Flexital (Tablets, Concentrate) Instructions for Use

ATC Code

C04AD03 (Pentoxifylline)

Active Substance

Pentoxifylline (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Drug improving microcirculation. Angioprotector

Pharmacotherapeutic Group

Vasodilating agent

Pharmacological Action

It blocks phosphodiesterase and promotes the accumulation of cyclic AMP in tissues. It increases the elasticity of erythrocyte membranes, inhibits the aggregation of platelets and erythrocytes, reduces the increased plasma fibrinogen concentration and enhances fibrinolysis, which leads to a decrease in blood viscosity and improves its rheological properties.

It has a weak myotropic vasodilating effect, slightly reduces total peripheral vascular resistance and has a positive inotropic effect. As a result of the drug’s use, an improvement in microcirculation and tissue oxygen supply is noted, to a greater extent in the extremities and central nervous system, and to a moderate degree in the kidneys.

It slightly dilates the coronary vessels. The therapeutic effect usually occurs after 2-4 weeks of treatment.

Pharmacokinetics

After oral administration, it is almost completely absorbed from the gastrointestinal tract. During the “first pass” through the liver, it is metabolized to form various metabolites. When administered orally at a dose of 100 mg, T_max is 1 hour.

The main metabolites are metabolite 1 (1-[5-hydroxyhexyl]-3,7-dimethylxanthine) and metabolite V (1-[3-carboxypropyl]-3,7-dimethylxanthine). The plasma concentrations of these metabolites are 5 and 8 times higher, respectively, than the concentration of the active substance.

The T_1/2 of pentoxifylline ranges from 0.4 to 0.8 hours; the T_1/2 of the metabolites is 1-1.6 hours.

It is excreted primarily by the kidneys in the form of metabolites. Less than 4% of the administered dose is excreted in the feces. When administered orally at a dose of 400 mg, the maximum concentration of the main substance and metabolites is determined after 2-4 hours and remains stable for a long period of time.

The controlled release of pentoxifylline from the tablet excludes significant fluctuations in the plasma concentration of the drug.

Indications

• Peripheral circulation disorders caused by atherosclerosis, diabetes mellitus (diabetic angiopathy);
• Chronic ischemic-type cerebral circulation disorders;
• Atherosclerotic and dyscirculatory encephalopathies; angioneuropathies (paresthesias, Raynaud’s disease);
• Trophic tissue disorders due to impaired arterial or venous microcirculation (trophic ulcers, post-thrombophlebitic syndrome, frostbite, gangrene);
• Obliterating endarteritis;
• Subacute and chronic circulatory insufficiency in the retina or choroid of the eye;
• Hearing disorders of vascular origin.

ICD codes

Dosage Regimen

Tablets

Orally, during meals, without chewing, with a small amount of liquid. It is established individually, taking into account the severity of circulatory disorders, the patient’s body weight and drug tolerance.

It is prescribed at a dose of 400 mg 2-3 times a day. The maximum daily dose is 1200 mg. The duration of the treatment course is at least 8 weeks. If side effects occur, the drug dose should be reduced to 400 mg twice a day.

For patients with chronic renal failure (creatinine clearance less than 30 ml/min), 50-70% of the usual dose is prescribed.

Concentrate

The duration of treatment and dosing regimen are established by the attending physician individually, depending on the clinical picture of the disease and the therapeutic effect obtained. The drug is administered intravenously in a lying position, slowly, for at least 5 minutes. The drug is usually used at the beginning of a course of treatment or when a faster therapeutic effect is needed during a course of treatment with Flexital.

For drip intravenous administration, Flexital 100 mg (1 ampoule) is diluted in 250-500 ml of 0.9% sodium chloride solution or 5% glucose solution. The duration of infusion is usually 120-180 minutes.

The initial infusion dose of 100 mg can be increased to 300 mg per day if necessary. At the maximum allowable daily infusion dose of 300 mg, the infusion lasting 120-180 minutes is performed twice in the morning and evening hours.

For patients with chronic renal failure (creatinine clearance less than 10 ml/min), 50-70% of the usual dose is administered.

Adverse Reactions

From the digestive system: dry mouth, decreased appetite, nausea, vomiting, epigastric pain, diarrhea, intestinal atony are possible; bleeding from the vessels of the stomach, intestines, intestinal atony.

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

From the central nervous system: headache, dizziness, anxiety, sleep disorders; convulsions.

Allergic reactions: skin rash, itching, urticaria, bleeding from the vessels of the skin and mucous membranes, skin hyperemia, angioedema, anaphylactic shock.

From the liver: cholecystitis, hepatitis, jaundice.

From the skin and subcutaneous tissue: facial skin hyperemia, “flushing” of blood to the facial skin and upper chest, edema.

From the hematopoietic organs and hemostasis system: thrombocytopenia, leukopenia, pancytopenia, hypofibrinogenemia; changes in the peripheral blood picture.

Laboratory parameters: increased activity of “hepatic” transaminases (ALT, AST, LDH) and alkaline phosphatase.

Very rarely: development of aseptic meningitis.

Rarely: malaise, unpleasant taste in the mouth, hypersalivation, conjunctivitis, scotoma, blurred vision, ear pain, increased nail brittleness, changes in body weight, gland swelling, nasal congestion.

Contraindications

• Acute myocardial infarction;
• Massive bleeding;
• Nasal bleeding, acute hemorrhagic stroke, cerebral hemorrhage;
• Massive hemorrhage into the retina of the eye;
• Pregnancy, breastfeeding period;
• Age under 18 years (safety and efficacy of the drug in children have not been established);
• Hypersensitivity to pentoxifylline and other methylxanthine derivatives.

With caution: labile blood pressure or a tendency to arterial hypotension, chronic heart failure, atherosclerosis of cerebral and/or coronary vessels, gastric and duodenal ulcer, conditions after recently performed surgical interventions, hepatic and/or renal failure, severe arrhythmias, increased tendency to bleeding, for example, as a result of using anticoagulants or disorders in the blood coagulation system (risk of developing more severe bleeding).

Use in Pregnancy and Lactation

Contraindicated during pregnancy and breastfeeding.

Use in Hepatic Impairment

Use with caution in hepatic insufficiency.

Use in Renal Impairment

Use with caution in renal insufficiency.

Pediatric Use

Contraindicated in children under 18 years of age.

Special Precautions

Caution is necessary when prescribing Flexital to patients with severe cerebral or/and coronary atherosclerosis of the vessels, especially with concomitant arterial hypertension and cardiac rhythm disorders. In these patients, angina attacks, arrhythmias and arterial hypotension are possible.

It should be prescribed with caution to patients with gastric and duodenal ulcers (including in the anamnesis); to patients who have recently undergone surgery (in these cases, there is an increased risk of bleeding, so systematic monitoring of hemoglobin concentration and hematocrit is necessary). In case of using the drug in patients with chronic heart failure, the phase of circulatory compensation should first be achieved.

For patients with labile blood pressure or a tendency to arterial hypotension, the drug dose is increased gradually.

For patients with severe renal impairment, the drug dose is selected individually.

In case of simultaneous use of Flexital and oral anticoagulants, regular monitoring of prothrombin time is necessary. With simultaneous use of Flexital and antidiabetic or antihypertensive agents, the dose of the latter drugs should be reduced. In case of retinal hemorrhage during treatment with Flexital, the drug should be discontinued immediately.

Treatment with the drug should be carried out under blood pressure control.

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

The safety and efficacy of pentoxifylline in children have not been sufficiently studied. Smoking may reduce the therapeutic effectiveness of the drug.

Overdose

Symptoms: nausea, weakness, dizziness, tachycardia, decreased blood pressure, hyperthermia, drowsiness or agitation, loss of consciousness, areflexia, clonic-tonic convulsions, as a sign of gastrointestinal bleeding – vomiting resembling “coffee grounds”.

Treatment: there is no specific antidote.

If little time has passed since taking the drug, gastric lavage should be performed (to prevent further absorption of the drug) and activated charcoal should be prescribed. If vomiting with traces of blood occurs, gastric lavage is unacceptable. Symptomatic therapy is carried out.

Drug Interactions

Pentoxifylline potentiates the anticoagulant effect of heparin, fibrinolytic drugs, enhances the effect of antihypertensive and hypoglycemic agents (insulin and oral hypoglycemic agents).

Pentoxifylline may enhance the effect of antibiotics (including cephalosporins – cefamandole, cefotetan), valproic acid.

Cimetidine increases the plasma concentration of pentoxifylline (risk of side effects).

Concomitant administration with other xanthines may lead to excessive nervous excitement in patients.

Storage Conditions

List B. In a dry place protected from light at a temperature not exceeding 25°C (77°F). Keep out of reach of children.

Shelf Life

Shelf life – 4 years.

Dispensing Status

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.