No-h-sha®

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

Composition:

Active substance: drotaverine hydrochloride;

1 suppository contains 0.04 g (40 mg) of drotaverine hydrochloride calculated as dry substance;

Excipient: hard fat.

Pharmaceutical form. Rectal suppositories.

Main physicochemical properties: suppositories from light yellow to yellow in color, bullet-shaped. A surface bloom on the suppository is permissible.

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

Pharmacological Properties.

Pharmacodynamics.

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

In vitro, drotaverine inhibits the activity of PDE IV enzyme and does not affect the activity of phosphodiesterase III (PDE III) and phosphodiesterase V (PDE V) isoenzymes. PDE IV has significant functional importance 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; thus, drotaverine acts as an effective spasmolytic agent without causing significant adverse effects on the cardiovascular system and does not exert strong therapeutic effects on this system.

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

It enhances tissue blood flow due to its ability to dilate blood vessels.

Pharmacokinetics.

The effect of drotaverine is stronger than that of papaverine, with faster and more complete absorption and lower binding to serum proteins. An additional advantage of drotaverine is that, unlike papaverine, respiratory stimulation as a side effect is not observed after parenteral administration.

Drotaverine is rapidly and completely absorbed after oral administration. It binds extensively (95–98%) to plasma proteins, including albumin, gamma- and beta-globulins. Maximum plasma concentration is reached within 45–60 minutes after oral administration. After primary 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, colitis, spastic colitis with constipation and irritable bowel syndrome accompanied by meteorism;
• 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. Concomitant use of No-Spa® with levodopa should be done with caution, as the anti-parkinsonian effect of levodopa may be diminished and rigidity and tremor may be exacerbated.

Special precautions for use.

The drug should be prescribed with caution to patients with arterial hypotension and patients with benign prostatic hyperplasia.

Use during pregnancy or breastfeeding.

Pregnancy. Clinical studies and studies in animals have shown that administration of drotaverine did not cause any signs of direct or indirect effects on pregnancy, embryonic development, labor, or postnatal development. However, the drug should be used with caution in pregnant women.

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

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

If patients experience dizziness after administration of the drug, they should avoid potentially hazardous activities such as driving a vehicle or performing tasks requiring heightened attention.

Method of Administration and Dosage.

Before using the suppository, it is necessary to:

• tear off 1 suppository in the primary packaging along the perforation line of the blister pack;
• then pull the edges of the film apart in opposite directions to remove the suppository from the primary packaging.

The drug is intended for rectal administration.

Dosage for adults and children aged 12 years and older: 1 suppository twice daily. The duration of treatment is determined individually by the physician.

Children.

The drug should not be used for treatment of children under 12 years of age.

Overdose.

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

In case of overdose, the patient must be under strict medical supervision and receive symptomatic treatment.

Adverse reactions.

Adverse events observed during clinical trials and possibly associated with drotaverine, categorized by organ system.

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

Cardiovascular system disorders: tachycardia, arterial hypotension.

Nervous system disorders: headache, dizziness, insomnia.

Gastrointestinal disorders: nausea, constipation, vomiting.

Shelf life.

2 years.

Storage conditions.

Store in the original packaging, out of reach of children, at a temperature not exceeding 25 °C.

Packaging.

5 suppositories per blister; 2 blisters per carton.

Supply category.

Over-the-counter.

Manufacturer.

Private Joint-Stock Company "Lekhim-Kharkiv".

Manufacturer's address and location of business activity.

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