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

Excipients: sodium chloride - 6.0 mg, sodium dihydrogen phosphate dihydrate - 1.0 mg, 0.1 M solution of sodium hydroxide - to a pH of 6.0 to 8.0, water for injection - up to 1.0 ml.

Description:transparent colorless or slightly colored liquid.

Pharmacotherapeutic group:vasodilating agent.

ATX: & nbsp

C.04.A.D.03 Pentoxifylline

Pharmacodynamics:

Pentoxifylline is a derivative of xanthine.Improves microcirculation and rheological properties of blood. The mechanism of action is associated with inhibition of phosphodiesterase, and an increase in content of cyclic 3,5-adenosine monophosphate (AMP 3.5) in platelets and adenosine triphosphate (ATP) in erythrocytes with simultaneous saturation of the energy potential, which in turn leads to vasodilation, some reduction in total peripheral vascular resistance, an increase in systolic and minute blood volume without a significant change in heart rate.

Slightly dilates coronary arteries. With intravenous administration leads to an increase in collateral circulation, an increase in the volume of flowing blood through a unit of section. It leads to an increase in the content of ATP in the brain, favorably affects the bioelectric activity of the central nervous system. 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 circulation.

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:

Pentoxifylline is rapidly metabolized in the liver with the formation of 2 major pharmacologically active metabolites: 1-5-Hydroxyhexyl-3,7-dimethylxanthine (metabolite 1) and 1-3-carboxypropyl-3,7-dimethylxanthine (metabolite 5). Their concentrations in the blood plasma are 5 and 8 times (respectively) higher than the concentration of the starting substance.

When liver function is disrupted, the half-life is prolonged and bioavailability is increased. Pentoxifylline and its metabolites do not bind to blood plasma proteins. 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, 2% of pentoxifylline is excreted. Excreted in breast milk. With severe renal dysfunction, excretion of metabolites is slowed down.

Indications:

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

- trophic tissue disorders due to violation of arterial and venous microcirculation (varicose ulcers, gangrene, frostbite);

- angioneuropathy (paresthesia, acrocyanosis, Raynaud's disease);

- chronic cerebrovascular disorders of the ischemic type (including cerebral atherosclerosis);

- 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 functions of the middle ear of vascular genesis, accompanied by deafness.

Contraindications:

- Hypersensitivity to pentoxifylline, other xanthine derivatives or other components included in the preparation;

- severe coronary or cerebral atherosclerosis;

- acute myocardial infarction;

- severe cardiac rhythm disturbances;

- uncontrolled arterial hypotension;

- massive bleeding;

- hemorrhage in the retina of the eye;

- hemorrhage in the brain;

- pregnancy, lactation;

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

Carefully:

patients with labile arterial pressure, a tendency to arterial hypotension (risk of lowering blood pressure), with chronic heart failure, a tendency to bleeding, incl.as a result of the use of anticoagulants or with a clotting disorder, a condition after recent surgery, severe hepatic insufficiency, renal failure (creatinine clearance less than 30 ml / min).

Pregnancy and lactation:

The use of pentoxifylline during pregnancy and during breastfeeding is contraindicated. Pentoxifylline in small amounts penetrates into breast milk.

Dosing and Administration:

Intravenously. When carrying out infusions, the patient should be in the "lying" position. The usual dose is two intravenous infusions per day (morning and afternoon), each containing 200 mg of pentoxifylline (2 ampoules of 5 ml) or 300 mg of pentoxifylline (3 ampoules of 5 ml) in 250 ml or 500 ml of a 0.9% solution sodium chloride or Ringer's solution.

Compatibility with other infusion solutions should be tested separately; Only transparent solutions can be used. 100 mg of pentoxifylline should be administered for at least 60 minutes. Depending on the attendant diseases (heart failure), there may be a need for reduction of input volumes.In such cases it is recommended to use a special infuser for controlled infusion.

Long-term intravenous infusion of pentoxifylline for 24 hours is indicated in more severe cases, especially in patients with severe pain at rest, with gangrene or trophic ulcers (III-IV stage of Fontaine).

The dose of pentoxifylline administered parenterally within 24 hours, as a rule, should not exceed 1200 mg of pentoxifylline, and the individual dose can be calculated by the formula: 0.6 mg pentoxifylline per kg of body weight per hour. The daily dose thus calculated will be 1000 mg of pentoxifylline for a patient weighing 70 kg and 1150 mg of pentoxifylline for a patient with a body weight of 80 kg.

In severe cases (pain at rest, gangrene, etc.), a daily dose of 1200 mg can be administered as two separate slow intravenous infusions of 600 mg of pentoxifylline with an interval of at least 6 hours between infusions.

In patients with renal insufficiency (creatinine clearance below 30 ml / min), it is necessary to reduce the dosage by 30-50%, which depends on the patient's individual tolerance of the drug.

Dose reduction, taking into account individual tolerability, is necessary in patients with severe impairment of liver function.

Treatment can be initiated in small doses in patients with low blood pressure, as well as in people at risk because of possible pressure reduction (patients with severe ischemic heart disease or hemodynamically significant stenoses of cerebral vessels). In these cases, the dose can be increased only gradually.

Side effects:

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

From the cardiovascular system: tachycardia, arrhythmia, cardialgia; progression of angina pectoris, lowering of arterial pressure.

From the skin: hyperemia of the skin of the face, "tides" of blood to the skin of the face and upper chest, swelling, increased brittleness of the nails.

From the digestive tract: xerostomia, decreased appetite, intestinal atony, intrahepatic cholestasis, gastrointestinal bleeding.

From the sense organs: impaired vision, scotoma.

From the hemostasis and hematopoiesis system: Thrombocytopenia, leukopenia, pancytopenia, hypofibrinogenemia; bleeding from the mucous membranes of the skin vessels, nosebleeds.

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

Laboratory indicators: increased activity of "liver" transaminases: alanine aminotransferase (ALT), aspartate aminotransferase (ACT) and alkaline phosphatase.

Other: aseptic meningitis (rarely).

Overdose:

Symptoms: weakness, dizziness, lowering of arterial pressure, tachycardia, arrhythmia, drowsiness, loss of consciousness, tonic-clonic convulsions, increased nervous excitability, hyperthermia, areflexia, signs of gastrointestinal bleeding (vomiting like "coffee grounds").

Treatment: symptomatic, aimed at maintaining the function of respiration and blood pressure. At the first signs of an overdose, immediately stop the injection of the drug, the patient is placed in the "lying" position with the raised leg end. Convulsions stop with the introduction of diazepam.

Interaction:

Pentoxifylline may enhance the effect of drugs that affect the blood coagulation system (indirect and direct anticoagulants, thrombolytics), antibiotics (including cephalosporins).

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

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

Co-administration with other xanthines or sympathomimetics can lead to excessive nervous excitement.

Pentoxifylline may increase the concentration of theophylline (risk of side effects).

Special instructions:

Treatment should be carried out under the control of arterial pressure. In patients with chronic heart failure should be compensated for blood circulation.

In patients with diabetes, who take hypoglycemic drugs, the use of large doses of pentoxifylline can cause severe hypoglycemia (dose adjustment is required). When used concomitantly with anticoagulants it is necessary to carefully monitor the parameters of the blood coagulation system. Have patients who have recently undergone surgical intervention, a systematic control of hemoglobin and hematocrit.

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 another infusion solution should be checked in each case.

Effect on the ability to drive transp. cf. and fur:Given the likelihood of side effects: headache, dizziness, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Concentrate for the preparation of a solution for infusions of 20 mg / ml.

5 ml per ampoule of colorless neutral glass type I with a color fracture ring or with a colored dot and notch or without a rupture ring, a colored dot and a notch. One, two or three color rings and / or a two-dimensional bar code, and / or alphanumeric coding or without additional color rings, a two-dimensional bar code, and alphanumeric coding can additionally be applied to the ampoules.

5 ampoules per circuit cell packaging made of polyvinylchloride film and aluminum foil foil or polymer film or without foil and without film. Or 5 ampoules are placed in a prefabricated form (tray) made of cardboard with cells for laying ampoules.

One or two contour squares or cardboard application and scarifier ampoule or a knife ampoule, or without a scarifier ampoule and a knife ampullum placed in a cardboard package (bundle).

Packaging:ampoules (5) / complete with a knife ampoule or scarifier, if necessary for ampoules of this type / - trays cardboard packs cardboard
ampoules (5) / complete with a knife ampoule or scarifier, if necessary for ampoules of this type / - packaging, cell outlines without cover-packs cardboard
ampoules (5) / complete with a knife ampoule or scarifier, if necessary for ampoules of this type / - packaging, cellular contour-packs cardboard

Storage conditions:In the dark place at a temperature of no higher than 25 ° C. Do not freeze.

Keep out of the reach of children.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-002643

Date of registration:01.10.2014

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZON PHARM, LLC Russia

Information update date: & nbsp22.08.2015

Illustrated instructions

Instructions

Pentoxifylline (Pentoxifylline)