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

Active substance:
drotaverina hydrochloride	40.00 mg	80.00 mg
Excipients:
lactose monohydrate (milk sugar)	16.60 mg	33.20 mg
microcrystalline cellulose	20.00 mg	40.00 mg
corn starch	10.00 mg	20.00 mg
croscarmellose sodium	4.00 mg	8.00 mg
povidone-K25	3.50 mg	7.00 mg
magnesium stearate	0.90 mg	1.80 mg

Description:Round flat-cylindrical tablets from light yellow with a greenish shade to yellow with a greenish tint of color with a risk on one side and a facet.

Pharmacotherapeutic group:Spasmolytic agent

ATX: & nbsp

A.03.A.D.02 Drotaverine

Pharmacodynamics:

Drotaverine is an isoquinoline derivative, in chemical structure and pharmacological properties close to papaverine, but with a stronger and longer action. Drotaverine has a powerful antispasmodic effect on the smooth musculation due to inhibition of the enzyme phosphodiesterase (PDE).Enzyme phosphodiesterase is required for the hydrolysis of cAMP (cyclic adenosine-3 ', 5'-monophosphate) to AMP (adenosine-5'-monophosphate). Inhibition of enzyme phosphodiesterase leads to an increase in the concentration of cAMP, which triggers the following cascade reaction: high concentrations of cAMP activate cAMP dependent phosphorylation of light chain kinos of myosin (CMLC). Phosphorylation of CMLC leads to a decrease in its affinity for calcium ions, the Kalmodulin complex, as a result of which the inactivated form of CClM supports Muscular relaxation of cAMP, in addition it affects the cytosolic concentration of calcium ion by stimulating the transport of calcium ion into the extracellular space and the sarcoplasmic reticulum. This effect of drotaverin on lowering the cytosolic concentration of the calcium ion through cAMP explains its antagonistic effect with respect to the calcium ion.

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.PDE4 is the most important to suppress the contractile activity of smooth muscle, in connection with which the selective inhibition of PDE 4 could be useful for the treatment of hyperkinetic dyskinesias and various diseases accompanied by spastic conditions of the gastrointestinal tract. Hydrolysis of cAMP in the myocardium and vascular smooth musculature occurs mainly via isoenzyme PDE 3, which explains the fact that at high spasmolytic activity in drotaverine no serious side effects of heart and vascular n 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 It relaxes the smooth muscles of the gastrointestinal tract, biliary tract, urinary tract, blood vessels.

Due to its vasodilating action drotaverine improves the blood supply of tissues.

Pharmacokinetics:

Absorption

After oral administration drotaverine quickly and completely absorbed. Bioavailability is 100%.After presystemic metabolism, 65% of the accepted dose of drotaverine enters the systemic circulation. The maximum plasma concentration (C_m_Oh) is reached in 45-60 minutes.

Distribution

In vitro drotaverin has a high association with plasma proteins (95-97%), especially with albumin, γ and β-globulins.

Drotaverin is evenly distributed among the tissues, penetrates into the smooth muscle cells. Does not penetrate the blood-brain barrier. Drotaverine and / or its metabolites can penetrate insignificantly through the placental barrier.

Metabolism

In humans drotaverine almost completely metabolized in the liver by O-de-ethylation. Its metabolites are rapidly conjugated to glucuronic acid. The main metabolite is 4'-desotidrodeterin, in addition to which 6-deethyldrothaverin and 4'-desethyldovernavidine were identified.

Excretion

The half-life of drotaverin is 8-10 hours.

For 72 hours drotaverine almost completely eliminated from the body, more than 50% of the drug is excreted by the kidneys (mainly in the form of metabolites) and about 30% through the gastrointestinal tract (excretion in bile). Unchanged drotaverine in the urine is not found.

Indications:

- Spasm of smooth muscles in diseases of the bile ducts: cholecystolithiasis, cholangiolithiasis, cholecystitis, pericholecystitis, cholangitis, inflammation of the papilla of the duodenum;

- Spasm of smooth muscles in diseases of the urinary tract: nephrolithiasis, urethrolithiasis, pyelitis, cystitis, bladder spasm;

As an auxiliary therapy:

- with spasms of smooth muscles of the gastrointestinal tract: peptic ulcer of stomach and duodenum, gastritis, spasm of cardia and pyloric, enteritis, colitis, spastic colitis with constipation and irritable bowel syndrome with flatulence after exclusion of diseases manifested by the syndrome of "acute abdomen" (appendicitis, peritonitis, perforation of the ulcer, acute pancreatitis, etc.);

- with headaches of tension;

- with dysmenorrhea.

Contraindications:

- Pincreased sensitivity to drotaverine and / or excipients included in the formulation;

severe hepatic or renal insufficiency;

- severe heart failure (low cardiac output syndrome);

- the period of breastfeeding;

- Children's age (up to 6 years);

- hereditary lactose intolerance, lactase insufficiency or glucose / galactose malabsorption syndrome.

Carefully:

Arterial hypotension, pregnancy, simultaneous reception with levodopa.

Pregnancy and lactation:

According to animal experiments and retrospective studies of clinical data drotaverine does not have a teratogenic and embryotoxic effect. However, the use of the drug during pregnancy is recommended only after a careful weighing of the ratio of potential benefits for the mother and the possible risk to the fetus. It is not recommended to use the drug during breastfeeding.

Dosing and Administration:

Inside.

Adults: but 40 to 80 mg (1-2 tablets) 2-3 times a day. The maximum single dose is 80 mg, the maximum daily dose is 240 mg.

Children aged 6 to 12 years the maximum daily dose is 80 mg, divided into 2 divided doses.

Children over 12 years - the maximum daily dose is 160 mg, divided into 2-4 admission.

The recommended duration of treatment without a doctor's consultation is 1-2 days.

Side effects:

From the nervous system: headache, dizziness, insomnia.

From the cardiovascular system: heart palpitations, decrease blood pressure.

From the gastrointestinal tract: nausea, constipation.

From the immune system: allergic reactions (angioedema, urticaria, rash, itching).

Overdose:

Symptoms of overdose may be cardiac arrhythmias and conduction disorders (including a complete blockade of the bundle of the bundle), cardiac arrest, up to a lethal outcome.

Treatment: gastric lavage, symptomatic therapy.

Interaction:

FROM levodopa

With simultaneous application drotaverine can weaken the antiparkinsonian effect of levodopa, that is, to increase rigidity and tremor.

With other antispasmodic agents, included m-holinoblokatory

Mutual increase of spasmolytic effect.

With morphine

Reduces the spasmogenic activity of morphine.

With phenobarbital

Phenobarbital enhances the spasmolytic effect of drotaverine.

FROM tricyclic antidepressants, quinidine, procainamide

Increases the severity of lowering blood pressure caused by these drugs.

Drugs that significantly bind to plasma proteins (more than 80%)

Drotaverine is significantly associated with plasma proteins, mainly albumin, γ and β-globulins (see the section "Pharmacokinetics").

There are no data on the interaction of drotaverine with preparations that significantly bind to plasma proteins, but there is a hypothetical possibility of their interaction with drotaverin at the level of binding to protein (displacement of one of the drugs to another from the link with the protein and an increase in the concentration of free fraction in the blood of the drug with a less strong connection with protein), which hypothetically may increase the risk of pharmacodynamic and / or toxic side effects of this drug.

Special instructions:

Use of the drug with arterial hypotension requires increased caution. This form of the drug is contraindicated for patients with lactose intolerance, lactase deficiency, glucose malabsorption / galactose syndrome.

The use of the drug in children aged 6 years is strictly according to the indications and only according to the doctor's prescription.

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

When administered orally in therapeutic doses drotaverine does not affect the ability to drive vehicles and perform work that requires increased attention.In case of any side effects, the issue of driving or engaging in other potentially hazardous activities requires individual consideration. In case of dizziness after taking the drug, you should avoid practicing potentially dangerous activities, such as management, vehicles and working with mechanisms.

Form release / dosage:

Tablets 40.0 mg, 80.0 mg.

Packaging:

By 10, 14, 25, 30, 50 tablets into a contour cell pack of film polyvinylchloride and aluminum foil printed lacquered.

For 10, 20, 30, 40, 50 or 100 tablets in cans of polyethylene terephthalate or in polymer cans for medicines.

One jar or 1, 2, 3, 4, 5 or 10 contour mesh packages together with the instruction for use are placed in a cardboard package (bundle).

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.

Terms of leave from pharmacies:Without recipe

Registration number:LP-002834

Date of registration:23.01.2015

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Information update date: & nbsp29.11.2015

Illustrated instructions

Instructions

Drotaverine (Drotaverine)