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 oppression of phosphodiesterase andincrease in the content of cyclic 3,5-adenosine monophosphate (3.5-AMP) in platelets and adenosine triphosphate (ATP) in erythrocytes with simultaneous saturation of the energy potential, which in turn leads to vasodilatation, some decrease in total peripheral vascular resistance, an increase in systolic and minute volume blood 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 system.

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

In the occlusal lesion of peripheral arteries ("intermittent" lameness), leads to lengthening the distance of walking, eliminating night cramps 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-dimstilxanthine (metabolite 1) and 1-3-carboxypropyl-3,7-dimethylxaptin (metabolite 5). Their concentrations in the blood plasma are 5 and 8 times (respectively) higher than the concentration of the starting substance.

When the liver function is disturbed, lengthening of the period of excretion and an increase in bioavailability are noted. Pentoxifylline and its metabolites nc 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 disruption of the function of the nights excretion of metabolites is slowed.

Indications:

- violations of peripheral circulation against the background of atherosclerotic, diabetic and inflammatory processes (including "intermittent" lameness caused by atherosclerosis, diabetic angiopathy, obliterating epidarthritis);

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

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

- chronic disorders of cerebral circulation of ischemic tyna (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);

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

Contraindications:

- increased sensitivity to pentoxifylline, other xanthine derivative 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;

- acute hemorrhagic stroke;

- 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.

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 concomitant diseases (heart failure), there may be a need to reduce the amount administered. Such case it is recommended to use a special infusion for controlled infusion.

Long-term intravenous infusion of pentoxifylline in 24 hours is shown in more severe cases, especially in patients with severe pain at rest, with gangrene or trophic ulcers (III-IV stage by 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 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 tolerability of the patient.

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, "hot flashes" of blood to the skin of the face and upper chest, swelling, increased fragility of the priest.

From the digestive tract: xerostomia, decreased appetite, intestinal atony, intrahepatic cholestasis, bleeding from the stomach, intestines.

From the sense organs: impaired vision, scotoma.

From the hemostasis and hematopoiesis system: thrombocytopsenia, leukopenia, pantoptopsy, hypofibrinogenesis; bleeding from the mucous membranes, vessels of the skin, nosebleeds.

Allergic reactions: skin itching, skin hyperemia, to swelling, anaphylactic shock.

Laboratory indicators: increased activity

alanipaminotransferase (ALT), asnatrataminotransferase (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, areflavsia, signs of gastrointestinal bleeding ("coffee grounds" type vomiting).

Treatment: symptomatic, aimed at maintaining the function of breathing 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 tsfalosporiiov).

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

Cimetidine increases the concentration of psnotifillipa in 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. Patients with chronic cardiac insufficiency should be compensated for blood circulation. In patients with diabetes mellitus, who take hypoglycemic agents, 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 coagulation blood system. Have patients who had recently undergone surgery needed 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 the solution with a different infusion solution should be checked in each specific 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.

To 5 ml in ampoules of colorless neutral glass (type I) with a color break point. For each ampoule a label is applied or labeled with a quick-clotting paint.

10 ampoules per blister of PVC, 1 blister, along with instructions for use in a pack of cardboard.

5 ampoules per PVC blister. 1 or 2 blisters together with instructions for use in a cardboard pack.

Packaging:ampoules (10) - blister packs, cardboard
ampoules (5) - blister packs, cardboard

Storage conditions:

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

Keep out of the reach of children.

Shelf life:3 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003040

Date of registration:18.06.2015

The owner of the registration certificate:ALVILS, LTD. ALVILS, LTD. Russia

Manufacturer: & nbsp

Nortist Pharmaceutical Group Shenyang No. 1 China

Representation: & nbspAlvils, OOOAlvils, OOO

Information update date: & nbsp22.08.2015

Illustrated instructions

Instructions

Pentoxifylline (Pentoxifylline)