Drotaverine-darnitsa

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT DROTAVÉRINE-DARNYTSIA (DROTAVERINE-DARNYTSIA)

Composition:

Active substance: drotaverine;

One tablet contains 40 mg of drotaverine hydrochloride;

Excipients: lactose monohydrate, corn starch, microcrystalline cellulose, colloidal anhydrous silicon dioxide, magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: tablets of light yellow or dark yellow color with speckles, flat cylindrical shape, beveled edge and a score line.

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

Pharmacological Properties

Pharmacodynamics

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

In vitro, drotaverine inhibits the activity of the enzyme PDE IV and also inhibits the isoenzymes phosphodiesterase III (PDE III) and phosphodiesterare 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 acts as an effective spasmolytic agent without significant adverse effects on the cardiovascular system or strong therapeutic effects on this system.

Drotaverine-Darnitsia 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 independently of their type of 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 lower plasma protein binding. An additional advantage of drotaverine is that, unlike papaverine, it does not cause respiratory stimulation as a side effect following parenteral administration.

Pharmacokinetics

Drotaverine-Darnitsia is rapidly and completely absorbed after oral administration. It binds extensively (95–98%) to plasma proteins, particularly to albumin, gamma-, and beta-globulins. Maximum plasma concentration is reached within 45–60 minutes after oral intake. Following first-pass metabolism, 65% of the administered dose enters systemic circulation unchanged. The drug is metabolized in the liver. The 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 approximately 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:

• Spasms of smooth musculature associated with biliary tract disorders: cholelithiasis, cholangiolithiasis, cholecystitis, pericholecystitis, cholangitis, papillitis;
• Spasms of smooth musculature in urinary tract disorders: nephrolithiasis, ureterolithiasis, pyelitis, cystitis, urinary bladder tenesmus.

As adjunctive therapy in:

• Spasms of gastrointestinal smooth musculature: peptic ulcer disease 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 other component of the medicinal product; severe hepatic, renal or cardiac insufficiency (low cardiac output syndrome).

Interaction with other medicinal products and other forms of interaction.

When used concomitantly with levodopa, a reduction in the antiparkinsonian effect of the latter may occur. This combination should be used with caution, as the antiparkinsonian effect of levodopa is diminished, while rigidity and tremor are intensified.

Special precautions for use.

The medicinal product should be used with caution in patients with arterial hypotension.

Excipients.

Drotaverine-Darnitsia contains 64.0 mg of lactose monohydrate; therefore, the medicinal product must not be administered to patients with rare hereditary forms of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.

Hypersensitivity reactions.

Drotaverine belongs to medicinal products that release histamine and may cause non-allergic (pseudoallergic) reactions, which lack immunological mechanisms but mimic allergic symptoms (phenomenon of mimicry). These reactions are usually associated with non-immune release of histamine, bradykinin, activation of complement, and induction of leukotriene synthesis, which in turn may induce bronchospasm and skin manifestations. The medicinal product should be prescribed with caution to patients with a history of allergic reactions or bronchial asthma. If symptoms of hypersensitivity reactions occur after taking drotaverine (rash, itching, swelling of upper respiratory tract tissues), the drug should be discontinued immediately and appropriate therapy initiated. In case of angioedema or urticarial rash, oral antihistamines should be administered.

If the patient has a known history of asthma, an inhaled beta-2 agonist should be administered. The patient should be observed for the next 4 hours. In the presence of persistent vomiting and/or abdominal pain, intramuscular administration of epinephrine should be considered.

Use during pregnancy or breast-feeding.

Animal studies have shown that oral administration of drotaverine does not cause any signs of direct or indirect effects on pregnancy, embryonic development, labor, or postnatal development. However, the medicinal product should be used with caution during pregnancy.

Due to the lack of adequate studies during lactation, use of the medicinal product is not recommended.

Ability to influence reaction rate while driving or operating machinery.

If patients experience dizziness after taking the medicinal product, they should avoid potentially hazardous activities such as driving a car or performing tasks requiring increased attention.

Method of administration and dosage.

Drotaverine-Darnytsia should be administered orally.

Adults: the average daily dose is 120–240 mg (3–6 tablets), divided into 2–3 doses.

Children aged 6–12 years: maximum daily dose is 80 mg, divided into 2 doses.

Children aged 12 years and older: maximum daily dose is 160 mg, divided into 2–4 doses.

Duration of treatment is determined individually.

Children. The use of the medicinal product 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 cases of significant overdose, disturbances in cardiac rhythm and conduction have been observed, including complete bundle branch block of His and cardiac arrest, which may be fatal.

Treatment: 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, are categorized by organ system 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).

Gastrointestinal tract. Rare: nausea, constipation, vomiting.

Nervous system. Rare: headache, dizziness, insomnia.

Cardiovascular system. Rare: tachycardia, arterial hypotension.

Immune system. Rare: allergic reactions, including angioedema, urticaria, skin rash, pruritus, skin hyperemia, fever, chills, elevated body temperature, weakness.

Shelf life. 3 years.

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

Storage conditions. Store in a place inaccessible to children, in the original packaging, at a temperature not exceeding 25 °C.

Packaging. 10 tablets in a blister pack; 2 or 3 blisters per carton.

Availability category. Over-the-counter.

Manufacturer. JSC "Pharmaceutical Company "Darnitsya".

Manufacturer's location and address of business activity.

Ukraine, 02093, Kyiv, Borispilska St., 13.

INSTRUCTIONS

for medical use of the medicinal product

DROTAVERINE-DARNITSA

(DROTAVERINE-DARNITSA)

Composition:

Active substance: drotaverine;

1 tablet contains 40 mg of drotaverine hydrochloride;

Excipients: monohydrate lactose, corn starch, microcrystalline cellulose, colloidal anhydrous silicon dioxide, magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: light yellow or dark yellow tablets with speckles, flat cylindrical in shape, beveled edges and a score line.

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

Pharmacological properties.

Pharmacodynamics.

Drotaverine-Darnitsa is an isoquinoline derivative that exerts a spasmolytic effect on smooth muscle by inhibiting phosphodiesterase IV (PDE IV) enzyme activity, leading to increased cAMP concentration. This inactivates the myosin light chain kinase (MLCK), resulting in relaxation of smooth muscles.

In vitro, drotaverine inhibits PDE IV enzyme activity and also inhibits isoenzymes phosphodiesterase III (PDE III) and phosphodiesterase V (PDE V). PDE IV plays a significant functional role in reducing contractile activity of smooth muscles; therefore, selective inhibitors of this enzyme may be beneficial in treating conditions associated with hypermotility, as well as various disorders 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 acts as an effective spasmolytic agent without significant cardiovascular side effects or strong therapeutic effects on this system.

Drotaverine-Darnitsa is effective against smooth muscle spasms of both neural and muscular origin. It acts on smooth muscles of the gastrointestinal, biliary, urogenital, and vascular systems regardless of their type of autonomic innervation. The drug improves tissue blood flow due to its vasodilatory properties.

The spasmolytic effect of drotaverine is stronger than that of papaverine, with faster and more complete absorption and lower plasma protein binding. An advantage of drotaverine is that, unlike papaverine, it does not cause respiratory stimulation as a side effect following parenteral administration.

Pharmacokinetics.

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

Clinical characteristics.

Indications.

For therapeutic use in:

• Smooth muscle spasms associated with biliary tract diseases: cholelithiasis, choledocholithiasis, cholecystitis, pericholecystitis, cholangitis, papillitis;
• Smooth muscle spasms in urinary tract disorders: nephrolithiasis, ureterolithiasis, pyelitis, cystitis, bladder tenesmus.

As adjunctive treatment in:

• Gastrointestinal smooth muscle spasms: peptic ulcer disease 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 conditions (dysmenorrhea).

Contraindications.

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

Interaction with other medicinal products and other forms of interaction.

Concomitant use of this medicinal product with levodopa may reduce the antiparkinsonian effect of the latter. This combination should be used with caution, as the antiparkinsonian effect of levodopa may be diminished, while rigidity and tremor may worsen.

Special precautions.

The medicinal product should be used with caution in patients with arterial hypotension.

Excipients.

Drotaverine-Darnitsa contains 64.0 mg of monohydrate lactose; therefore, the drug should not be administered to patients with rare hereditary forms of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.

Hypersensitivity reactions.

Drotaverine belongs to the group of histamine-liberating drugs and may cause non-allergic (pseudoallergic) reactions that lack immunological mechanisms but mimic allergic symptoms (mimicry phenomenon). These are usually associated with non-immune release of histamine and bradykinin, complement activation, and induction of leukotriene synthesis, which in turn may induce bronchospasm and skin manifestations. The drug should be prescribed with caution to patients with a history of allergic reactions or bronchial asthma. If symptoms of hypersensitivity occur after drotaverine intake (rash, pruritus, swelling of upper respiratory tract tissues), the drug should be discontinued immediately and appropriate therapy initiated. In case of angioedema or urticarial rash, oral antihistamines should be administered.

If the patient has a history of asthma, an inhaled beta-2 agonist should be administered. The patient should be monitored for the next 4 hours. In case of persistent vomiting and/or abdominal pain, intramuscular epinephrine should be considered.

Use during pregnancy or breastfeeding.

Animal studies have shown that oral administration of drotaverine does not cause any signs of direct or indirect adverse effects on pregnancy, embryonic development, delivery, or postnatal development. However, the drug should be used with caution during pregnancy.

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

Ability to affect reaction speed when driving or operating machinery.

If patients experience dizziness after taking the drug, they should avoid potentially hazardous activities such as driving or performing tasks requiring high concentration.

Method of administration and dosage.

Drotaverine-Darnitsa should be taken orally.

Adults: The average daily dose is 120–240 mg (3–6 tablets), divided into 2–3 doses.

Children aged 6–12 years: Maximum daily dose is 80 mg, divided into 2 doses.

Children over 12 years: Maximum daily dose is 160 mg, divided into 2–4 doses.

Duration of treatment is determined individually.

Children. 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 trials.

Overdose.

Symptoms: In cases of significant overdose, cardiac rhythm and conduction disturbances have been observed, including complete bundle branch block and cardiac arrest, which may be fatal.

Treatment: In case of overdose, the patient must 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 are categorized by organ system 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).

Gastrointestinal tract. Rare: nausea, vomiting, constipation.

Nervous system. Rare: headache, dizziness, insomnia.

Cardiovascular system. Rare: tachycardia, arterial hypotension.

Immune system. Rare: allergic reactions, including angioedema, urticaria, skin rash, pruritus, skin hyperemia, fever, chills, elevated body temperature, weakness.

Shelf life. 3 years.

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

Storage conditions. Store in a place inaccessible to children, in the original packaging, at a temperature not exceeding 25 °C.

Packaging. 10 tablets in a contour cell pack; 2 or 3 contour cell packs per carton.

Availability category. Over-the-counter.

Manufacturer. JSC "Pharmaceutical Company "Darnitsya".

Manufacturer's location and address of business activity.

Ukraine, 02093, Kyiv, Borispilska St., 13.