular relaxation of cAMP, in addition, it affects the cytosolic concentration of calcium ions by stimulating the transport of calcium ions 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. 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 Effective in spasms of smooth muscles, both neurogenic and muscular.

Pharmacokinetics:

When parenteral administration is rapidly absorbed. Bioavailability - 100%.

The maximum concentration in the blood plasma is reached after 30-40 minutes.

Drotaverin and / or its metabolites can penetrate the placental 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 is 4'-desethyltraderin, the other metabolites are 6-deethyldrothaverin and 4'-deethyldrothaveraldin. The half-life (T 1/2) - 8-10 hours. For 72 hours almost completely removed from the body, more than 50% of 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 in diseases of the biliary tract: cholecystolithiasis, cholangiolithiasis, cholecystitis, pericholecystitis, cholangitis, inflammation of the papilla of the duodenum.

Spasm of smooth muscles in diseases of the urinary tract: nephrourolythiasis, urethrolithiasis, 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 gynecological diseases (dysmenorrhea).

In the conduct of some of the instrumental studies, including cholecystography.

Contraindications:

Hypersensitivity to the active ingredient or to any of the excipients of the drug, increased sensitivity to sodium disulfite (see section "Special instructions"), severe hepatic and renal insufficiency, severe chronic heart failure, childbirth period, breastfeeding period, children under 18 years of age .

Carefully:

With arterial hypotension (risk of collapse), pregnancy.

Pregnancy and lactation:

Application in pregnancy is possible only in cases where the potential benefit to the mother exceeds the potential risk to the fetus.

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

Dosing and Administration:

Adults: The daily average dose is 40-240 mg of drotaverine hydrochloride (divided by 1-3 doses per day) by intramuscular injection. In acute colic (renal or cholelithiasis) - 40-80 mg intravenously slowly (duration of administration is approximately 30 seconds).

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

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

From the digestive system: infrequently - nausea, constipation.

Allergic reactions: infrequently - angioedema, urticaria, rash, itching, anaphylactic shock.

Local reactions: rarely - reactions at the injection site.

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:

Relieves the antiparkinsonian effect of levodopa (increased rigidity and tremor). Enhances the spasmolytic effect of papaverine, bendazole and other antispasmodics, including M-holinoblokatory.

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

Reduces the spasmogenic activity of morphine.

Phenobarbital enhances the spasmolytic effect of drotaverine.

Special instructions:

When intravenously administered Drotaverina patient should be in a horizontal position in connection with the risk of development 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, parenteral drug disulfite should be avoided (see "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 dangerous activities that require an increased concentration of attention and speed of psychomotor reactions (within 1 hour after parenteral, especially intravenous administration).

Form release / dosage:

Solution for injection 20 mg / ml.

Packaging:

2 ml each in ampoules of light-protective glass.

For 10 ampoules with instruction for use and a knife for opening ampoules or a scarifier ampullum is placed in a box of cardboard.

5 or 10 ampoules are placed in a contoured cell pack of a polyvinylchloride film or polyethylene terephthalate tape and aluminum foil or paper with a polyethylene coating or without a foil, or without paper.

For 1 or 2 contour packs with instructions for use and a knife for opening ampoules or a scarifier ampullum is placed in a pack of cardboard.

When you pack the ampoules with a break ring or break point, the ampoule opener or ampoule scapper is not put in.

Storage conditions:

Store in a dark place at a temperature of 5 to 25 ° C.

Keep out of the reach of children.

Shelf life:

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

Terms of leave from pharmacies:On prescription

Registration number:P N000110 / 01

Date of registration:02.07.2013

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

Manufacturer: & nbsp

NOVOSIBHIMFARM, OJSC Russia

Information update date: & nbsp29.11.2015

Illustrated instructions

Instructions

Drotaverine (Drotaverine)