Noxhaverin "oz"

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NOXHAWARIN "OZ"

Composition:

Active substance: drotaverine;

1 ml of solution contains drotaverine hydrochloride 20 mg;

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

Pharmaceutical form. Injection solution.

Main physicochemical properties: clear greenish-yellow liquid.

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 on smooth muscle by inhibiting the enzyme phosphodiesterase IV (PDE IV), leading to increased concentrations of cyclic adenosine monophosphate (cAMP) and, consequently, inactivation of myosin light chain kinase (MLCK), resulting in smooth muscle relaxation.

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 has significant functional importance 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 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; hence, drotaverine is an effective spasmolytic agent without significant adverse effects on the cardiovascular system or pronounced therapeutic action 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, genitourinary, and vascular systems independently of their type of 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 lower binding to serum proteins. An additional advantage of drotaverine is that, unlike papaverine, respiratory stimulation as an adverse effect is not observed following parenteral administration.

Pharmacokinetics. Absorption. Drotaverine is rapidly absorbed after parenteral administration.

Distribution. It has a high degree of binding to plasma albumins (95–98%) and to α- and β-globulins.

Metabolism. After first-pass metabolism, 65% of the administered dose enters systemic circulation unchanged. It is metabolized in the liver.

Elimination. The half-life of elimination is 8–10 hours. Within 72 hours, drotaverine is almost completely eliminated from the body, with over 50% excreted in urine and approximately 30% in feces. Drotaverine is mainly excreted in the form of metabolites; the unchanged compound is not detected in urine.

Clinical characteristics.

Indications. Smooth muscle spasms associated with biliary tract diseases: 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 medicinal product (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 performed 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 supine position during intravenous administration of the drug.

Use with caution in arterial hypotension.

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

The drug contains sodium metabisulfite (E 223), which may rarely cause hypersensitivity reactions and bronchospasm.

This medicinal product contains 9.01 % v/v ethanol (alcohol), i.e. 853.32 mg per 12 ml dose (240 mg of drotaverine). It is harmful for patients suffering from alcoholism. Caution is advised when used in pregnant women, patients with liver disease, and patients with epilepsy.

Use during pregnancy or breastfeeding.

Pregnancy. The drug should be prescribed with caution to pregnant women. Drotaverine should not be used during labor.

Breastfeeding. Administration of the drug is not recommended during breastfeeding.

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

Ability to affect 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 and performing tasks requiring heightened attention.

Method of Administration and Dosage.

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

In acute colic in adult patients with calculi in urinary or biliary tracts – 40–80 mg intravenously.

Children. The drug must not be administered to children.

Overdose.

Symptoms: in significant overdose of drotaverine, disturbances in 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 must be under close medical supervision and receive symptomatic and supportive treatment, including induction of emesis and/or gastric lavage.

Adverse reactions.

Immune system disorders: allergic reactions, including angioneurotic edema, urticaria, rash, pruritus, urticaria, chills, increased body temperature, weakness, especially in patients with hypersensitivity to metabisulfite; cases of anaphylactic shock, including fatal outcomes, have been reported with the use of the injectable form.

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. 5 years.

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

Packaging. 2 ml in ampoules, 5 ampoules per pack; 5 in blister pack in a carton.

Prescription status. Prescription only.

Manufacturer.

Limited Liability Company "Experimental Plant "GNCLS".

LIMITED LIABILITY COMPANY "KORPORATSIYA "ZDOROVYA".

Manufacturer's location and address of business activity.

8 Vorobiova Street, Kharkiv, Kharkiv region, 61057, Ukraine.

(Limited Liability Company "Experimental Plant "GNCLS")

22 Shevchenka Street, Kharkiv, Kharkiv region, 61013, Ukraine.

(LIMITED LIABILITY COMPANY "KORPORATSIYA "ZDOROVYA")