Papaverine hydrochloride
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PAPAVERINE HYDROCHLORIDE (PAPAVERINE HYDROCHLORIDE)
Composition:
Active substance: papaverine hydrochloride;
1 ml of solution contains papaverine hydrochloride 20 mg;
Excipients: DL-methionine, disodium edetate, water for injections.
Pharmaceutical form. Solution for injection.
Main physicochemical properties: clear, slightly yellowish liquid.
Pharmacotherapeutic group. Agents used in functional disorders of the gastrointestinal tract. Papaverine and its derivatives. ATC code A03A D01.
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 thereby exerts vasodilatory and spasmolytic effects. Papaverine is an inhibitor of the enzyme phosphodiesterase, which leads to intracellular accumulation of cyclic 3',5'-adenosine monophosphate (cAMP). 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 readily penetrates histohematic barriers. Metabolized in the liver. Approximately 60% is excreted as conjugates, predominantly phenolic conjugates with glucuronic acid, and only a small amount is excreted unchanged. The elimination 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);
- urinary tract spasms, renal colic;
- cerebral vessel spasm;
- peripheral vessel spasms (endarteritis).
Contraindications.
Hypersensitivity to any component of the drug, arterial hypotension, atrioventricular conduction disorders, 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), sodium metamizole (analgin), and diclofenac. The hypotensive effect is enhanced when used concomitantly 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 concomitantly with alprostadil for intracavernous injection, there is a risk of priapism development. Phentolamine potentiates the effect of papaverine on the corpora cavernosa of the penis when administered together.
When used concomitantly with cardiac glycosides, a pronounced enhancement of myocardial contractile function occurs due to decreased total peripheral vascular resistance. When used together with procainamide, enhancement of the hypotensive effect is possible.
A possible reduction in the tonic effect of anticholinesterase agents on smooth musculature 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 with concomitant use with furadantin.
When reserpine-containing drugs are combined with papaverine, antihypertensive action is enhanced.
When combined with antidepressants, enhancement of the hypotensive effect is possible.
When used concomitantly, papaverine potentiates the effect of alcohol.
In patients who smoke, papaverine metabolism is accelerated, and its plasma concentration and pharmacokinetic effects are reduced.
Pharmaceutically compatible with dibazole.
Special precautions for use.
The medicinal product should be administered with caution and in doses lower than the average therapeutic dose:
- in elderly and debilitated patients;
- in patients with traumatic brain injury;
- 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 (ECG).
Intravenous injections of the drug should be administered with caution in patients with stenosing coronary atherosclerosis.
Hyperthermia may occur in elderly individuals.
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 influence reaction rate 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, or intravenously.
Subcutaneous and intramuscular administration in adults and children aged 14 years and older: 0.5–2 mL (10–40 mg) of the 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 the 2% solution).
Maximum doses for adults:
- Subcutaneous or intramuscular: single dose – 100 mg (5 mL of the 2% solution), daily dose – 300 mg (15 mL of the 2% solution)
- Intravenous: single dose – 20 mg (1 mL of the 2% solution), daily dose – 120 mg (6 mL of the 2% solution)
For children aged 1 to 14 years, administer the drug 2–3 times daily. The single dose is 0.7–1 mg/kg body weight.
Maximum daily doses for children (regardless of route of administration):
- Age 1–2 years: 20 mg (1 mL of the 2% solution)
- Age 3–4 years: 30 mg (1.5 mL of the 2% solution)
- Age 5–6 years: 40 mg (2 mL of the 2% solution)
- Age 7–9 years: 60 mg (3 mL of the 2% solution)
- Age 10–14 years: 100 mg (5 mL of the 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 fibrillation, collapse. When high doses are used or the drug is rapidly injected intravenously, arrhythmias or complete atrioventricular block may develop. With very high doses, papaverine may produce mild sedative effects.
Treatment: discontinue the drug and provide symptomatic therapy. There is no specific antidote. Papaverine is completely removed from blood during hemodialysis.
Adverse Reactions
Eye disorders: vision disturbances, diplopia.
Respiratory, thoracic and mediastinal disorders: apnea.
Gastrointestinal disorders: anorexia, nausea, constipation, dry mouth, diarrhea.
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 arms.
General disorders and administration site conditions: increased body temperature, reactions at the injection site, including thrombosis at the injection site.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.
Shelf life. 2 years.
Storage conditions.
Store in the original packaging at a temperature not exceeding 25 °C.
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 polyethylene ampoule. 10 or 50 ampoules per cardboard pack.
Prescription status. Prescription only.
Manufacturer. LLC "FARMASEL".
Manufacturer's address and location of business activity.
3, Prorizna Street, village Kvitneve, Brovary District, Kyiv Oblast, Ukraine, 07408.