Ticlopidine

Ticlopidine (ticlopidine) is a drug from the group of antiaggregants that is used to prevent blood clots (blood clotting) in blood vessels. It is a platelet aggregation inhibitor, which means it prevents platelets from sticking together in the blood, which helps prevent clots from forming and reduces the risk of thromboembolism.

Ticlopidine is commonly prescribed to people with cardiovascular disease, such as coronary heart disease, strokes or peripheral arterial disease, to reduce the risk of blood clots and improve blood flow.

However, because ticlopidine can cause serious side effects, such as agranulocytosis (decreased white blood cell count), the drug is usually reserved for when other anticoagulants and antiaggregants are inappropriate or ineffective.

Indications Ticlopidine

Ticlopidine is usually prescribed in the following cases:

1. Coronary heart disease: Ticlopidine may be used to prevent thrombosis in patients with stable angina pectoris (chest pain due to reduced blood flow to the heart) or after myocardial infarction (reduced blood supply to the heart muscle).
2. Ischemic Stroke: The drug may be used to prevent secondary ischemic strokes in patients who have already had a stroke due to vascular thrombosis.
3. Peripheral arterial disease: Ticlopidine may help improve blood flow in the lower extremities in patients with peripheral arterial disease such as peripheral arterial disease.
4. Vascular stenting: Used together with aspirin to prevent thrombosis after coronary artery stenting (a procedure in which a special tubular stent is placed in a narrowed vessel).
5. Other Conditions: In rare cases, ticlopidine may be prescribed for the treatment of other conditions associated with thrombosis, but use in these cases requires caution and may require special considerations.

Release form

Ticlopidine is available as tablets for oral (intravenous) administration. Ticlopidine tablets usually have the standard shape and size typical of tablets and are usually coated to make them easier to swallow and protect them from breaking down in the stomach.

Typically, ticlopidine is available in a variety of dosages to allow individualization of therapy based on the patient's specific needs and physician recommendations.

Pharmacodynamics

The pharmacodynamics of ticlopidine is related to its ability to inhibit platelet aggregation, that is, to prevent platelets from sticking together. It belongs to a group of drugs known as antiaggregants, which help prevent the formation of blood clots in blood vessels.

Ticlopidine exerts its action through several mechanisms:

1. Inhibition of ADP-induced platelet aggregation: Ticlopidine blocks ADP receptors on platelets, which prevents them from sticking together.
2. Increase in bleeding time: Suppression of platelet aggregation leads to increase in bleeding time, which is one of the indicators of antiaggregant activity of the drug.
3. Effect on the fibrinolysis system: Ticlopidine may have an effect on the fibrinolysis system, enhancing clot dissolution.
4. Effects on endothelial function: A positive effect of ticlopidine on vascular endothelial function has been observed, which may also contribute to the antithrombotic effect.

The drug begins to act 24-48 hours after taking it, and the maximum effect is achieved after about 3-5 days of regular intake. The effect of ticlopidine is irreversible, and after discontinuation of the drug the recovery of platelet function occurs slowly, over several days.

Pharmacokinetics

The pharmacokinetics of ticlopidine is characterized by the following main aspects:

1. Absorption: Ticlopidine is well absorbed from the gastrointestinal tract. Food intake improves its absorption. The maximum concentration in blood plasma is reached approximately 1-2 hours after administration.
2. Distribution: Ticlopidine binds to plasma proteins by more than 90%, indicating a high degree of binding to plasma proteins. It is distributed in organs and tissues, penetrating into platelets.
3. Metabolism: Ticlopidine is metabolized in the liver to form active metabolites. Metabolism of ticlopidine is carried out by cytochrome P450 enzymes in the liver. The main metabolite is thienopyridine derivative, which has antiaggregant effect.
4. Excretion: Ticlopidine and its metabolites are excreted through the kidneys and with bile. Approximately 60% of the dose is excreted with urine and about 23% with feces. The elimination half-life of ticlopidine from blood plasma is 12 to 15 hours, which provides prolonged action.
5. Time of action: The onset of action of ticlopidine does not occur immediately, it takes from several days to a week of taking the drug to develop the full effect. This is due to the need for accumulation of active metabolites in the body. The effect persists for a long time after discontinuation of the drug due to slow reverse metabolism and a long half-life.

Dosing and administration

The method of use and dosage of Ticlopidine may vary depending on your doctor's specific instructions and the purpose of treatment. The following are general recommendations for the use of ticlopidine:

1. Standard dosage for adults:

   • The usual starting and maintenance dose is 250 mg twice daily, with administration after meals to improve absorption and reduce the risk of gastrointestinal side effects.

2. Duration of treatment:

   • The duration of ticlopidine treatment course depends on the patient's state of health, the goal of therapy and response to treatment. The doctor determines the duration of the course based on the individual characteristics of the patient.

3. Special Instructions:

   • It is important to have regular medical control while taking ticlopidine, including blood tests, to monitor your health and detect possible side effects in time.
   • Ticlopidine should be started and stopped only when prescribed by your doctor.

4. Use in special patient populations:

   • Dose adjustment may be required in patients with renal or hepatic dysfunction and in the elderly. Close monitoring of these patients is mandatory.

5. Discontinuation of treatment:

   • Sudden discontinuation of ticlopidine may increase the risk of thrombotic events. Therefore, any changes in the treatment regimen should be discussed with your doctor.

Use Ticlopidine during pregnancy

No studies directly addressing the use of ticlopidine during pregnancy were found.

Contraindications

Taking Ticlopidine carries certain risks and has a number of contraindications:

1. Allergy to ticlopidine or any other component of the drug: Patients with known hypersensitivity to ticlopidine should avoid its use.
2. Hematological diseases: Ticlopidine may cause neutropenia, thrombocytopenia, aplastic anemia and other serious disorders of hematopoiesis. Therefore, the drug is contraindicated in the presence of hematologic diseases, including severe leukopenia and thrombocytopenia.
3. Severe hepatic impairment: Ticlopidine is metabolized in the liver and its use may aggravate the condition in the presence of severe hepatic disease.
4. Chronic renal failure: In patients with severe renal impairment, the use of ticlopidine requires caution due to the risk of accumulation of toxic metabolites.
5. Active bleeding or tendency to bleed: Including peptic ulcers and internal bleeding as ticlopidine increases bleeding time.
6. Acute phase of stroke: The use of ticlopidine immediately after acute stroke is not recommended due to the lack of data on safety and efficacy in this case.
7. Pregnancy and lactation: The use of ticlopidine during pregnancy and lactation is contraindicated due to lack of sufficient safety data.
8. Severe clotting disorders: Since ticlopidine increases the risk of bleeding, its use may be dangerous in the presence of clotting disorders.

Side effects Ticlopidine

Like any medication, Ticlopidine can cause a number of side effects:

1. Hematologic side effects: Include thrombotic thrombocytopenic purpura (TTP), which can occur within weeks of treatment initiation. TTP is a serious condition characterized by thrombosis in small vessels, which can lead to acute kidney failure, neurological changes, and an increased risk of death. Early discontinuation of the drug and initiation of plasma therapy can significantly improve outcome (Kupfer, Tessler, 1997).
2. Neutropenia: Ticlopidine may cause a decrease in the number of neutrophils in the blood, which increases the risk of infections.
3. Increased risk of bleeding: As an antiaggregant, ticlopidine increases bleeding time, which may lead to increased bleeding, including internal bleeding.
4. Liver disorders: Including jaundice and elevated liver enzymes, which may indicate impaired liver function. Cholestatic hepatitis has been reported in some cases (Han et al., 2002).
5. Allergic reactions: Skin rashes, pruritus, angioedema.
6. Diarrhea and other gastrointestinal disorders: Ticlopidine frequently causes GI disorders including diarrhea, nausea and vomiting.
7. Neurologic effects: Dizziness, headache and fatigue can also be side effects of ticlopidine.

Overdose

Overdose with ticlopidine can lead to serious side effects, especially those associated with an increase in its antiaggregant action, which increases the risk of bleeding. Symptoms of overdose may include:

• Increased bleeding time.
• Bleeding in various organs and tissues.
• Appearance of bruises and bruises even with minor injuries.
• Nausea, vomiting, diarrhea.
• Dizziness and general malaise.

What to do in case of an overdose:

1. Seek medical attention immediately. At the first signs of overdose, go to a medical facility or call an ambulance immediately.
2. Symptomatic treatment. There is no specific antidote for ticlopidine, so treatment will be aimed at eliminating symptoms and maintaining vital functions of the body. Blood transfusion or its components may be required to correct clotting disorders.
3. Condition Monitoring. The patient will require close health monitoring, including monitoring of blood clotting, kidney and liver function.
4. Discontinuation of ticlopidine. Further, depending on the severity of the condition and doctor's recommendations, dosage adjustment or complete discontinuation of the drug may be required.

Interactions with other drugs

Ticlopidine may interact with different medicines, altering their effectiveness or increasing the risk of side effects. Here are some examples of such interactions:

1. Interaction with theophylline: Ticlopidine may increase theophylline concentration in blood, which increases the risk of theophylline toxic effects, including cardiac rhythm disturbances and increased nervous excitability. It is important to monitor theophylline levels when co-administered with ticlopidine and adjust the theophylline dose if necessary (Colli et al., 1987).
2. Interaction with phenytoin: Ticlopidine may decrease the clearance of phenytoin, leading to increased blood concentrations and increased risk of toxic reactions such as ataxia, visual disturbances and cognitive impairment. Phenytoin levels should be monitored and dosage adjusted when co-administered with ticlopidine (Riva et al., 1996).
3. Anticoagulants and other antiaggregants: Ticlopidine may increase the effect of anticoagulants (e.g. Warfarin) and other antiaggregants (e.g. Aspirin), increasing the risk of bleeding. Close monitoring of the patient's condition and dosage adjustment may be necessary when using these drugs together.
4. Drugs metabolized by cytochrome P450: Ticlopidine may inhibit the activity of certain cytochrome P450 enzymes, which affects the metabolism of many drugs, including statins, antidepressants, and beta-blockers. This can lead to increased levels of these drugs in the blood and an increased risk of side effects.
5. Digoxin: There are reports that ticlopidine may increase the plasma concentration of digoxin, which requires caution when using them together.

Storage conditions

Storage conditions for ticlopidine should comply with the general recommendations for storage of medicinal products, as well as the instructions given by the manufacturer on the drug package. In general, it is recommended to observe the following conditions:

1. Temperature: Ticlopidine should be stored at room temperature, usually between 15 and 25 degrees Celsius. Avoid storing the drug in places with high temperature or direct sunlight.
2. Humidity: The drug should be stored in a dry place, away from sources of moisture, to prevent spoilage and reduced efficacy.
3. Availability to children: The medicine should be kept out of the reach of children to avoid accidental swallowing.
4. Packaging: Store ticlopidine in its original packaging to protect it from light and moisture and for easy tracking of expiration date.

Shelf life

Do not use ticlopidine after the expiration date stated on the package. Expired medicines should be disposed of properly.