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

Excipients: sodium chloride - 6 mg; sodium dihydrogen phosphate dihydrate (sodium phosphate monosubstituted 2-water) - 1 mg; 1 M solution of sodium hydroxide - to pH 6.0 - 8.0; water for injection - up to 1 ml.

Description:Transparent, colorless or slightly yellowish liquid.

Pharmacotherapeutic group:Vasodilator

ATX: & nbsp

C.04.A.D.03 Pentoxifylline

Pharmacodynamics:

Pentoxifylline improves the rheological properties of blood (fluidity) by affecting the pathologically altered erythrocyte deformability, inhibiting platelet aggregation and decreasing the increased blood viscosity.Improves microcirculation in areas of impaired blood circulation.

Pentoxifylline is a derivative of xanthine. The mechanism of its action is associated with the inhibition of phosphodiesterase and the accumulation of cyclic adenosine monophosphate (cAMP) in the cells of the smooth muscles of blood vessels and blood cells.

Having a weak myotropic vasodilating effect, pentoxifylline somewhat reduces the overall peripheral vascular resistance and slightly dilates the coronary vessels.

Treatment with Pentoxifylline leads to an improvement in the symptoms of brain damage 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 extensively metabolized in erythrocytes and the liver. Among the most known metabolites - metabolite-1 (M-1; hydroxypentoxifylline) is formed due to cleavage, and metabolite-4 (M-IV) and metabolite-5 (M-V; carboxypentoxifylline) - due to the oxidation of the basic substance. M-1 has the same pharmacological activity as pentoxifylline. More than 90% of the dose of pentoxifylline is excreted through the kidneys and 3-4% with feces.

The half-life of pentoxifylline after administration of 100 mg intravenously was approximately 1.1 hours. In patients with severe impairment of liver function, the half-life of pentoxifylline increased.

Pentoxifylline has a large volume of distribution (168 L after a 30-minute infusion of 200 mg) and a high clearance of approximately 4,500-5100 ml / min.

Pentoxifylline and its metabolites do not bind to blood plasma proteins.

With severe disruption of kidney and liver function, excretion of metabolites is slowed down.

Excreted in breast milk.

Indications:

- Violations of the peripheral circulation of atherosclerotic genesis (including, "intermittent" lameness, diabetic angiopathy, obliterating endarteritis);

- trophic disorders (including trophic ulcers of the lower leg, gangrene), frostbite, postthrombotic syndrome, etc .;

- disorders of cerebral circulation (consequences of cerebral atherosclerosis: attention deficit disorder, dizziness, memory impairment), ischemic and post-insult conditions;

- disorders of blood circulation in the retina and choroid of the eye,otosclerosis, degenerative changes on the background of the pathology of the vessels of the inner ear and hearing loss.

Contraindications:

- Hypersensitivity to pentoxifylline or other xanthine derivatives, as well as other components of the drug;

- severe atherosclerotic lesions of the coronary or cerebral arteries;

acute myocardial infarction;

uncontrolled arterial hypotension;

- massive bleeding;

- hemorrhage into the retina of the eye;

- Hemorrhage in the brain;

- severe arrhythmias;

- Pregnancy;

- the period of breastfeeding;

- age under 18 years (efficiency and safety not established).

Carefully:

It should be used with caution in patients with labile arterial pressure, hypotension, chronic heart failure, impaired renal function (creatinine clearance below 30 ml / min) (risk of accumulation and increased risk of side effects), severe impairment of liver function (risk of accumulation and increased risk of side effects), increased tendency to bleeding, including, as a result of use of anticoagulants or with violations in the blood coagulation system (riskdevelopment of more severe bleeding), after recent surgery.

Pregnancy and lactation:

Pentoxifylline is contraindicated in pregnancy, because the experience of using the drug in pregnant women is limited.

If it is necessary to administer Pentoxifylline during lactation, breastfeeding should be discontinued due to the fact that pentoxifylline penetrates into breast milk (according to the section "Pharmacokinetics").

Dosing and Administration:

Intravenous or intra-arterial.

The dose and method of administration are determined by the severity of circulatory disorders, and also on the basis of individual drug tolerance.

Dosage is set by the doctor in accordance with the individual characteristics of the patient.

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. AT Depending on the concomitant diseases (heart failure), there may be a need to reduce the amount administered. In such cases it is recommended to use a special infuser for controlled infusion.

After a daytime infusion, 2 additional pentoxifylline tablets may be prescribed. If two infusions are separated by a longer interval, then one tablet of Pentoxifylline from the additionally assigned two can be taken earlier (at about noon).

If, due to clinical conditions, the implementation of intravenous infusion is possible only once a day, additionally after it can be prescribed 3 pills Pentoxifylline (2 tablets - at noon and 1 - in the evening).

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 by Fontaine).

The dose of Pentoxifylline administered parenterally within 24 hours, as a rule, should not exceed 1200 mg, 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 weighing 80 kg.

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

At the expressed atherosclerosis of vessels of a brain the preparation should not be entered into a carotid artery.

Older patients may need a dose reduction (increased bioavailability and reduced elimination rate).

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.

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

Side effects:

The frequency of possible side effects, listed below,is defined as follows: very often (> 1/10); often (> 1/100 to <1/10); infrequently (> 1/1000 to <1/100); rarely (> 1/10000 to <1/1000); very rarely (<1/10000); frequency is unknown (can not be estimated from available data).

Violations from the blood and lymphatic system:

Very rarely: thrombocytopenia, thrombocytopenic purpura, aplastic anemia, pancytopenia.

Rarely: bleeding (including nasal bleeding, gastrointestinal bleeding, bleeding from the urinary tract, etc.).

The frequency is unknown: leukopenia, hypofibrinogenemia.

Immune system disorders:

Infrequent: hypersensitivity reactions, skin itching, erythema, urticaria.

Very rarely: severe anaphylactic or anaphylactoid reactions occurring within a few minutes after the administration of pentoxifylline, Quincke's edema, bronchospasm, anaphylactic shock, toxic epidermal necrolysis, Stevens-Johnson syndrome, increased sweating.

Disorders of the psyche:

Infrequent: increased excitability, insomnia.

Impaired nervous system:

Infrequent: dizziness, tremor, headache.

Very rarely: paresthesia, convulsions, intracranial hemorrhage, aseptic meningitis.

Disorders from the side of the organ of vision:

Infrequent: impaired vision, conjunctivitis.

Very rarely: hemorrhage into the retina of the eye, detachment of the retina of the eye.

Heart Disease:

Infrequent: a violation of the rhythm of the heart, tachycardia.

Rarely: stenocardia, dyspnea.

Vascular disorders:

Often: hyperemia of the skin of the face.

Rarely: lowering blood pressure, peripheral edema.

Very rarely: increased blood pressure.

Disorders from the gastrointestinal tract:

Often: nausea, vomiting, bloating, a feeling of heaviness in the stomach, diarrhea.

The frequency is unknown: xerostomia, anorexia, intestinal atony, constipation, hypersalivation.

Disorders from the liver and bile ducts:

Very rarely: intrahepatic cholestasis, increased activity of "liver" transaminases.

General disorders and disorders at the site of administration:

Infrequent: increased body temperature.

Overdose:

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

Treatment: symptomatic, aimed at maintaining the function of breathing and blood pressure. Fits convulsions with diazepam.

When the first signs of an overdose appear, stop the injection immediately. Provide a lower position of the head and upper body.

Interaction:

Pentoxifylline is able to enhance the action of drugs that reduce blood pressure (angiotensin converting enzyme inhibitors, nitrates).

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

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

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

The sugar-reducing effect of insulin or oral antidiabetic agents can be enhanced by taking pentoxifylline (an increased risk of developing hypoglycemia).Strict monitoring of such patients is necessary.

In some patients, simultaneous administration of pentoxifylline and theophylline may lead to an increase in the level of theophylline. This may lead to an increase or increase in side effects associated with theophylline.

Special instructions:

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

Patients with chronic heart failure should be compensated for blood circulation. In patients with diabetes mellitus taking hypoglycemic agents, 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 concentration is necessary.

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

In elderly patients and patients with liver and kidney disease, a dose reduction may be required (increased bioavailability and reduced elimination rate).

Tobacco smoking can reduce the therapeutic effectiveness of the drug.

The compatibility of Pentoxifylline with other infusion solutions should be checked in each case.

During the therapy, it is required to monitor the sodium content in the blood plasma, especially in patients who observe a diet with restriction of table salt (total sodium content in an ampoule of 5 ml - 11.8 mg, in an ampoule of 10 ml - 23.6 mg.

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:

Solution for injection 20 mg / ml.

Packaging:

5 ml into neutral glass ampoules.

10 ampoules together with the instruction for use are placed in a box of cardboard.

5 ampoules per contour cell packaging made of polyvinyl chloride film.

2 contour mesh packs together with instructions for use are placed in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of 2 to 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-004626

Date of registration:12.01.2018

Expiration Date:12.01.2023

The owner of the registration certificate:DALHIMFARM, OJSC DALHIMFARM, OJSC Russia

Manufacturer: & nbsp

DALHIMFARM, OJSC Russia

Information update date: & nbsp20.02.2018

Illustrated instructions

Instructions

Pentoxifylline (Pentoxifylline)