DROTAVERINE

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DROTAVERINE (DROTAVERINE)

Composition:

Active substance: drotaverine;

1 tablet contains 40 mg of drotaverine hydrochloride, calculated as 100% dry substance;

Excipients: lactose monohydrate; potato starch; povidone; magnesium stearate; sodium croscarmellose.

Pharmaceutical form. Tablets.

Main physical and chemical properties: tablets from light yellow to yellowish-green in color.

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

Pharmacological properties.

Pharmacodynamics. Drotaverine is an isoquinoline derivative that exerts a spasmolytic effect directly on smooth muscle by inhibiting the enzyme phosphodiesterase IV (PDE IV), leading to increased concentrations of cyclic adenosine monophosphate (cAMP). This, in turn, results in the inactivation of the myosin light chain kinase (MLCK), causing relaxation of smooth muscles.

In vitro, drotaverine inhibits the activity of PDE IV enzyme and does not affect the activity of phosphodiesterase III (PDE III) and phosphodiesterase V (PDE V) isoenzymes. 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 diseases associated with hypermotility, 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 is an effective spasmolytic agent that does not cause significant adverse effects on the cardiovascular system or exert strong therapeutic effects on this system.

Drotaverine is effective against smooth muscle spasms of both neural and muscular origin. It acts on the smooth muscle of the gastrointestinal, biliary, genitourinary, and vascular systems independently of their type of autonomic innervation. It enhances tissue circulation 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 albumins, α- and β-globulins. Maximum blood concentration is reached within 45–60 minutes after oral administration. Following 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: approximately 50% is excreted in urine and approximately 30% in feces. Drotaverine is mainly excreted in the form of metabolites; the unchanged form is not detected in urine.

Clinical characteristics.

Indications. Use for the treatment of:

− smooth muscle spasms associated with biliary tract diseases: cholelithiasis, cholangiolithiasis, cholecystitis, pericholecystitis, cholangitis, papillitis;

− smooth muscle spasms in urinary tract diseases: nephrolithiasis, ureterolithiasis, pyelitis, cystitis, bladder tenesmus.

As an adjunctive treatment 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 and irritable bowel syndrome accompanied by meteorism;

− tension headache;

− gynecological disorders (dysmenorrhea).

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

Interaction with other medicinal products and other forms of interaction. Phosphodiesterase inhibitors, such as papaverine, reduce the antiparkinsonian effect of levodopa. Concomitant use of this medicinal product with levodopa should be administered with caution, since the antiparkinsonian effect of levodopa is reduced and rigidity and tremor are intensified.

Special precautions for use

Use with particular caution in patients with arterial hypotension.

The preparation contains lactose. If the patient has been diagnosed with intolerance to certain sugars, medical advice should be sought before taking this medicinal product.

Use during pregnancy or breastfeeding

Pregnancy. After oral administration of drotaverine to animals, no signs of direct or indirect effects on pregnancy, embryonic development, labour, or postnatal development have been observed. However, the drug should be used with caution in pregnant women.

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

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

Ability to influence reaction speed when driving or operating machinery. If patients experience dizziness after taking the drug, they should avoid potentially hazardous activities such as driving a car or working that requires heightened attention.

Method of administration and dosage.

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

In case of drotaverine use in children:

for children aged 6–12 years, the maximum daily dose is 80 mg (divided into 2 doses);

for children aged 12 years and older, the maximum daily dose is 160 mg (divided into 2–4 doses).

Children. The use of the drug is contraindicated in children under 6 years of age.

Overdose.

Symptoms: in cases of significant drotaverine overdose, cardiac rhythm and conduction disturbances 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 treatment, including induction of vomiting and/or gastric lavage.

Adverse reactions.

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

Cardiovascular system disorders: tachycardia, arterial hypotension.

Nervous system disorders: headache, dizziness, insomnia.

Gastrointestinal disorders: nausea, constipation, vomiting.

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. Tablets: 10 in a blister; 10, or 10 × 2 in blisters, in a box.

Release category: Over-the-counter (without prescription).

Manufacturer:

LIMITED LIABILITY COMPANY "CORPORATION "ZDOROV'YA".

Limited Liability Company "Research Plant "GNCLC".

Limited Liability Company "FARMEKS GROUP".

Manufacturer's address and place of business:

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

(LIMITED LIABILITY COMPANY "CORPORATION "ZDOROV'YA")

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

(Limited Liability Company "Research Plant "GNCLC")

08301, 100 Shevchenka Street, Boryspil, Kyiv Oblast, Ukraine.

(Limited Liability Company "FARMEKS GROUP")