No-h-sa®

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

Composition:

Active substance: drotaverine;

1 ml of solution contains 20 mg of drotaverine hydrochloride calculated as the dry substance;

Excipients: ethanol 96%, sodium metabisulfite (E 223), water for injections.

Pharmaceutical form. Injection solution.

Main physicochemical properties: clear greenish-yellow liquid.

Pharmacotherapeutic group. Drugs used in functional gastrointestinal disorders. Drotaverine. ATC code A03AD02.

Pharmacological Properties

Pharmacodynamics

Drotaverine is an isoquinoline derivative that exerts a spasmolytic effect on smooth muscle by inhibiting the activity of phosphodiesterase IV (PDE IV) enzyme, leading to increased intracellular cAMP concentration. This results in inactivation of myosin light chain kinase (MLCK), thereby causing 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 plays a significant functional role in reducing contractile activity of smooth muscles; therefore, selective inhibitors of this enzyme may be beneficial in the treatment of disorders associated with hypermotility, as well as various conditions accompanied by gastrointestinal tract spasms.

In smooth muscle, cardiac and vascular cells, cAMP is predominantly hydrolyzed by the isoenzyme PDE III; hence, drotaverine acts as an effective spasmolytic agent without significant adverse effects or strong therapeutic action on the cardiovascular 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.

The effect of drotaverine is stronger than that of papaverine, with faster and more complete absorption, and it exhibits lower plasma protein binding. An additional advantage of drotaverine is that, unlike papaverine, respiratory stimulation as a side effect is not observed following parenteral administration.

Pharmacokinetics

Drotaverine is rapidly and completely absorbed after parenteral administration. It is highly bound (95–98%) to human plasma proteins, particularly to albumin, gamma- and beta-globulins. After initial metabolism, 65% of the administered dose enters systemic circulation in unchanged form.

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: more than 50% is excreted via urine and approximately 30% via feces. Drotaverine is primarily excreted in the form of metabolites; the unchanged compound is not detected in urine.

Clinical characteristics.

Indications.

Smooth muscle spasms associated with biliary tract disorders: cholelithiasis, choledocholithiasis, cholecystitis, pericholecystitis, cholangitis, papillitis.

Smooth muscle spasms in urinary tract disorders: nephrolithiasis, ureterolithiasis, pyelitis, cystitis, bladder tenesmus.

As adjunctive treatment (when administration of the drug in tablet form is not possible):

• in smooth muscle spasms of the gastrointestinal tract: peptic ulcer of the stomach and duodenum, gastritis, cardio- and/or pylorospasm, enteritis, colitis;
• in gynecological disorders: dysmenorrhea.

Contraindications.

• Hypersensitivity to the active substance or to any component of the drug (especially to sodium metabisulfite);
• hypersensitivity to sodium disulfite;
• severe hepatic, renal or cardiac insufficiency (low cardiac output syndrome).

Interaction with other medicinal products and other forms of interaction.

Phosphodiesterase inhibitors (drotaverine, papaverine) reduce the antiparkinsonian effect of levodopa. Concomitant use of the drug with levodopa should be undertaken with caution, as the antiparkinsonian effect of the latter is diminished, while rigidity and tremor are intensified.

Special precautions for use.

Due to the risk of collapse, the patient must be in a lying position during intravenous administration of the drug!

Use with caution in patients with arterial hypotension.

The drug contains metabisulfite, which may cause allergic-type reactions, including symptoms of anaphylactic shock and bronchospasm in sensitive individuals, particularly in those with a history of asthma or allergy. In case of hypersensitivity to sodium metabisulfite, parenteral administration of the drug should be avoided.

Caution should be exercised when administering the drug parenterally to pregnant women (see section "Use during pregnancy or breastfeeding").

Children. Clinical studies on the use of the drug in children have not been conducted.

Use during pregnancy or breastfeeding.

Pregnancy. Retrospective clinical studies have shown that oral administration of the drug did not result in any cases of teratogenicity or embryotoxicity. However, the drug should be prescribed to pregnant women with caution. Drotaverine should not be used during labor.

Breastfeeding. Due to the lack of appropriate animal studies during the breastfeeding period, administration of the drug is not recommended.

Fertility. There are no data regarding the effect on human fertility.

Ability to influence reaction speed when driving or operating machinery.

Patients should be warned that after parenteral, especially intravenous, administration of the drug, they should refrain from driving a vehicle or performing tasks requiring heightened attention.

Dosage and Administration.

The usual average daily dose for adults is 40–240 mg (in 1–3 separate administrations) administered intramuscularly.

In cases of acute colic in adult patients with calculi in the urinary or biliary tract – 40–80 mg administered intravenously.

Children. Clinical studies on the use of the drug in children have not been conducted.

Overdose.

Symptoms: overdose with drotaverine has been associated with cardiac arrhythmias and conduction disturbances, including complete bundle-branch block of the His bundle 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 vomiting and/or gastric lavage.

Side effects.

Adverse reactions observed during clinical trials and possibly attributed to drotaverine, classified by organ system.

Immune system disorders.

Allergic reactions, including angioneurotic edema, urticaria, rash, pruritus, urticaria, chills, fever, weakness, particularly in patients with hypersensitivity to metabisulfite.

Cases of anaphylactic shock with fatal and non-fatal outcomes have been reported following administration of the injectable form.

The product contains metabisulfite, which may cause allergic-type reactions, including symptoms of anaphylactic shock and bronchospasm in sensitive individuals, especially those with a history of asthma or allergy.

Cardiovascular system disorders.

Tachycardia, arterial hypotension.

Nervous system disorders.

Headache, dizziness, insomnia.

Gastrointestinal disorders.

Nausea, constipation, vomiting.

General disorders and administration site reactions.

Local reactions at the injection site.

Shelf life.

3 years.

Storage conditions.

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

Packaging.

2 ml in ampoules. 5 or 100 ampoules per carton; or 5 ampoules in a blister, 1 blister per carton.

Prescription status.

Prescription only.

Manufacturer.

Private Joint-Stock Company "Lekhym-Kharkiv".

Manufacturer's address.

36 Severina Pototskogo Street, Kharkiv, Kharkiv region, 61115, Ukraine.