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

Drotaverin - an antispasmodic, isoquinoline derivative, is close in chemical structure and pharmacological properties to papaverine, but has a more pronounced and prolonged effect. The drug is effective in spasms of smooth muscles of both nervous and muscular etiology.Spasmolytic effect on smooth muscle is due to inhibition of phosphodiesterase, type 4 (PDE-4). PDE-4 hydrolyses cyclic adenosine monophosphate (cAMP) to AMP.Inhibition of PDE-4 leads to an increase in the concentration of cAMP, which activates the cAMP-dependent phosphorylation of light chain kinos of myosin (CMLC). Phosphorylation of CLIM leads to a decrease in its affinity for the Ca2 + calmodulin complex, as a result of which the inactivated form of KLMC supports muscular relaxation of cAMP, in addition it affects the cytosolic Ca2 + concentration by stimulating the Ca2 + 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, which explains the high activity of drotaverin as an antispasmodic in the absence of a pronounced effect on the cardiovascular system, since the hydrolysis of cAMP in the myocardium and smooth muscle of the blood vessels occurs mainly with using PDE-3. The content of PDE-4 in different tissues is different. The greatest effectiveness of the action of drotaverin is noted in the bile and urinary tract, uterus, gastrointestinal tract, in which the content of PDE-4 is high.

Pharmacokinetics:

When taken orally, it is quickly and completely absorbed in the gastrointestinal tract. It is exposed to the effect of "first passage" through the liver (the amount determined in the systemic circulation is 65 % of the dose). Time to reach the maximum concentration (TCmah) - 45-60 minutes.

The connection with plasma proteins is 95-97%, mainly with albumin, gamma and beta-globin, as well as high-density lipoproteins. Evenly distributed on the tissues, penetrates into the smooth muscle cells. It does not penetrate the hemato-encephalic barrier. Drotaverine and / or its metabolites can penetrate insignificantly through the placental barrier.

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

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

Indications:

- smooth muscle spasms, musculature associated with diseases of the biliary tract: cholelithiasis, cholecystitis, pericholecystitis, cholangitis, inflammation of the papilla of the duodenum;

- spasms of smooth muscles associated with diseases of the urinary system: urolithiasis, pyelitis, cystitis, bladder spasm.

As an auxiliary therapy:

- with spasms of smooth muscles of the digestive tract: peptic ulcer of the stomach and duodenum, gastritis, cardia and pyloric spasms, enteritis, colitis, spastic colitis with constipation and irritable bowel syndrome with meteorism;

- tensor headaches (tension headaches);

- Algodismenorea (pain in menstruation);

- to reduce excitability of the uterus during pregnancy (threatening miscarriage, threatening premature birth); spasm of the uterus pharynx during labor, prolonged opening of the throat, postnatal contractions;

- in the conduct of some instrumental studies, including cholecystography.

Contraindications:

- hypersensitivity to the components of the drug;

- lactose intolerance, lactase deficiency, glucose-galactose malabsorption;

- severe renal failure;

- severe hepatic impairment;

- severe heart failure;

- lactation period;

- Children's age under 3 years (for this dosage form).

Carefully:FROM caution should apply the drug with arterial hypotension (risk, further lowering blood pressure (BP)); during pregnancy.

Pregnancy and lactation:

Drotaverine does not have teratogenic and embryotoxic effects. However, the use of the drug during pregnancy is recommended only if the intended benefit to the mother exceeds the potential risk to the fetus.

Due to the lack of necessary clinical data drotaverine it is not recommended to appoint during the lactation period, during the treatment should stop breastfeeding.

Dosing and Administration:

Inside, regardless of food intake.

Adults on 40-80 mg up to 3 times a day, the maximum daily dose - 240 mg.

Children aged 3-6 years, 40-120 mg in 2-3 divided doses, the maximum daily dose - 120 mg; children 6-18 years - 80-200 mg in 2-5 receptions, the maximum daily dose - 240 mg.

Side effects:

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

From the side of the cardiovascular system: infrequently - a tachycardia, depression of a BP.

From the digestive system: infrequently - nausea, constipation.

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

Overdose:

Symptoms: may increase the side effects.

Treatment: abolition of the drug, gastric lavage; reception of activated carbon, giving the patient a horizontal position with raised legs, symptomatic treatment (measures aimed at maintaining blood pressure).

Interaction:

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

Reduces the spasmogenic activity of morphine.

Phenobarbital enhances the spasmolytic effect of drotaverine.

Special instructions:In patients with low and unstable blood pressure, treatment should be performed under the control of blood pressure.

Effect on the ability to drive transp. cf. and fur:When administered orally in therapeutic doses drotaverine does not affect the performance of potentially hazardous activities,requiring special attention and quick reactions (driving and other vehicles, moving machinery, dispatcher and operator work, etc.).

Form release / dosage:Tablets of 40 mg.

Packaging:

For 10 tablets, in a contour cell: packaging from a film of polyvinylchloride and aluminum foil printed lacquered.

2 or 5 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

For 200 contour mesh packages are placed in a group package with application instructions in an amount equal to the number of packages.

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 expiration date printed on the package.

Terms of leave from pharmacies:Without recipe

Registration number:P N001122 / 01

Date of registration:23.09.2011

The owner of the registration certificate:VALENTA PHARM, PAO VALENTA PHARM, PAO Russia

Manufacturer: & nbsp

VALENTA PHARMACEUTICS, JSC Russia

Information update date: & nbsp02.12.2015

Illustrated instructions

Instructions

Drotaverine (Drotaverine)