Drotaverine

Pharmacological properties

Drotaverin, a derivative of isoquinoline, has an antispasmodic effect on smooth muscles by inhibiting the action of the PDE iv enzyme, which leads to an increase in cAMP concentration and, due to inactivation of the myosin kinase (mlck) light chain, leads to relaxation of smooth muscles.

In vitro, drotaverin inhibits the action of the PDE IV enzyme and inhibits PDE III and V isoenzymes. PDE IV is of great functional importance for reducing contractile activity of smooth muscles, therefore, selective inhibitors of this enzyme can be useful for treating patients with diseases that are accompanied by hypermotility, as well as with various diseases in which gastrointestinal spasms occur.

In cells of smooth muscles of the myocardium and blood vessels, cAMP is hydrolyzed mainly by PDE III isoenzyme, therefore Drotaverine is an effective antispasmodic, does not cause significant side effects from the cardiovascular system and a pronounced therapeutic effect on this system.

Drotaverin is effective for smooth muscle spasms of both nervous and muscular origin. Drotaverin acts on the smooth muscles of the digestive, biliary, genitourinary and vascular systems, regardless of the type of autonomic innervation. The tool enhances blood circulation in the tissues due to its ability to dilate blood vessels.

The effect of drotaverine is stronger than the action of papaverine, absorption is faster and more complete, it is less associated with plasma proteins. The advantage of drotaverine is also that, unlike papaverine, after its parenteral administration, such a side effect as respiratory stimulation is not observed.

Pharmacokinetics Drotaverin is rapidly and completely absorbed after oral administration. In many ways (95–98%) it binds to blood plasma proteins, especially albumin, gamma and beta globulins. C_max in the blood after ingestion is achieved after 45-60 minutes. After primary metabolism, 65% of the dose taken enters the bloodstream unchanged. Metabolized in the liver. T_½ is 8–10 hours. In 72 hours, drotaverin is almost completely excreted, more than 50% is excreted in the urine, and 30% is excreted. Basically, drotaverin is excreted in the form of metabolites, unchanged in the urine is not determined.

Indications

For therapeutic purposes, for smooth muscle spasms associated with diseases of the biliary tract (cholecystolithiasis, cholangiolithiasis, cholecystitis, pericholecystitis, cholangitis, papillitis); smooth muscle spasms in diseases of the urinary tract (nephrolithiasis, urethrolithiasis, pyelitis, cystitis, tenesmus of the bladder).

As an adjunct treatment for gastrointestinal smooth muscle spasms (gastric and duodenal ulcers, gastritis, cardio and / or pylorospasm, enteritis, colitis, spastic colitis with constipation and irritable bowel syndrome, accompanied by flatulence); tension headache; gynecological diseases (dysmenorrhea).

Application

Tablets. apply the drug inside.

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

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

Children over the age of 12 years: the maximum daily dose is 160 mg, distributed in 2–4 doses.

The duration of treatment is determined individually.

Rr. The drug is used for adults in oil at a dose of 40–240 mg in 1-3 injections.

In acute colic, the drug should be used by adults iv slowly in a dose of 40–80 mg.

Contraindications

Hypersensitivity to drotaverine or other components of the drug (for solution, to sodium metabisulfite), severe hepatic, renal or heart failure (low cardiac output syndrome).

Side effects

The side effects that were observed during clinical trials and may have been caused by drotaverine are divided by organ systems and frequency of occurrence: very often (1/10), often (1/100, 1/10), infrequently (1/1000, 1/100), rarely (1/10 000, 1/1000), very rarely (1/10 000).

From the gastrointestinal tract: rarely - nausea, vomiting, constipation.

From the nervous system: rarely - headache, dizziness, insomnia.

From the cardiovascular system: rarely - heart palpitations, arterial hypotension.

On the part of the immune system: rarely - allergic reactions, including angioedema, urticaria, skin rashes, itching, flushing of the skin, fever, chills, fever, weakness.

The solution in the form of a solution contains metabisulfite, which can cause allergic reactions, including symptoms of anaphylactic shock and bronchospasm in sensitive patients, especially with AD or a history of allergies.

General disorders: hypersensitivity reactions at the injection site.

special instructions

Use the drug with caution in case of arterial hypotension.

Excipients. Drotaverin-Darnitsa contains 64 mg of lactose, therefore, the drug should not be used in patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.

Hypersensitivity reactions. Drotaverine refers to drugs - histamine liberators and can cause non-allergic (false-allergic) reactions that do not have immunological mechanisms, but mimic allergic symptoms (the phenomenon of mimicry). They are usually associated with non-immune secretion of histamine, bradykinin, complement activation, induction of the synthesis of leukotrienes, which, in turn, induces bronchospasm and skin manifestations. The drug should be used with caution in patients with a history of allergic reactions or AD. If symptoms of a hypersensitivity reaction appear after taking drotaverin (rash, itching, swelling of the tissues of the upper respiratory tract), the drug should be immediately discontinued and appropriate therapy prescribed. In case of symptoms of angioedema or urticaria rash, oral antihistamines should be used.

If AD is known in the patient, inhaled β₂-agonist. It is necessary to monitor the patients condition over the next 4 hours. In the presence of continuous vomiting and / or abdominal pain, the possibility of administering epinephrine IM should be considered.

With the on / in the introduction of the drug, the patient should be in a horizontal position due to the risk of collapse.

Use the drug with caution in case of arterial hypotension.

Caution should be exercised during parenteral administration of the drug in pregnant women (see Use during pregnancy and lactation).

The solution in the form of a solution contains metabisulfite, which can cause allergic reactions, including symptoms of anaphylactic shock and bronchospasm in sensitive patients, especially those who have a history of AD or allergies.

In case of hypersensitivity to sodium metabisulfite, parenteral administration of the drug should be avoided.

Use during pregnancy and lactation. As the results of animal studies have shown, the oral administration of the drug did not cause any signs of any direct or indirect effect on pregnancy, fetal development, childbirth or postpartum development. However, it is necessary to use the drug with caution during pregnancy. Do not use drotaverine during childbirth.

Due to the lack of data from relevant studies during breastfeeding, the use of the drug is not recommended.

Children. For children under 6 years of age, the use of the drug is contraindicated.The use of drotaverine in children has not been evaluated in clinical studies. The drug in the form of a solution is not used in children.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. If a patient is dizzy after using the drug, they should avoid potentially dangerous activities, such as driving vehicles and performing work that requires increased attention. You should refrain from driving vehicles or working with other mechanisms during the use (especially iv) of the drug.

Interactions

With simultaneous use with levodopa, a decrease in the antiparkinsonian effect of the latter is possible. this combination should be used with caution, since the antiparkinsonian effect of levodopa is reduced, and rigidity and tremor are enhanced.

Overdose

Symptoms: with a significant overdose of drotaverin, cardiac rhythm and conduction disturbances were noted, including complete blockage of the bundle of the duct and cardiac arrest, which can be fatal.

Treatment: in case of overdose, the patient should be under close medical supervision and receive symptomatic treatment, including inducing vomiting and / or gastric lavage.

Storage conditions

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