No-shpa, 40 mg 24 pcs

Drotaverine is an isoquinoline derivative that has a powerful antispasmodic effect on the smooth muscles by inhibiting the enzyme, phosphodiesterase (PDE). Phosphodiesterase enzyme is needed to hydrolyze cyclic adenosine monophosphate (cAMP) to adenosine monophosphate (AMP).

Inhibition of the enzyme phosphodiesterase leads to an increase in the concentration of cAMP; this triggers the following cascade reaction: high concentrations of cAMP activate cAMP-dependent phosphorylation of myosin light chain kinase (CLKM). Phosphorylation of CLSM decreases its affinity for the Ca2+-calmodulin complex, resulting in the inactivated form of CLSM supporting muscle relaxation. cAMP also affects cytosolic Ca2+ ion concentration by stimulating Ca2+ transport into the extracellular space and the sarcoplasmic reticulum. This downregulation of Ca2+ ion concentration by drotaverine via the cAMP explains the antagonistic effect of drotaverinate toward Ca2+.

In vitro, drotaverine inhibits the FDE IV isoenzyme without inhibiting the FDE III and FDEV isoenzymes. Therefore, the effectiveness of drotaverine depends on the concentration of FDE IV in tissues, the content of which varies from tissue to tissue. FDE IV is most important for inhibition of contractile activity of smooth muscles, therefore selective inhibition of FDE IV may be useful for treatment of hyperkinetic dyskinesias and various diseases accompanied by spastic state of the gastrointestinal tract.

The hydrolysis of CAMP in the myocardium and vascular smooth muscle occurs primarily via the FDE III isoenzyme, which explains the fact that with its high antispasmodic activity, drotaverine has no serious cardiovascular side effects and no pronounced cardiovascular effects.

Drotaverine is effective for smooth muscle spasms of both neurogenic and muscular origin. Regardless of the type of autonomic innervation, drotaverine relaxes the smooth muscles of the gastrointestinal tract, biliary tract, and urogenital system.

Pharmacokinetics

Absorption:

After oral administration, drotaverine is quickly and completely absorbed. After presystemic metabolism, 65% of the administered dose of drotaverine enters the systemic bloodstream. Maximum plasma concentration (Cmax) is reached after 45-60 minutes.

Distribution

In vitro drotaverine has high binding to plasma transactions (95-98%), especially to albumin γ and β-globumin.

Drotaverine is evenly distributed in tissues and penetrates smooth muscle cells. It does not penetrate the blood-brain barrier. Drotaverine and/or its metabolites may slightly penetrate through the placental barrier.

Metabolism

In humans, drotaverine is almost completely metabolized in the liver by O-deletion. Its metabolites rapidly conjugate to glucuronic acid. The main metabolite is, 4′-dezethyldrotaverine, in addition to which 6-dezethyldrotaverine and 4′-dezethyldrotaveraldine have been identified.

Exhaustion

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

Within 72 hours, drotaverine is almost completely eliminated from the body. More than 50% of drotaverine is excreted by the kidneys and about 30% through the gastrointestinal tract (excretion into the bile). Drotaverine is mainly excreted as metabolites, unchanged drotaverine is not detected in the urine.

Indications

• smooth muscle spasms associated with diseases of the biliary tract: cholecystolithiasis, cholangiolithiasis, cholecystitis, pericholecystitis, cholangitis, papillitis.
• spasms of the smooth muscles of the urinary tract: nephrolithiasis, urethrolithiasis, pyelitis, cystitis, bladder tenesm.

Auxiliary therapy:

• In spasms of the smooth muscles of the gastrointestinal tract: Gastric and duodenal ulcer, gastritis, cardiac and gatekeeper spasms, enteritis, colitis, spastic, colitis with constipation and irritable bowel syndrome with flatulence after excluding diseases manifesting the “acute abdomen” syndrome (appendicitis, peritonitis, perforated ulcer, acute pancreatitis, etc.
• Tension headaches.
• Dysmenorrhea.

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Active ingredient

Drotaverine

Composition

Active ingredient:

drotaverine hydrochloride – 40 mg;

excipients:

magnesium stearate – 3 mg,

talc – 4 mg,

povidone – 6 mg, <

Corn starch – 35 mg,

lactose monohydrate – 52 mg.

How to take, the dosage

Adults

The average daily dose in adults is usually 120-240 mg (the daily dose is divided into 2-3 doses). The maximum single dose is 80 mg. The maximum daily dose is 240 mg.

Children

There have been no clinical studies with drotaverine in children.

In case of prescribing drotaverine in children:

– For children from 6 to 12 years of age, the maximum daily dose is 80 mg divided into 2 doses.

– for children over 12 years of age, the maximum daily dose is 160 mg divided into 2 to 4 doses. Duration of treatment without consulting a physician

When taking the drug without consulting a physician, the recommended duration of taking the drug is usually 1-2 days. If the pain syndrome does not decrease during this period, the patient should see a doctor to clarify the diagnosis and, if necessary, change the therapy. In cases where drotaverine is used as adjunctive therapy, the duration of treatment without consulting a doctor may be longer (2-3 days).

The efficacy evaluation method

If the patient can easily self-diagnose the symptoms of his disease because they are well known to him, the effectiveness of treatment, namely the disappearance of pain, is also easily assessed by the patient. If there is a moderate decrease in pain or, no decrease in pain within a few hours of taking the maximum daily dose, or if there is no significant decrease in pain after taking the maximum daily dose, it is recommended that a physician be consulted.

Interaction

With levodopa

Papaverine-like phosphodiesterase inhibitors reduce the antiparkinsonian effects of levodopa. When drotaverine is administered simultaneously with levodopa, rigidity and tremor may be increased. With other antispasmodic agents, including m-cholinoblockers Mutual enhancement of antispasmodic effects.

Drugs significantly binding to plasma proteins (more than 80%)

Drotaverine significantly binds to plasma proteins, primarily albumin,

γ and β-globulin (see section “Pharmacokinetics”). There are no data on the interaction of drotaverine. with drugs that significantly bind to plasma proteins, but there is a hypothetical possibility of their interaction with drotaverine at the level of protein binding (displacement of one drug by another from protein binding and increased concentration of free fraction in blood of the drug with less strong protein binding), which hypothetically may increase the risk of pharmacodynamic and/or toxic side effects of this drug.

Special Instructions

No-Spa® 40 mg tablets contain 52 mg of lactose. This may cause gastrointestinal complaints in persons with lactose intolerance. This form is not acceptable for patients with lactose deficiency, galactosemia or impaired glucose/galactose absorption syndrome.

Impact on the ability to drive and operate machinery

When taken orally in therapeutic doses, drotaverine has no effect on the ability to drive and perform work requiring increased attention. In case of any side effects the issue of driving and working with mechanisms requires individual consideration. In case of dizziness after taking the drug, potentially dangerous activities such as driving and working with mechanisms should be avoided.

Contraindications

• high sensitivity to the active ingredient or any of the excipients of the drug
• Severe hepatic or renal failure

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• Severe heart failure (low cardiac output syndrome)
• Children under 6 years
• Breastfeeding period (no clinical data).
• Rare hereditary galactose intolerance, lactase deficiency, and glucose-galactose malabsorption syndrome (due to the presence of lactose in the drug).

With caution:

– In arterial hypotension.

– In children (insufficient clinical experience of use).

– In pregnant women.

Side effects

The adverse reactions observed in clinical trials, divided by system, organ, and frequency according to the following gradations, are as follows: Very frequent (≥10%), frequent (≥1%, < 10); infrequent (≥0.1%, < 1%); rare (≥0.01%, < 0.1%) and very rare, including individual reports (< 0.01%), unknown frequency (frequency cannot be determined from available data).

Cardiovascular system disorders

Rare – palpitations, decreased blood pressure.

Nervous system disorders

Rare – headache, dizziness, insomnia.

Gastrointestinal tract disorders

Rare – nausea, constipation.

Immune system disorders

Rare – allergic reactions (angioedema, urticaria; rash, itching)

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Overdose

There are no data on overdose of the drug.

In case of overdose, patients should be under medical supervision and if necessary, they should be treated with symptomatic and aimed at maintaining basic body functions, including artificial inducement of vomiting or gastric lavage.

Pregnancy use

As demonstrated by animal reproductive experiments and retrospective studies of clinical data, the use of drotaverine during pregnancy leads to neither teratogenic nor embryotoxic effects. However, use of the drug is recommended only after careful weighing of the benefit-risk ratio.

Due to the lack of necessary clinical data, administration during lactation is not recommended.

Similarities

No-shpa, Drotaverine, Spasmonet, Drotaverine-Teva