Pentoksifillin

General characteristics. Structure:

Active ingredient: 20 mg of a pentoksifillin.

Excipients: sodium dihydrophosphate, sodium chloride, solution of sodium of hydroxide of 0,1 M, water for injections.

Pharmacological properties:

Pharmacodynamics. Derivative xanthine. Improves microcirculation and rheological properties of blood. The mechanism of action is connected with oppression of phosphodiesterase and increase in contents cyclic 3,5 AMF in thrombocytes and ATP in erythrocytes with simultaneous saturation of energy potential that in turn leads to a vazodilatation, decrease in the general peripheric vascular resistance, increase of systolic and minute volume of heart without considerable change of ChSS. Expanding coronary arteries, increases delivery of oxygen to a myocardium (anti-anginal effect), vessels of lungs - improves blood oxygenation.

Raises a tone of respiratory muscles (intercostal muscles and a diaphragm). At intravenous administration leads to strengthening of collateral circulation, increase in volume of the proceeding blood through section unit. Leads to increase of content of ATP in a brain, favorably influences bioelectric activity of TsNS. Reduces viscosity of blood, causes disaggregation of thrombocytes, increases elasticity of a membrane of erythrocytes (due to influence on patholologically the changed deformirovannost of erythrocytes).

Improves microcirculation in zones of the broken blood circulation. At occlusal damage of peripheral arteries (the alternating lameness), leads to lengthening of a distance of walking, elimination of night spasms of gastrocnemius muscles and pains at rest.

Pharmacokinetics. Drug is quickly metabolized in a liver. In the course of metabolism several active metabolites are formed, basic of which are a metabolite 1 and a metabolite 5. Their concentration in a blood plasma in 5 and 8 times are (respectively) higher than concentration of initial substance. It is allocated in the form of metabolites (94%) and through intestines (4%), in the first 4 hours it is removed to 90% of a dose. In an invariable look 2% of drug are removed.

Pentoksifillin and his metabolites do not contact proteins of a blood plasma. At a heavy renal failure removal of metabolites is slowed down. At an abnormal liver function lengthening of an elimination half-life and increase in bioavailability is noted.

Indications to use:

- disturbances of peripheric circulation against the background of atherosclerotic, diabetic, and inflammatory processes (including at the "alternating" lameness caused by atherosclerosis, a diabetic angiopatiya, an obliterating endarteritis);

- trophic disturbances of fabrics owing to disturbance of arterial or venous microcirculation (varicose ulcers, gangrene, freezing injuries),

- angioneyropatiya (paresthesias, Crocq's disease, Raynaud's disease);

- acute and chronic disorders of cerebral circulation of ischemic type (including at cerebral atherosclerosis),

- states after a hemorrhagic or ischemic stroke;

- disturbances of blood circulation in eye vessels (acute and chronic insufficiency of blood supply of mesh and vascular covers of an eye);

- the dysfunctions of a middle ear of vascular genesis which are followed by relative deafness.

Route of administration and doses:

It is entered intravenously and vnutriarterialno. When performing infusions of the patient has to be in a prone position. Intravenously – 100 mg (1 ampoule) in 250 - 500 ml of 0,9% of solution of sodium of chloride or in 5% solution of a dextrose (glucose) kapelno within 1,5-3 hours. At good tolerance the dose can be increased by 100 mg a day. The maximum daily dose - 300 mg.

Vnutriarterialno - in the beginning 100 mg of drug in 20-50 ml of 0,9% of solution of sodium of chloride, in the next days - on 200 - 300 mg in 30 - 50 ml of solvent. Enter with a speed of 100 mg (5 ml of 2% of solution of drug) within 10 minutes.

At the expressed atherosclerosis of vessels of a brain it is impossible to enter into a carotid artery.

Features of use:

Treatment should be carried out under control of arterial pressure.

At patients with chronic heart failure it is necessary to reach blood circulation compensation.

At the patients with a diabetes mellitus accepting hypoglycemic means, purpose of high doses of a pentoksifillin can cause the expressed hypoglycemia (dose adjustment is required).

At appointment along with anticoagulants it is necessary to watch indicators of coagulant system of blood carefully. At the patients who transferred recently an operative measure systematic control of concentration of hemoglobin and a hematocrit is necessary.

The entered dose has to be reduced at patients with low and unstable arterial pressure. At elderly patients reduction of a dose (increase in bioavailability and reduction in the rate of removal) can be required.

Tobacco smoking can reduce a therapeutic effectiveness of drug.

Compatibility of solution of a pentoksifillin with infusion solution should be checked in each konkyoretny case.

Side effects:

From the central nervous system: headache, dizziness; uneasiness, sleep disorders, spasms.

From cardiovascular system: tachycardia, arrhythmia, cardialgias, it is rare - progressing of symptoms of stenocardia, lowering of arterial pressure.

From integuments: a dermahemia a linden, "inflows" of blood to face skin and an upper part of a thorax, hypostases, the increased fragility of nails.

From a digestive tract: nausea, vomiting, dryness in a mouth, feeling of weight in a stomach, a loss of appetite, an exacerbation of cholecystitis, cholestatic hepatitis, an atony of intestines, bleeding from mucous membranes of a stomach, intestines.

From sense bodys: vision disorder, scotoma.

From system of a hemostasis and bodies of a hemopoiesis: thrombocytopenia, leukopenia, pancytopenia, hypofibrinogenemia, nasal bleedings.

Allergic reactions: seldom - a skin itch, a dermahemia, a small tortoiseshell, a Quincke's disease, anafilaktichesyoky shock.

Laboratory indicators: increase in activity of "hepatic" transaminases: alaninaminotranspherases (ALT), aspartate aminotransferases (ACT), lactate dehydrogenases (LDG) and alkaline phosphatase.

Others: aseptic meningitis (seldom)

Interaction with other medicines:

Pentoksifillin can strengthen effect of the medicines influencing coagulant system of blood (indirect and direct anticoagulants, trombolitik), antibiotics (including cephalosporins – a tsefamandol, a tsefoperazon, a tsefotetan), valproic acid.

Increases efficiency of hypotensive drugs, insulin and hypoglycemic means for intake.

Cimetidinum increases concentration of a pentoksifillin in a blood plasma (risk of emergence of side effects).

Joint appointment with other xanthines can lead to excessive nervous excitement.

Contraindications:

- hypersensitivity to a pentoksifillin, other derivatives of xanthine or other components, vkhodyayoshchy in composition of drug,
- the expressed coronary or cerebral atherosclerosis,
- acute myocardial infarction,
- the expressed disturbances of a heart rhythm,
- uncontrollable arterial hypotension,
- massive bleeding,
- eye retinal apoplexy;
- hemorrhagic stroke,
- pregnancy, lactation period;
- age up to 18 years (efficiency and safety are not established).

With care: the patient with the labile arterial pressure, tendency to arterial hypotension, chronic heart failure, tendency to hemorrhages, a state after recently postponed operative measures, a liver and/or renal failure.

Overdose:

Symptoms: weakness, dizziness, the expressed lowering of arterial pressure, tachycardia, drowsiness, a loss of consciousness, toniko-clonic spasms, the increased nervous irritability, a hyperthermia, an areflexia, symptoms of gastrointestinal bleeding (vomiting like "coffee thick").

Treatment: symptomatic, directed to maintenance of function of breath and arterial pressure.

Storage conditions:

In the place protected from light at a temperature not above 25 °C. In the place, unavailable to children. A period of validity - 2 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Concentrate for preparation of solution for intravenous and intra arterial administration of 20 mg/ml. 5 ml of drug in ampoules. On 10 ampoules place in a pack from a cardboard with partitions or lattices, or a separator from a cardboard. On 10 ampoules in a box from a cardboard. Put the application instruction, a knife in each pack or a box ampoule or the scarificator ampoule. When using ampoules with notches, rings of a break or points of a break the knife ampoule or the scarificator ampoule is not put.