No-h-sa® forte

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NO-H-SHA® FORTE (NO-H-SHA® FORTE)

Composition:

Active substance: drotaverine;

1 tablet contains: drotaverine hydrochloride, calculated as dry substance – 80 mg (0.08 g);

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

Pharmaceutical form. Tablets.

Main physicochemical properties: tablets from light yellow to yellowish-green in color, cylindrical, flat with a dividing line on one side.

Pharmacotherapeutic group. Agents used in functional gastrointestinal disorders. ATC code A03A D02.

Pharmacological Properties

Pharmacodynamics

Drotaverine is an isoquinoline derivative that exerts a spasmolytic effect directly on smooth muscle by inhibiting phosphodiesterase IV (PDE IV) enzyme activity. This inhibition leads to increased intracellular cAMP concentration and, through inactivation of myosin light chain kinase (MLCK), results in smooth muscle relaxation.

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

In smooth muscle cells of the myocardium and blood vessels, cAMP is predominantly hydrolyzed by the PDE III isoenzyme. Therefore, drotaverine acts as an effective spasmolytic agent without significant adverse cardiovascular effects or pronounced therapeutic impact 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 regardless of their type of 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 lower plasma protein binding. Another advantage of drotaverine is that, unlike papaverine, it does not produce side effects such as respiratory stimulation 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 plasma concentration is reached within 45–60 minutes after oral administration. After first-pass metabolism, 65% of the administered dose enters systemic circulation unchanged.

Drotaverine 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 the urine and about 30% in feces. Drotaverine is primarily excreted in the form of metabolites; the unchanged drug is not detected in urine.

Clinical characteristics.

Indications.

For treatment of:

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

As an adjunctive treatment in:

• Spasms of gastrointestinal tract smooth musculature: 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).

No-Spa**®** forte tablets contain lactose. Should not be used in patients with rare hereditary disorders such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption syndrome. Breastfeeding period. Children under 12 years of age.

Interaction with other medicinal products and other forms of interaction.

Phosphodiesterase inhibitors, such as papaverine, reduce the antiparkinsonian effect of levodopa.

No-Spa**®** forte should be used with caution concomitantly with levodopa, as the antiparkinsonian effect of the latter is diminished and rigidity and tremor may be exacerbated.

Special precautions for use.

Use with particular caution in patients with arterial hypotension.

Clinical studies with drotaverine in children have not been conducted.

The drug contains lactose, which should be taken into account for patients with lactose intolerance.

Do not use for treatment of patients with lactase deficiency, galactosemia, 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 with caution to pregnant women.

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

Fertility. There is no information regarding effects on human fertility.

Ability to influence reaction rate while driving or operating machinery.

If dizziness occurs after administration of the drug, driving vehicles and performing tasks requiring heightened attention should be avoided.

Method of Administration and Dosage.

Adults: the usual average dose is 120–240 mg per day in 2–3 divided doses.

Children aged 12 years and older: the maximum daily dose is 160 mg (divided into ½ tablet 2–4 times daily).

The duration of treatment is determined individually by a physician depending on the nature and course of the disease.

Children. The use of drotaverine in children has not been evaluated in clinical studies. The use of the drug for treatment of children under 12 years of age is contraindicated. For children aged 12 years and older, the drug should be used only as prescribed by a physician.

Overdose.

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

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

Side effects.

Adverse reactions observed during clinical trials and possibly caused by drotaverine, listed by organ system:

Immune system disorders: allergic reactions, including angioneurotic edema, urticaria, rash, itching, skin hyperemia, chills, fever, weakness.

Cardiovascular system disorders: tachycardia, arterial hypotension.

Nervous system disorders: headache, dizziness, insomnia.

Gastrointestinal disorders: nausea, constipation, vomiting.

Shelf life.

5 years.

Storage conditions.

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

Keep out of reach of children.

Packaging.

10 tablets in a blister pack, 3 blisters per carton.

Availability.

Over-the-counter (without prescription).

Manufacturer.

Private Joint-Stock Company "Lekhim-Kharkiv".

Manufacturer's address and place of business.

36 Severina Pototskoho Street, Kharkiv, Kharkiv Oblast, 61115, Ukraine.