NO-H-XA®

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT NO-H-SHA® (NО-H-SHA®)

Composition:

Active substance: drotaverine;

1 tablet contains: drotaverine hydrochloride, calculated as dry substance – 40 mg (0.04 g);

Excipients: lactose monohydrate, maize starch, magnesium stearate, talc.

Pharmaceutical form. Tablets.

Main physico-chemical properties: tablets from light yellow to yellowish-green in color.

Pharmacotherapeutic group. Agents used in functional gastrointestinal disorders. ATC code A03AD02.

Pharmacological Properties.

Pharmacodynamics.

Drotaverine is an isoquinoline derivative that exerts a spasmolytic effect directly on smooth muscle by inhibiting the enzyme phosphodiesterase IV (PDE IV), leading to increased intracellular concentration of cyclic adenosine monophosphate (cAMP). This results in the inactivation of myosin light chain kinase (MLCK), thereby causing relaxation of smooth muscle.

In vitro, drotaverine inhibits the activity of PDE IV and does not affect the isoenzymes phosphodiesterase III (PDE III) and phosphodiesterase V (PDE V). PDE IV plays a significant functional role in reducing the contractile activity of smooth muscles; therefore, selective inhibitors of this enzyme may be beneficial in treating diseases associated with hypermotility, as well as various conditions involving spasms of the gastrointestinal tract.

In smooth muscle cells of the myocardium and blood vessels, cAMP is predominantly hydrolyzed by the isoenzyme PDE III; hence, drotaverine acts as an effective spasmolytic agent with minimal side effects on the cardiovascular system and lacks pronounced therapeutic effects on this system.

Drotaverine is effective against smooth muscle spasms of both neural and myogenic origin. It acts on the smooth musculature of the gastrointestinal, biliary, urogenital, and vascular systems independently of the type of their autonomic innervation.

It enhances tissue blood flow due to its vasodilatory properties.

Pharmacokinetics.

The effect of drotaverine is stronger than that of papaverine, with faster and more complete absorption, and it binds less extensively to plasma proteins. An additional advantage of drotaverine is that, unlike papaverine, it does not cause respiratory stimulation as a side effect following parenteral administration.

Drotaverine is rapidly and completely absorbed after oral administration. It is highly bound (95–98%) to plasma proteins, including albumin, gamma-, and beta-globulins. Maximum serum concentration is reached within 45–60 minutes after oral administration. After first-pass metabolism, 65% of the administered dose enters systemic circulation unchanged.

It is metabolized in the liver. The elimination half-life is 8–10 hours.

Within 72 hours, drotaverine is almost completely eliminated from the body: approximately 50% is excreted in urine and about 30% in feces. Drotaverine is mainly excreted in the form of metabolites; the unchanged compound is not detected in urine.

Clinical characteristics.

Indications.

For therapeutic use in:

• Spasms of smooth muscle associated with biliary tract disorders: cholelithiasis, choledocholithiasis, cholecystitis, pericholecystitis, cholangitis, papillitis;
• Spasms of smooth muscle in urinary tract disorders: nephrolithiasis, ureterolithiasis, pyelitis, cystitis, vesical tenesmus.

As adjunctive treatment in:

• Spasms of gastrointestinal smooth muscle: peptic ulcer of the stomach and duodenum, gastritis, cardio- and/or pylorospasm, enteritis, colitis, spastic colitis with constipation and irritable bowel syndrome accompanied by meteorism;
• Tension headache;
• Gynecological disorders (dysmenorrhea).

Contraindications.

Hypersensitivity to drotaverine or to any component of the drug. Severe hepatic, renal or cardiac insufficiency (low cardiac output syndrome).

Interaction with other medicinal products and other forms of interaction.

Phosphodiesterase inhibitors, such as papaverine, reduce the anti-parkinsonian effect of levodopa.

No-shpa® should be used with caution concomitantly with levodopa, as the anti-parkinsonian effect of the latter is diminished, while rigidity and tremor are intensified.

Special precautions for use.

Use with particular caution in arterial hypotension.

No-Spa® tablets contain lactose. Do not use for treatment of patients suffering from rare hereditary disorders such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption syndrome.

Use during pregnancy or breastfeeding.

Pregnancy. Results of retrospective clinical studies and animal studies have shown that oral administration of the drug did not cause any signs of direct or indirect effects on pregnancy, embryonic development, labor, or postnatal development. However, the drug should be prescribed to pregnant women with caution.

Breastfeeding. Due to the lack of data during breastfeeding, use of the drug is not recommended.

Ability to influence reaction rate when driving vehicles or operating machinery.

If patients experience dizziness after taking the drug, they should avoid potentially hazardous activities such as driving a car or performing tasks requiring increased attention.

Administration and Dosage.

Adults: The usual average dose is 120–240 mg per day, divided into 2–3 doses.

When using drotaverine in children:

Children aged 6–12 years: The maximum daily dose is 80 mg (divided into 2 doses);

Children aged 12 years and older: The maximum daily dose is 160 mg (divided into 2–4 doses).

Children. The use of the drug is contraindicated in children under 6 years of age.

The use of drotaverine in children has not been evaluated in clinical studies.

Overdose.

Symptoms: In significant overdose, cardiac rhythm and conduction disturbances have been observed, including complete bundle branch block and cardiac arrest, which may be fatal.

In case of overdose, the patient must be under close medical supervision and receive symptomatic treatment, including induction of vomiting and/or gastric lavage.

Adverse Reactions.

Adverse events observed during clinical trials and possibly related to drotaverine, categorized by organ system.

Immune system: allergic reactions, including angioedema, urticaria, rash, pruritus, skin hyperemia, flushing, chills, fever, weakness.

Cardiovascular system: tachycardia, arterial hypotension.

Nervous system: headache, dizziness, insomnia.

Gastrointestinal tract: nausea, constipation, vomiting.

Shelf life.

5 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Packaging.

10 tablets per blister, 1 or 3 blisters per carton.

Prescription status.

Over-the-counter (without prescription).

Manufacturer.

Private Joint-Stock Company "Lekhim-Kharkiv".

PJSC "Tekhnolog".

Manufacturer's name and address of manufacturing site.

Ukraine, 61115, Kharkiv region, Kharkiv city, Severina Pototskoho Street, 36.

Ukraine, 20300, Cherkasy region, Uman city, Stara Prorizna Street, 8.