Vasonit^® (Tablets) Instructions for Use

Marketing Authorization Holder

Bausch Health, LLC (Russia)

Manufactured By

G.L. Pharma, GmbH (Austria)

Contact Information

Bausch Health LLC (Russia)

ATC Code

C04AD03 (Pentoxifylline)

Active Substance

Pentoxifylline (Rec.INN registered by WHO)

Dosage Form

Vasonit®

Prolonged-release film-coated tablets, 600 mg: 20 pcs.

Dosage Form, Packaging, and Composition

Prolonged-release film-coated tablets white, oblong, biconvex, with a score on both sides; the tablet core is white.

Excipients: hypromellose 15000 cP, microcrystalline cellulose, crospovidone, colloidal silicon dioxide, magnesium stearate; coating: macrogol 6000, talc, titanium dioxide, hypromellose 5 cP, polyacrylic acid [as a 30% dispersion].

10 pcs. – blisters (2) – cardboard packs.

Clinical-Pharmacological Group

Drug improving microcirculation. Angioprotector

Pharmacotherapeutic Group

Peripheral vasodilators; purine derivatives

Pharmacological Action

Pharmacodynamics

A xanthine derivative. Improves microcirculation in areas of impaired blood supply. Improves the rheological properties of blood (fluidity) by acting on pathologically altered erythrocyte deformability, increases the elasticity of erythrocyte membranes, inhibits the aggregation of erythrocytes and platelets, and reduces increased blood viscosity. The mechanism of action of the drug is associated with the inhibition of phosphodiesterase and the accumulation of cyclic adenosine monophosphate (cAMP) in vascular smooth muscle cells and in blood cells. Pentoxifylline inhibits platelet and erythrocyte aggregation, reduces plasma fibrinogen levels and enhances fibrinolysis, which leads to a decrease in blood viscosity and an improvement in its rheological properties. Improves tissue oxygen supply in areas of impaired circulation (including in the extremities, CNS, and to a lesser extent – in the kidneys). In occlusive peripheral arterial disease (intermittent claudication), it leads to an increase in walking distance, elimination of nocturnal calf muscle cramps, and reduction of pain at rest. In cerebrovascular disorders, it improves symptoms. It has a weak myotropic vasodilatory effect, slightly reduces total peripheral vascular resistance and slightly dilates coronary vessels.

Pharmacokinetics

Absorption and Metabolism

After oral administration, Pentoxifylline is almost completely absorbed from the gastrointestinal tract. The prolonged-release form ensures continuous release of the active substance and its uniform absorption.

Pentoxifylline undergoes first-pass metabolism in the liver, resulting in the formation of two pharmacologically active metabolites: 1-5-hydroxyhexyl-3,7-dimethylxanthine (metabolite I) and 1-3-carboxypropyl-3,7-dimethylxanthine (metabolite V). The plasma concentrations of metabolites I and V are 5 and 8 times higher, respectively, than that of pentoxifylline.

After oral administration of Vasonit^® tablets, the C_max of pentoxifylline and its active metabolites is reached in 3-4 hours and remains at a therapeutic level for about 12 hours.

Excretion

The drug is excreted mainly (94%) by the kidneys in the form of metabolites. It is excreted in breast milk.

Pharmacokinetics in Special Clinical Cases

In severe renal impairment, the excretion of metabolites is slowed.

In hepatic impairment, an increase in T_1/2 and an increase in bioavailability are noted.

Indications

• Peripheral circulation disorders against the background of atherosclerotic, diabetic and inflammatory processes (including intermittent claudication caused by atherosclerosis, obliterating endarteritis, diabetic angiopathy);
• Acute and chronic cerebrovascular disorders of ischemic origin;
• Symptomatic treatment of the consequences of cerebrovascular disorders of atherosclerotic origin (impaired concentration, dizziness, memory impairment);
• Atherosclerotic and dyscirculatory encephalopathy, angiopathies (paresthesias, Raynaud’s disease);
• Trophic tissue disorders due to impaired arterial or venous microcirculation (post-thrombophlebitic syndrome, trophic ulcers, gangrene, frostbite);
• Ocular circulation disorders (acute and chronic circulatory insufficiency in the retina or choroid of the eye);
• Vascular disorders of the middle ear function, accompanied by hearing loss.

ICD codes

Dosage Regimen

Vasonit^® tablets are taken orally, without chewing, with a sufficient amount of liquid, preferably after meals.

The drug is usually prescribed 1 tab. (600 mg) 2 times/day (morning and evening). The maximum dose is 1200 mg.

The duration of treatment and dosing regimen is determined by the doctor individually depending on the clinical picture of the disease and the therapeutic effect achieved.

In patients with chronic renal failure (creatinine clearance less than 30 ml/min), the daily dose should be reduced to 600 mg.

In patients with severe hepatic impairment, a dose reduction is necessary, taking into account individual tolerance.

In patients with low blood pressure, as well as in patients at risk due to possible blood pressure reduction (patients with severe coronary artery disease or with hemodynamically significant cerebral vascular stenoses), treatment may be started with low doses. In these cases, the dose can only be increased gradually.

Adverse Reactions

From the CNS headache, dizziness, anxiety, sleep disorders, convulsions, cases of aseptic meningitis have been noted.

From the skin and subcutaneous tissue: skin hyperemia, “flushes” of blood to the skin of the face and upper chest, edema, increased nail brittleness.

From the digestive system: dry mouth, feeling of pressure and fullness in the stomach, decreased appetite, nausea, vomiting, diarrhea, intestinal atony, exacerbation of cholecystitis, cholestatic hepatitis.

From the organ of vision scotoma, visual impairment.

From the cardiovascular system tachycardia, arrhythmia, cardialgia, progression of angina pectoris, decreased blood pressure.

From the hematopoietic system and hemostasis rarely – bleeding (from mucous membranes, skin vessels, stomach, intestines), thrombocytopenia, leukopenia, pancytopenia, hypofibrinogenemia, aplastic anemia. In this regard, during treatment with Vasonit^®, regular monitoring of the peripheral blood picture is necessary.

Allergic reactions skin itching, skin hyperemia, urticaria, angioedema, anaphylactic shock.

From laboratory parameters increased activity of liver transaminases – ALT, AST, as well as LDH and ALP.

Contraindications

• Hypersensitivity to pentoxifylline, other methylxanthine derivatives or other components of the drug
• Acute myocardial infarction;
• Massive bleeding;
• Acute hemorrhagic stroke;
• Retinal hemorrhage;
• Pregnancy;
• Breastfeeding period;
• Age under 18 years (efficacy and safety not established).

With caution atherosclerosis of cerebral and/or coronary vessels, especially in cases of arterial hypotension and cardiac rhythm disturbances; chronic heart failure; hepatic insufficiency; renal insufficiency (creatinine clearance less than 30 ml/min – risk of accumulation and increased risk of adverse reactions); peptic ulcer of the stomach and duodenum; recently undergone surgery (risk of bleeding); increased tendency to bleeding (for example, when using anticoagulants or in case of blood clotting system disorders) – risk of developing more severe bleeding).

Use in Pregnancy and Lactation

The use of the drug during pregnancy and breastfeeding is contraindicated.

Use in Hepatic Impairment

The drug should be prescribed with caution in hepatic insufficiency.

Use in Renal Impairment

With caution renal insufficiency (creatinine clearance less than 30 ml/min – risk of accumulation and increased risk of adverse reactions).

Pediatric Use

Contraindicated: age under 18 years (efficacy and safety not established).

Geriatric Use

In elderly patients, a dose reduction may be required (increased bioavailability and reduced elimination rate).

Special Precautions

Patients with severe renal impairment during treatment with Vasonit^® require particularly careful medical supervision. If retinal hemorrhages occur in patients during the use of the drug, the drug should be discontinued immediately.

Treatment should be carried out under blood pressure control. In patients with low and unstable blood pressure, the dose should be reduced.

In diabetic patients taking hypoglycemic drugs, the use of the drug in high doses may cause hypoglycemia (dose adjustment is required).

When used simultaneously with anticoagulants, it is necessary to monitor the parameters of the blood coagulation system, including INR.

In patients who have recently undergone surgery, systematic monitoring of hemoglobin and hematocrit is necessary.

In elderly patients, a dose reduction may be required (increased bioavailability and reduced elimination rate).

Smoking may reduce the therapeutic effectiveness of the drug.

During the drug intake, it is not recommended to consume alcoholic beverages.

Effect on the ability to drive vehicles and operate machinery

Due to the possible occurrence of dizziness, caution is recommended when driving vehicles and servicing complex machinery.

Overdose

Symptoms weakness, dizziness, tachycardia, drowsiness, marked decrease in blood pressure, redness of the skin, loss of consciousness, increased body temperature (chills), areflexia, tonic-clonic convulsions, signs of gastrointestinal bleeding (vomiting “coffee grounds”).

Treatment gastric lavage followed by oral administration of activated charcoal. If vomiting with traces of blood occurs, gastric lavage is unacceptable. Further treatment is symptomatic, aimed at maintaining respiratory function and blood pressure. For convulsions – diazepam.

Drug Interactions

Pentoxifylline may enhance the effect of drugs affecting the blood coagulation system (indirect and direct anticoagulants, thrombolytics), antibiotics (including cephalosporins – cefamandole, cefotetan, cefoperazone), valproic acid.

Increases the effectiveness of antihypertensive agents, insulin and oral hypoglycemic agents.

Cimetidine increases the plasma concentration of pentoxifylline (risk of adverse reactions).

Concomitant administration with other xanthines may lead to excessive nervous excitation of patients.

In some patients, simultaneous administration of pentoxifylline and theophylline may lead to an increase in theophylline concentration (risk of theophylline-related adverse reactions).

Storage Conditions

The drug should be stored in a light-protected place, out of the reach of children, at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 5 years. Do not use after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.