Product trade name

Pentoxifylline

 

Active substance (INN)

Pentoxifylline

 

Product

Injection 2% 5 ml ampoules

 

Pharmacotherapeutic group

Drugs for treatment of peripheral blood circulation

 

Pharmacological properties

Pentoxifylline is a methylxanthine derivative. The mechanism of pentoxifylline action is associated with inhibition of phosphodiesterase and the accumulation of cAMP in vascular smooth muscle cells, blood cells, and other tissues and organs. Pentoxifylline inhibits the aggregation of platelets and erythrocytes increases their flexibility decreases increased concentration of fibrinogen in plasma and enhances fibrinolysis, which reduces the viscosity of the blood-vi and improves its flow characteristics. Moreover, pentoxifylline miotroponoe causes weak vasodilating effect somewhat decreases total peripheral vascular resistance and has a positive inotropic effect. As a result, pentoxifylline improves microcirculation and oxygen supply in the most power necks in the limbs, CNS, moderate - in the kidneys. The drug is slightly dilates coronary vessels.

 

Pharmacokinetics

The main pharmacologically active metabolite 1 - (5-hydroxyhexyl) -3,7-dimethylxanthine (metabolite I) is determined in plasma concentration in excess of 2 times the concentration of unchanged substance and stored them in the biochemical state of reversible equilibrium. Therefore, pentoxifylline and its metabolite should be considered as an active unit. The half-life (T1 / 2) of pentoxifylline is 1.6 hours.
Pentoxifylline is metabolized completely; more than 90% is excreted by the kidneys in the form of water-soluble non-conjugated polar metabolites. Less than 4% of the dose excreted in the feces. In patients with severely impaired renal excretion of metabolites of slowing down. In patients with impaired liver function observed lengthening T1 / 2 of pentoxifylline.

 

Instructions for use

Arteriosclerotic encephalopathy, ischemic cerebral stroke; encephalopathy, peripheral circulatory disorders caused by atherosclerosis Sohm, diabetes (including diabetic angiopathy), inflammation; trophic disorders in the tissues, associated with damage to the veins or impaired microcirculation (in sttromboflebichesky syndrome, ulcers, gangrene, frostbite); occlusive disease; angioneyropatiya (Raynaud's disease), poor circulation eyes (acute, subacute, chronic circulatory insufficiency in the retina and choroid of the eye's); inner ear dysfunction of vascular origin, accompanied by hearing weakening.

 

Dosage and methods of usage

Intravenous (w / w) are most efficient infusion of parenteral administration forms which are better tolerated. Dosage regimen determined by a physician and depends on the severity of circulatory disorders, body weight and tolerance of treatments. Infusion may be carried out only if the solution is clear.

Recommended for adults such regimens:
1. Intravenous infusion of 100-600 mg of pentoxifylline in 100-500 ml of Ringer's lactate, 0.9% solution of sodium chloride or 5% glucose solution 1-2 times a day. Duration in / drip infusion of 60-360 minutes, that is the introduction of 100 mg pentoxifylline should last at least 60 minutes. Infusion may be supplemented by oral pentoxifylline (400 mg) on the basis that the maximum daily dose (infusion and oral) is 1200 mg.
2. When a serious condition of the patient (especially with the constant pain, with gangrene or trophic ulcers) may conduct drug infusion for 24 hours. In this scheme, the dose of administration is determined by calculating 0.6 mg / kg / h. The calculated daily dose for a patient weighing 70 kg is 1000 mg for a patient weighing 80 kg -1150 mg.
Regardless of the patient's body weight, the maximum daily dose is 1,200 mg.
The volume of infusion solution is calculated individually, taking into account the related diseases, the patient's condition and averages 1-1.5 liters per day.
3. In some cases, the drug is applied by intravenous injection 5 ml
(100 mg). Injection is performed slowly for 5 minutes, with the patient lying down.
Elderly patients. For elderly patients is not necessary to adjust the dosage.
Duration of parenteral treatment is determined by the doctor who is treating.
After the improvement of the patient's condition is recommended to continue treatment, using the tablet form of the drug.

 

Adverse effects

The frequency of adverse reactions on the individual systems of the body:
Cardiovascular system: rarely tachycardia; not often peripheral edema, facial flushing and feeling of heat (hot flashes), very rare atypical chest pain, arterial hypotension, worsening angina, hypertension, shortness of breath, irregular heartbeat.

From the blood and lymphatic system disorders: isolated cases of thrombocytopenia and thrombocytopenic purpura, leukopenia, pancytopenia (which can be fatal), prolonged prothrombin time, gipofibrinogenemia, anemia, aplastic anemia, bleeding (eg, from the vessels of the skin, mucous membranes , stomach, intestine, nose).

The nervous system: rarely headache, dizziness, aseptic meningitis (with high doses); isolated cases of hand tremor, insomnia, agitation, anxiety, fear, loss of consciousness, sleep disturbances, hallucinations, blackouts, numbness, rash, cramps, paresthesia.
From the senses: blurred vision, scotoma, lacrimation, conjunctivitis, ear pain, migraine, retinal hemorrhages, retinal detachment.

The gastro-intestinal tract: gastrointestinal disorders, feelings of pressure in the stomach, it overflows, diarrhea; not often nausea, vomiting (including repeated), bloating, epigastric pain, anorexia, intestinal, constipation dry throat, thirst.

On the part of metabolism: very rarely hypoglycemia, hypokalemia.
Immune system: isolated cases of allergic reactions (anaphylactic-cal / anaphylactoid reactions up to shock, angioedema, bronchospasm, turning red in the skin, itching, rash, urticaria), toxic epidermal necrolysis syndrome (Lai Yella), Stevens-Johnson.

On the part of the hepatobiliary system: very rare intrahepatic cholestasis, increased liver enzymes, increased cholecystitis, cholestatic hepatitis.
Skin and subcutaneous tissue: very rarely increased sweating, flushing of the face and upper chest, swelling, maculopapular rash, nail fragility.
Changes at the injection site: pain at the injection site, redness, swelling, rash.
Other: taste disturbance, increased salivation, malaise, sore throat / neck la ring, nasal congestion, increase / decrease of body weight, chills, feeling of fever, fever, hyperthermic syndrome.
Laboratory parameters: increase in liver transaminases (ALT, AST, LDH) and alkaline phosphatase.
Most of the adverse reactions associated with the dosage. They can be minimized or avoided altogether in dose reduction.
If there are severe side effects, treatment should cease.

 

Contraindications

- Hypersensitivity to pentoxifylline, to the other components of the drug or to other drugs in the group of methylxanthines such as theophylline, caffeine, choline teofilinat, aminophylline or theobromine;
- Massive bleeding (increased bleeding risk);
- Bleeding in the retina of the eye, the brain; If during treatment with pentoxifylline is bleeding in the retina of the eye, the use of the drug should be immediately to discontinue;
- Hemorrhagic diathesis;
- Acute myocardial infarction;
- Liver or kidney failure;
- Gastric and / or intestinal ulcers;
- Porphyria;
- Pregnancy and lactation;
- Children's age.

 

Interactions

The simultaneous use of pentoxifylline and antihypertensive drugs (in particular, angiotensin converting enzyme inhibitors) enhances the effect of the latter, therefore requires a corresponding adjustment of doses of antihypertensive drugs.
Anticoagulants, drugs that reduce blood coagulation. Simultaneous reception of pentoxifylline and medications that reduce blood coagulation, increases the possibility of bleeding, so you should frequently monitor the prothrombin time. When assigned to or from changing the dosing of pentoxifylline, advisable to check that the anticoagulant activity in these patients.

Cimetidine. Simultaneous administration of cimetidine is a significant increase in the concentration of pentoxifylline in serum. It should be closely monitored for any signs of possible overdose pentoxifylline. Other H2 receptor antagonists (famotidine, nizatidine and ranitidine) are considerably less influence on the metabolism of pentoxifylline.

Theophylline. Simultaneous administration of theophylline and pentoxifylline may lead to increased concentrations of theophylline in serum. It is therefore necessary to monitor the concentration of theophylline in serum, when necessary to reduce the dose.
Ketorolac, meloxicam. The simultaneous use of pentoxifylline and ketorolac may cause an increase in prothrombin time and increase the risk of bleeding. The risk of bleeding may also be increased, while the use of pentoxifylline and meloxicam. Therefore, concomitant treatment with these drugs is not recommended.

Ciprofloxacin. Ciprofloxacin inhibits the metabolism of pentoxifylline in the liver, so the simultaneous use of pentoxifylline and ciprofloxacin may lead to increased concentrations of pentoxifylline in serum. When the need for simultaneous treatment with pentoxifylline and ciprofloxacin is recommended to halve the dose of pentoxifylline.

Insulin and preoral antidiabetic drugs. Large intravenous doses of pentoxifylline may increase hypoglycemic effects of insulin and oral antidiabetic drugs, so you should adjust dosage of insulin or hypoglycemic medication.

Nitrates. Pentoxifylline enhances the effect of nitrates.
Erythromycin. No data on possible interactions of pentoxifylline and erythromycin. However, when used in combination with pentoxifylline and erythromycin marked increase in plasma levels of theophylline with the manifestations of toxic reactions.

 

Special instructions

Pentoxifylline should not be used during pregnancy or breastfeeding.
Experience with the drug in children missing.
At the first signs of an anaphylactic / anaphylactoid reaction should discontinue drug treatment and seek medical advice. When using the drug in patients with chronic heart failure should reach pre-compensation phase circulation. In patients with diabetes and treated with insulin or oral antidiabetic agents, with high doses of the drug may increase the effects of these drugs on blood sugar levels in these cases should reduce the dose of insulin or oral antidiabetic agents and carefully observe the patient.
Patients with systemic lupus erythematosus (SLE) or other connective tissue diseases pentoxifylline can only be assigned after a detailed analysis of the possible risks and benefits. Because during treatment with pentoxifylline of the risk of aplastic anemia, need regular monitoring blood count.
In patients with renal insufficiency (creatinine clearance less than 30 ml / min) or severe liver dysfunction excretion of pentoxifylline may be delayed. Need proper monitoring.

Elderly patients may need to reduce the medium therapist dose due to enhanced bioavailability and reduce the rate of excretion of the active substance. Smoking may reduce the therapeutic efficacy of the drug.
Especially close observation is necessary to:
- Patients with severe cardiac arrhythmias;
- Patients with myocardial infarction;
- Patients with hypotension;
- Patients with severe cerebral atherosclerosis and coronary vessels, especially in patients with concomitant hypertension and cardiac arrhythmias. In these patients, the drug can experience angina, arrhythmias, and hypertension;
-Patients with renal insufficiency (creatinine clearance (CC) below 30 ml / min);
- Patients with severe hepatic impairment;
- Patients with a high propensity for bleeding caused by, for example, treatment with anticoagulants or blood clotting disorders. Or bleeding, see "Contraindications";
- Patients with gastric ulcer and duodenal ulcer in history, patients undergoing non-surgical treatment for a long time (increased risk of bleeding, and therefore requires systematic monitoring of hemoglobin levels and hematocrit);
- Patients for whom a decrease in blood pressure is high risk (eg, patients with severe coronary artery disease or stenosis of the vessels that carry blood to the brain);
- Patients while receiving treatment with pentoxifylline and antivitamin K (coumarins);
- Patients while receiving treatment with pentoxifylline and antidiabetic means.
You should also consider the likelihood of adverse reactions from the central nervous system.
You should not mix the drug with other drugs in the same capacity, with the exception of the solutions mentioned in the "Dosing and Administration."
The drug should be stored out of reach of children and do not use after the expiration date.

 

Overdose

Symptoms: weakness, nausea, dizziness, decrease / increase in blood pressure, fainting, tachycardia, drowsiness or agitation, loss of consciousness, hyperthermia, areflexia, tonic-clonic seizures, signs of gastrointestinal bleeding vomiting (vomitus color of coffee grounds), fever, feeling heat (hot flashes).
Treatment: If the first symptoms of overdose (sweating, nausea, cyanosis) immediately stop using the product. Necessary to provide a lower position of the head and upper torso, control free airway. Symptomatic therapy, special attention should be paid to the maintenance of blood pressure and respiratory function. For relief of seizures administered diazepam.

 

Storage conditions

In the dark place at a temperature not exceeding 25 ยบ C.

 

Expiration date

2 years.

 

Terms of supply of pharmacies

On prescription.

 

Pentoxifylline-NOVO

Hepatoprotectors
Antibiotics
Local anaesthetic drugs
Nootropic drugs
Antihypertensive drugs
Drugs for a parenteral food
Medicines applied at poisonings and intoxications
Medicines for metabolic processes correction
Medicines for peripheric blood circulation
Mineral drugs, microcells
Salt solutions
Analgesic and antispasmodic drugs
Nonsteroidal anti-inflammatory drugs
Haemostatics