Composition

One tablet contains:active substance – drotaverine hydrochloride 40 mg
Excipients: magnesium stearate (E470), talc (E553), povidone (E1201), corn starch, lactose monohydrate.

Pharmacotherapeutic group:Medicinal product for the treatment of functional disorders of the gastrointestinal tract. Papaverine and its derivatives.

Pharmacological action
Mechanism of action:Drotaverine is an isoquinoline derivative that exhibits a spasmolytic effect on smooth muscle by inhibiting the enzyme phosphodiesterase IV (PDE IV). Inhibition of PDE IV leads to an increased concentration of cAMP, which causes inactivation of myosin light-chain kinase and results in relaxation of smooth muscle.
In vitro, drotaverine inhibits PDE IV without inhibiting the isoenzymes PDE III and PDE V. To reduce smooth muscle contractility, PDE IV is functionally very important, andits selective inhibitors may be useful in the treatment of hyperkinetic diseases and various symptoms caused by spasmodic conditions of the gastrointestinal tract.
The PDE III isoenzyme hydrolyzes cAMP in the myocardium and vascular smooth muscle; this explains the fact thatdrotaverine is an effective spasmolytic agent without serious cardiovascular adverse effects and without strong therapeutic activity on the cardiovascular system.

The product is effective in spasms of smooth muscle of both neurogenic and muscular etiology caused by disturbances of nervous regulation and self-regulation. Regardless of the type of autonomic innervation, drotaverine acts on the smooth muscles of the gastrointestinal, biliary, urogenital, and vascular systems.
Due to its vasodilatory effect, it improves blood circulation in tissues.
Compared with papaverine, its effect is stronger, and absorption is faster and more complete; it binds less to plasma proteins. An advantage of drotaverine is the absence of a stimulating effect on the respiratory system, which was observed after parenteral administration of papaverine.

Pharmacokinetics
Absorption:Drotaverine is rapidly and completely absorbed after both oral administration and intramuscular injection.

Distribution:Drotaverine binds to plasma proteins to a high degree, especially albumin (95–98%), alpha- and beta-globulins. Maximum plasma concentration is reached 45–60 minutes after administration.

Biotransformation and excretion:
Drotaverine is metabolized in the liver; its elimination half-life is 8–10 hours. After first-pass hepatic metabolism, 65% of the dose is present in the bloodstream in unchanged form. Within 72 hours, drotaverine is almost completely eliminated from the body; more than 50% is excreted in urine and about 30% with feces. Drotaverine is mainly excreted in the form of metabolites; the parent compound is not detected in urine.

Indications for use:
• Spasm of smooth muscle associated with diseases of the biliary tract: cholelithiasis, cholangiolithiasis, cholecystitis, pericholecystitis, cholangitis, papillitis;
• Spasm of smooth muscle of the urinary tract: nephrolithiasis, ureterolithiasis, pyelitis, cystitis, bladder tenesmus;
• Spasm of smooth muscle of the gastrointestinal tract: gastric and duodenal ulcer disease, gastritis, spasm of the cardiac and pyloric regions of the stomach, enteritis, colitis, spastic colitis with constipation and mucous colitis with flatulence;
• Tension-type headache (muscle-tension headache, psychogenic, stress-related, chronic daily headache, transformed migraine);
• In gynecology: painful menstruation.

Contraindications:
• Hypersensitivity to the active substance or any excipient of the product;
• Severe hepatic or renal insufficiency;
• Severe heart failure.

Method of administration and dosage:

Adults
The usual daily dose is 120–240 mg, i.e. 3–6 tablets per day, taken in 2–3 divided doses. A single dose for adults is 40–80 mg (1–2 tablets).

Children
Clinical studies on the use of drotaverine in children have not been conducted.
If the use of drotaverine in children is necessary:
Children aged 6–12 years:the recommended daily dose for children over 6 years of age is 80 mg, i.e. 2 tablets per day in two doses. A single dose for children aged 6–12 years is 40 mg (1 tablet).
Children over 12 years of age:the recommended daily dose is 160 mg, i.e. 4 tablets per day in 2–4 doses. A single dose for children over 12 years of age is 40–80 mg, i.e. 1–2 tablets.
There are no data on the use of the product in children under 6 years of age.

Overdose:
Overdose of drotaverine may cause disturbances of cardiac rhythm and conduction, including complete block of the bundle of His and cardiac arrest, which may lead to a fatal outcome.
In case of overdose, the patient should be kept under observation and receive symptomatic and supportive treatment. Induction of vomiting and/or gastric lavage is recommended.

Adverse reactions:
• Gastrointestinal disorders:
Rare: nausea, constipation
• Nervous system disorders:
Rare: headache, dizziness, insomnia
• Cardiovascular disorders:
Rare: palpitations, decreased arterial blood pressure
• Immune system disorders:
Rare: allergic reactions (angioedema, urticaria, rash, itching) (see section “Contraindications”).

If adverse reactions occur, use of the product should be discontinued.
If any of the listed adverse reactions or reactions not mentioned in this leaflet occur,consult a doctor.

Interaction with other medicinal products:
Caution is required when used concomitantly with levodopa, as the antiparkinsonian effect of the latter is reduced and an increase in tremor or rigidity may be observed.

Special warnings and precautions:

Use with caution in cases of decreased arterial blood press

The product contains 52 mg of lactose. According to the recommended dosage, each dose contains up to 156 mg of lactose. This may cause gastrointestinal complaints in patients with lactose intolerance.

This dosage form is not suitable for patients with lactase deficiency, galactosemia, or glucose/galactose malabsorption syndrome.

Use in children should be strictly according to indication, since the use of drotaverine in this group of patients has been insufficiently studied (see “Indications for use” and “Method of administration and dosage”). Clinical studies in children have not been conducted.

Pregnancy, breastfeeding, and fertility:
According to data from retrospective clinical studies and animal studies, oral use of drotaverine during pregnancy does not cause direct or indirect harmful effects on the course of pregnancy, embryonic development, childbirth, or postnatal development. However, caution is required when prescribing the product during pregnancy. Due to the lack of sufficient clinical data, use during breastfeeding is not recommended.
There are no data on the effect of the product on fertility.

Effects on ability to drive vehicles or operate machinery:
In case of dizziness, refrain from potentially hazardous activities such as driving vehicles and operating machinery.

Shelf life:3 years. Do not use after the expiry date.

Storage conditions:
Keep out of the reach of children!
Tablets in PVC/aluminum blister packaging: store at a temperature not exceeding 25°C, protected from light.
Tablets in a bottle: store at a temperature not exceeding 25°C, protected from light.

Dispensing conditions:Pharmaceutical product group III, dispensed without a prescription.

Marketing authorization holder:“Opella Healthcare Commercial Ltd.”
Manufacturer:“Opella Healthcare Hungary Ltd.”