Pentoksifillin-Darnitsa

General characteristics. Structure:

Active ingredient: pentoxifylline;

1 ml contains 20 mg of a pentoksifillin;

excipients: sodium chloride, water for injections.

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. 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 reversible biochemical balance. Therefore пентоксифиллин and its metabolite it is necessary to consider as active whole.

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 is noted.

Pharmaceutical characteristics.

Main physical and chemical properties: transparent colourless liquid.

Incompatibility.

It is not necessary to mix drug with other medicines in one capacity, except for the solutions specified in the section "Route of Administration and Doses".

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:

Intravenous infusions are the most effective forms of parenteral administration of drug which are better transferred. The mode of dosing is defined by the doctor and depends on severity of circulator disturbances, body weight and portability of treatment. Infusion can be carried out only if solution is transparent. 

Such schemes of treatment are recommended to adults:

1. Intravenous infusion of 100-600 mg of a pentoksifillin in 100-500 ml of solution of Ringer of a lactate, 0,9% of solution of sodium of chloride or 5% of solution of glucose 1-2 times a day. Duration of intravenous drop infusion makes 60-360 minutes, that is introductions of 100 mg of a pentoksifillin not less than 60 minutes have to last. Infusion can be added with oral administration Pentoksifillin-Darnitsa (400 mg) from calculation that the maximum daily dose (infusional and peroral) makes 1200 mg.

2. At serious condition of the patient (especially at constant pain, at gangrene or trophic ulcers) performing infusion of Pentoksifillin-Darnits within 24 hours is possible. At such scheme of introduction the dose is defined at the rate of 0,6 mg/kg/h of Rasschitanaya thus a daily dose for the patient with the body weight of 70 kg makes 1000 mg, for the patient with the body weight   of 80 kg – 1150 mg.

Irrespective of the body weight of the patient the maximum daily dose makes 1200 mg.

The volume of infusion solution is calculated individually taking into account associated diseases, a condition of the patient and makes on Wednesday 1-1,5 l a day.

3. In some cases drug is used by an intravenous injection on 5 ml
(100 mg). The injection is carried out slowly, within 5 minutes, position of the patient – lying.

Patients of advanced age. For patients of advanced age there is no need for correction of a dosage.

Duration of a parenteral course of treatment is defined by the doctor who carries out treatment.

After improvement of a condition of the patient it is recommended to continue treatment, applying the tableted drug form Pentoksifillin-Darnitsa.

Features of use:

Use during pregnancy or feeding by a breast.

Pentoksifillin-Darnitsa is not recommended to apply during pregnancy or feeding by a breast.

Children. Experience of use of drug 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 with heavy cardiac arrhythmias;

–       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);

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

–        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").

 

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:

Side reactions which can take place during treatment pentoksifilliny are specified on emergence frequency: very often:> 1/10, it is frequent:> 1/100, <1/10, infrequently:> 1/1000, ≤ 1/100, it is rare:    1/10000, <1/1000, it is very rare <1/10000, including isolated cases.

Frequency of emergence of side reactions on separate systems of an organism:

From cardiovascular system: seldom – tachycardia; infrequently – peripheral hypostasis, face reddening or feeling of heat (inflows), it is very rare – an atypical stethalgia, arterial hypotension, progressing of stenocardia, arterial hypertension, an asthma, arrhythmia, heartbeat.

 From blood and lymphatic system: isolated cases – thrombocytopenia з a Werlhof's disease, a leukopenia, a pancytopenia (which can have a lethal outcome), lengthening of a prothrombin time, a hypofibrinogenemia, anemia, aplastic anemia, bleedings (for example, from vessels of skin, mucous membranes, a stomach, intestines, nose).

From a nervous system: seldom – a headache, dizziness, aseptic meningitis (at use of high doses); isolated cases – a tremor of hands, sleeplessness, excitement, concern, sensation of fear, a loss of consciousness, sleep disorders, hallucinations, blackout, a zanemeniye of extremities, a hyperhidrosis, spasms, paresthesias.

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

From digestive tract: often – gastrointestinal frustration, feeling of pressure in a stomach, overflow, diarrhea; infrequently – nausea, vomiting (including numerous), a meteorism, epigastric pains, anorexia, an intestines atony, locks, dryness in a throat, thirst.

From metabolism: very seldom – a hypoglycemia, a hypopotassemia.

From immune system: isolated cases – allergic reactions (anaphylactic/anaphylactoid reactions up to shock, a Quincke's disease, a bronchospasm, erubescence, an itch, rash, a small tortoiseshell), a toxic epidermal necrolysis (Lyell's disease), Stephens-Johnson's syndrome.

From gepatobiliarny system: very seldom – an intra hepatic cholestasia, increase in activity of enzymes of a liver, an exacerbation of cholecystitis, cholestatic hepatitis.

From skin and hypodermic cellulose: very seldom – the raised potovydeleniye, a dermahemia of the person and an upper part of a thorax, hypostases, makulopapulezny rash, the increased fragility of nails.

Changes in an injection site: pain in an injection site, a hyperemia, hypostasis, rash.

Others: taste disturbances, the raised slyunovydeleniye, an indisposition, throat/neck pains, laryngitis, a nose congestion, increase/reduction of body weight, a fever, feeling of heat, fever, a hyper thermal syndrome.

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

The majority of side reactions are connected with a dosage. They can be minimized or at all to avoid at reduction of a dose.

If heavy side reactions take place, treatment should be stopped.

Interaction with other medicines:

Simultaneous use of a pentoksifillin and anti-hypertensive drugs (in particular, inhibitors of an angiotensin-converting enzyme) strengthens action of the last therefore the corresponding correcting of doses of hypotensive drugs is required.
The anticoagulants, drugs reducing blood coagulation. The concomitant use of a pentoksifillin and the drugs reducing blood coagulation raises a possibility of bleeding, therefore the thicket should control 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. At simultaneous introduction of Cimetidinum there is a substantial increase of concentration of a pentoksifillin in blood serum. It is necessary to watch closely possible emergence of signs of overdose of a pentoksifillin. Other antagonists         of H2 receptors (famotidine, ranitidine and низатидин) influence metabolism of a pentoksifillin much less.
Theophylline. Simultaneous introduction 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, if necessary – to reduce its dose.
Ketorolak, to meloksika. 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 simultaneous use of a pentoksifillin and meloksikam. Therefore simultaneous treatment by these drugs is not recommended.
Ciprofloxacin. Ciprofloxacin slows down metabolism of a pentoksifillin in a liver therefore simultaneous use 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.

Insulin and peroral antidiabetic drugs. High intravenous doses of a pentoksifillin can strengthen hypoglycemic effects of insulin and peroral antidiabetic drugs therefore it is necessary to adjust respectively dosages of insulin or hypoglycemic drug.

Nitrates. Pentoksifillin strengthens effect of nitrates.

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:

Symptoms: weakness, nausea, dizziness, decrease/increase in arterial pressure, an unconscious condition, tachycardia, drowsiness or excitement, a loss of consciousness, a hyperthermia, an areflexia, toniko-clonic spasms, symptoms of gastrointestinal bleeding – vomiting (emetic mass of color of a coffee thick), fever, feeling of heat (inflows).

Treatment: at emergence of the first symptoms of overdose (perspiration, nausea, cyanosis) immediately stop drug use, it is necessary to provide lower position of the head and an upper part of a trunk, to control free passability of respiratory tracts. Carry out symptomatic therapy, special attention should be paid to maintenance of the ABP and function of breath. For stopping of convulsive attacks enter diazepam.

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. Not to freeze.

Issue conditions:

According to the recipe

Packaging:

On 5 ml in an ampoule; on 10 ampoules in a box; on 5 ml in an ampoule; on 5 ampoules in a blister strip packaging, on 1 or 2 blister strip packagings in a pack.