Papaverine-zdorovya

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PAPAVERINE-ZDOROVYE (PAPAVERINE-ZDOROVYE)

Composition:

Active substance: papaverine;

1 ml of solution contains papaverine hydrochloride 20 mg;

Excipients: disodium edetate, methionine, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear solution with a slightly yellowish tint.

Pharmacotherapeutic group. Agents used in functional disorders of the gastrointestinal tract. Papaverine and its derivatives. ATC code A03A D01.

Pharmacological properties.

Pharmacodynamics.

Myotropic, spasmolytic, and antihypertensive agent.

The mechanism of action involves inhibition of the phosphodiesterase enzyme, promoting intracellular accumulation of cyclic 3',5'-adenosine monophosphate, which, as a result, leads to impaired contractility of smooth muscles and their relaxation in spastic conditions. Reduces intracellular calcium levels. Decreases tone and relaxes smooth muscles of internal organs (gastrointestinal, respiratory, and urogenital systems) and blood vessels. Causes arterial dilation and enhances blood flow, including cerebral circulation. In high doses, reduces myocardial excitability and slows intracardiac conduction. Effects on the central nervous system are weak (sedative effect may occur at high doses).

Pharmacokinetics.

High absorption rate. Plasma protein binding – 90%, forming stable complexes with serum albumin. Well distributed in body tissues and penetrates histohematogenous barriers. Metabolized in the liver. T½ – 0.5–2 hours (may be prolonged up to 24 hours). Excreted predominantly by the kidneys as metabolites.

Clinical Characteristics.

Indications.

• Smooth muscle spasms of abdominal organs (pylorospasm, irritable bowel syndrome, cholecystitis, biliary colic attacks);
• urinary tract spasms, renal colic;
• cerebral vessel spasm;
• peripheral vessel spasms (endarteritis).

Contraindications.

Hypersensitivity to any component of the drug, arterial hypotension, atrioventricular conduction disturbances, comatose state, respiratory depression, concurrent use of monoamine oxidase inhibitors, glaucoma, hepatic insufficiency, bronchoobstructive syndrome, age over 75 years (risk of hyperthermia).

Interaction with other medicinal products and other types of interactions.

The spasmolytic effect of papaverine is enhanced by barbiturates, diphenhydramine (dimenhydrinate), metamizole sodium (analgin), and diclofenac. The hypotensive effect is enhanced when used concurrently with antihypertensive agents of other classes, as well as with tricyclic antidepressants, procainamide, reserpine, and quinidine. Papaverine may reduce the antiparkinsonian effect of levodopa and the hypotensive effect of methyldopa. When used concurrently with alprostadil for intracavernous injection, there is a risk of priapism. Phentolamine potentiates the effect of papaverine on the corpora cavernosa of the penis when administered together.

When used concurrently with cardiac glycosides, a pronounced enhancement of myocardial contractile function occurs due to a reduction in total peripheral vascular resistance. When used together with procainamide, an enhanced hypotensive effect is possible.

A possible reduction in the tonic effect of anticholinesterase agents on smooth muscle under the influence of papaverine may occur.

A possible reduction in the spasmolytic activity of papaverine under the influence of morphine may occur. However, papaverine is used together with morphine to reduce the spasmogenic effect of the latter, and with promedol for pain associated with smooth muscle spasms.

There are reports of hepatitis development when used concomitantly with furadantin (nitrofurantoin).

When reserpine-containing drugs are used in combination with papaverine, the antihypertensive effect is enhanced.

When combined with antidepressants, an enhanced hypotensive effect is possible.

When used concurrently, papaverine potentiates the effect of alcohol.

In patients who smoke, the metabolism of papaverine is accelerated, and its plasma concentration and pharmacokinetic effects are reduced.

Pharmaceutically compatible with dibazol (diazoxide).

Special precautions.

The medicinal product should be prescribed with caution and in doses lower than the average therapeutic dose:

• in elderly and debilitated patients;
• in patients with head trauma;
• in patients with chronic renal insufficiency;
• in patients with supraventricular tachycardia, severe heart failure with signs of decompensation;
• in adrenal insufficiency, hypothyroidism, benign prostatic hyperplasia, shock states.

The intravenous administration of the drug should be performed very slowly with monitoring of arterial pressure, heart rate, and electrocardiogram.

Intravenous injections of the drug should be administered with caution in patients with stenosing coronary sclerosis.

Hyperthermia may occur in elderly patients.

Smoking reduces the effectiveness of the drug.

Alcohol consumption should be avoided during treatment with this drug.

This medicinal product contains less than 1 mmol/dose of sodium, i.e., it is practically sodium-free.

Use during pregnancy or breastfeeding.

The safety and efficacy of the drug during pregnancy or breastfeeding have not been established. Breastfeeding should be discontinued during treatment with this drug.

Ability to affect reaction speed when driving or operating machinery.

During treatment with this drug, patients should refrain from driving or operating complex machinery.

Administration and Dosage

The drug should be administered subcutaneously, intramuscularly, and intravenously.

Subcutaneously and intramuscularly, administer to adults and children aged 14 years and older 0.5–2 mL (10–40 mg) of a 2% solution. For intravenous administration, inject very slowly at a rate of 3–5 mL/min, after dissolving 1 mL of 2% papaverine hydrochloride solution (20 mg) in 10–20 mL of 0.9% sodium chloride solution. Intravenous administration is the most effective.

For elderly patients, the initial single dose should not exceed 10 mg (0.5 mL of 2% solution).

Maximum doses for adults:

• Subcutaneous or intramuscular administration: single dose – 100 mg (5 mL of 2% solution), daily dose – 300 mg (15 mL of 2% solution).
• Intravenous administration: single dose – 20 mg (1 mL of 2% solution), daily dose – 120 mg (6 mL of 2% solution).

Children aged 1 to 14 years should receive the drug 2–3 times daily. The single dose is 0.7–1 mg/kg of body weight.

Maximum daily dose for children (regardless of route of administration):

• 1–2 years: 20 mg (1 mL of 2% solution)
• 3–4 years: 30 mg (1.5 mL of 2% solution)
• 5–6 years: 40 mg (2 mL of 2% solution)
• 7–9 years: 60 mg (3 mL of 2% solution)
• 10–14 years: 100 mg (5 mL of 2% solution)

Children

The medicinal product may be used in children aged 1 year and older.

Overdose

Symptoms: visual disturbances, diplopia, weakness, dry mouth, constipation, facial flushing, hyperventilation, nystagmus, ataxia, tachycardia, arterial hypotension, asystole, ventricular flutter, collapse. When high doses are used or when the drug is rapidly injected intravenously, arrhythmias or complete atrioventricular block may develop. When used in very high doses, papaverine may produce moderate sedative effects.

Treatment: discontinue the drug and provide symptomatic therapy. There is no specific antidote. The drug is completely removed from the blood by hemodialysis.

Adverse reactions.

Central nervous system: drowsiness, increased sweating, weakness, headache, dizziness.

Sensory organs: visual disturbances, diplopia.

Gastrointestinal system: anorexia, nausea, constipation, dry mouth, diarrhea.

Hepatobiliary system: jaundice, liver function disorders, increased activity of liver transaminases.

Cardiovascular system: arrhythmias, tachycardia, arterial hypotension, partial or complete atrioventricular block, asystole, ventricular extrasystoles, ventricular fibrillation, ventricular flutter, collapse.

Blood system: eosinophilia.

Respiratory system: apnea.

Skin, subcutaneous tissue, and immune system: hypersensitivity reactions, including respiratory manifestations, anaphylactic shock, pruritus, skin rash, urticaria, hyperemia of the skin of the upper trunk, face, and arms.

Other: reactions at the injection site, including thrombosis at the injection site.

Shelf life. 4 years.

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

Keep out of reach of children.

Incompatibility. Pharmaceutically compatible with dibazol; chemically incompatible with sodium caffeine-benzoate. Use only the recommended solvent.

Packaging. 2 ml in vials, № 10 in a box; № 5×2, № 10 in blister packs in a box.

Prescription status. Prescription only.

Manufacturer: LIMITED LIABILITY COMPANY "CORPORATION "ZDOROV'YA".

Manufacturer's address and place of business activity.

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