But-shpa forte - instructions for use, dose, side effects, contraindications

Drotaverin is a derivative of isoquinoline, a chemical structure and pharmacological properties close to papaverine, but possessing a stronger and longer action. Drotaverine has a powerful spasmolytic effect on smooth muscle by inhibiting the enzyme phosphodiesterase (PDE).The phosphodiesterase enzyme is necessary for the hydrolysis of cAMP (cyclic adenosine-3 ', 5'-monophosphate) to AMP (adenosine-5'-monophosphate). Inhibition of the 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 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. cAMP, in addition, affects the cytosolic concentration of the 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 the Ca²⁺ through cAMP explains its antagonistic effect in relation to Ca²⁺.

In vitro drotaverin inhibits the isoenzyme PDE IV without inhibiting the isoenzymes PDE III and PDE V. Therefore, the effectiveness of drotaverine depends on the concentrations of PDE IV in tissues, the content of which varies in different tissues. PDE IV is most important for Suppression of contractile activity of smooth muscles,therefore selective inhibition of PDE IV can be 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 is mainly due to the isoenzyme PDE III, which explains the fact that with high spasmolytic activity, drotaverin has no serious side effects from the heart and vessels and the 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:

Compared with papaverine drotaverine when ingested faster and more fully absorbed from the gastrointestinal tract. Absorption is 100%. However, after metabolism at the "first passage through the liver," 65% of the blood flow enters the systemic circulation,the accepted dose. The maximum plasma concentration (C_max) is reached in 45-60 minutes.

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

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'-desethyltraderin, in addition to which 6-desethyltraverin and 4'-desethyldutaveraldine have been identified.

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:

- Spasms of smooth muscles in diseases of the biliary tract: cholecystolithiasis, cholangiolithiasis, cholecystitis, pericholecystitis, cholangitis, inflammation of the papilla of the duodenum.

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

As an auxiliary therapy:

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

- with tensor headaches (headaches of tension);

- with algodismenorrhea.

Contraindications:

- Hypersensitivity to drotaverine and / or excipients included in the preparation.

- Pronounced hepatic or renal insufficiency.

- Severe heart failure (reduction of cardiac output).

- The period of breastfeeding (see the section "Pregnancy and lactation period").

- Children's age (clinical studies in children were not performed).

- Hereditary lactose intolerance, lactase deficiency, galactosemia or glucose / galactose malabsorption syndrome (due to the presence of lactose in the formulation) (see "Special instructions").

Carefully:

- With arterial hypotension.

- In pregnant women (see.section "Pregnancy and lactation period").

Pregnancy and lactation:

For a limited number of retrospective data on the use of the drug in humans and animal studies, when taking drotaverine inside, there is no evidence of teratogenic or embryotoxic effects, as well as adverse effects on the course of pregnancy. Despite this, when using the drug in pregnant women, care should be taken and prescribing the drug only after a careful weighing of the ratio of benefit and risk to the mother and the risk to the child.

Studies on the excretion of drotaverine in breast milk have not been conducted in animals. Due to the lack of such studies in animals and clinical data, prescribe drotaverine in the lactation period is not recommended.

Dosing and Administration:

The drug is taken internally. Usually the average daily dose is 120-240 mg (the daily dose is divided into 2-3 doses).

Side effects:

The following side effects, which in clinical studies were regarded as at least possibly associated with drotaverine,are given in accordance with the following gradations of the frequency of their occurrence: very often (> 1/10), often (> 1/100, <1/10); rarely (> 1/1000, <1/100); sometimes (> 1/10000, <1/1000); very rarely (including individual messages) (<1/10000); an unknown frequency (it is impossible to determine the frequency of occurrence according to available data) and grouped according to organ systems.

From the nervous system

- Sometimes: headache, dizziness, insomnia.

From the side of the cardiovascular system

- Sometimes: heart palpitations, lowering blood pressure.

From the gastrointestinal tract

- Sometimes: nausea, constipation.

From the immune system

- Sometimes - allergic reactions (angioedema, urticaria, rash, itching) (see section "Contraindications").

Overdose:

The overdose of drotaverin was associated with cardiac 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 medical supervision and, if necessary, they should be treated symptomatically and aimed at maintaining the basic functions of the body treatment.

Interaction:

With levodopa

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

With papaverine, bendazole and other antispasmodics (including m-holinoblokatorami)

Strengthening spasmolytic action.

With morphine

Reduction of spasmogenic activity of morphine.

With phenobarbital

Increased spasmolytic effect of drotaverine.

Special instructions:

Use of the drug with arterial hypotension requires increased caution.

Each No-shpa® forte tablet contains 104 mg of lactose. When administered according to the recommended dosing regimen, 156 mg of lactose (1.5 tablets of No-sppa® forte) can be delivered with each dose, which can cause disorders in the gastrointestinal tract in patients suffering from lactose intolerance. This form of the drug is unacceptable for patients suffering from a deficiency of lactase, galactoseemia or glucose / galactose malabsorption syndrome.

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 the event of dizziness, potentially hazardous activities, such as driving and handling machinery, should be avoided.

Form release / dosage:Tablets 80 mg.

Packaging:

For 10 tablets in a blister of aluminum foil / aluminum foil, laminated with a polymer.
For 10 tablets in a blister of PVC / aluminum foil.
2 blisters together with instructions for use in a cardboard box.
For 24 tablets in a blister of PVC / aluminum foil.
1 blister with instructions for use in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:For tablets in blisters of aluminum foil / shiominium foil, Laminated Polymer: 5 years.

For tablets in PVC /aluminum foil: 3 years.

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

Terms of leave from pharmacies:Without recipe

Registration number:P N 015632/01

Date of registration:18.03.2009

The owner of the registration certificate:HINOIN Pharmaceutical and Chemical Products Plant, ZAO HINOIN Pharmaceutical and Chemical Products Plant, ZAO Hungary

Manufacturer: & nbsp

CHINOIN Pharmaceutical and Chemical Works, Co. Ltd. Hungary

Representation: & nbspSanofi Russia, JSCSanofi Russia, JSCRussia

Information update date: & nbsp07.02.2013

Illustrated instructions

Instructions

But-shpa Forte (No-Spa® forte)