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

core: lactose monohydrate - 91,940 mg, corn starch - 23,000 mg, talc - 2,200 mg, magnesium stearate - 2,200 mg, silicon dioxide colloid - 0.660 mg; shell: carmellose sodium 1,442 mg, sucrose crystalline 80.174 mg sucrose powder 16,994 mg talc 22,907 mg titanium dioxide 5.090 mg colloidal silicon 0.848 mg acacia 2.545 mg.

Description:White, round, glossy biconvex tablets, covered with a shell.

Pharmacotherapeutic group:Vasodilating agent.

ATX: & nbsp

C.04.A.D.03 Pentoxifylline

Pharmacodynamics:

Pentoxifylline improves microcirculation and rheological properties of blood. The mechanism of action is associated with inhibition of the enzyme phosphodiesterase and an increase in the content of cyclic adenosine monophosphate (cAMP) in platelets and adenosine triphosphate (LTP) in erythrocytes with simultaneous saturation of the energy potential, which in turn leads to vasodilation, a decrease in the total peripheral vascular resistance (OG1SS), an increase in the shock and minute blood volume without a significant change in the heart rate (HR).

Pentoxifylline reduces blood viscosity, increases the elasticity of the erythrocyte membrane (by affecting the pathologically altered erythrocyte deformability), reduces aggregation of erythrocytes, platelets and neutrophils, reduces fibrinogen content in the blood, reduces the adhesiveness of leukocytes to the vascular endothelium, reduces the stimulation of leukocytes and, as a result, destruction of the endothelium.

Improves microcirculation in areas of impaired blood circulation.In occlusive diseases of peripheral arteries ("intermittent" lameness) leads to an increase in the distance of walking, removal of night cramps calf muscles and pain at rest.

Pharmacokinetics:

After oral administration pentoxifylline almost completely absorbed from the gastrointestinal tract. The drug undergoes a "first pass" through the liver with the formation of 2 major pharmacologically active metabolites: 1-5-hydroxycisyl-3,7-dimstilxanthin (metabolite I) and 1-3-carboxypropyl-3,7-dimethylxaite (metabolite V). The concentration of metabolites I and V in the blood plasma, respectively, is 5 and 8 times higher than pentoxifylline. Metabolite 1 is found with pentoxifylline in reversible biochemical redox equilibrium. therefore pentoxifylline and the metabolite I are considered together as the active unit. As a consequence, the availability of the active substance is much greater. The half-life (T1 / 2,) is 1.6 hours. Pentoxifylline is mainly excreted by the kidneys - 94% in the form of metabolites (mainly metabolite V), intestine - 4%, in the first 4 hours it is deduced up to 90% of the dose. Excreted in breast milk.

Patients with impaired renal function

With severe renal dysfunction, excretion of metabolites is slowed down.

Patients with hepatic impairment

If the liver function is abnormal, Tu lengthening is noted, and bioavailability is increased.

Indications:

- Occlusal disease of peripheral arteries of atherosclerotic or diabetic origin (for example, "intermittent" lameness, diabetic angiopathy).

- Disorders of cerebral circulation (consequences of cerebral atherosclerosis, such as violations of concentration, dizziness, memory impairment), ischemic and post-insult conditions.

- Trophic tissue disorders due to violation of arterial or venous microcirculation (trophic ulcers, post-thrombophilic syndrome, frostbite, gangrene).

- Disturbances of blood circulation in the vessels of the eye (acute and chronic circulatory insufficiency in the mesh or in the choroid of the eye).

- Disorders of the function of the middle ear of vascular genesis, accompanied by deafness.

Contraindications:

- Hypersensitivity to pentoxifylline, other methylxanthine derivatives or other components that make up the drug.

- Acute myocardial infarction.

- Massive bleeding (risk of increased bleeding).

- Hemorrhage in the retina of the eye (risk of increased bleeding).

- Acute hemorrhagic stroke.

- Pregnancy.

- Breastfeeding period.

- Age to 18 years (effectiveness and safety not established).

- Intolerance to fructose, lactose, deficiency of lactase, sugarase / isomalyase. Glucose-galactose malabsorption (the preparation contains lactose and sucrose).

Carefully:

Use with caution in patients with a marked decrease in blood pressure (BP) (risk of further lowering blood pressure) and hemodynamically significant violations of the heart rhythm; chronic heart failure (CHF); expressed violations of liver function (risk of cumulation and an increased risk of side effects, see section "Method of administration and dose"); violations kidney function (creatinine clearance (CK) less than 30 ml / min) (risk of cumulation and an increased risk of side effects, see section "Method of administration and dose"); peptic ulcer of the stomach and duodenum; with increased incidence of bleeding, for example, as a result of the use of indirect anticoagulants [vitamin K antagonists] or in disorders in the blood coagulation system (the risk of developing more severe bleeding) (e.section "Interaction with other drugs"); after a recent surgery (risk of bleeding); with proliferative diabetic retinopathy. Care should be taken when using the drug simultaneously Pentoxifylline Zsntiva with hypoglycemic agents (insulin and hypoglycemic agents for oral administration) and ciprofloxacin (see section "Interaction with other drugs").

Pregnancy and lactation:

Application of the drug Pentoxifylline Zsntiva during pregnancy it is contraindicated.

The use of Pentoxifylline Zentiva in the period of breastfeeding is contraindicated, since the active substance penetrates into breast milk. If you need to take the drug should refrain from breastfeeding.

Dosing and Administration:

Tablets are taken orally, without chewing, regularly, at the same time, preferably during or after a meal, with plenty of water and without chewing. The drug begins to take 200 mg (2 tablets) 3 times a day for the first week.With a sharp decrease in blood pressure and symptoms of irritation from the gastrointestinal tract or central nervous system, the initial dose is reduced to 100 mg (1 tablet) 3 times a day.

At course treatment appoint but 100 mg (1 tablet) 3 times a day.

The maximum daily dose is 1200 mg per day.

Patients with low blood pressure, as well as those at risk, in view of a possible sharp decrease in blood pressure (patients with severe ischemic heart disease or hemodynamically significant stenoses of cerebral vessels), Pentoxifylline Zentiva should be treated with small doses followed by a gradual increase in the daily dose.

Occlusal disease of the peripheral artery of stage II ("intermittent claudication") The daily dosage for this category of patients is 1200 mg per day, preferably in the form of tablets with sustained release 400 mg three times a day or 600 mg twice a day.

Patients with impaired hepatic function

When Pentaxylphyllium Zentiva is used in patients with severe liver dysfunction, caution should be exercised, a possible reduction in the dose should be made taking into account the individual tolerability of the drug.

Patients with impaired renal function

Caution should be exercised when using Pentoxifylline Zentiva in patients with a QC value below 30 ml / min. The dose of Pentoxifylline Zentiva can be reduced by 50-70%.

Children and teens

The use of Pentoxylophilia Zentiva in patients under the age of 18 years is contraindicated. The safety and efficacy of Pentoxifylline Zentiva has not been established in this age group.

Side effects:

When Pentoxylphyllium Zentiva is used, the following side effects may appear, which are separated according to the system-organ classes according to the classification of the Medical Dictionary of Regulatory Activities (McDDRA). To indicate the frequency of side effects, the classification 1303 was used: very frequent (> 10%); frequent (> 1% and <10%); infrequent (> 0.1% and <1%); rare (> 0.01% and <0.1%); very rare (<0.01%); the frequency is unknown (it is not possible to determine the incidence of side effects from the available data).

Impaired nervous system: frequency unknown - headache, dizziness, convulsions, aseptic meningitis.

Disorders from the psyche: frequency unknown - agitation, sleep disturbance, anxiety.

Heart Disease: the frequency is unknown - tachycardia, arrhythmia, angina, lowering blood pressure.

Vascular disorders: the frequency is unknown - the "tides" of blood to the skin, bleeding (including bleeding from the vessels of the skin, mucous membranes, gastrointestinal bleeding, nasal bleeding).

Disturbances from the skin and subcutaneous tissues: the frequency is unknown - itching, erythema (reddening of the skin), urticaria, swelling, increased brittleness of the nails.

Disorders from the gastrointestinal tract: frequency unknown - anorexia, intestinal atony, epigastric discomfort, bloating (sensation of stomach overflow), vomiting, diarrhea, dry mouth.

Disorders from the side of the organ of vision: frequency unknown - impaired vision, scotoma. Violations from the blood and lymphatic system: the frequency is unknown - thrombocytesons, leukopenia, pancytopenia, hypofibrinogenemia.

Immune system disorders: frequency unknown

anaphylactic / anaphylactoid reactions, angioedema, anaphylactic shock, bronchospasm.

Disorders from the liver and bile ducts: frequency is unknown - intrahepatic cholestasis, increased activity of alanine aminotransferase (ALT) and aspartate aminotransferase (ACT), increased activity of alkaline phosphatase.

Overdose:

Symptoms: dizziness, nausea, vomiting like "coffee grounds", expressed reduction of blood pressure, tachycardia, arrhythmia, reddening of the skin, loss of consciousness, chills, areflexia, topic-clopic convulsions.

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

Treatment: treatment is 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

The drug Pentoxifylline Zentiva can enhance the reduction in blood pressure when used simultaneously with antihypertensive drugs (eg, AIF inhibitors) or other drugs,possessing potential hypotensive effect (for example, nitrates).

FROM drugs affecting the blood coagulation system The drug Pentoxifylline Zentiva can enhance the effect of drugs that affect the blood coagulation system (direct and indirect anticoagulants, thrombolytics, antibiotics, such as 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 control the degree of anticoagulant effect in patients taking this combination of drugs (for example, to regularly monitor the international normalized relationship (INR)).

With cimetidine

Cimetidine may increase the concentration of pentoxifylline in the blood plasma (risk of adverse reactions).

With other xanthines

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

FROM hypoglycemic agents (insulin and hypoglycemic agents for oral administration)

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

With theophylline

In some patients with simultaneous preparation Pentoxifylline Zentiva and theophylline an increase in the concentration of theophylline in the blood plasma is noted. In the future, the ego can lead to an increase in the incidence of adverse reactions associated with theophylline.

With ciprofloxation

In some patients with simultaneous use of Pentoxifylline Zentiva and ciprofloxacin, there is an increase in the concentration of pentoxifylline in the blood plasma. In the future, this can lead to an increase or increase in adverse reactions associated with the use of this combination.

With veldproic acid

When combined, the Pentoxifylline Zentiva drug can enhance the action of valproic acid.

Special instructions:

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

In patients with diabetes mellitus taking hypoglycemic agents, administration of large doses of Pentoxifylline Zentiva may cause severe hypoglycemia (dose adjustment is required).

When Pentoxifylline Zentiva is prescribed concomitantly with anticoagulants, it is necessary to closely monitor the parameters of the blood coagulation system.

In patients who have recently undergone surgery, systematic monitoring of hemoglobin and hematocrit is necessary.

Patients with low and unstable blood pressure should choose the dose Pentoxifylline Zentiva individually.

In elderly patients, a reduction in the dose of Pentoxifylline Zentiva may be required (increased bioavailability and reduced elimination rate).

The safety and efficacy of Pentoxifylline Zentiva in children have not been adequately studied. Care should be taken when using Pentoxifylline Zentiva in patients with impaired hepatic function. Given the risk of cumulation of the drug and an increased risk of side effects, dose reduction should be carried out taking into account individual tolerability.Patients with severe renal dysfunction (CC below 30 ml / min) while taking Pentoxifylline Zentiva need to be closely monitored.

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.

Smoking can reduce the therapeutic efficacy of Pentoxifylline Zentiva.

The drug Pentoxifylline Zentiva contains lactose and sucrose, so patients with intolerance to fructose, lactose, lactase deficiency, sucrose / isomaltase, glucose-galactose malabsorption, the drug is contraindicated.

Effect on the ability to drive transp. cf. and fur:The negative effect of Pentoxifylline Zentiva on the ability to drive vehicles and mechanisms was not noted. However, care should be taken when driving vehicles and during occupations requiring increased concentration and speed of psychomotor reactions, due to the possibility of dizziness and visual impairment when Pentoxifylline Zentiva is used.

Form release / dosage:

Tablets, coated with a coating, 100 mg.

Packaging:For 60 tablets in a vial of dark glass, sealed with a plastic screw cap with the control of the first autopsy. Each bottle, along with the instructions, is placed in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N012051 / 01

Date of registration:10.06.2010

The owner of the registration certificate:Zentiva as.Zentiva as. The Slovak Republic

Manufacturer: & nbsp

Saneka Pharmaceuticals as. The Slovak Republic

Representation: & nbspZENTIVA ZENTIVA Czech Republic

Information update date: & nbsp23.08.2015

Illustrated instructions

Instructions

Pentoxifylline Zentiva (Pentoksifillin Zentiva)