Hypatone

Ipaton is an antithrombotic drug. Contains the component ticlopidine. It inhibits platelet adhesion and aggregation, as well as the processes of platelet factor release. In addition, it prolongs the bleeding period, reduces the retraction of blood clots, reduces blood viscosity and fibrinogen levels, and at the same time increases the filtration activity of red blood cells with whole blood.

The effects revealed in various tests show that the drug reduces the likelihood of thrombosis in the arteries (mainly in the case of vascular lesions in the legs and cerebral blood flow disorders). [ 1 ]

Ticlopidine does not affect fibrinolysis and blood clotting processes. [ 2 ]

Indications Hypatone

It is used to prevent the development of ischemic complications (cardiovascular or cerebrovascular) in people with arterial blood flow disorders (peripheral or cerebral).

It is prescribed to correct or prevent platelet dysfunction associated with artificial blood flow during operations or long-term hemodialysis.

It is used to prevent the development of subacute occlusion affecting the implanted coronary stent.

In the above-described disorders, the drug is usually used in people with aspirin intolerance or when its use is ineffective.

Release form

The drug is released in tablets - 10 pieces in a blister pack; there are 2 such packs in a box.

Pharmacodynamics

Ticlopidine has a blocking effect on platelet aggregation by inhibiting ADP-related synthesis of fibrinogen and glycoproteins IIb/IIIa (specific endings of platelet walls). The drug has no effect on platelet activity associated with AMP and COX. Although the biochemical principle of action and the mediators involved have been well studied, inhibition of platelet aggregation occurs only in vivo; in vitro, ticlopidine does not alter platelet function. [ 3 ]

Therapeutic doses of ticlopidine allow to suppress platelet aggregation induced by the ADP element (indicator 2.5 μmol/l) by 50-70%. After oral administration, the antiplatelet activity of ticlopidine depends on the dosage size up to a daily dose of 0.5 g, but does not increase with subsequent increases.

In the case of twice-daily administration of the drug in a dose of 0.25 g, inhibition of platelet aggregation develops after 2 days, and the maximum effect is observed by the 5th-8th day.

In most patients, the bleeding period and other platelet function values stabilize after 7 days from the moment the drug is discontinued.

Pharmacokinetics

When administered orally in a single dose, ticlopidine is absorbed almost completely and at a high rate. In plasma, its Cmax values are recorded after 2 hours.

In case of taking the drug after meals, its bioavailability increases by 20%. Stable plasma parameters are achieved after 7-10 days of using the drug in a dose of 0.25 g 2 times a day.

Synthesis of ticlopidine with lipoproteins, albumin, and α1-glycoproteins is 98%. The inhibitory effect of ticlopidine on platelet aggregation is not associated with the plasma level of the drug. A large amount of ticlopidine is involved in intrahepatic metabolism with the formation of 20 metabolic components that do not have medicinal activity.

About 50-60% of the administered dose is excreted in the urine, and the remainder in the feces. The half-life of ticlopidine is approximately 30-50 hours.

Dosing and administration

To reduce the incidence of gastrointestinal disorders, tablets are taken with food.

An adult should take 1 tablet 2 times a day.

To prevent the development of subacute occlusion associated with coronary stent implantation, therapy begins before or immediately after implantation - take 1 tablet of the drug 2 times a day in combination with aspirin (0.1-0.325 g per day). Such a combined cycle should last at least 1 month.

Use in people with liver dysfunction.

Therapy should be carried out very carefully; sometimes it is necessary to reduce the dosage of Ipaton. In case of jaundice or hepatitis, the therapy should be discontinued. The drug should not be used in case of liver failure, which has a severe form.

Severe renal impairment may require a reduction in the ticlopidine dosage or discontinuation of therapy.

• Application for children

The medication is not used in pediatrics.

Use Hypatone during pregnancy

Due to the small amount of information regarding the use of Ipaton during breastfeeding and pregnancy, it is not prescribed during these periods.

Contraindications

Among the contraindications:

• severe intolerance to ticlopidine or other components of the drug;
• hemorrhagic diathesis;
• organic lesions that are caused by a tendency to bleeding (including exacerbation of ulcers inside the gastrointestinal tract or a hemorrhagic type of stroke in the active phase);
• blood pathologies in which the bleeding period is prolonged;
• severe liver failure;
• thrombocytopenia or leukopenia, as well as agranulocytosis, present in the anamnesis.

It is strictly forbidden to use the medication in healthy people as a means of primary prevention of thromboembolism.

Side effects Hypatone

Main side effects:

• Blood and lymphatic system disorders: neutropenia (also its severe form). During the first 3 months of therapy, severe neutropenia or agranulocytosis was mainly observed. Bone marrow aplasia, pancytopenia or thrombocytopenia (indicators <80,000/mm3) may develop. Development of TTP was noted, as well as hemolytic anemia associated with thrombocytopenia. Severe neutropenia may provoke sepsis. Septic shock is possible, which may lead to death. There is a risk of hyponatremia;
• immune disorders: immunological symptoms of various types may be observed - among them signs of allergy, anaphylactic manifestations, arthralgia, nephropathy, Quincke's edema, vasculitis, eosinophilia, lupus-like syndrome and interstitial pneumonitis of allergic origin;
• problems with the functioning of the nervous system: headaches or pain in other areas, tinnitus, polyneuropathy, drowsiness, nervousness, weakness, dizziness and impaired concentration;
• lesions affecting the cardiovascular system: tachycardia or palpitations;
• vascular dysfunction: hematomas, hyperemia or bleeding. Hemorrhagic complications were often observed in nosebleeds. Pre- and postoperative bleeding may occur, as well as hematuria, bruises and hemorrhages in the conjunctiva. Intracerebral hemorrhages are also possible;
• Gastrointestinal disorders: colitis may occur (including the lymphocytic form), which is accompanied by severe diarrhea. In the case of a persistent and severe stage of the disease, therapy should be discontinued. Usually, diarrhea with nausea develops. Diarrhea is often short-term and moderate (appears during the first 3 months of therapy). Basically, this negative effect goes away in 7-14 days without the need to discontinue the drug. In addition, ulcers may develop or appetite may worsen;
• problems with the hepatobiliary system: occasionally during the first month of therapy, hepatitis (cholestatic or hemolytic jaundice) occurs. These symptoms usually disappear after discontinuing the drug. Fulminant hepatitis may be observed. The use of ticlopidine may provoke an increase in liver enzyme values (an increase in the activity of non-isolated or isolated alkaline phosphatase and serum transaminases twice the norm). During therapy, a slight increase in serum bilirubin values is possible;
• lesions of the epidermis and subcutaneous layer: during the first 3 months of the treatment course, rashes often appear (maculopapular or urticaria, which often develop itching). Dermatological signs can become generalized, but after discontinuing the drug, they disappear within the first few days. Polyform erythema, TEN or SSD appear sporadically;
• systemic signs: development of a feverish state;
• change in laboratory data: an increase of 8-10% in the values of LDL-C, HDL-C, VLDL-C and serum triglycerides during the first 1-4 months of the course without subsequent progression with continued therapy. The level of proportions of lipoprotein fractions (especially HDL/LDL) remains within the previous limits. Information obtained from clinical tests shows that this reaction is not associated with gender, age, the presence of diabetes, alcohol consumption, and does not increase the likelihood of cardiovascular diseases;
• other disorders: pharyngitis, arthropathy, ulcers in the oral mucosa, nephrotic syndrome and sore throat occasionally occur. Prolongation of the bleeding period (twofold/fivefold) compared to the values at the start of therapy may occur. The drug can reduce the blood fibrinogen index.

Overdose

Animal testing data show that drug poisoning can cause severe gastrointestinal intolerance.

In case of intoxication, induction of vomiting, gastric lavage and administration of supportive procedures are necessary.

Interactions with other drugs

Because ticlopidine may interfere with the effects of certain medications, it should be combined with the following medications with extreme caution.

Theophylline.

Its plasma levels increase with the use of ticlopidine. If it is necessary to use these drugs together, the patient's condition should be closely monitored and plasma theophylline levels should be monitored if necessary. Theophylline dosage may need to be adjusted at the beginning of therapy with Ipaton and at its completion.

Digoxin.

A slight (≈15%) decrease in plasma digoxin levels is possible.

Cyclosporine.

Administration with the drug may decrease plasma levels of cyclosporine, so its levels should be closely monitored.

Phenytoin.

It is necessary to monitor intraplasmic values of phenytoin. Sometimes the combination of Ipaton with phenytoin can increase its indicators and the development of toxic signs.

Due to the increased risk of bleeding, the drug and the substances described below should be combined with extreme caution, closely monitoring laboratory values:

• Oral anticoagulants (INR levels should be monitored regularly);
• NSAIDs;
• heparin agents (when using unfractionated heparin, APTT values should be monitored more frequently);
• antiplatelet agents (for example, salicylic acid derivatives).

Antacids reduce the absorption of the drug, causing its plasma levels to drop.

Cimetidine, which blocks the oxidation processes of microsomes, reduces the clearance rate by half.

Storage conditions

Ipaton should be stored in a place closed to small children. Temperature values - no more than 25°C.

Shelf life

Ipatone can be used for a period of 36 months from the date of manufacture of the medicinal substance.

Analogues

Analogues of the drug are the drugs Vazotik and Ticlopidine with Ticlid and Aklotin.