How ticagrelor works
The anticoagulant ticagrelor specifically inhibits a certain binding site on the surface of blood platelets (thrombocytes), the so-called P2Y12 receptor for ADP. This suppresses the activation of further platelets and also further “self-activation” of platelets. The combination of ticagrelor with acetylsalicylic acid (ASA) in dual platelet inhibition additionally prevents the formation of thromboxanes, which further reduces the platelets’ ability to clot.
When blood leaks from the body’s vascular system, the body tries to stop the blood loss. To do this, blood clotting is activated. It causes clots to form precisely at the affected site in order to seal the leak. Platelets, which make up the third type of blood cell along with red and white blood cells, have an important function in this process.
The platelets’ task is to detect a vascular leak and subsequently initiate clotting. To do this, the platelets attach themselves to the injured site with the help of other proteins in the blood and are activated, thus initiating everything to close the vessel as quickly as possible.
If this process is disturbed by various factors so that it can be activated excessively sensitively, a clotting disorder is present. In this case, larger clots can form in intact blood vessels. These can then block important vessels that supply the brain or heart, for example – with consequences such as stroke or heart attack.
To prevent this, drugs are used to interfere with the clotting process, for example ticagrelor.
Absorption, degradation and excretion
After ingestion, about one-third of ticagrelor is absorbed from the intestine into the bloodstream, where it reaches its maximum blood level after one and a half hours. The anticoagulant is partially converted in the liver by the cytochrome P450 enzyme system to another compound that is also effective.
Both ticagrelor itself and its conversion product are excreted from the body to a small extent in the urine, but mainly in the stool. After seven to eight hours, the blood level of ticagrelor has dropped to about half the absorbed dose.
When is ticagrelor used?
Ticagrelor is indicated in combination with acetylsalicylic acid (ASA) for the prevention of clot formation in adult patients with:
- Acute coronary syndrome (collective term for unstable angina, myocardial infarction, and sudden cardiac death).
In the lower dosage of 60 milligrams, ticagrelor is prescribed in combination with ASA for the prevention of atherothrombotic events in patients with known myocardial infarction that occurred at least 12 months previously.
Ticagrelor must be taken on a long-term basis to provide sustained suppression of clot formation. The duration of treatment is invididually determined and is usually one year.
How ticagrelor is used
At the beginning of treatment with ticagrelor, 180 milligrams of the active ingredient are taken, followed by 90 milligrams twice daily at intervals of about twelve hours. It can be taken with or without a meal.
If the patient has difficulty swallowing or is fed through a stomach tube, the ticagrelor tablet can be crushed and given suspended in water. Alternatively, there are ticagrelor melting tablets that already dissolve in the mouth.
For follow-up treatment in high-risk patients after heart attack, 60 milligrams of ticagrelor is taken twice daily, about twelve hours apart.
If you miss a dose, you should not take it later. Instead, simply take the next dose at the usual time. Do not take two doses at the same time!
What are the side effects of ticagrelor?
Occasionally, dizziness, headache, bleeding in the skull, bleeding of the eyes, bloody cough, vomiting of blood, gastrointestinal ulcers, bleeding in the oral cavity, skin rash, itching, bleeding of the urinary tract and vaginal mucosa, and weakening of the immune system are also seen.
What should be considered when taking ticagrelor?
Contraindications
Ticagrelor should not be taken by:
- hypersensitivity to the active substance or to any of the other ingredients of the drug
- active bleeding
- history of bleeding inside the skull (intracranial hemorrhage)
- severe liver dysfunction
- concomitant use of strong CYP3A4 inhibitors (such as clarithromycin, itraconazole, ritonavir)
Drug interactions
A variety of interactions of ticagrelor with other drugs are possible. Therefore, before starting treatment, it should be checked which other medications the patient is taking.
Ticagrelor is broken down in the liver by the enzyme cytochrome P450 3A4, which also breaks down many other active ingredients in the body. Some of these agents can inhibit the enzyme, causing the blood level of ticagrelor to increase.
Conversely, some substances can increase the amount of the enzyme cytochrome P450 3A4, which increases the degradation of ticagrelor. This applies, for example, to drugs for epilepsy and seizures (such as phenytoin, carbamazepine, phenobarbital), some foods (such as ginger, garlic, licorice), and the herbal antidepressant St. John’s wort.
Ticagrelor can also affect the breakdown of other drugs by inhibiting certain proteins. For example, the anticoagulant may increase the concentration of drugs such as digoxin (heart medication), ciclosporin (for autoimmune diseases and after organ transplants), atorvastatin (cholesterol-lowering drug), and verapamil (e.g., for cardiac arrhythmias).
Close monitoring is recommended at the beginning of ticagrelor treatment, especially for drugs with a narrow therapeutic range. Such drugs are therapeutically effective only in a narrow dose range; when the dose is increased, overdosage occurs rapidly with corresponding side effects.
Age restriction
Safety and efficacy of ticagrelor in children and adolescents under 18 years of age have not been established.
Pregnancy and Lactation
In studies in animals, ticagrelor and its active metabolite passed into breast milk. It is not known whether this is also the case in humans. A risk to the infant if the nursing mother takes ticagrelor can therefore not be ruled out. Based on a risk-benefit assessment, a decision should be made on a case-by-case basis as to whether breastfeeding should be discontinued as a precautionary measure or whether ticagrelor should be stopped.
How to obtain medicines containing ticagrelor
Preparations containing the active ingredient ticagrelor require a prescription in Germany, Austria and Switzerland and can therefore only be obtained from pharmacies on prescription.
How long has ticagrelor been known?
Ticagrelor was developed as the first active ingredient to reversibly inhibit platelet activation by ADP. It was introduced to the European market in 2011.
The novelty and considerable additional benefit of the active ingredient were also recognized in Germany by the Federal Joint Committee, which sets the fixed prices of drugs in this country. For this reason, preparations containing the active ingredient ticagrelor are comparatively expensive, but have the advantage that they can reduce mortality after a heart attack more than previous therapies.