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

Excipients: lactose monohydrate (sugar milk) - 53,420 mg; potato starch - 18,000 mg; povidone-K25 - 7,200 mg; methylcellulose-0.480 mg; magnesium stearate - 0.900 mg.

Shell composition: Acryl-from white 93A - 7,200 mg, including: methacrylic acid and ethyl acrylate copolymer (1: 1) - 4.752 mg, talc - 1.188 mg, titanium dioxide 1.080 mg, silicon dioxide colloid - 0.072 mg, sodium hydrogen carbonate - 0.072 mg , sodium lauryl sulfate - 0.036 mg, triethyl citrate - 0.800 mg.

Description:

The tablets are round, cylindrical, biconvex, covered with a white or almost white coating. On the cross-section, a film shell and a white or almost white core are visible.

Pharmacotherapeutic group:vasodilator

ATX: & nbsp

C.04.A.D.03 Pentoxifylline

Pharmacodynamics:

A drug Pentoxifylline reduces the viscosity of the blood and improves the rheological properties of blood (fluidity) due to:

- improvement of the deformed erythrocytes;

- reduction of aggregation of platelets and erythrocytes;

- decrease in the concentration of fibrinogen;

- decreasing the activity of leukocytes and reducing the adhesion of leukocytes to the vascular endothelium.

As an active ingredient, the drug Pentoxifylline contains a xanthine derivative - pentoxifylline. 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 vasodilator effect, pentoxifylline somewhat reduces the overall peripheral vascular resistance and slightly dilates the coronary vessels. Pentoxifylline has a weak positive inotropic effect on the heart. Improves microcirculation in areas of impaired blood circulation.

Treatment with drug Pentoxifylline leads to an improvement in the symptoms of cerebral circulation disorders. In occlusive diseases of peripheral arteries, the use of pentoxifylline leads to an increase in the walking distance, elimination of night cramps in the gastrocnemius muscles and the disappearance of pain at rest.

Pharmacokinetics:

After oral administration pentoxifylline almost completely absorbed.

Pentoxifylline is subjected to the effect of "primary transmission" through the liver. Absolute bioavailability of the original substance is 19±13%. The concentration of the primary active metabolite 1- (5-hydroxyhexyl) -3,7-dimethylxanthine (metabolite 1) in blood plasma is twice the concentration of the original pentoxifylline. Metabolite 1 is found with pentoxifylline in reversible biochemical redox equilibrium. therefore pentoxifylline and metabolite 1 are considered together as the active unit. As a consequence, the availability of the active substance is much greater.

The prolonged release of pentoxifylline allows maintaining its constant (peak-free) concentration in the blood,which provides better tolerability of the drug in this dosage form.

The half-life of pentoxifylline after ingestion is 1.6 hours. Pentoxifylline is completely metabolized and more than 90% is excreted through the kidneys in the form of unconjugated water-soluble metabolites.

Patients with impaired renal function

In patients with impaired renal function, excretion of metabolites slows down.

Patients with hepatic impairment

In patients with impaired hepatic function, the half-life of pentoxifylline lengthens, and absolute bioavailability increases.

Indications:

- Peripheral arterial occlusive disease or diabetic atherosclerotic origin (e.g., intermittent claudication, diabetic angiopathy);

- trophic disorders (for example, trophic ulcers of the lower leg, gangrene);

- cerebrovascular accidents (the effects of cerebral arteriosclerosis, such as poor concentration, dizziness, memory impairment), ischemic and post stroke state;

- circulatory disorders 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, other methylxanthines or to any of the components of the drug;

- massive bleeding, extensive hemorrhage in the retina of the eye;

- acute myocardial infarction;

- hemorrhage in the brain;

- pronounced atherosclerosis of the coronary arteries;

- pregnancy;

- the period of breastfeeding;

- children's age till 18 years;

- lactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome.

Carefully:

- Hemodynamically significant disorders of the heart rhythm (risk of worsening of arrhythmia);

- arterial hypotension (risk of further lowering blood pressure (BP), see section "Method of administration and dose");

- chronic heart failure; ischemic heart disease (IHD), hemodynamically significant stenoses of cerebral vessels;

- peptic ulcer of the stomach and duodenum;

- impaired renal function (creatinine clearance less than 30 ml / min) (risk of cumulation and an increased risk of side effects, see the section "Dosage and administration", "Special instructions");

- severe dysfunction of the liver (risk of cumulation and an increased risk of side effects, see the sections "Dosing and Administration", "Special instructions");

- after recently transferred surgical interventions;

- proliferative diabetic retinopathy;

- increased tendency to bleeding, for example, as a result of the use of anticoagulants (including indirect anticoagulants [vitamin K antagonists] or in disorders in the blood coagulation system (risk of developing more severe bleeding), see "Interaction with Other Drugs"

- Simultaneous use with platelet aggregation inhibitors (clopidogrel, eptifibatide, tirofiban, abciximab, epoprostenol, iloprost, anagrelide NSAIDs [other than selective inhibitors cyclooxygenase-2], acetylsalicylic acid, ticlopidine, dipyridamole), see the section "Interaction with other drugs".

- simultaneous use with hypoglycemic agents (insulin and hypoglycemic agents for oral administration), see section "Interaction with other drugs";

- simultaneous use with ciprofloxacin and theophylline (see.section "Interaction with other drugs").

Pregnancy and lactation:

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

Pentoxifylline and its metabolites are excreted in breast milk. If necessary, use during lactation should stop breastfeeding.

Dosing and Administration:

Dosage is set by the doctor in accordance with the individual characteristics of the patient. The drug should be swallowed whole during or immediately after eating, squeezed with enough water.

The usual dose is: one tablet of Pentoxifylline three times a day, followed by an increase in the dose to 200 mg 2-3 times a day. The maximum single dose is 400 mg. The maximum daily dose is 1200 mg.

With occlusive disease of peripheral arteries of the II stage (intermittent claudication) the recommended dose of Pentoxifylline is 1200 mg per day (preferably in the form of tablets with sustained release 400 mg three times daily or 600 mg twice a day).

In patients with impaired renal function (CC less than 30 ml / min), the dosage can be reduced to 1-2 tablets per day.

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

Treatment can be started in small doses in patients with low blood pressure, as well as in patients at risk for possible lowering of blood pressure (patients with severe CAD or with hemodynamically significant stenoses of cerebral vessels). In these cases, the dose can be increased only gradually.

Side effects:

Undesirable reactions are presented according to the systems of organs in accordance with the Medical Dictionary of Regulatory Activities (MedDRA).

From the nervous system: headache, dizziness, aseptic meningitis, convulsions.

From the side of the psyche: agitation, sleep disturbance, anxiety.

From the side of the cardiovascular system: tachycardia, arrhythmia, stenocardia, lowering blood pressure, "tides" of blood to the skin, bleeding (including bleeding from the vessels of the skin, mucous membranes, stomach, intestines).

From the skin and subcutaneous tissues: skin itch, skin rash, erythema (reddening of the skin), urticaria, increased brittleness of the nails, swelling.

From the side of the digestive tract: xerostomia (dry mouth), anorexia, nausea, vomiting, feeling of pressure and overflow in the stomach, intestinal atony, diarrhea, constipation, hypersalivation (increased salivation), intrahepatic cholestasis, increased activity of "liver" transaminases, increased activity of alkaline phosphatase.

From the side of the organ of vision: visual impairment, scotoma.

From the hemostasis and hematopoiesis system: thrombocytopenia, leukopenia / neutropenia, pancytopenia, hypofibrinogenemia.

From the immune system: anaphylactic / anaphylactoid reactions, angioedema, anaphylactic shock, bronchospasm.

Overdose:

Symptoms: dizziness, nausea, vomiting like "coffee grounds", falling blood pressure, tachycardia, arrhythmia, redness of the skin, loss of consciousness, chills, areflexia, tonic-clonic convulsions.

In case of occurrence of the violations described above, you should immediately call your doctor.

Treatment: symptomatic.When the first signs of an overdose (sweating, nausea, cyanosis) immediately stop taking the drug. If the drug is taken recently, measures should be taken to prevent further absorption of the drug by removing it (gastric lavage) or slowing the absorption (for example, taking activated charcoal). Particular attention should be paid to maintaining blood pressure and respiratory function. When seizures are injected diazepam.

The specific antidote is unknown.

Interaction:

With antihypertensive drugs

Pentoxifylline increases the risk of developing arterial hypotension with simultaneous use with antihypertensive agents (eg, angiotensin-converting enzyme (ACE) inhibitors) or other drugs, possessing a potential antihypertensive effect (for example, nitrates).

With medicines, affecting the blood coagulation system

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

With the combined use of pentoxifylline and indirect anticoagulants (vitamin K antagonists) in post-marketing studies, there have been cases of increased anticoagulant action (risk of bleeding). Therefore, at the beginning of taking pentoxifylline or changing its dose, it is recommended to monitor the degree of anticoagulant effect in patients taking this combination of drugs, for example, to regularly monitor INR (the international normalized ratio).

With cimetidine

Cimetidine increases the concentration of pentoxifylline and active metabolite 1 in blood plasma (risk of side effects).

With other xanthines

Joint application with other xanthines can lead to excessive nervous excitation.

With hypoglycemic cpedctyouu (insulin and hypoglycemic agents for oral administration)

Hypoglycemic action of insulin or hypoglycemic agents for oral administration may be intensified with simultaneous administration of pentoxifylline (an increased risk of hypoglycemia). Strict monitoring of the condition of such patients is required, including regular glycemic control.

With theophylline

In some patients, concomitant use of pentoxifylline and theophylline shows an increase in the concentration of theophylline in the blood plasma. In the future, this may lead to an increase or increase in side effects associated with theophylline.

With ciprofloxacin

In some patients with the simultaneous use of pentoxifylline and ciprofloxacin, there is an increase in the concentration of pentoxifylline in the blood plasma. In the future, this may lead to an increase or increase in side effects associated with the use of this combination.

With platelet aggregation inhibitors

With the simultaneous use of pentoxifylline with platelet aggregation inhibitors (clopidogrel, eptifibatide, tirofiban, epoprostenol, iloprost, abciximab, anagrelideNSAIDs [besides selective inhibitors of cyclooxygenase-2] acetylsalicylic acid, ticlopidine, dipyridamole) it is possible to develop a potential additive effect that increases the risk of bleeding. Therefore, due to the risk of bleeding, caution should be exercised pentoxifylline simultaneously with the above inhibitors of platelet aggregation (see the section "With caution").

Special instructions:

Treatment should be carried out under the control of blood pressure. Patients with chronic heart failure should be compensated for blood circulation before starting the drug.

In patients with diabetes mellitus taking hypoglycemic agents, the administration of large doses of the drug 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.

Patients who have recently undergone surgical intervention need systematic monitoring of hemoglobin and hematocrit concentration.

Patients with low and unstable blood pressure, it is necessary to select the dose of the drug Pentoxifylline individually.

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

The safety and efficacy of Pentoxifylline in children is not established.

Smoking can reduce the therapeutic effectiveness of the drug.

When using the drug Pentoxifylline Care should be taken in patients with severe liver dysfunction.Given the risk of cumulation of the drug and an increased risk of side effects, an increase in the dose should be carried out taking into account individual tolerability.

Patients with severe renal dysfunction (QC less than 30 mL / min) when taking the drug Pentoxifylline need careful medical supervision.

In the event that during the period of application of the drug the patients have hemorrhages in the retina of the eye, the drug is immediately canceled.

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

During the treatment period, there may be headache and dizziness, so care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Intestine-soluble film coated tablets, 100 mg.

Packaging:

For 10, 14, 25 or 30 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 10, 20, 30, 40, 50, 60, 100 or 120 tablets in cans of polyethylene terephthalate for medicines,closed with caps screwed on with first opening control or by a "push-turn" system of polypropylene or polyethylene, or polypropylene cans for drugs sealed with lids pulled with the control of the first opening from polyethylene, or polypropylene cans for medicines sealed with lids pulled with the control of the first autopsy from high-density polyethylene.

One jar or 1, 2, 3, 4, 5, 6 or 12 contour squares, together with the instructions for use, are placed in a cardboard package (bundle).

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-003789

Date of registration:17.08.2016

Expiration Date:17.08.2021

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

Manufacturer: & nbsp

OZONE, LLC Russia

Representation: & nbspOZONE LLC OZONE LLC Russia

Information update date: & nbsp09.10.2016

Illustrated instructions

Instructions

Pentoxifylline (Pentoxifylline)