Pentoxifylline - instructions for use, dose, side effects, contraindications

Pentoxifylline is a derivative of xanthine.Improves microcirculation and rheological properties of blood. The mechanism of action is associated with the inhibition of phosphodiesterase and an increase in the content of cyclic 3,5-adenosine monophosphate in platelets and adenosine triphosphate in erythrocytes with a simultaneous saturation of the energy potential, which in turn leads to vasodilation, a decrease in total peripheral vascular resistance, an increase in the shock and minute blood volume without significant change heart rate.

Expanding the vessels of the lung, improves oxygenation of the blood.

Intravenous injection, along with the above action, leads to an increase in collateral circulation, an increase in the volume of flowing blood through a unit of section.

Reduces the viscosity of blood, causes disaggregation of platelets, increases the elasticity of erythrocytes (due to the impact on pathologically altered erythrocyte deformability). Improves microcirculation in areas of impaired blood flow.

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

Pharmacokinetics:

The drug is rapidly metabolized in the liver. In the process of metabolism, several active metabolites are formed, the main ones being the metabolite I (1-5-hydroxyhexyl-3,7-dimethylxanthine) and the metabolite V (1-3-carboxypropyl-3,7-dimethylxanthine). The concentration of metabolites I and V in blood plasma, respectively, is 5 and 8 times higher than pentoxifylline.

It is excreted by the kidneys in the form of metabolites (94%) and through the intestine (4%), in the first 4 hours up to 90% of the dose is excreted. Unchanged displays 2 % preparation. Pentoxifylline and its metabolites do not bind to blood plasma proteins.

With severe renal dysfunction, excretion of metabolites is slowed down. When liver function is disrupted, the half-life is prolonged and bioavailability is increased.

Indications:

- Violations of peripheral blood circulation against atherosclerotic, diabetic and inflammatory processes (including intermittent claudication caused by atherosclerosis, diabetic angiopathy);

- trophic tissue disorders due to disturbed arterial and venous microcirculation (varicose ulcers);

- angioneuropathy (paresthesia, acrocyanosis);

- acute and chronic disorders of cerebral circulation of the ischemic type (including cerebral atherosclerosis);

- post-ischemic stroke;

- disorders of blood circulation in the vessels of the eye (acute and chronic insufficiency of the blood supply to the retina and choroid of the eye);

disturbances in the function of the middle ear of vascular genesis, accompanied by deafness.

Contraindications:

- Hypersensitivity to pentoxifylline, other methylxanthine derivatives or other components of the drug;

- pronounced coronary and cerebral atherosclerosis;

- recently suffered myocardial infarction;

- hemodynamically significant violations of the rhythm of the heart;

- uncontrolled arterial hypotension;

- porphyria;

- massive bleeding;

- hemorrhage in the retina of the eye;

- hemorrhage in the brain;

- pregnancy, the period of breastfeeding;

- age to 18 years (efficacy and safety not established).

Carefully:at a labile arterial pressure, propensity to arterial hypotension, chronic heart failure, propensity to hemorrhages (for example, with peptic ulcer of stomach and duodenum, disorders of blood coagulability),in a condition after recently transferred surgical interventions, with hepatic insufficiency, severe chronic renal failure (creatinine clearance less than 30 ml / min), hemorrhagic diathesis.

Pregnancy and lactation:

Application during pregnancy is contraindicated.

Pentoxifylline penetrates into breast milk in small amounts, therefore, if you need to use the drug during lactation, breastfeeding should be discontinued.

Dosing and Administration:

The drug can be administered intravenously, intraarterially (the patient should be in the "lying" position).

Intravenously drip slowly in a dose of 100 mg in 250-500 ml of 0.9% solution of sodium chloride or in a 5% solution of dextrose (glucose) (duration of administration - 90-180 minutes).

Intraarterially - first in a dose of 100 mg in 20-50 ml of 0.9% solution of sodium chloride, and in the following days - 200-300 mg in 30-50 ml of 0.9% sodium chloride solution (rate of administration: 10 mg / min ).

Use in special patient groups

1. Patients with chronic renal insufficiency

For patients with severe chronic renal insufficiency (creatinine clearance less than 30 ml / min), the dose of pentoxifylline should be reduced by about 30-50% (ie, about 50-70% of the usual dose).

2. Patients with hepatic insufficiency

In severe hepatic insufficiency, a dose reduction of pentoxifylline is recommended under the control of individual tolerability.

3. Patients with arterial hypotension and unstable arterial pressure It is necessary to begin therapy with pentoxifylline with reduced doses in patients with arterial hypotension, as well as in patients with severe atherosclerosis of the coronary and / or cerebral arteries (an additional decrease in blood pressure can lead to deterioration of the blood supply to the heart and / or brain).

Side effects:

The frequency of possible side effects listed below is determined as follows: very often (> = 1/10); often (> = 1/100 to <1/10); infrequently (> = 1/1000 to <1/100); rarely (> = 1 / 10,000 to <1/1000); very rarely (<1/10000).

From the nervous system:

Infrequent: headache, dizziness.

Very rarely: convulsions, anxiety, sleep disturbances, aseptic meningitis.

From the cardiovascular system:

Infrequently: tachycardia, arrhythmia, cardialgia.

Rarely: lowering blood pressure, progressing angina.

From the skin and subcutaneous fat:

Infrequent: hyperemia of the skin of the face, "hot flashes" of blood to the skin of the face and upper chest, swelling, increased brittleness of the nails.

From the digestive system:

Often: nausea, vomiting, a feeling of heaviness in the stomach, a decrease in appetite.

Rarely: gastrointestinal bleeding, intestinal atony, exacerbation of cholecystitis, cholestatic hepatitis.

From the sense organs:

Infrequent: impaired vision.

Rarely: scotoma.

On the part of the organs of hematopoiesis and the system of hemostasis:

Rarely: epistaxis.

Very rarely: thrombocytopenia, pancytopenia, leukopenia, hypofibrinogenemia. Allergic reactions:

Infrequent: itching, hyperemia of the skin, hives.

Very rarely: bronchospasm, angioedema, anaphylactic shock. Laboratory indicators:

Very rarely: increased activity of "hepatic" transaminases (alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase) and alkaline phosphatase.

Overdose:

Symptoms: weakness, dizziness, marked decrease in blood pressure, tachycardia, drowsiness, loss of consciousness, tonic convulsions, increased nervous excitability, hyperthermia, areflexia, signs of gastrointestinal bleeding (vomiting like "coffee grounds").

Treatment: symptomatic, aimed at maintaining the function of breathing and blood pressure.

Interaction:

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

Strengthens the effect of antihypertensive drugs, insulin and oral hypoglycemic drugs.

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

The combined use of pentoxifylline with theophylline may lead to an increase in the concentration of theophylline in the blood and an increase in its side effects.

It is undesirable to co-prescribe pentoxifylline with ketorolac in connection with an increased risk of bleeding and / or prolongation of prothrombin time.

Special instructions:

Treatment should be carried out under the control of arterial pressure.

In patients with diabetes mellitus, who take hypoglycemic drugs, the administration of large doses of pentoxifylline can cause severe hypoglycemia (dose adjustment is required).

At appointment simultaneously with anticoagulants it is necessary to watch carefully indicators of a coagulating system of a blood. In patients who have recently undergone surgery, systematic monitoring of hemoglobin and hematocrit is necessary.

The administered dose should be reduced in patients with low and unstable blood pressure.

In elderly people, a dose reduction may be required (increased bioavailability and reduced rate of excretion).

Smoking can reduce the therapeutic effectiveness of the drug.

The compatibility of a solution of pentoxifylline with the infusion solution should be checked in each case.

When carrying out intravenous infusions, the patient should be in the "lying" position. If a patient experiences symptoms of anaphylactic / anaphylactoid reactions, the drug should be discontinued immediately and appropriate care should be provided immediately.

In the case of appointing or increasing the dose of pentoxifylline, patients receiving antagonism of vitamin K should monitor anticoagulant activity.

During therapy, pentoxifylline requires monitoring of sodium in the blood plasma, especially in patients who follow a diet with restriction of table salt. The total sodium content in one ampoule is 5 ml - 12.8 mg.

Effect on the ability to drive transp. cf. and fur:

Form release / dosage:

Solution for intravenous and intravenousarterial administration of 20 mg / ml in ampoules

5 ml each.

For 10 ampoules with instructions for use, with a knife ampoule or scarifier ampoule in a pack or box of cardboard.

When packaging ampoules that have a ring kink or point of dissection, knife ampoule ampoule or scarifier Do not invest.

5 ampoules in the cassette contour packaging. 2 cassette contour packaging with instructions for use in pack of cardboard.

Packaging:solution for intravenous and intraarterial administration, 20 mg / ml (ampoule) 5 ml x 10 (cardboard package / carton box)

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:2 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N002458 / 01

Date of registration:25.05.2009

The owner of the registration certificate:MICROGEN FGUP Scientific and Production Association MICROGEN FGUP Scientific and Production Association Russia

Manufacturer: & nbsp

MICROGEN FGUP NGO Russia

Information update date: & nbsp24.08.2015

Illustrated instructions

Instructions

Pentoxifylline (Pentoxifylline)