Pentoksifillin-Darnitsa

General characteristics. Structure:

Active ingredient: pentoxifylline;

1 tablet contains 200 mg of a pentoksifillin;

excipients: lactose monohydrate, potato starch, calcium stearate, povidone.

Pharmacological properties:

Pharmacodynamics. Pentoksifillin is derivative methylxanthine. The mechanism of action of a pentoksifillin is connected with oppression of phosphodiesterase and accumulation of tsAMF in cells of smooth muscles of vessels, blood cells, and also in other fabrics and bodies. Pentoksifillin slows down aggregation of thrombocytes and erythrocytes, increases their flexibility, reduces the increased concentration of fibrinogen in a blood plasma and strengthens a fibrinolysis that reduces viscosity of blood and improves its rheological properties. Besides, пентоксифиллин causes weak myotropic vasodilating action, reduces the general peripheric vascular resistance a little and has a positive inotropic effect. As a result of use of a pentoksifillin microcirculation and supply of fabrics with oxygen, most in extremities, TsNS improves, it is moderate – in kidneys. Drug slightly expands coronary vessels.

Pharmacokinetics. After intake of 100 mg of a pentoksifillin drug is almost completely absorbed from digestive tract. The maximum concentration of a pentoksifillin and its main metabolite (a metabolite of I) is registered in 1 hour after reception. The phenomenon of "the first passing" through a liver is inherent in drug. Bioavailability of not changed substance averages 19% (fluctuations from 6% to 32%). The active metabolite main pharmacological 1-(5 hydroxyhexyl) - 3,7 dimethylxantine (a metabolite of I) is defined in a blood plasma in the concentration exceeding twice concentration of not changed substance and is with it in a condition of the return biochemical balance. Therefore пентоксифиллин and its metabolite it is necessary to consider as active whole, and it is possible to consider that bioavailability of active agent is much higher.

The elimination half-life of a pentoksifillin makes 1,6 hours.

Pentoksifillin is metabolized completely, more than 90% are removed by kidneys in a look
 not conjugated water-soluble polar metabolites. Less than 4% of a dose are removed with a stake. At patients with heavy renal failures excretion of metabolites is slowed down. At patients with the broken function of a liver lengthening of an elimination half-life of a pentoksifillin and increase in its bioavailability is noted.

Pharmaceutical characteristics.

Main physical and chemical properties: tablets of white color, a round form, with a flat surface, a facet and risky.

Indications to use:

Atherosclerotic encephalopathy, ischemic cerebral stroke; distsirkulyatorny encephalopathy, the disturbances of peripheric circulation caused by atherosclerosis, a diabetes mellitus (including a diabetic angiopatiya), an inflammation; the trophic frustration in fabrics connected with damage of veins or disturbance of microcirculation (a posttromboflebitichesky syndrome, trophic ulcers, gangrene, freezing injury); obliterating endarteritis; an angioneyropatiya (Raynaud's disease), disturbance of blood circulation of an eye (an acute, subacute, chronic circulatory unefficiency in a retina and a choroid of an eye); dysfunction of an inner ear of vascular genesis, followed by decrease in hearing.

Route of administration and doses:

Pentoksifillin-Darnitsa appoint 2-4 tablets 2-3 times a day. A pill should be taken after food, without chewing, washing down with enough liquid. The maximum daily dose should not exceed 1200 mg.

At renal failures (the clearance of creatinine <30 ml/min.) is applied   the dose lowered by 50-70%, according to individual sensitivity.

Patients with heavy hepatic dysfunction require also reduction of a dosage according to individual sensitivity.

At patients with hypotension, and also at patients with risk of a sharp lowering of arterial pressure (for example, with defeat of coronary arteries or with the expressed stenosis of cerebral arteries) treatment should be begun with small doses, gradually raising them before therapeutic effect.

Drug in tablets can be appointed as addition to parenteral administration or as a maintenance therapy after its intravenous administration.

Duration of treatment is defined by the doctor individually.

Features of use:

Use during pregnancy or feeding by a breast.

As there is no sufficient experience of use of a pentoksifillin to pregnant women, it is not necessary to appoint it during pregnancy.

Pentoksifillin in insignificant quantities gets into breast milk. In need of treatment by drug Pentoksifillin-Darnitsa it is necessary to stop feeding by a breast.

Children. Experience of use of drug Pentoksifillin-Darnitsa to children is absent.

At the first signs of development of anaphylactic/anaphylactoid reaction treatment by drug Pentoksifillin-Darnitsa it is necessary to stop and ask for the help the doctor.
At drug use Pentoksifillin-Darnitsa patients with chronic heart failure should reach previously a blood circulation compensation phase.
At the patients having diabetes and receiving treatment by insulin or peroral anti-diabetic means at use of high doses of drug strengthening of influence of these drugs on sugar level in blood is possible (see the section "Interaction with Other Medicines and Other Types of Interactions"). In these cases it is necessary to reduce a dose of insulin or peroral antidiabetic means and to watch especially carefully the patient.

Patients with the system lupus erythematosus (SLE) or others пентоксифиллин can appoint a disease of connecting fabric only after the detailed analysis of possible risks and advantage.
As during treatment pentoksifilliny there is a risk of development of aplastic anemia, regular control of the general blood test is necessary.

Patients with a renal failure (clearance of creatinine less than 30 ml/min.) or heavy dysfunction of a liver can have a slowed down removal of a pentoksifillin. Appropriate monitoring is necessary.

Patients of advanced age can have a need for reduction of a sredneterapevtichesky dose because of increase in bioavailability and reduction in the rate of removal of active agent. Smoking can reduce a therapeutic effectiveness of drug.

Especially attentive observation is necessary for:

–       patients for whom the lowering of arterial pressure represents high risk (for example, patients with heavy coronary heart disease or a stenosis of vessels which deliver blood in a brain);

–       patients with heavy cordial artimiya;

–       patients with a myocardial infarction;

–       patients with arterial hypotension;

–       patients with the expressed atherosclerosis of cerebral and coronary vessels, especially at the accompanying arterial hypertension and disturbances of a cordial rhythm. At these patients at administration of drug attacks of stenocardia, arrhythmia and arterial hypertension are possible;

–       patients with a renal failure (the clearance of creatinine is lower than 30 ml/min.);

–       patients with a heavy liver failure;

–       patients with high the tendency to bleedings caused, for example, by treatment by anticoagulants or disturbances of a blood coagulation. Concerning bleedings – see the section "Contraindications";

–       patients with stomach ulcer and a duodenum in the anamnesis, the patients who recently transferred operational treatment (the increased risk of developing of bleeding, in
 communication with what needs systematic control of level of hemoglobin and a hematocrit);

–        the patients who are at the same time receiving treatment pentoksifilliny and antivitamins K (see the section "Interaction with Other Medicines and Other Types of Interactions");

–       the patients who are at the same time receiving treatment pentoksifilliny and antidiabetic means (see the section "Interaction with Other Medicines and Other Types of Interactions").

Drug contains lactose therefore to patients with rare hereditary forms of intolerance of a galactose, insufficiency of lactase or a syndrome of glyukozo-galaktozny malabsorption it is not necessary to use drug.

Ability to influence speed of response at control of motor transport or work    with other mechanisms.

There are no data, however it is necessary to consider probability of emergence of side reactions from the central nervous system.

Side effects:

At some patients manifestation of side effect of drug is possible, namely:

 from a nervous system: headache, dizziness, uneasiness, sleep disorder; spasms; aseptic meningitis, tremor, paresthesias, excitement, hallucinations;

 from skin: a dermahemia of the person (rush of blood to face skin) and an upper part of a thorax, hypostases, the increased fragility of nails, rash (including vesicular);

 from a digestive tract: gastrointestinal frustration, an abdominal pain, nausea, vomiting, diarrhea, anorexia, an intestines atony, a lock, an intra hepatic cholestasia, an exacerbation of cholecystitis, cholestatic hepatitis, dryness in a throat, thirst, feeling of pressure in a stomach, a meteorism;

 from sense bodys: vision disorder, scotoma, dacryagogue, conjunctivitis, ear pain, migraine, retinal apoplexies, retina amotio;

 from cardiovascular system: tachycardia, arrhythmia, cardialgia, peripheral hypostases, progressing of stenocardia, lowering of arterial pressure, increase in arterial pressure, asthma;

 from system of blood and bodies of a krovoobrazovaniye: thrombocytopenia with a Werlhof's disease, a leukopenia, a pancytopenia which can have a lethal outcome, a hypofibrinogenemia, anemia, aplastic anemia; bleedings from vessels of skin, mucous membranes, a stomach, intestines, nose;

allergic reactions: anaphylactic and anaphylactoid reactions, Quincke's disease, bronchospasm and acute anaphylaxis, itch, dermahemia, small tortoiseshell, rashes, toxic epidermal necrolysis (Lyell's disease) and Stephens-Johnson's syndrome;

others: taste disturbances, hypersalivation, an indisposition, increase and morbidity of nodes in a throat and on a neck, laryngitis, a nose congestion, increase/reduction of weight, fever, a hyper thermal syndrome, a hypoglycemia, the increased perspiration;

laboratory indicators: increase in activity of hepatic transaminases (ALT, nuclear heating plant, LDG) and alkaline phosphatase.

Interaction with other medicines:

Antacids: at patients with gastrointestinal side effects it is possible to appoint antacids with pentoksifilliny. In a comparative research of bioavailability antacids did not change absorption of a pentoksifillin.

Pentoksifillin strengthens effect of anti-hypertensive and other vasodilating substances (APF inhibitors and nitrates) which can cause heavy arterial hypotension. At simultaneous use with adrenergic and ganglioblokiruyushchy drugs the considerable lowering of arterial pressure can be observed.

Simultaneous use of adrenergic substances or xanthines leads to excitement of the central nervous system.

The highest doses of a pentoksifillin exponentiate effect of insulin and peroral hypoglycemic drugs. Because of risk of emergence of a hypoglycemia it is recommended to measure more often glucose level in blood and over time to carry out correction of anti-diabetic therapy.

Pentoksifillin increases the frequency of hemorrhages at patients who are at the same time treated by anticoagulants, antithrombocytic and thrombolytic drugs. Patients who are at the same time treated anticoagulants need to measure to a thicket a prothrombin time. In the post-marketing period it was reported about cases of increase in anticoagulating activity at patients who at the same time received treatment pentoksifilliny and antivitamins K. When dosing of a pentoksifillin is appointed or changes, it is recommended to carry out control of anticoagulating activity at these patients.

Cimetidinum increases concentration of a pentoksifillin in a blood plasma owing to what the risk of development of side reactions increases. Other antagonists of H2 receptors (famotidine, ranitidine and низатидин) influence metabolism of a pentoksifillin much less.

Simultaneous use of a pentoksifillin and theophylline can lead to increase in concentration of theophylline in blood serum. Therefore it is necessary to watch concentration of theophylline in blood serum and in case of need to reduce its dose.

Simultaneous use of a pentoksifillin and ketorolak can lead to increase in a prothrombin time and increase risk of bleeding. The risk of bleeding can also increase at combined use of a pentoksifillin and meloksikam. Therefore simultaneous treatment by these drugs is not recommended.

Ciprofloxacin slows down metabolism of a pentoksifillin in a liver therefore simultaneous introduction of a pentoksifillin and ciprofloxacin can lead to increase in concentration of a pentoksifillin in blood serum. In need of performing simultaneous treatment pentoksifilliny and ciprofloxacin it is recommended to reduce a dose of a pentoksifillin twice.

Erythromycin. There are no data on possible interaction of a pentoksifillin and erythromycin. However at combined use of a pentoksifillin and erythromycin increase in plasma level of theophylline with manifestations of toxic reactions is noted.

Contraindications:

–       Hypersensitivity to a pentoksifillin, to other components of drug or to other drugs of group of methylxanthines, such as theophylline, caffeine, sincaline теофилинат, Aminophyllinum or theobromine;

–       massive bleedings (risk of strengthening of bleeding);

–       eye retinal apoplexies, brain; if during treatment pentoksifilliny there is a retinal apoplexy of an eye, uses of medicine should be stopped at once;

–       hemorrhagic diathesis;

–       acute myocardial infarction;

–       liver or renal failure;

–       stomach ulcer and/or intestinal ulcers;

–       porphyria;

–       pregnancy and period of feeding by a breast;

–       children's age.

Overdose:

Nausea, dizziness or lowering of arterial pressure is initial symptoms of acute overdose pentoksifilliny. Besides, such symptoms as fever, excitement, feeling of heat (inflows), a loss of consciousness, an areflexia, toniko-clonic spasms, vomiting, emetic mass of color of a coffee thick as a symptom of gastrointestinal bleeding can develop.

Treatment. The specific antidote is unknown. If reception of overdoses of drug just happened, it is necessary to take measures for the prevention of further system absorption of active ingredient by primary elimination (for example, a gastric lavage) or prevention of its absorption (for example, by means of absorbent carbon).
For the purpose of treatment of acute overdose and the prevention of emergence of complications the general and specific intensive medical observation and use of therapeutic actions is necessary.

Storage conditions:

Period of validity. 3 years. To store in the place, unavailable to children, in original packaging at  a temperature not above 25 °C.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in a blister strip packaging; on the 2nd blister strip packagings in a pack.