Trenpental^® (Concentrate) Instructions for Use

Marketing Authorization Holder

Bryntsalov-A, JSC (Russia)

ATC Code

C04AD03 (Pentoxifylline)

Active Substance

Pentoxifylline (Rec.INN registered by WHO)

Dosage Form

Trenpental®

Concentrate for solution for i/v and i/a administration 2% (100 mg/5 ml): amp. 5 or 10 pcs.

Dosage Form, Packaging, and Composition

Concentrate for preparation of solution for intravenous and intra-arterial administration in the form of a transparent, colorless or slightly yellowish liquid.

Excipients: sodium chloride – 7 mg, sodium hydroxide solution 0.01M – to pH 6.5-7.5, water for injection – to 1 ml.

5 ml – glass ampoules (5) – plastic contour packs (1) – cardboard boxes.
5 ml – glass ampoules (5) – plastic contour packs (2) – cardboard boxes.

Clinical-Pharmacological Group

Drug improving microcirculation. Angioprotector

Pharmacotherapeutic Group

Vasodilating agent

Pharmacological Action

A drug that improves microcirculation, an angioprotector, a dimethylxanthine derivative. Pentoxifylline reduces blood viscosity, causes platelet disaggregation, increases the elasticity of erythrocytes (by acting on pathologically altered erythrocyte deformability), improves microcirculation and increases the concentration of oxygen in tissues.

It increases the concentration of cAMP in platelets and ATP in erythrocytes with simultaneous saturation of the energy potential, which in turn leads to vasodilation, a decrease in total peripheral vascular resistance, an increase in stroke volume and minute volume of blood without a significant change in heart rate.

By dilating the coronary arteries, it increases oxygen delivery to the myocardium; by dilating the pulmonary vessels, it improves blood oxygenation. It increases the tone of the respiratory muscles (intercostal muscles and diaphragm).

Intravenous administration, along with the above action, leads to enhanced collateral circulation, an increase in the volume of blood flowing per unit cross-section.

It increases the concentration of ATP in the brain and has a beneficial effect on the bioelectrical activity of the central nervous system. It improves microcirculation in areas of impaired blood supply.

In occlusive lesions of peripheral arteries (intermittent claudication), it leads to an increase in walking distance, elimination of night cramps of the calf muscles and pain at rest.

Pharmacokinetics

After oral administration, it is well absorbed from the gastrointestinal tract. Slight metabolism is noted during the “first pass” through the liver. It binds to erythrocyte membranes. It undergoes biotransformation first in erythrocytes, then in the liver. Some metabolites are active. The T_1/2 from plasma of the unchanged substance is 0.4-0.8 hours, of metabolites – 1-1.6 hours. After 24 hours, most of the dose is excreted in the urine as metabolites, a smaller part (about 4%) – through the intestines.

The elimination of pentoxifylline is reduced in elderly patients and in liver diseases.

Indications

Peripheral circulation disorders (including intermittent claudication) associated with chronic occlusive circulatory disorders in the arterial vessels of the lower extremities. Ischemic cerebrovascular accident, ischemic stroke and post-stroke conditions; cerebral atherosclerosis (dizziness, headache, memory impairment, sleep disorders), dyscirculatory encephalopathy, viral neuroinfection (prevention of possible microcirculation disorders). Coronary artery disease, condition after myocardial infarction. Diabetic angiopathy. Acute circulatory disorders in the retina and choroid, acute ischemic optic neuropathy. Otosclerosis, degenerative changes against the background of pathology of the vessels of the inner ear with gradual hearing loss. Chronic obstructive pulmonary disease, bronchial asthma. Impotence of vascular origin.

ICD codes

Dosage Regimen

Administer the concentrate only after dilution for intravenous or intra-arterial infusion. Do not administer intramuscularly or subcutaneously.

For intravenous infusion, dilute the required dose in 250-500 ml of a compatible infusion solution, such as 0.9% sodium chloride or Ringer’s solution.

For intra-arterial infusion, dilute the required dose in 20-50 ml of a compatible infusion solution.

Initiate therapy with a slow intravenous infusion. The initial recommended dose is 100 mg (one 5 ml ampoule) of pentoxifylline in 250-500 ml of infusion solution, administered over 60-180 minutes.

Subsequently, administer 200 mg (two 5 ml ampoules) of pentoxifylline in 250-500 ml of infusion solution twice daily. Infuse each dose over at least 60 minutes.

For intra-arterial administration, administer 100 mg (one 5 ml ampoule) of pentoxifylline diluted in 20-50 ml of infusion solution over 10-30 minutes, once or twice daily.

Adjust the infusion rate based on individual patient tolerance. Continuously monitor the patient’s blood pressure and heart rate during administration.

Reduce the dose or discontinue therapy if severe hypotension or cardiovascular side effects occur. The maximum single dose should not exceed 300 mg.

The total daily dose for infusion should generally not exceed 600 mg of pentoxifylline.

Adjust the dosage regimen in patients with severe renal impairment or significant hepatic dysfunction.

Adverse Reactions

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

Dermatological reactions skin hyperemia of the face, “flushes” of blood to the skin of the face and upper chest, edema, increased brittleness of nails.

From the digestive system dry mouth, decreased appetite, intestinal atony, exacerbation of cholecystitis, cholestatic hepatitis, increased activity of hepatic transaminases and alkaline phosphatase.

From the organ of vision visual impairment, scotoma.

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

From the hematopoietic system thrombocytopenia, leukopenia, pancytopenia.

From the blood coagulation system hypofibrinogenemia, bleeding from skin vessels, mucous membranes, stomach, intestines.

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

Contraindications

Acute myocardial infarction, porphyria, massive bleeding, hemorrhagic stroke, retinal hemorrhage, pregnancy, lactation period. For intravenous administration (additionally) – arrhythmias, severe atherosclerosis of coronary or cerebral arteries, uncontrolled arterial hypotension.

Hypersensitivity to pentoxifylline and other xanthine derivatives.

Use in Pregnancy and Lactation

Adequate and well-controlled clinical studies of the safety of pentoxifylline use during pregnancy have not been conducted.

Pentoxifylline and its metabolites are excreted in breast milk. If it is necessary to use during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

In severe liver function disorders, correction of the pentoxifylline dosing regimen is required.

Use in Renal Impairment

In renal function disorders, correction of the pentoxifylline dosing regimen is required.

Pediatric Use

Use with caution in children and adolescents under 18 years of age (efficacy and safety have not been studied).

Special Precautions

Use with caution in case of blood pressure lability (tendency to arterial hypotension), chronic heart failure, gastric and duodenal ulcer (for oral administration), after recent surgical interventions, in case of hepatic and/or renal insufficiency, in children and adolescents under 18 years of age (efficacy and safety have not been studied).

In case of renal function disorders or severe liver function disorders, correction of the pentoxifylline dosing regimen is required.

During treatment, blood pressure levels should be monitored.

With simultaneous use with antihypertensive agents, insulin, oral hypoglycemic drugs, a reduction in the dose of pentoxifylline may be required.

With simultaneous use with anticoagulants, blood coagulation parameters should be carefully monitored.

Drug Interactions

Pentoxifylline may potentiate the effect of antihypertensive drugs.

Against the background of parenteral use of pentoxifylline in high doses, an enhancement of the hypoglycemic effect of insulin in patients with diabetes mellitus is possible.

With simultaneous use with ketorolac, an increased risk of bleeding and/or increased prothrombin time is possible; with meloxicam – an increased risk of bleeding; with sympatholytics, ganglion blockers and vasodilators – a decrease in blood pressure is possible; with heparin, fibrinolytic drugs – enhancement of the anticoagulant effect.

Cimetidine significantly increases the plasma concentration of pentoxifylline, in connection with this, with simultaneous use, the likelihood of side effects may increase.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.