No-spa solution 20mg / ml, No. 5

• 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, tenesmus of the bladder.

As an adjunct therapy (when the tablet form cannot be applied)

• With spasms of smooth muscles of gastrointestinal origin: gastric ulcer and duodenal ulcer, gastritis, spasms of the cardia and pylorus, enteritis, colitis.

• For gynecological diseases: dysmenorrhea

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

One ampoule (2 ml) contains:

active substance: drotaverine hydrochloride - 40 mg;
excipients: sodium disulfite (sodium metabisulfite) - 2.0 mg, ethanol 96% - 132.0 mg, water for injection - up to 2.0 ml.

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

• Hypersensitivity to sodium disulfite (see section 'Special instructions').

• Severe hepatic or renal impairment.

• Severe chronic heart failure.

• Children's age (the use of drotaverine in children has not been studied in clinical studies).

• Breastfeeding period.

With caution
In case of arterial hypotension (risk of collapse, see section 'Special instructions').
In pregnant women (see section 'Pregnancy and lactation').

Trade name: No-shpaЃ.

International non-proprietary name: drotaverine.

Dosage form: solution for intravenous and intramuscular administration.

Composition
One ampoule (2 ml) contains:

active substance: drotaverine hydrochloride - 40 mg;
excipients: sodium disulfite (sodium metabisulfite) - 2.0 mg, ethanol 96% - 132.0 mg, water for injection - up to 2.0 ml.

Description: transparent liquid of greenish-yellow color.

Pharmacotherapeutic group: antispasmodic agent.

ATX code: A03AD02.

Pharmacological properties
Drotaverine is an isoquinoline derivative that exhibits a potent antispasmodic effect on smooth muscle by inhibiting the enzyme phosphodiesterase (PDE). The enzyme phosphodiesterase is required for the hydrolysis of c-AMP to AMP. Inhibition of the enzyme phosphodiesterase leads to an increase in the concentration of c-AMP, which triggers the following cascade reaction: high concentrations of c-AMP activate c-AMP-dependent phosphorylation of myosin light chain kinase (MLCK). Phosphorylation of MLCK leads to a decrease in its affinity for calcium (Ca2 +) - the calmodulin complex, as a result of which the inactivated form of MLCK maintains muscle relaxation. c-AMP, in addition, affects the cytosolic concentration of Ca2 +, due to the stimulation of Ca2 + transport into the extracellular space and the sarcoplasmic reticulum.This Ca2 + concentration-lowering effect of drotaverine through c-AMP explains the antagonistic effect of drotaverine in relation to Ca2 +.

In vitro, drotaverine inhibits the PDE-4 isoenzyme without inhibiting the PDE-3 and PDE-5 isoenzymes. Therefore, the effectiveness of drotaverine depends on the concentrations of PDE-4 in tissues, the content of which in different tissues differs. PDE-4 is most important for suppressing the contractile activity of smooth muscles, and therefore selective inhibition of PDE-4 may be useful for the treatment of hyperkinetic dyskinesias and various diseases accompanied by a spastic state of the gastrointestinal tract.

Hydrolysis of c-AMP in the myocardium and vascular smooth muscle occurs mainly with the help of the isoenzyme PDE-3, which explains the fact that with high antispasmodic activity, drotaverine has no serious side effects from the heart and blood vessels and pronounced effects on the cardiovascular system ...

Drotaverine is effective for smooth muscle spasms of both neurogenic and muscular origin. Regardless of the type of autonomic innervation, drotaverine has a relaxing effect on the smooth muscles of the gastrointestinal tract, biliary tract, and the genitourinary system.

Pharmacokinetics
Drotaverine and / or its metabolites can slightly penetrate the placental barrier.

In vitro - drotaverine has a high connection with plasma proteins (95-97%), especially with albumin, y and p-globumin, as well as a-HDL (high density lipoprotein).

In humans, drotaverine is almost completely metabolized by O-desethylation. Its metabolites are rapidly conjugated with glucuronic acid. The main metabolite is 4'-desethyldrotaverine, in addition to which 6-desethyldrotaverine and 4'-desethyldrotaverine have been identified.

In humans, a two-chamber mathematical model was used to assess the indicators of the pharmacokinetics of drotaverine. The final half-life of plasma radioactivity was 16 hours.

The half-life is 8-10 hours.

Within 72 hours, it is almost completely excreted from the body, more than 50% through the kidneys (mainly in the form of metabolites) and about 30% through the intestines. Unchanged drotaverine is not detected in urine.

Indications for use

• 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, tenesmus of the bladder.

As an adjunct therapy (when the tablet form cannot be applied)

• With spasms of smooth muscles of gastrointestinal origin: gastric ulcer and duodenal ulcer, gastritis, spasms of the cardia and pylorus, enteritis, colitis.

• For gynecological diseases: dysmenorrhea.

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 or renal impairment.

• Severe chronic heart failure.

• Children's age (the use of drotaverine in children has not been studied in clinical studies).

• Breastfeeding period.

With caution
In case of arterial hypotension (risk of collapse, see section 'Special instructions').
In pregnant women (see section 'Pregnancy and lactation').

Pregnancy and the period of lactation
As shown by studies on reproductive toxicity in animals and retrospective studies of clinical data, the use of drotaverine during pregnancy did not have either teratogenic or embryotoxic effects. Despite this, when prescribing drotaverine to pregnant women, caution should be exercised and it should be used only in cases where the potential benefit to the mother outweighs the potential risk to the fetus, while prescribing an injectable dosage form of No-shpaЃ in pregnant women should be avoided.
The drug should not be used during childbirth (potential risk of developing postpartum atonic bleeding).
Due to the lack of the necessary clinical data during lactation, it is not recommended to prescribe the drug.

Dosing and Administration
Adults
The daily average dose is 40-240 mg drotaverine hydrochloride (divided into 1-3 doses per day) intramuscularly.
In acute colic (renal or gallstone) - 40-80 mg intravenously slowly (duration of administration is approximately 30 seconds).

Side effects
Below are the adverse reactions observed in clinical studies, divided by organ systems, indicating the frequency of their occurrence in accordance with the following gradations: very frequent (? 10%), frequent (? 1% and <10%); infrequent (? 0.1 and <1%); rare (? 0.01% and <0.1%) and very rare, including individual messages (<0.01%), unknown frequency (frequency cannot be determined from available data).

From the side of the cardiovascular system
Rare: increased heart rate, decreased blood pressure.

From the nervous system
Rare: headache, dizziness, insomnia.

From the gastrointestinal tract
Rare: nausea, constipation.

From the immune system
Rare: allergic reactions (angioedema, urticaria, rash, itching) (see section 'Contraindications').

Unknown frequency
Fatal and non-fatal anaphylactic shock has been reported with the drug.

Local reactions
Rare: reactions at the injection site.

Overdose An
overdose of drotaverine has been associated with cardiac arrhythmias and conduction disturbances, including complete bundle branch block and cardiac arrest, which can be fatal.
In the event of an overdose, patients should be under close medical supervision and symptomatic therapy and treatment should be carried out to maintain basic body functions.

Interaction with other medicinal products
With levodopa
Phosphodiesterase inhibitors, like papaverine, weaken the antiparkinsonian effect of levodopa. When drotaverine is prescribed simultaneously with levodopa, an increase in rigidity and tremor is possible.

With papaverine, bendazole and other antispasmodics (including m-anticholinergics),
Drotaverin enhances the antispasmodic effect of papaverine, bendazole and other antispasmodics, including m-anticholinergics.

With tricyclic antidepressants, quinidine and procainamide.
Increases hypotension caused by tricyclic antidepressants, quinidine and procainamide.

With morphine
Reduces the spasmodic activity of morphine.

With phenobarbital
Phenobarbital enhances the antispasmodic effect of drotaverine.

Special instructions
The drug contains disulfite, which can cause allergic reactions, including anaphylactic symptoms and bronchospasm in sensitive individuals, especially those with asthma or a history of allergic diseases. In case of hypersensitivity to disulfite, parenteral administration of the drug should be avoided (see section 'Contraindications').
With intravenous administration of drotaverine in patients with low blood pressure, the patient should be in a horizontal position due to the risk of collapse.

Influence on the ability to drive a car and other mechanisms
During the period of treatment, it is necessary to refrain from driving and engaging in other potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.

Release form
Solution for intravenous and intramuscular administration of 20 mg / ml.
2 ml in amber glass ampoules (hydrolytic class, type I) with a fracture point applied.
5 ampoules in a plastic blister packaging without coating (pallet).
1 or 5 pallets with instructions for use in a cardboard box.

Storage
conditions Store in a dark place at a temperature of 15-25 ? C.
Keep out of the reach of children.

Shelf life is
5 years.
Do not use after the expiration date printed on the package.

Terms of dispensing from pharmacies
Prescription.