No-spa® for injection

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NO-SPA® FOR INJECTIONS (NO-SPA® FOR INJECTIONS)

Composition:

Active substance: drotaverine;

1 ml of solution contains drotaverine hydrochloride 20 mg;

Excipients: sodium metabisulfite, ethanol 96%, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear yellowish-green 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 intracellular concentration of cyclic adenosine monophosphate (cAMP). This results in the inactivation of myosin light chain kinase (MLCK), thereby causing smooth muscle relaxation.

In vitro, drotaverine inhibits the activity of the PDE IV enzyme and does not affect the isoenzymes phosphodiesterase III (PDE III) or 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 disorders 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 PDE III isoenzyme. Thus, drotaverine acts as an effective spasmolytic agent without causing significant adverse effects on the cardiovascular system and without exerting strong 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, regardless 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 lower binding to serum proteins. An additional advantage of drotaverine is that, unlike papaverine, it does not cause respiratory stimulation as a side effect following parenteral administration.

Pharmacokinetics

Absorption. Drotaverine is rapidly absorbed both after oral administration and parenteral injection.

Distribution. It has a high degree of binding to plasma proteins, primarily albumin (95–98%), as well as alpha- and beta-globulins. Maximum serum concentration is reached within 45–60 minutes after oral administration.

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

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

Clinical characteristics.

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

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

Special precautions.

Due to the risk of collapse, the patient must be in a supine position during intravenous administration of No-shpa® for injection.

Use with caution in arterial hypotension.

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

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.

Interaction with other medicinal products and other forms of interaction.

Phosphodiesterase inhibitors (No-shpa®, papaverine) reduce the anti-Parkinson effect of levodopa. No-shpa® for injection should be used with caution concomitantly with levodopa, as the anti-Parkinson effect of the latter is diminished, while rigidity and tremor are intensified.

Special precautions for use.

This medicinal product contains less than 1 mmol (or 23 mg)/dose of sodium, i.e. it is practically sodium-free.

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 adverse effects on pregnancy, embryonic development, delivery, or postnatal development. However, this drug should be used with caution in pregnant women. Drotaverine should not be used during labour.

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

Fertility.

There are no data regarding effects 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 a vehicle or performing tasks that require heightened attention.

Method of administration and dosage.

Dosing.

Adults.

The recommended daily dose is 40–240 mg (in 1–3 separate administrations) given intramuscularly.

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

Administration method.

The drug is administered intramuscularly and intravenously.

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

Overdose.

Symptoms: in cases of 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 treatment, including induction of vomiting and/or gastric lavage.

Adverse reactions.

Adverse reactions observed during clinical trials and possibly caused by drotaverine, classified by organ systems and frequency of occurrence: very common (> 1/10), common (> 1/100, < 1/10), uncommon (> 1/1,000, < 1/100), rare (> 1/10,000, < 1/1,000), very rare (< 1/10,000), frequency not known (cannot be estimated from available data).

Immune system disorders.

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

Frequency not known: there have been reports of cases of anaphylactic shock with fatal and non-fatal outcomes following administration of the injectable form.

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

Cardiovascular system disorders.

Rare: tachycardia, arterial hypotension.

Nervous system disorders.

Rare: headache, dizziness, insomnia.

Gastrointestinal disorders.

Rare: nausea, constipation, vomiting.

General disorders and administration site conditions: local reactions at the injection site.

Shelf life. 3 years.

Storage conditions. Keep out of reach of children.

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

Packaging. No. 25 (5x5): 2 ml in an ampoule, 5 ampoules placed in a tray, 5 trays in a cardboard box.

Prescription status. Prescription only.

Manufacturer. Gedeon Richter Ltd.

Address of manufacturer and location of manufacturing site.

Csanyikvölgy, Miskolc, 3510, Hungary.

Marketing Authorization Holder. Opella Healthcare Ukraine LLC, Ukraine.

Address of the Marketing Authorization Holder and/or its representative.

48-50A Zhylianska St., Kyiv, 01033, Ukraine.