PENTOXIFYLLINE-ZDOROVYA

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PENTOXIFYLLINE-ZDOROVYE (PENTOXIFYLLINE-ZDOROVYE)

Composition:

active substance: pentoxifylline;

1 ml| of solution contains|contains| 20 mg of pentoxifylline;

excipients: sodium chloride, water for injections.

Pharmaceutical form. Solution for injection.

Main physico-chemical|physico-chemical| properties: |physico-chemical| transparent colorless|colorless| or with a slightly yellowish tint solution.

Pharmacotherapeutic group. Peripheral vasodilators. ATC code C04AD03.

Pharmacological properties.

Pharmacodynamics.

Pentoxifylline is a methylxanthine derivative. The mechanism of action of pentoxifylline is associated with inhibition of phosphodiesterase and accumulation of cAMP in vascular smooth muscle cells, blood cells, as well as in other tissues and organs. Pentoxifylline inhibits platelet and erythrocyte aggregation, increases their flexibility, reduces elevated plasma fibrinogen concentration, and enhances fibrinolysis, thereby decreasing blood viscosity and improving its rheological properties. In addition, pentoxifylline exerts a weak myotropic vasodilatory effect, slightly reduces total peripheral vascular resistance, and demonstrates a positive inotropic effect. As a result of pentoxifylline administration, microcirculation and tissue oxygen supply are improved, most notably in the extremities and CNS, and moderately in the kidneys. The drug slightly dilates coronary vessels.

Pharmacokinetics.

The main pharmacologically active metabolite, 1-(5-hydroxyhexyl)-3,7-dimethylxanthine (metabolite I), is present in blood plasma at concentrations exceeding those of the unchanged substance by two-fold and is in reversible biochemical equilibrium with it. Therefore, pentoxifylline and its metabolite should be considered as an active entity. The half-life (T½) of pentoxifylline is 1.6 hours.

Pentoxifylline is completely metabolized; over 90% is excreted by the kidneys as non-conjugated, water-soluble, polar metabolites. Less than 4% of the administered dose is excreted in feces. In patients with severe renal impairment, metabolite excretion is delayed. In patients with impaired liver function, prolonged T½ of pentoxifylline has been observed.

Clinical characteristics.

Indications.

Atherosclerotic encephalopathy; ischemic cerebral stroke; dyscirculatory encephalopathy; peripheral circulatory disorders due to atherosclerosis, diabetes mellitus (including diabetic angiopathy), or inflammation; trophic disturbances in tissues associated with venous damage or impaired microcirculation (post-thrombophlebitic syndrome, trophic ulcers, gangrene, frostbite); obliterative endarteritis; angioneuropathy (Raynaud's disease); ocular circulation disorders (acute, subacute, chronic insufficiency of blood flow in the retina and choroid); vascular-origin inner ear function disorders accompanied by hearing loss.

Contraindications.

The drug is contraindicated in:

• Patients with hypersensitivity to pentoxifylline, to other methylxanthines, or to any of the excipients of the drug;
• Patients with massive bleeding (risk of bleeding exacerbation);
• Patients with extensive retinal hemorrhage or intracerebral hemorrhage (risk of bleeding exacerbation). If retinal hemorrhage occurs during pentoxifylline treatment, the drug should be discontinued immediately;
• Patients during the acute phase of myocardial infarction;
• Patients with gastric ulcer and/or intestinal ulcers;
• Patients with hemorrhagic diathesis.

Interaction with other medicinal products and other forms of interaction.

The blood glucose-lowering effect of insulin or oral antidiabetic agents may be enhanced. Therefore, patients receiving medication for diabetes mellitus should be under close monitoring.

There are reports of increased anticoagulant activity in patients concurrently receiving pentoxifylline and vitamin K antagonists. When pentoxifylline is administered or its dosage changed, monitoring of anticoagulant activity in this patient group is recommended.

The drug may enhance the hypotensive effect of antihypertensive agents and other drugs that may cause a reduction in arterial pressure.

Concomitant use of pentoxifylline and theophylline in some patients may lead to increased serum theophylline levels. Therefore, an increased frequency and severity of theophylline-related adverse reactions is possible.

In some patients, concomitant use with ciprofloxacin may increase pentoxifylline plasma concentration. As a result, the frequency and severity of adverse reactions associated with concomitant drug use may increase.

Potential additive effect with platelet aggregation inhibitors: due to an increased risk of bleeding, concomitant use of platelet aggregation inhibitors (e.g., clopidogrel, eptifibatide, tirofiban, epoprostenol, iloprost, abciximab, anagrelide, NSAIDs except selective COX-2 inhibitors, acetylsalicylates [ASA/ASA], ticlopidine, dipyridamole) with pentoxifylline should be performed with caution.

Concomitant use with cimetidine may increase plasma concentrations of pentoxifylline and metabolite I.

Special precautions for use.

At the first signs of anaphylactic/anaphylactoid reaction, treatment with the drug should be discontinued immediately and medical help sought.

In patients with chronic heart failure, treatment should be initiated only after achieving circulatory compensation.

In patients with diabetes mellitus receiving insulin or oral antidiabetic agents, high doses of pentoxifylline may enhance the effect of these agents on blood glucose levels. In such cases, the dose of insulin or oral antidiabetic agents should be reduced, and particularly careful monitoring of the patient is required.

Pentoxifylline may be prescribed to patients with systemic lupus erythematosus or other connective tissue diseases only after a thorough assessment of potential risks and benefits.

Since there is a risk of developing aplastic anemia during pentoxifylline treatment, regular monitoring of complete blood count is required.

In patients with renal impairment (creatinine clearance less than 30 mL/min) or severe hepatic dysfunction, elimination of pentoxifylline may be delayed. Appropriate monitoring is necessary.

Particularly careful monitoring is required for:

• Patients with severe cardiac arrhythmias;
• Patients with arterial hypotension;
• Patients with pronounced atherosclerosis of cerebral and coronary vessels, especially with concomitant arterial hypertension and cardiac rhythm disturbances. In these patients, angina attacks, arrhythmias, and arterial hypotension may occur during drug administration;
• Patients with renal impairment (creatinine clearance less than 30 mL/min);
• Patients with severe hepatic insufficiency;
• Patients with a high predisposition to bleeding, e.g., due to anticoagulant therapy or coagulation disorders. For details on bleeding, see section "Contraindications";
• Patients who have recently undergone surgery (increased risk of bleeding, requiring systematic monitoring of hemoglobin and hematocrit levels);
• Patients for whom a reduction in arterial pressure poses a high risk (e.g., patients with severe ischemic heart disease or stenosis of vessels supplying blood to the brain);
• Patients concurrently receiving pentoxifylline and vitamin K antagonists or platelet aggregation inhibitors;
• Patients concurrently receiving pentoxifylline and antidiabetic agents;
• Patients concurrently receiving pentoxifylline and ciprofloxacin;
• Patients concurrently receiving pentoxifylline and theophylline.

This medicinal product contains 7.12 mmol (or 163.8 mg) of sodium per 1200 mg dose of pentoxifylline. Caution is advised when administering to patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding.

Pregnancy. There is insufficient experience with the use of the drug in pregnant women; therefore, the drug is not recommended during pregnancy.

Period of breastfeeding. Pentoxifylline passes into breast milk in small amounts. If treatment with the drug is required, breastfeeding should be discontinued.

Ability to affect reaction rate while driving or operating machinery. Does not affect.

Administration and dosage.

Intravenous infusions are the most effective and better-tolerated forms of parenteral administration. The dosage regimen is determined by the physician and depends on the severity of circulatory disorders, body weight, and treatment tolerance. Infusion may be performed only if the solution is clear.

Recommended treatment regimens for adults:

1. Intravenous infusion of 100–600 mg pentoxifylline in 100–500 mL of Ringer's lactate solution, 0.9% sodium chloride solution, or 5% glucose solution, 1–2 times daily. The duration of intravenous drip infusion is 60–360 minutes; thus, administration of 100 mg pentoxifylline should last at least 60 minutes. The infusion may be supplemented with oral administration of Pentoxifylline-Health (400 mg), provided that the maximum daily dose (infusion and oral) does not exceed 1200 mg.
2. In severe patient condition (especially with persistent pain, gangrene, or trophic ulcers), 24-hour infusion of the drug may be performed. In such cases, the dose should be calculated at 0.6 mg/kg/hour. The calculated daily dose is 1000 mg for a patient weighing 70 kg and 1150 mg for a patient weighing 80 kg. Regardless of patient body weight, the maximum daily dose is 1200 mg. The volume of infusion solution is individually calculated based on concomitant diseases and patient condition and averages 1–1.5 L per day.
3. In individual cases, the drug may be administered by intravenous injection of 5 mL (100 mg). The injection should be performed slowly over 5 minutes, with the patient in a supine position.

The duration of parenteral treatment course is determined by the treating physician. After improvement of the patient's condition, continuation of treatment with the tablet form of Pentoxifylline-Health is recommended.

Children. Experience with use in children is lacking.

Overdose.

Initial symptoms of acute pentoxifylline overdose include nausea, dizziness, or decreased arterial pressure. Additionally, symptoms such as fever, excitement, hot flushes, tachycardia, loss of consciousness, areflexia, arrhythmia, tonic-clonic seizures, and coffee-ground vomiting (indicative of gastrointestinal bleeding) may develop.

Treatment of overdose. For treatment of acute overdose and prevention of complications, general and specific intensive medical monitoring and therapeutic interventions are required.

Adverse Reactions.

Laboratory findings: increased transaminase levels.

Cardiac disorders: arrhythmia, tachycardia, angina pectoris, decreased blood pressure, increased blood pressure.

Blood and lymphatic system disorders: thrombocytopenia with thrombocytopenic purpura and aplastic anemia (partial or complete cessation of blood cell formation, pancytopenia), which may be fatal, leukopenia/neutropenia.

Nervous system disorders: dizziness, headache, aseptic meningitis, tremor, paresthesia, seizures.

Gastrointestinal disorders: gastrointestinal disturbances, sensation of pressure in the stomach, flatulence, nausea, vomiting, diarrhea, constipation, hypersalivation.

Skin and subcutaneous tissue disorders: pruritus, skin redness and urticaria, Lyell's syndrome and Stevens–Johnson syndrome, rash.

Vascular disorders: sensation of warmth (flushing), hemorrhage, peripheral edema.

Immune system disorders: anaphylactic reactions, anaphylactoid reactions, angioneurotic edema, bronchospasm, and anaphylactic shock.

Hepatobiliary disorders: intrahepatic cholestasis.

Psychiatric disorders: excitement and sleep disturbances, hallucinations.

Eye disorders: visual disturbances, conjunctivitis, retinal hemorrhages, retinal detachment.

Other: cases of hypoglycemia, increased sweating, increased body temperature.

Shelf life. 4 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach and sight of children.

Incompatibility. The drug should not be mixed with other solutions in the same container except for solutions specified in the section “Directions for use and dosage”.

Packaging. 5 ml in ampoules, 5 in a box; 5, 5x2 in blisters in a box.

Prescription status. Prescription only.

Manufacturer. LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVTYA".

Manufacturer's address and location of business activity. Ukraine, 61013, Kharkiv region, city of Kharkiv, Shevchenko Street, 22.