Nispazm forte®

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT NISPASM FORTE®

Composition:

Active substance: drotaverine hydrochloride;

One tablet contains 80 mg of drotaverine hydrochloride;

Excipients: lactose monohydrate, corn starch, maltodextrin, magnesium stearate, sodium croscarmellose, coating mixture Opadry® yellow 07F220004: hypromellose, titanium dioxide (E 171), talc, sodium saccharin (E 954), macrogol 4000, quinoline yellow aluminum lake (E 104), iron oxide red (E 172).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: yellow-colored, round, biconvex tablets with a dividing line on both sides.

Pharmacotherapeutic group. Agents used in functional gastrointestinal disorders. ATC code A03AD02.

Pharmacological Properties.

Pharmacodynamics.

Drotaverine is an isoquinoline derivative with spasmolytic action on smooth muscle by inhibiting the activity of phosphodiesterase IV (PDE IV), thereby increasing cAMP concentration and, through inactivation of myosin light chain kinase, leads to relaxation of smooth muscles.

In vitro, drotaverine inhibits PDE IV activity but does not inhibit phosphodiesterase isoenzymes III and V. PDE IV has significant functional importance in reducing contractile activity of smooth muscles; therefore, selective inhibitors of this enzyme may be beneficial in treating disorders accompanied by hyperperistalsis, as well as various conditions involving gastrointestinal tract spasms.

In smooth muscle cells of the myocardium and blood vessels, cAMP is predominantly hydrolyzed by the PDE III isoenzyme; thus, drotaverine does not have significant adverse cardiovascular effects or strong therapeutic influence on the circulatory system.

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

The drug enhances tissue blood flow due to vasodilation.

The effect of drotaverine is more pronounced than that of papaverine, with faster and more complete absorption, and it binds less to serum proteins. Unlike papaverine, drotaverine does not produce the same adverse effect of respiratory stimulation following parenteral administration.

Pharmacokinetics.

Drotaverine is rapidly and completely absorbed after oral administration. It binds extensively (95–98%) to plasma proteins, particularly albumin, gamma-, and beta-globulins. Maximum concentration is reached within 45–60 minutes after oral intake. Approximately 65% of the administered dose enters systemic circulation unchanged.

Drotaverine is metabolized in the liver. Its elimination half-life is 8–10 hours.

Within 72 hours, drotaverine is almost completely eliminated from the body: more than 50% is excreted in urine and about 30% in feces. It is mainly excreted in the form of metabolites and is not detectable in unchanged form in urine.

Clinical characteristics.

Indications.

Treatment of:

• Smooth muscle spasms associated with biliary tract diseases: cholelithiasis (cholecystolithiasis, cholangiolithiasis), cholecystitis, pericholecystitis, cholangitis, papillitis;

• Smooth muscle spasms in urinary tract disorders: nephrolithiasis, urolithiasis, pyelitis, cystitis, bladder spasms.

As an adjunctive agent in:

• Smooth muscle spasms of the gastrointestinal tract in: peptic ulcer of the stomach and duodenum, gastritis, cardio- and/or pylorospasm, enteritis, colitis, spastic colitis with constipation, irritable bowel syndrome accompanied by flatulence;
• Tension headache;
• Gynecological disorders (dysmenorrhea).

Contraindications.

Hypersensitivity to any component of the drug.

Severe hepatic, renal, or cardiac insufficiency (low cardiac output syndrome).

Hereditary lactase deficiency, galactosemia, or glucose-galactose malabsorption syndrome. Pediatric use under 12 years of age.

Second- and third-degree atrioventricular block.

Interaction with other medicinal products and other forms of interactions.

Concomitant use with levodopa should be cautious, as the antiparkinsonian effect of the latter is reduced and rigidity and tremor may be exacerbated.

Special precautions for use.

Caution should be exercised when using drotaverine:

• in patients with hypotension,
• in children under 12 years of age, as studies on the effects of drotaverine in these patients have not been conducted (see section "Dosage and administration"),
• in pregnant women.

Drotaverine should not be used during labour (see section "Use during pregnancy or breastfeeding").

Important information about some excipients of Nispazm Forte®.

Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

Due to the presence of lactose, the medicinal product may cause gastrointestinal symptoms in patients with lactose intolerance.

Due to the presence of quinoline yellow aluminium lake dye, the medicinal product may cause allergic reactions.

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

Use during pregnancy or breastfeeding.

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, labour or postnatal development. Due to insufficient clinical data, the drug should be prescribed to pregnant women only if the expected benefits outweigh the potential risks. The active substance crosses the placenta. The drug should not be used during labour due to the increased risk of bleeding in the postpartum period.

It is unknown whether drotaverine is excreted in breast milk. Use of the drug during breastfeeding is not recommended.

Fertility. There is no information regarding the effect on human fertility.

Ability to affect reaction speed when driving vehicles or operating machinery.

At therapeutic doses, when administered orally, drotaverine does not affect reaction speed when driving vehicles or operating machinery. Patients should be informed that if dizziness occurs, they should avoid driving a car and performing tasks requiring increased attention.

Dosage and Administration.

For oral use.

Adults: the average daily dose is 120–240 mg administered in 2–3 divided doses.

Children aged 12 years and older: the maximum daily dose is 160 mg (1/2 tablet 2–4 times daily).

The duration of treatment is determined individually by a physician.

Children.

The use of the drug for treatment of children under 12 years of age is contraindicated.

Overdose.

Cases of overdose with drotaverine are unknown.

Symptoms: in studies, significant overdose of drotaverine has been associated with cardiac rhythm and conduction disturbances, including complete bundle branch block and cardiac arrest, which may be fatal.

In case of significant overdose, the patient should be under close medical supervision. Induction of vomiting and/or gastric lavage is recommended, along with symptomatic and supportive treatment.

Adverse reactions.

Adverse reactions observed during clinical trials and possibly caused by drotaverine, categorized by organ systems and frequency of occurrence: very common (> 1/10), common (> 1/100, < 1/10), uncommon (> 1/1000, < 1/100), rare (> 1/10000, < 1/1000), very rare (< 1/10000).

Reporting of suspected adverse reactions.

Reporting of suspected adverse reactions during the post-marketing period is very important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions.

Shelf life. 5 years.

Storage conditions. Store out of reach of children at a temperature not exceeding 30 °C.

Packaging. 2 blisters of 10 tablets in a cardboard box.

Classification for supply. Over-the-counter (without prescription).

Manufacturer. mibe GmbH Arzneimittel.

Manufacturer's address.
Muenchenstrasse 15, Brehna, Saxony-Anhalt, 06796, Germany.

Date of latest revision.