Papaverine-darnitsa

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

Composition:

Active substance: papaverine;

1 ml of solution contains papaverine hydrochloride 20 mg;

Excipients: disodium edetate, DL-methionine, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear, slightly yellowish liquid.

Pharmacotherapeutic group. Agents used in functional gastrointestinal disorders. Papaverine and its derivatives. Papaverine. ATC code A03AD01.

Pharmacological properties.

Pharmacodynamics.

Papaverine is an alkaloid found in opium. Papaverine is a myotropic spasmolytic agent. It reduces muscle tone, decreases contractile activity of smooth muscles, and thus produces vasodilating and spasmolytic effects. Papaverine is an inhibitor of the enzyme phosphodiesterase, which leads to intracellular accumulation of cyclic 3',5'-adenosine monophosphate (cAMP). The accumulation of cAMP results in impaired contractility of smooth muscles and their relaxation in spastic conditions. The drug's effect on the central nervous system is weak; only at higher doses does it exhibit a slight sedative effect.

Pharmacokinetics.

After parenteral administration, the drug rapidly forms stable complexes with serum albumins. It easily penetrates histohematological barriers. It is metabolized in the liver. Approximately 60% is excreted as conjugates, predominantly phenolic conjugates with glucuronic acid, and only in insignificant amounts in unchanged form. The half-life (T1/2) is 0.5–2 hours.

Clinical characteristics.

Indications.

• Smooth muscle spasms of abdominal organs (pylorospasm, irritable bowel syndrome, cholecystitis, biliary colic attacks).
• Ureteral spasms, renal colic.
• Cerebral vessel spasm.
• Peripheral vessel spasms (endarteritis).

Contraindications.

Hypersensitivity to the components of the drug, arterial hypotension, atrioventricular conduction disturbances, comatose state, respiratory depression, concomitant 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 (dimedrol), metamizole (analgin), diclofenac. Hypotensive effect is enhanced when used concomitantly with antihypertensive agents of other classes, as well as with tricyclic antidepressants, procainamide, reserpine, quinidine. Papaverine may reduce the antiparkinsonian effect of levodopa and the hypotensive effect of methyldopa. When used simultaneously with alprostadil for intracavernous administration, there is a risk of developing priapism. Phentolamine potentiates the effect of papaverine on the corpora cavernosa of the penis when administered concurrently.

When used concomitantly with cardiac glycosides, a pronounced enhancement of myocardial contractile function is observed due to a decrease in total peripheral vascular resistance. After concomitant use with procainamide, an enhanced hypotensive effect is possible.

A possible reduction in the tonic effect of anticholinesterase medicinal products on smooth musculature may occur under the influence of papaverine hydrochloride.

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

There are reports of hepatitis development with concomitant use with furadantin (nitrofurantoin).

In combined use of reserpine with papaverine hydrochloride, antihypertensive action is enhanced.

In combination with antidepressants, an enhanced hypotensive effect is possible.

Pharmaceutically compatible with dibazol (diazoxide).

When papaverine hydrochloride is used simultaneously, it potentiates the effect of alcohol.

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

Special precautions for use.

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

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

The medicinal product should be administered intravenously very slowly, with continuous monitoring of arterial pressure, heart rate, and electrocardiogram (ECG).

Intravenous injections of the medicinal product should be administered with caution to patients with stenosing coronary atherosclerosis.

Hyperthermia may occur in elderly individuals.

Smoking reduces the effectiveness of the medicinal product.

Alcohol consumption must be discontinued during treatment with the medicinal product.

Important information about excipients.

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 medicinal product during pregnancy or breastfeeding have not been established. Breastfeeding should be discontinued during treatment with this medicinal product.

Ability to influence reaction speed when driving or operating machinery.

During treatment with the medicinal product, patients should refrain from driving or operating other complex machinery.

Administration and Dosage.

The medicinal product is 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 the 2 % solution. For intravenous administration, dissolve 1 ml of the 2 % papaverine hydrochloride solution (20 mg) in 10–20 ml of 0.9 % sodium chloride solution and inject very slowly at a rate of 3–5 ml/min. Intravenous administration is the most effective.

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

Maximum doses for adults:
For subcutaneous or intramuscular administration: single dose – 100 mg (5 ml of the 2 % solution), daily dose – 300 mg (15 ml of the 2 % solution);
For intravenous administration: single dose – 20 mg (1 ml of the 2 % solution), daily dose – 120 mg (6 ml of the 2 % solution).

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

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

Ages 1–2 years – 20 mg (1 ml of the 2 % solution);
Ages 3–4 years – 30 mg (1.5 ml of the 2 % solution);
Ages 5–6 years – 40 mg (2 ml of the 2 % solution);
Ages 7–9 years – 60 mg (3 ml of the 2 % solution);
Ages 10–14 years – 100 mg (5 ml of the 2 % solution).

Children.

The medicinal product can be administered to children from the age of 1 year.

Overdose.

Symptoms: visual disturbances, diplopia, weakness, dry mouth, constipation, redness of the skin on the upper part of the trunk, hyperventilation, nystagmus, ataxia, tachycardia, arterial hypotension, asystole, ventricular flutter, collapse. When high doses of the drug are used or when it is rapidly injected intravenously, arrhythmias or complete atrioventricular block may develop. Papaverine in very high doses exerts a moderate sedative effect.

Treatment: discontinue the drug. Symptomatic treatment. The drug is completely removed from the blood by hemodialysis. There is no specific antidote.

Adverse reactions.

Eye disorders: vision disturbances, diplopia.

Respiratory, thoracic and mediastinal disorders: apnoea.

Gastrointestinal disorders: anorexia, nausea, constipation, dry mouth, diarrhoea.

Hepatobiliary disorders: jaundice, hepatic function abnormalities, increased liver transaminase activity.

Nervous system disorders: somnolence, increased sweating, weakness, headache, dizziness.

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

Blood and lymphatic system disorders: eosinophilia.

Immune system disorders: hypersensitivity reactions, including respiratory tract involvement, anaphylactic shock, urticaria.

Skin and subcutaneous tissue disorders: pruritus, skin rash, hyperemia of the upper trunk, face and hands.

General disorders and administration site reactions: increased body temperature, reactions at the injection site, including thrombosis at the injection site.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after registration of the medicinal product is an important procedure. It allows continuous monitoring of the benefit-risk ratio of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions through the national reporting system.

Shelf life. 3 years.

Storage conditions.

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

Keep out of reach of children.

Incompatibilities.

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

Packaging.

2 ml in a vial; 5 vials in a blister pack; 2 blisters in a carton.

Prescription category. Prescription only.

Manufacturer. JSC "Pharmaceutical company "Darnytsia".

Manufacturer's address and place of business.

13, Boryspilska Street, Kyiv, 02093, Ukraine.