Brand name Drotaverine

Form tablets

Active substance / Dosage

drotaverine · 40 mg

Prescription type over-the-counter (OTC)

ATC code

A03AD02

Registration number UA/6289/01/01

Manufacturer PJSC "Kyivmedpreparat"

Table of Contents

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT DROTAVERINE
Composition:
Pharmacological Properties
Clinical Characteristics
Special precautions for use.
Method of administration and dosage.
Side effects.

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT DROTAVERINE

Composition:

Active ingredient: 1 tablet contains 40 mg of drotaverine hydrochloride, calculated as 100 % substance;

Excipients: potato starch; lactose monohydrate; povidone; calcium stearate.

Pharmaceutical form: Tablets.

Main physico-chemical properties: tablets of light yellow, light yellow with greenish tint, yellow, or yellow with greenish tint color, round-shaped with flat surface and bevelled edge. Marbling may be present on the tablet surface.

Pharmacotherapeutic group: Drugs used in functional gastrointestinal disorders.

ATC code: A03AD02.

Pharmacological Properties

Pharmacodynamics

Drotaverine is an isoquinoline derivative that exerts a spasmolytic effect on smooth muscle by inhibiting the enzyme phosphodiesterase IV (PDE IV), leading to increased concentrations of cAMP and, consequently, inactivation of myosin light chain kinase (MLCK), resulting in smooth muscle relaxation.

In vitro, drotaverine inhibits the activity of the enzyme PDE IV and does not affect the activity of the isoenzymes phosphodiesterase III (PDE III) and phosphodiesterase V (PDE V). PDE IV has significant functional importance 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 isoenzyme PDE III; thus, 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.

It enhances tissue blood flow due to its ability to dilate blood vessels.

Pharmacokinetics

The effect of drotaverine is stronger than that of papaverine, with faster and more complete absorption, and it binds less to serum proteins. Another advantage of drotaverine is that, unlike papaverine, respiratory stimulation as a side effect is not observed following parenteral administration.

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 first-pass metabolism, 65% of the administered dose enters the 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 the urine and approximately 30% in the feces. Drotaverine is mainly excreted in the form of metabolites and is not detected in unchanged form in urine.

Clinical Characteristics

Indications.

For therapeutic purposes in:

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

As adjunctive treatment in:

Spasms of gastrointestinal smooth muscle: 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 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 anti-parkinsonian effect of levodopa. Drotaverine should be used with caution concomitantly with levodopa, as the anti-parkinsonian effect of the latter is diminished, while rigidity and tremor are intensified.

Special precautions for use.

Use with particular caution in patients with arterial hypotension.

Each tablet of Drotaverine contains 50 mg of lactose. Do not use in patients with rare hereditary disorders such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption syndrome.

Use during pregnancy or breastfeeding.

Pregnancy. Results of retrospective clinical and animal studies have shown that oral administration of the drug did not cause any signs of direct or indirect effects on pregnancy, embryonal development, delivery, or postnatal development. However, the drug should be prescribed to pregnant women with caution.

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

Ability to influence reaction rate when driving or operating machinery.

If patients experience dizziness after taking the drug, they should avoid potentially hazardous activities such as driving a vehicle or performing tasks requiring heightened attention.

Method of administration and dosage.

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

When using drotaverine 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. Drotaverine 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.

In case of overdose, the patient must be under close medical supervision and receive symptomatic treatment, including induction of emesis and/or gastric lavage.

Side effects.

Adverse reactions possibly caused by drotaverine, classified 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 angioedema, urticaria, rash, pruritus, skin hyperemia, chills, fever, increased body temperature, weakness.

Cardiovascular system disorders: rare: tachycardia, arterial hypotension.

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

Gastrointestinal disorders: rare: nausea, constipation, vomiting.

Shelf life. 5 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging. 10 tablets per blister; 1, 2, or 3 blisters per carton.

Release category. Over-the-counter.

Manufacturer. JSC "Kyivmedpreparat".

Manufacturer's location and address of place of business activity.

Ukraine, 01032, Kyiv, Saksaganskogo St., 139.

INSTRUCTIONS

for medical use of medicinal product

DROTAVERINE

Composition:

Active ingredient: 1 tablet contains 40 mg drotaverine hydrochloride, calculated as 100% substance;

Excipients: potato starch; lactose monohydrate; povidone; calcium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: tablets are light yellow, light yellow with greenish tint, yellow or yellow with greenish tint, round-shaped with flat surface and bevelled edges. Marbling may be present on the tablet surface.

Pharmacotherapeutic group. Drugs used in functional gastrointestinal disorders.

ATC code A03AD02.

Pharmacological properties.

Pharmacodynamics.

Drotaverine 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 and, via inactivation of myosin light chain kinase (MLCK), resulting in smooth muscle relaxation.

In vitro, drotaverine inhibits PDE IV enzyme activity and does not affect phosphodiesterase III (PDE III) or phosphodiesterase V (PDE V) isoenzymes. PDE IV has significant functional importance 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 conditions involving gastrointestinal tract spasms.

In cardiac and vascular smooth muscle cells, cAMP is primarily hydrolyzed by PDE III isoenzyme; thus, drotaverine acts as an effective spasmolytic agent without significant cardiovascular side effects or pronounced therapeutic action on this system.

Drotaverine is effective against smooth muscle spasms of both neural and myogenic origin. It acts on smooth muscles of the gastrointestinal, biliary, urogenital, and vascular systems regardless of their type of autonomic innervation.

It enhances tissue blood flow due to its vasodilatory properties.

Pharmacokinetics.

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

Drotaverine is rapidly and completely absorbed after oral administration. It is highly bound (95–98%) to plasma proteins, including albumin, gamma- and beta-globulins. Maximum serum concentration is reached within 45–60 minutes after oral intake. After first-pass metabolism, 65% of the administered dose enters systemic circulation unchanged.

Metabolized in the liver. Elimination half-life is 8–10 hours.

Within 72 hours, drotaverine is almost completely eliminated from the body: more than 50% is excreted via urine and approximately 30% via feces. Drotaverine is mainly excreted as metabolites; unchanged drug is not detected in urine.

Clinical characteristics.

Indications.

For therapeutic use in:

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

As additional therapy in:

Spasms of gastrointestinal smooth musculature: 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-type headache;
Gynecological conditions (dysmenorrhea).

Contraindications.

Hypersensitivity to drotaverine or 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 may reduce the antiparkinsonian effect of levodopa. Concomitant use of Drotaverine with levodopa should be performed with caution, as the antiparkinsonian effect of levodopa may be reduced and rigidity and tremor may worsen.

Special precautions.

Use with particular caution in patients with arterial hypotension.

Each tablet of Drotaverine contains 50 mg of lactose. Should not be used in patients with rare hereditary conditions such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption syndrome.

Use during pregnancy or breastfeeding.

Pregnancy. Results of retrospective clinical studies and animal studies indicate that oral administration of the drug does not produce any signs of direct or indirect adverse effects on pregnancy, embryonic development, labor, or postnatal development. However, the drug should be used with caution in pregnant women.

Breastfeeding. Due to lack of data during lactation, use of the drug 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 a vehicle or performing tasks requiring high concentration.

Method of administration and dosage.

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

When using drotaverine in children:

for children aged 6–12 years: maximum daily dose is 80 mg (divided into 2 doses);
for children aged 12 years and older: maximum daily dose is 160 mg (divided into 2–4 doses).

Children. Drotaverine 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, 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 treatment, including induction of emesis and/or gastric lavage.

Side effects.