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

talc - 0.01050 / 0.02000 g, magnesium stearate - 0.00300 / 0.00500 g; shell: sepiphilm 752 white (hypromellose 35.0% -45.0%, microcrystalline cellulose 27.0% -37.0%, macrogol stearate 6.0% -10.0%, titanium dioxide 18.0% -22, 0%) - 0.01500 / 0.01970 g, emulsion of dimethicone - 0.000075 / 0.00010 g, macrogol 6000 - 0.000175 / 0.00020 g.

Description:

Tablets of prolonged action, film-coated, 400 mg:

White or almost white color round biconvex tablets, covered with a film membrane.

Tablets of prolonged action, film-coated, 600 mg:

White or almost white oval biconvex tablets covered with a film sheath with a risk for separation from one side.

Pharmacotherapeutic group:Vasodilator

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 phosphodiesterase enzyme and an increase in the content of cyclic adenosine monophosphate (cAMP) in platelets and adenosine triphosphate (ATP) in erythrocytes with a simultaneous saturation of the energy potential, which in turn leads to vasodilation, a reduction in total peripheral vascular resistance), an increase in the shock and minute volume of blood without a significant change in the heart rate (heart rate).

Pentoxifylline reduces the viscosity of the blood, increases the elasticity of the erythrocyte membrane (due to the effect on the pathologically altered erythrocyte deformability), reduces the aggregation of erythrocytes,platelets and neutrophils, reduces fibrinogen in the blood, reduces the adhesiveness of leukocytes to the vascular endothelium, reduces the stimulation of leukocytes and, as a result, the 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-hydroxyhexyl-3,7-dimethylxanthine (metabolite I) and 1-3-carboxypropyl-3,7-dimethylxanthine (metabolite V). The concentration of metabolites I and V in the blood plasma, respectively, is 5 and 8 times higher than pentoxifylline. Metabolite I is 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. Half-life (T1 / 2) is - 1,6 hours. Pentoxifylline is excreted primarily by the kidneys - 94% in the form of metabolites (mainly metabolite V), intestine - 4%, in the first 4 hours up to 90% of the dose is excreted. Excreted in breast milk.

Patients with impaired renal function

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

Patients with hepatic impairment

If there is a violation of the liver, lengthening T1 / 2, and increased bioavailability.

Indications:

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

- Cerebrovascular disease (consequences of cerebral atherosclerosis, such as attention deficit disorder, dizziness, memory impairment), ischemic and post-stroke conditions.

- Trophic tissue disorders due to violation of arterial or venous microcirculation (trophic ulcers, postthrombophlebic 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).

- Dysfunction 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).

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; from increased inclination to bleeding, for example, in the result of the use of indirect anticoagulants [antagonists vitamin K] or for violations in the blood coagulation system (the risk of developing more severe bleeding) (see section "Interaction with other medicinal products"); after a recent surgery (risk of bleeding); with proliferative diabetic retinopathy. Care should be taken when applying simultaneously Pentoxifylline SR Zentiva with platelet aggregation inhibitors (clopidogrel, eptifibatid, tirofiban, epoprostenol, iloprost, abciximab, anagrelide, NSAIDs [other than selective cyclooxygenase-2 inhibitors], acetylsalicylic acid, ticlopidine, dipyridamole), hypoglycemic agents (insulin and hypoglycemic agents for oral administration), ciprofloxacin and theophylline (see section "Interaction with other drugs").

Pregnancy and lactation:

The use of Pentoxifylline SR Zentiva during pregnancy is contraindicated.

The use of Pentoxifylline SR Zentiva during 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.

Cerebrovascular disease

The drug Pentoxifylline SR Zentiva is taken 400 mg 2-3 times a day or 600 mg 1-2 times a day ..

Occlusion disease of peripheral arteries II stage ("intermittent" lameness)

The drug Pentoxifylline SR Zentiva is taken 400 mg 3 times a day or 600 mg 2 times a day. The daily dose is 1200 mg per day.

Trophic tissue disorders due to disturbed arterial or venous microcirculation

The drug Pentoxifylline SR Zentiva is taken 400 mg 2-3 times a day or 600 mg 1-2 times a day.

The maximum daily dose of 1200 mg per day.

The duration of treatment and the dosage regimen of Pentoxifylline SR Zentiva are determined individually by the attending physician, depending on the clinical picture of the disease and the therapeutic effect obtained.

Patients with impaired hepatic function

When using the drug Pentoxifylline SR Zentiva in patients with impaired liver function of severe severity, caution should be exercised,a possible dose reduction should be carried out taking into account the individual tolerability of the drug.

Patients with impaired renal function

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

Children and teens

The use of Pentoxifylline SR Zentiva in patients under the age of 18 years is contraindicated. Safety and efficacy of Pentoxifylline SR Zentiva in this age group is not established.

Side effects:

With the use of Pentoxifylline SR Zentiva, the following side effects may occur, which are classified according to the system-organ classes according to the classification of the Medical Dictionary of Regulatory Activities (MedDRA). The WHO classification was used to indicate the frequency of side effects: 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: frequency unknown - skin itch, skin rash, erythema (reddening of the skin), urticaria, swelling, increased brittleness of the nails.

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

Disorders from the side of the organ of vision: frequency unknown - impaired vision, scotoma.

Violations from the blood and lymphatic system: frequency unknown - thrombocytopenia, leukopenia / neutropenia, pancytopenia, hypofibrinogenemia.

Immune system disorders: frequency unknown - anaphylactic / anaphylactoid reactions, angioedema, anaphylactic shock, bronchospasm.

Disorders from the liver and bile ducts: frequency 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, 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: 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 SR Zentiva may enhance the reduction in blood pressure when used simultaneously with antihypertensive agents (eg, ACE inhibitors) or other drugs that have a potential hypotensive effect (for example, nitrates).

With drugs that affect the blood coagulation system

The drug Pentoxifylline SR Zentiva can enhance the effect of drugs affecting the blood coagulation system (direct and indirect anticoagulants, thrombolytics, antibiotics, such as cephalosporins).

With the joint use of pentoksifillina and indirect anticoagulants (antagonists vitamin K) in postmarketing studies have been reported cases anticoagulant actions (risk of development bleeding). Therefore, at the beginning of taking pentoxifylline or changing its dose, it is recommended to control the degree anticoagulant effect in patients taking this combination of drugs (for example, a normalized attitude (INR)).

With cimetidine

Cimetidine can increase the concentration of pentoxifylline and active metabolite I in blood plasma (risk of adverse reactions).

With other xanthines

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

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

Hypoglycemic act insulin or hypoglycemic agents for oral ingestion may strengthen with simultaneous application of the drug Pentoxifylline SR Zentiva (an increased risk of developing hypoglycemia). Strict monitoring of the condition of such patients is required, including regular glycemic control.

With theophylline

In some patients with concomitant drug Pentoxifylline of SR Zentiva and theophylline there is an increase in the concentration of theophylline in the blood plasma. In the future, this can lead to an increase in the incidence of adverse reactions associated with theophylline.

With ciprofloxacin

In some patients with simultaneous application drug Pentoxifylline SR Zentiva and ciprofloxacin, 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 valproic acid

When used together, the drug Pentoxifylline SR Zentiva can enhance the action of valproic acid.

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 taken with the Pentoxifylline SR Zentiva drug concomitantly with the platelet aggregation inhibitors listed above (see "With caution").

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 SR Zentiva may cause severe hypoglycemia (dose adjustment is required).

When Pentoxifylline SR 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 a dose of Pentoxifylline SR Zentiva individually.

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

The safety and efficacy of Pentoxifylline SR Zentiva in children have not been adequately studied.

Care should be taken when using Penoxifylline SR 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) when taking Pentoxifylline SR 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 SR Zentiva.

Effect on the ability to drive transp. cf. and fur:The negative effect of Pentoxifylline SR Zentiva on the ability to control 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 SR Zentiva is used.

Form release / dosage:

Tablets of prolonged action, film-coated, 400 mg and 600 mg.

Packaging:For 10 tablets in a blister of PVC / PVDC / A1. For 2, 5 or 10 blisters together with instructions for use are placed in a cardboard box.

Storage conditions:

Does not require special storage conditions.

Keep out of the reach of children!

Shelf life:2 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N011768 / 01

Date of registration:23.01.2009 / 14.02.2014

Expiration Date:Unlimited

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

Manufacturer: & nbsp

Saneca Pharmaceuticals a.s. The Slovak Republic

Representation: & nbspZENTIVA ZENTIVA Czech Republic

Information update date: & nbsp19.08.2016

Illustrated instructions

Instructions

Pentoxyfylline SR Zentiva (Pentoksifillin SR Zentiva)