Papaverine

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PAPAVERINE (PAPAVERIN)

Composition:

Active substance: papaverine hydrochloride;

1 suppository contains papaverine hydrochloride 20 mg;

Excipient: hard fat.

Medicinal form. Suppositories.

Main physicochemical properties: white or cream-colored suppositories. The presence of an air-porous core and a pit-like depression on the cross-section is permissible.

Pharmacotherapeutic group.

Agents used in functional gastrointestinal disorders.

ATC code A03AD01.

Pharmacological properties.

Pharmacodynamics.

Papaverine hydrochloride is a myotropic spasmolytic agent. It inhibits phosphodiesterase synthesis, leading to accumulation of intracellular cyclic 3,5-AMP and reduction of Ca content. It relaxes smooth muscles of internal organs (gastrointestinal tract, respiratory tract, urinary and genital systems) and blood vessels.

In high doses, it reduces excitability of cardiac muscle and slows intracardiac conduction.

Pharmacokinetics.

The bioavailability of the drug after rectal administration is approximately 25%. Papaverine is bound to plasma proteins (about 90%). It is metabolized in the liver and excreted in urine as glucuronide.

Clinical characteristics.

Indications.

Smooth muscle spasm: of abdominal organs (in cholecystitis, pylorospasm, spastic colitis, renal colic); peripheral vessels (in endarteritis); cerebral vessels.

Contraindications.

Increased individual sensitivity to the components of the drug. Atrioventricular block, glaucoma, severe hepatic insufficiency, respiratory depression, broncho-obstructive syndrome, arterial hypotension, comatose state, concomitant use of monoamine oxidase inhibitors (MAO inhibitors), elderly age (risk of hyperthermia development), childhood.

Interaction with other medicinal products and other types of interactions.

The drug reduces the antiparkinsonian effect of levodopa and the hypotensive effect of methyldopa. The spasmolytic action of papaverine is enhanced by diphenhydramine (dimedrol), metamizole (analgin), and diclofenac. The hypotensive effect is enhanced when used concomitantly with antihypertensive agents of other groups. When used simultaneously with cardiac glycosides, a pronounced enhancement of myocardial contractile function occurs due to a decrease in total peripheral vascular resistance. When used concomitantly with procainamide, tricyclic antidepressants, procainamide, reserpine, and sulfated quinidine, an enhanced hypotensive effect is possible.

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

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

There are data on the development of hepatitis with concomitant use with furadantin.

Papaverine hydrochloride potentiates the effect of alcohol.

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

The spasmolytic action of the drug is enhanced when used concomitantly with barbiturates.

Special precautions for use.

The medicinal product should be administered with caution and in small doses to debilitated patients, in conditions following head injuries, chronic renal insufficiency, adrenal insufficiency, hypothyroidism, prostate hyperplasia, supraventricular tachycardia, and shock states.

During treatment, alcohol consumption should be avoided. Vasodilatory effect is reduced by smoking.

Use during pregnancy or breastfeeding.

Safety during pregnancy and breastfeeding has not been established. Use of the medicinal product during pregnancy is possible only if prescribed by a physician, when the expected benefit to the mother outweighs the potential risk to the fetus or infant. Breastfeeding should be discontinued during treatment with this medicinal product.

Ability to affect reaction speed when driving or operating machinery.

Use with caution if adverse effects from the nervous system occur.

Method of Administration and Dosage

Insert the suppository deeply into the rectal passage after a cleansing enema or natural bowel movement.

For adults: administer 1 suppository 2–3 times daily.

Duration of treatment depends on the severity and course of the disease and is determined individually by the physician.

Children.

Do not use this medicinal product in children.

Overdose.

Symptoms: diplopia, weakness, drowsiness, arterial hypotension, dry mouth, gastrointestinal disturbances, visual disturbances, facial flushing, tachycardia, asystole, ventricular fibrillation, collapse, hyperventilation, nystagmus, ataxia; arrhythmia or complete atrioventricular block. Papaverine hydrochloride in very high doses exhibits moderate sedative effects.

Treatment: discontinue the drug, symptomatic therapy. There is no specific antidote. The drug is completely removed from the blood during hemodialysis.

Adverse reactions.

Skin and subcutaneous tissue disorders: allergic reactions, skin hyperemia, urticaria, pruritus, skin rash, anaphylactic shock.

Blood and lymphatic system disorders: eosinophilia.

Cardiac disorders: atrioventricular block, arrhythmia, ventricular fibrillation, ventricular extrasystoles, tachycardia, asystole, ventricular flutter, collapse.

Vascular disorders: arterial hypotension.

Nervous system disorders: somnolence, weakness, headache, dizziness; apnea.

Eye disorders: visual disturbances (diplopia).

Gastrointestinal disorders: increased liver transaminase activity, jaundice, nausea, diarrhea, constipation, anorexia, dry mouth.

Other: increased sweating.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after medicinal product authorization is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions.

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

Keep out of reach and sight of children.

Packaging.

5 suppositories in a blister pack. 2 blisters in a cardboard box.

Supply category. Over-the-counter.

Manufacturer.

Pharmyna Ltd.

Manufacturer's address and location of operations.

44 Liska Street, 30-721 Kraków, Poland.