Pentoxifylline, 20 mg/ml concentrate 5 ml 10 pcs

Pentoxifylline is a xanthine derivative. It improves microcirculation and rheological properties of blood. The mechanism of action is associated with inhibition of phosphodiesterase and increase of cyclic 3,5-adenosine monophosphate (3,5-AMP) in platelets and adenosine triphosphate (ATP) in red blood cells with simultaneous saturation of energy potential, which in turn leads to vasodilation, reduction of total peripheral vascular resistance, increase of systolic and minute blood volume without significant change in heart rate.

Dilating coronary arteries increases oxygen delivery to the myocardium (minor antianginal effect), pulmonary vessels – improves blood oxygenation. When administered intravenously it leads to increased collateral circulation, increased blood volume flowing through a unit section.

Limits blood viscosity, causes platelet disaggregation, increases the elasticity of red blood cells (by influencing the pathologically altered deformability of red blood cells). Improves microcirculation in the areas of impaired circulation. In occlusive lesions of the peripheral arteries (intermittent claudication), leads to extension of walking distance, elimination of night cramps of the calf muscles and pain at rest.

Pharmacokinetics

The drug is rapidly metabolized in the liver after administration. During metabolism two main metabolites are formed: 1-(5-hydroxyhexyl)-3,7-dimethylxanthine (metabolite I) and 1-(3-carboxypropyl)-3,7-dimethylxanthine (metabolite V), which have similar activity to pentoxifylline.

1.5-2 hours after infusion, plasma concentrations of metabolites I and V are, respectively, 5 and 8 times higher than those of the parent substance. By the 8th hour, the concentration of pentoxifylline and its metabolites in blood decreases significantly (up to 10% of the initial concentration). The elimination half-life is from 30 minutes to 1.5 hours.

It is excreted mainly by the kidneys (94%) as metabolites (mainly metabolite V), the intestine (4%), in the first 4 hours it is eliminated up to 90% of the dose. 2% of the drug is excreted unchanged. Pentoxifylline and its metabolites do not bind to plasma proteins. It is excreted with breast milk.

In severe renal dysfunction, excretion of metabolites is delayed. In liver dysfunction, prolongation of the elimination half-life and increased bioavailability are noted.

Indications

– Peripheral circulatory disorders on the background of atherosclerotic, diabetic and inflammatory processes (including. In intermittent claudication caused by atherosclerosis, diabetic angiopathy, obliterating endarteritis);

– trophic disorders of tissues due to arterial and venous microcirculation disorders (varicose ulcers, gangrene, frostbite);

– angio-neuropathy (paresthesias, acrocyanosis, Raynaud’s disease); – acute and chronic cerebral circulatory disorders of ischemic type (including cerebral apoplexy).

– conditions after hemorrhagic or ischemic stroke;

– circulatory disorders in the eye vessels (acute and chronic insufficiency of the blood supply of the retina and choroid); – middle ear disorders of vascular genesis, accompanied by hearing loss.

Active ingredient

Composition

1 ml of the drug contains:

The active ingredient:

pentoxifylline – 20 mg.

Excipients:

Sodium chloride – 6 mg,

Sodium dihydrophosphate dihydrate – 1 mg,

1 M sodium hydroxide solution – to pH 6.0-8.0,

water for injection – up to 1 ml.

How to take, the dosage

Intravenously and intra-arterially.

When administering the infusion, the patient should be in the “supine” position. The drug is administered intravenously by drip slowly in a dose of 100 mg in 250-500 ml of 0.9% sodium chloride solution or Ringer’s solution (duration of infusion – 90-180 minutes). 100 mg of pentoxifylline should be administered intravenously for at least 60 minutes.

The daily dose when administered intravenously may be increased to a maximum of 300 mg/day. Intra-arterially – at first in a dose of 100 mg in 20-50 ml of 0.9% sodium chloride solution, and on subsequent days – 200-300 mg in 30-50 ml of 0.9% sodium chloride solution (infusion rate – 10 mg/min).

In severe atherosclerosis of cerebral vessels the drug should not be injected into the carotid artery. In patients with chronic renal insufficiency (creatinine clearance less than 30 ml/min) 50-70% of the usual dose is prescribed. In elderly patients a dose reduction may be required (increased bioavailability and decreased excretion rate).

Dose reduction, taking into account individual tolerance, is necessary in patients with severe hepatic impairment. The administered dose should be reduced in patients with low and unstable blood pressure.

Polymer ampoule handling procedures:

1. Take the ampoule and shake it by holding the neck.

2. squeeze the ampoule with your hand, taking care not to release the product, and with a twisting motion, turn and release the valve.

3. immediately connect the syringe to the ampoule through the hole that is created.

4. Turn the ampoule over and slowly draw the contents into the syringe.

5. Slide the needle onto the syringe.

Interaction

Pentoxifylline may increase the effect of drugs that affect the clotting system (indirect and direct anticoagulants, thrombolytics), antibiotics (including cephallosporins – cefamandole, cefoperazone, cefotetan), valproic acid.

The simultaneous use of pentoxifylline with ketorolac increases the risk of bleeding and/or prolongation of the prothrombin time. Co-administration of these drugs is undesirable. Increases the effectiveness of hypotensive drugs, insulin, hypoglycemic agents for oral administration.

Cimetidine increases the plasma concentration of pentoxifylline (risk of side effects). Co-administration with other xanthines may lead to excessive nervous excitement.

In some patients, concomitant use of pentoxifylline and theophylline has increased theophylline blood concentrations. Subsequently, this may lead to an increase or intensification of theophylline-related side effects.

In some patients with concomitant use of pentoxifylline and ciprofloxacin an increase in plasma concentrations of pentoxifylline has been noted. Subsequently, this may lead to an increase or intensification of side effects associated with the use of this combination.

Special Instructions

Treatment should be performed under control of blood pressure. In patients with chronic heart failure compensation of blood circulation should be achieved.

In patients with diabetes mellitus taking hypoglycemic agents, administration of high doses of pentoxifylline may cause significant hypoglycemia (correction of doses of hypoglycemic agents and glycemic control may be required).

When prescribed concomitantly with anticoagulants, it is necessary to monitor blood clotting parameters. In patients who have recently undergone surgery, regular monitoring of hemoglobin and hematocrit is necessary.

The administered dose should be reduced in patients with low and unstable blood pressure as well as in patients with severe atherosclerosis of coronary and/or cerebral arteries, because in the latter case additional reduction of blood pressure may lead to worsening of blood supply to the heart and/or brain.

In elderly patients a dose reduction may be required (increased bioavailability and reduced excretion rate). Smoking may decrease the therapeutic effectiveness of the drug.

The compatibility of pentoxifylline solution with other infusion solutions should be checked on a case-by-case basis. During the therapy the plasma sodium content should be monitored, especially in patients on a diet with restriction of table salt (total sodium content in 5 ml ampoule is 11.8 mg).

Impact on the ability to drive vehicles and mechanisms:

Given the possible side effects (e.g., dizziness), caution should be exercised when driving vehicles and engaging in potentially hazardous activities that require increased concentration and rapid psychomotor reactions.

Contraindications

– Hypersensitivity to pentoxifylline or other xanthine derivatives, or to any excipient of the drug;

– Severe coronary or cerebral atherosclerosis;

– recent myocardial infarction;

– haemodynamically significant cardiac arrhythmias;

– uncontrolled arterial hypotension;

– massive bleeding (risk of increased bleeding);

– massive retinal hemorrhage (risk of increased bleeding);

– cerebral hemorrhage;

p> – gastric and duodenal ulcer;

– disorders of the clotting system;

– age under 18 years (effectiveness and safety not established).

With caution:

Patients with labile blood pressure, susceptibility to arterial hypotension, chronic heart failure, hemorrhagic diathesis, susceptibility to bleeding (including gastric and duodenal ulcers), condition after recent surgical interventions, severe hepatic and/or renal (creatinine clearance less than 10 ml/min) failure. Patient Pentoxifylline should be administered with caution together with direct and indirect anticoagulants due to the increased effect of the latter. Pregnancy and lactation: Pentoxifylline is contraindicated in pregnancy, because the experience of using the drug in pregnant women is limited. If pentoxifylline should be administered during lactation, breastfeeding should be discontinued due to the fact that pentoxifylline penetrates into the breast milk.

Side effects

The frequency of possible side effects listed below is defined as follows: Very common (1/10); common (1/100 to < 1/10); infrequent (1/1000 to < 1/100); rare (1/10000 to < 1/1000); very rare (< 1/10000);

frequency unknown (cannot be estimated from available data).

Disorders of the blood and lymphatic system:

Very rare: thrombocytopenia, thrombocytopenic purpura, aplastic anemia, pancytopenia.

Rare: bleeding (including nasal bleeding, gastrointestinal bleeding, bleeding from the urinary tract, etc.).

Immune system disorders: Infrequent: hypersensitivity reactions.

Very rare: severe, occurring within minutes after administration of pentoxifylline anaphylactic or anaphylactoid reactions, Quincke’s edema, bronchospasm, anaphylactic shock.

Mental disorders:

Infrequent: increased excitability, insomnia.

Nervous system disorders:

Infrequent: dizziness, tremor, headache.

Very rarely: paresthesia, seizures, intracranial hemorrhage, aseptic meningitis. Visual organ disorders:

Infrequent: visual disturbances, conjunctivitis.

very rarely: retinal haemorrhage, retinal detachment.

Cardiac disorders:

Infrequent: cardiac arrhythmia, tachycardia.

Rarely: angina pectoris, dyspnea.

Vascular disorders:

Often: facial skin hyperemia.

Rarely: decreased blood pressure, peripheral edema.

Very rarely: increase in blood pressure.

Gastrointestinal disorders: Often: nausea, vomiting, bloating, feeling of heaviness in the stomach, diarrhea.

Liver and biliary tract disorders:

very rarely: intrahepatic cholestasis, increased “hepatic” transaminase activity.

Skin and subcutaneous tissue disorders:

Infrequent: skin itching, erythema, urticaria.

very rarely: toxic epidermal necrolysis, Stevens-Johnson syndrome, increased sweating.

General disorders and disorders at the site of administration:

Infrequent: increased body temperature.

Overdose

Symptoms: weakness, dizziness, marked decrease of blood pressure, tachycardia, somnolence, loss of consciousness, tonic-clonic convulsions, increased nervous excitability, hyperthermia, areflexia, signs of gastrointestinal bleeding (vomiting like “coffee grounds”).

The treatment: symptomatic, aimed at maintaining respiratory function and blood pressure.

Similarities