No-spa® forte

Composition:

Active ingredient: drotaverine;

1 tablet contains drotaverine hydrochloride 80 mg;

Excipients: magnesium stearate, talc, povidone, corn starch, lactose monohydrate.

Pharmaceutical form. Tablets.

Main physicochemical properties: yellowish oblong tablets with a greenish or orange tint, convex on both sides; on one side marked "NOSPA", on the other – a break line.

The approximate dimensions of the tablet are: length 13 mm, width 6 mm, height 3.8 mm.

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

Pharmacological properties.

Pharmacodynamics.

Drotaverine – an isoquinoline derivative – exerts a spasmolytic effect on smooth muscle by inhibiting the activity of phosphodiesterase IV (PDE IV), leading to increased cAMP concentration. This results in the inactivation of myosin light chain kinase (MLCK), thereby causing smooth muscle relaxation.

In vitro, drotaverine inhibits the activity of PDE IV enzyme and does not inhibit isoenzymes phosphodiesterase III (PDE III) or phosphodiesterase V (PDE V). PDE IV is functionally significant 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; hence, drotaverine acts as an effective spasmolytic agent without significant adverse effects on the cardiovascular system or 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.

The drug 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 binds less to serum proteins. An additional advantage of drotaverine is that, unlike papaverine, parenteral administration does not produce the side effect of respiratory stimulation.

Pharmacokinetics.

Drotaverine is rapidly and completely absorbed after oral administration. It is highly bound (95–98%) to plasma proteins, particularly to albumin, gamma- and beta-globulins. Maximum concentration is reached within 45–60 minutes after oral administration. After first-pass 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, with more than 50% excreted in urine and approximately 30% in feces. Drotaverine is primarily excreted in the form of metabolites; the unchanged compound is not detected in urine.

Clinical characteristics.

Indications. For therapeutic use in:

• 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, bladder tenesmus.

As an adjunctive treatment in:

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

Contraindications. Hypersensitivity to drotaverine or any component of the drug. Severe hepatic or renal insufficiency. Cardiac insufficiency (low cardiac output syndrome).

Interaction with other medicinal products and other forms of interaction. Phosphodiesterase inhibitors (NO-SHPA® Forte, papaverine) reduce the anti-parkinsonian effect of levodopa.

NO-SHPA® Forte should be used with caution concomitantly with levodopa, as the anti-parkinsonian effect of the latter is diminished, while rigidity and tremor may be exacerbated.

Special precautions for use.

Use with particular caution in patients with arterial hypotension. Clinical studies with drotaverine involving children have not been conducted.

One tablet of NO-SHPA® forte contains 104 mg of lactose. When used according to recommended doses, up to 156 mg of lactose may enter the body per dose, which may lead to gastrointestinal complaints in patients with lactose intolerance.

Do not use for treatment of patients with lactase deficiency, galactosemia, or glucose-galactose malabsorption syndrome.

Use during pregnancy or breastfeeding. 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, labor, or postnatal development. However, the drug should be prescribed to pregnant women with caution.

Due to lack of data from appropriate studies during breastfeeding, use of the drug is not recommended.

Fertility

There is no information regarding effects on human fertility.

Ability to influence reaction rate while driving or operating machinery. If dizziness occurs after taking the drug, driving and performing tasks requiring high attention should be avoided.

Method of administration and dosage.

The NO-SHPA® forte tablet can be divided in half.

Adults: The usual average dose is 120–240 mg per day in 2–3 divided doses.

Children aged 12 years and older: If necessary, under medical prescription, 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. Use of the drug for treatment of children under 12 years of age is contraindicated. The use of drotaverine in children has not been evaluated in clinical studies.

Overdose. Symptoms: In cases of significant drotaverine overdose, 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 should be under close medical supervision and receive symptomatic and supportive treatment. Induction of vomiting and/or gastric lavage is recommended.

Adverse Reactions.

Adverse events observed during clinical trials and possibly associated with drotaverine are listed by system organ class and frequency of occurrence: very common (> 1/10), common (> 1/100, <1/10), uncommon (> 1/1000, <1/100), rare (> 1/10,000, <1/1000), very rare (<1/10,000).

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

Cardiovascular system disorders. Rare: tachycardia, arterial hypotension.

Nervous system disorders. Rare: headache, dizziness, insomnia.

Gastrointestinal disorders. Rare: nausea, constipation, vomiting.

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. 10: 10 tablets in a blister pack, 1 blister pack in a cardboard box.

No. 24: 24 tablets in a blister pack, 1 blister pack in a cardboard box.

Classification by prescription. Over-the-counter.

Manufacturers. Opella Healthcare Hungary Kft.

Opella Healthcare Poland Sp. z o.o.

Manufacturer addresses and locations of their operations.

5 Levei Street, Veresegyhaz, 2112, Hungary.

52 Lubelska Street, 35-233 Rzeszów, Poland.

Marketing Authorization Holder. Opella Healthcare Ukraine LLC, Ukraine.

Address of the marketing authorization holder and/or its representative.

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