Ipaton

Ipaton is an anti-thrombotic drug. Contains the component ticlopidine. It inhibits platelet adhesion and aggregation, as well as the processes of release of platelet factors. In addition, it prolongs the bleeding period, reduces the retraction of blood clots, reduces blood viscosity and fibrinogen indices, and at the same time increases the filtration activity of erythrocytes with whole blood.

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

Ticlopidine has no effect on the processes of fibrinolysis and blood clotting. [2]

Indications Ipaton

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

It is prescribed to correct or prevent platelet dysfunction associated with artificial blood flow during surgery or prolonged hemodialysis .

It is used to prevent the development of a subacute occlusion involving an implanted coronary stent .

For the disorders described above, the drug is usually used in people with aspirin intolerance or ineffectiveness of its use.

Release form

Medicines are produced in tablets - 10 pieces inside a blister pack; inside the box - 2 such packs.

Pharmacodynamics

Ticlopidine has a blocking effect on platelet aggregation, inhibiting the synthesis of fibrinogen and glycoproteins IIb / IIIa (specific endings of platelet walls) associated with ADP. The drug has no effect on platelet activity associated with AMP and COX. Despite the fact that the biochemical principle of influence and the mediators involved in it are well studied, inhibition of platelet aggregation is realized only in vivo; in vitro, ticlopidine does not alter platelet function. [3]

Therapeutic portions of ticlopidine allow inhibition of platelet aggregation induced by the ADP element (2.5 μmol / l) by 50-70%. After ingestion, the antiplatelet activity of ticlopidine depends on the size of the dosage up to a daily portion of 0.5 g, but with its subsequent increase it no longer increases.

In the case of 2-fold intake of the drug per day in a portion of 0.25 g, the inhibition of platelet aggregation develops after 2 days, and the maximum effect is observed by the 5-8th day.

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

Pharmacokinetics

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

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

The synthesis of ticlopidine with lipoproteins, albumin, and α1-glycoproteins is 98%. The suppressive effect of ticlopidine on platelet aggregation is not related to 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 drug activity.

About 50-60% of the applied portion is excreted in the urine, and the remainder in the faeces. 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 needs to take 1 tablet 2 times a day.

In order to prevent the development of subacute occlusion associated with coronary stent implantation, therapy is started before implantation or immediately after it - 1 tablet of the drug is taken 2 times a day in combination with aspirin (0.1-0.325 g per day). This combined cycle should last at least 1 month.

Use in people with hepatic dysfunction.

The therapy must be carried out very carefully; sometimes a dosage reduction of Ipaton is required. In case of jaundice or hepatitis, therapy should be canceled. You can not use the medicine in case of liver failure, which has a severe form.

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

• Application for children

The medication is not used in pediatrics.

Use Ipaton during pregnancy

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

Contraindications

Among the contraindications:

• severe intolerance to ticlopidine or other elements of the drug;
• diathesis of hemorrhagic type;
• having an organic nature of the lesion, which is caused by a tendency to bleeding (among them, exacerbation of ulcers inside the gastrointestinal tract or a hemorrhagic type of stroke in the active phase);
• blood pathologies in which there is a prolongation of the term of bleeding;
• severe liver failure;
• thrombocyto- or leukopenia, as well as agranulocytosis, present in history.

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

Side effects Ipaton

The main side effects:

• disorders associated with the blood system and lymph: neutropenia (also its severe form). During the first 3 months of therapy, there was mainly a severe stage of neutropenia or agranulocytosis. Perhaps the appearance of bone marrow aplasia, pancyto- or thrombocytopenia (indicators <80,000 / mm3). The development of TTP was noted, and in addition to this, a hemolytic type of anemia associated with thrombocytopenia. Severe neutropenia can cause sepsis. Possible septic shock, which can lead to death. There is a possibility of hyponatremia;
• immune disorders: immunological symptoms of different types can be noted - among them are signs of allergy, anaphylactic manifestations, arthralgia, nephropathy, Quincke's edema, vasculitis, eosinophilia, lupus-like syndrome and an interstitial form of pneumonitis of an allergic nature;
• problems with the activity of the NA: headaches or pain in other areas, ear noise, polyneuropathy, drowsiness, nervousness, weakness, dizziness and deterioration in concentration;
• lesions affecting the CVS: tachycardia or palpitation;
• dysfunction of blood vessels: hematomas, hyperemia or bleeding. With bleeding from the nose, complications of the hemorrhagic type were often observed. Pre- and postoperative bleeding may occur, as well as hematuria, bruising and hemorrhage in the conjunctival region. In addition, hemorrhages inside the brain are possible;
• disorders in the digestive tract: colitis may appear (among them the lymphocytic form), against which there is severe diarrhea. In the case of a stable and severe stage of the disease, therapy should be canceled. Diarrhea usually develops with nausea. Diarrhea is often short-lived and moderate (appears during the first 3 months of therapy). Basically, this negative effect disappears in 7-14 days without the need for drug withdrawal. In addition, ulcers may develop or appetite may deteriorate;
• problems with the work of the hepatobiliary system: occasionally, during the 1st month of therapy, hepatitis appears (cholestatic or hemolytic jaundice). Usually, these signs disappear after the drug is discontinued. Fulminant-type hepatitis may occur. The use of ticlopidine can provoke an increase in the values of liver enzymes (an increase in the activity of non-isolated or isolated alkaline phosphatase and serum transaminases twice the normal value). During therapy, an insignificant 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, in which itching often develops). Dermatological signs can become generalized, but after the drug is discontinued, they disappear in the first few days. Erythema polyform, PETN or SSD appears singly;
• systemic signs: the development of a febrile state;
• change in laboratory data: an 8-10% increase in the values of LDL-C, HDL-cholesterol, 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 same limits. Information obtained from clinical tests shows that this reaction is not associated with gender, age, diabetes, alcohol consumption, and also does not increase the likelihood of CVD diseases;
• other disorders: rarely occurs pharyngitis, arthropathy, ulcers in the oral mucosa, nephrotic-type syndrome and pain in the throat. There may be a prolongation of the bleeding period (twice / fivefold) in comparison with the values at the time of initiation of therapy. The medication is able to reduce the blood fibrinogen count.

Overdose

Data from tests carried out with animals show that in case of drug poisoning, severe gastrointestinal intolerance may occur.

In case of intoxication, induction of vomiting, gastric lavage and the appointment of supportive procedures are needed.

Interactions with other drugs

Because ticlopidine can affect the effects of certain drugs, it must be very carefully combined with the drugs listed below.

Theophylline.

Its plasma parameters increase with the use of ticlopidine. If you need to use these drugs together, you need to closely monitor the patient's condition and monitor the plasma values of theophylline, if necessary. At the beginning of therapy with Ipaton and at its completion, it may be necessary to adjust the dose of theophylline.

Digoxin.

An insignificant (by ≈15%) decrease in plasma digoxin values is possible.

Cyclosporine.

Administration with a drug can lower the plasma level of cyclosporine, which is why its indicators must be closely monitored.

Phenytoin.

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

Due to the increased likelihood of bleeding, the combination of the medication and the substances described below must be extremely careful, carefully monitoring the laboratory values:

• oral anticoagulants (you need to regularly monitor the level of INR);
• NSAIDs;
• means of heparin (when using unfractionated heparin, it is necessary to monitor the APTT indicators more often);
• antiplatelet substances (for example, derivatives of salicylic acid).

Antacids reduce the absorption of the drug, which causes its plasma index to fall.

Cimetidine, blocking the oxidation processes of microsomes, halves the level of clearance.

Storage conditions

Ipaton must be kept in a place closed from the penetration of small children. Temperature values - no more than 25 ° C.

Shelf life

Ipaton can be used for a 36-month term from the date of manufacture of the medicinal substance.

Analogs

The analogs of the drug are the drugs Vasotik and Ticlopidine with Tiklid and Aklotin.