Drotaverine

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT DROTAVERINE (DROTAVERINUM)

Composition:

Active ingredient: drotaverini hydrochloridum;

One tablet contains: drotaverini hydrochloridum – 0.04 g;

Excipients: cellulose microcrystalline, starch potato, lactose monohydrate, silicon dioxide colloidal anhydrous, calcium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: round tablets ranging from light yellow to dark yellow in color, with a biconvex surface; marbling is permissible.

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 directly on smooth muscle by inhibiting the enzyme phosphodiesterase IV (PDE IV), leading to increased cAMP concentration. This 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 and does not affect the activity of phosphodiesterase III (PDE III) and 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 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 without significant adverse effects on the cardiovascular system and lacks strong therapeutic effects on this system.

Drotaverine is effective against smooth muscle spasms of both neural and muscular 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 it binds less to serum proteins. An additional advantage of drotaverine is that, unlike papaverine, respiratory stimulation is not observed as a side effect following parenteral administration.

Pharmacokinetics.

Drotaverine is rapidly and completely absorbed after oral administration. It is highly bound (95–98%) to plasma albumins, gamma- and beta-globulins. Maximum serum concentration is achieved within 45–60 minutes after oral administration. After primary 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 approximately 50% excreted in urine and about 30% in feces. Drotaverine is mainly excreted in the form of metabolites; the unchanged form is not detected in urine.

Clinical characteristics.

Indications.

For therapeutic use in:

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

− smooth muscle spasms in urinary tract disorders: nephrolithiasis, ureterolithiasis, pyelitis, cystitis, vesical tenesmus.

As 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 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. Drotaverine should be used with caution concomitantly with levodopa, as the antiparkinsonian effect of the latter is diminished and rigidity and tremor are intensified.

Special precautions for use.

Use with caution in arterial hypotension.

Drotaverine medication contains lactose. Do not use for treatment of patients with rare hereditary disorders such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption syndrome.

Use during pregnancy or breastfeeding.

Pregnancy. Due to insufficient clinical data, the drug should be administered to pregnant women only if the expected benefits outweigh the potential risks. The active substance crosses the placental barrier. The drug must not be used during labor due to increased risk of postpartum hemorrhage.

Breastfeeding. Since drotaverine is excreted in breast milk, use of the drug during breastfeeding is not recommended.

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

Ability to influence reaction rate while driving or operating machinery.

If dizziness occurs after administration of the drug, driving and performing tasks requiring high attention should be avoided.

Method of administration and dosage.

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

Children: the use of drotaverine in children has not been studied in clinical trials; however, if administration of drotaverine is necessary, then:

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).

There are no data regarding the use of the drug in children under 6 years of age.

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

The use of drotaverine in children has not been evaluated in clinical studies.

Overdose.

Symptoms: in case of significant overdose of drotaverine, cardiac rhythm and conduction disturbances have been observed, including complete bundle branch block of His 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.

Side effects.

Adverse reactions observed during clinical trials and possibly caused by drotaverine, classified by organ system 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), frequency not known: cannot be estimated from available data.

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

Do not use after the expiry date stated on the packaging.

Storage conditions.

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

Keep out of reach of children.

Packaging.

10 tablets in a blister pack, 1 or 2 blisters per cardboard box.

Prescription status.

Over-the-counter (without prescription).

Manufacturer.

PJSC "CHIMFARMAZAVOD "CHERVONA ZIRKA".

Manufacturer's address and location of business activity.

1, Gordienkovska Street, Kharkiv, Kharkiv Oblast, 61010, Ukraine.