Ticatrom: composition and dosage form
One film-coated tablet contains 60 mg or 90 mg of ticagrelor. It may be taken with food or without it, and anyone who finds the whole tablet hard to swallow is allowed to grind it to a fine powder, mix it with half a glass of water and drink it at once, then rinse the glass with another half glass of water and finish that too.
The same mixture may be given through a nasogastric tube of size CH8 or larger, the tube being flushed with water afterwards without fail. But what matters most about this medicine is not its form: on its own it is not prescribed at all. The indication says plainly "in combination with acetylsalicylic acid", and without the second participant there simply is no treatment regimen.
How Ticatrom works
Ticagrelor blocks the P2Y12 receptor on platelets — the one through which adenosine diphosphate sets off their clumping. If the receptor is occupied, the signal does not get through, the platelets do not aggregate, and no clot forms on the damaged atherosclerotic plaque. That is the whole point of treatment after an acute coronary syndrome: to prevent renewed thrombosis in a coronary artery.
Such a mechanism has an unavoidable other side, and it is worth understanding before treatment begins. Everything that stops platelets clumping also stops any bleeding from being brought under control. The whole remaining conversation about ticagrelor is therefore a conversation about balance: how far the risk of a new heart attack in a particular patient outweighs the risk of bleeding, and what may and may not be taken alongside the medicine.
Indications
Formally there is one indication, but it has to be read together with a proviso that appears rarely in product information: the medicine is not prescribed on its own but in combination with acetylsalicylic acid. Then comes the aim — prevention of cardiovascular events in adults — and the two groups it is addressed to. The first: patients with an acute coronary syndrome. The second: those who have already had a myocardial infarction and remain at high risk of cardiovascular events.
It is therefore not a medicine for prevention "in general" nor a remedy for angina. It is prescribed in two specific situations: straight after an acute coronary syndrome, and later, as extended protection for those who have already had a heart attack and remain in the high-risk group. Those two situations correspond to the two strengths of the tablet.
Method of administration and dosage
In acute coronary syndrome treatment begins with a single loading dose of 180 mg — two 90 mg tablets — and continues at 90 mg twice a day. That regimen is planned for 12 months, unless clinical grounds appear for stopping it earlier. For extended treatment in patients with a previous heart attack and high risk, 60 mg twice a day is used.
And to all of this a second condition is attached, without which the regimen is incomplete: the patient should take a daily maintenance dose of acetylsalicylic acid of 75 to 150 mg, unless it is individually contraindicated. This is not advice to "take some aspirin as well" but part of the prescription — it is in exactly that combination that the medicine was studied and in it that it produced its result. Old age and impaired kidney function call for no dose adjustment; in mild and moderate hepatic impairment the dose likewise does not change, though caution is needed, and in severe impairment the medicine is contraindicated. In those under 18 neither safety nor efficacy has been established.
Contraindications
The list is short and consists almost entirely of bleeding in various forms: hypersensitivity to the active substance or to any excipient, active pathological bleeding, intracranial haemorrhage in the history. Severe hepatic impairment belongs here too.
The fifth point stands apart and concerns not a condition but medicines: concurrent use with strong inhibitors of the enzyme CYP3A4 — ketoconazole, clarithromycin, nefazodone, ritonavir and atazanavir — is contraindicated, because it leads to a substantial rise in exposure to ticagrelor. Since an excess of ticagrelor means an excess of bleeding tendency, the prohibition here is absolute, not a matter of "with caution".
Special warnings and precautions
The most unexpected warning concerns not an outside medicine but the partner in its own regimen. The PLATO study revealed a relationship between the maintenance dose of acetylsalicylic acid and how far ticagrelor outperforms clopidogrel: the higher the aspirin dose, the smaller the advantage. Combining ticagrelor with high maintenance doses of aspirin, above 300 mg, is therefore not recommended. The result is counterintuitive: there must be enough aspirin, but surplus aspirin works against the main medicine.
| What may happen | What it looks like | What is done |
| Breathlessness | usually mild or moderate, often settles by itself | withdrawing the medicine for it is mostly unnecessary; but before changing treatment other causes are ruled out, because breathlessness can also be a sign of heart failure |
| Breathlessness in asthma and chronic obstructive pulmonary disease | the absolute risk in these patients is higher | with a history of asthma or COPD the medicine is used with caution |
| Ventricular pauses | usually symptomless, longer than 3 seconds on Holter monitoring | in the acute phase of a coronary syndrome they were found more often than on clopidogrel; by the later period the difference had gone |
| Bradycardia | extending to fainting linked to a slow pulse | patients with sick sinus syndrome without a pacemaker and with second- or third-degree atrioventricular block were excluded from the studies, so data is scarce and caution is needed |
| Elective surgery | the antiplatelet effect is unwanted at that moment | the medicine is stopped 5 days before the procedure |
Separately, the product information warns of the opposite danger — not of bleeding but of stopping too early. Interrupting any antiplatelet treatment, this one included, may translate into an increased risk of death from cardiovascular causes, so giving it up on one's own is not acceptable even when it feels unpleasant. Two further restrictions: patients with an acute coronary syndrome who have previously had an ischaemic stroke may be treated with ticagrelor for no more than 12 months, and for extended treatment after a heart attack in those who have had an ischaemic stroke there is no data at all, so it is not recommended. Data on treatment lasting longer than three years is also limited, so extending the regimen indefinitely is not the practice.
Interaction with other medicines
Ticagrelor's interactions run in two directions. What acts on it goes through the enzyme CYP3A4: strong inhibitors are contraindicated, while inducers conversely lower its concentration and its efficacy. More interesting, though, is what ticagrelor does to other medicines, and there the figures are specific.
- simvastatin: ticagrelor raises its maximum concentration by 81% and the area under the curve by 56%, and in individual patients the rise was two- and threefold, so combining it with simvastatin doses above 40 mg a day is undesirable;
- digoxin: the maximum concentration rises by 75% and the area under the curve by 28%, while in the elimination phase mean concentrations go up by about 30% — appropriate monitoring is recommended;
- morphine reduces exposure to ticagrelor by 35%, probably by slowing gastrointestinal motility, and the same applies to other opioids;
- if morphine cannot be withheld and rapid inhibition of the P2Y12 receptor is judged critical, a parenteral P2Y12 inhibitor is considered;
- with heparin, enoxaparin, acetylsalicylic acid and desmopressin, neither ticagrelor's pharmacokinetics nor adenosine-diphosphate-induced platelet aggregation changed;
- combining it with medicines that slow the heart rate calls for caution because of the pauses and bradycardia observed, although the PLATO study found no clinically significant consequences of such a combination.
The last point is worth reading carefully, because it concerns almost every patient after a heart attack: in that same study 96% of participants were on beta-blockers, 33% on diltiazem or verapamil and 4% on digoxin. Combination with rate-slowing medicines is therefore the rule here rather than the exception, and caution means observation, not giving up the treatment.
Pregnancy and breastfeeding
There is no data on the use of ticagrelor in pregnant women, or it is very limited. Animal studies showed reproductive toxicity, so using the medicine during pregnancy is not recommended.
Women of childbearing age should use reliable contraception during treatment so that pregnancy does not occur. There is no data on ticagrelor passing into human milk; in animals both it and its active metabolites are excreted in milk, and a risk to the child cannot be ruled out, so the decision to stop feeding or to stop treatment is taken by weighing the benefit of each.
Adverse effects
Ticagrelor's two commonest adverse reactions are bleeding and breathlessness, and they are built differently. Bleeds vary in severity and can occur anywhere: from the nose, from the gastrointestinal tract, from the urinary tract, as subcutaneous bruises and haematomas, and after procedures and interventions. The practical guide is the same as for anticoagulants: an unexplained fall in haemoglobin or blood pressure is a reason to look for the source of bleeding rather than to wait for visible blood.
Breathlessness, by contrast, is usually not dangerous: it is mild or moderate and not seldom settles by itself, without any need to withdraw the medicine. Its main problem is that it frightens people and that it is easily confused with worsening heart failure. Of the rest there are headache and dizziness, a rise in blood uric acid extending to gout, nausea, diarrhoea, constipation and abdominal pain, rash and itching. Less often described are confusion, intracranial haemorrhage, bradycardia and a rise in creatinine. It is worth remembering too that gout here is not caused by diet: ticagrelor raises uric acid, and in a patient with gout in the history that can end in a flare which is easy to take for coincidence. Any severe bleeding and any neurological symptoms during treatment call for immediate medical help.
Overdose
An overdose of ticagrelor means above all an increased bleeding tendency, and alongside it gastrointestinal symptoms have been described — nausea, vomiting, diarrhoea — as well as slowing of the heart rate. Single doses of up to 900 mg were tolerated satisfactorily, and the commonest complaint was precisely digestive upset.
There is no specific antidote, and dialysis does not remove ticagrelor. Treatment is symptomatic: for bleeding the usual measures to stop it are used, and for marked bradycardia electrocardiogram monitoring is worth considering, since breathlessness and ventricular pauses are exactly what is named among the clinically significant manifestations of overdose. If considerably more than prescribed has been taken, medical help should be sought and the doctor told how many tablets were taken and when.
How to get a prescription for Ticatrom online
Ticagrelor is a medicine that does not work alone and whose partner is strictly dosed: the daily maintenance dose of acetylsalicylic acid should be 75 to 150 mg, and doses above 300 mg reduce ticagrelor's own advantage. What matters to the doctor is therefore to see the whole regimen, not a single prescription. On e-zdrowie.com you fill in a medical questionnaire, the doctor reviews the answers and, if the medicine is suitable, issues an electronic prescription: the code arrives by message, and any Polish pharmacy will dispense the tablets against it.
Begin the questionnaire with the event and its date: acute coronary syndrome, myocardial infarction, stenting — both the dose and the length of treatment depend on it. You must state how many milligrams of aspirin you take a day. Report any ischaemic stroke you have had: it limits the length of treatment and, in the extended regimen after a heart attack, makes it not recommended. Name separately any intracranial haemorrhage in the past, active bleeding, ulcers and severe liver disease — these are outright contraindications. List your medicines: antifungals, clarithromycin, HIV medicines, simvastatin together with its dose, digoxin, painkillers including opioids, anticoagulants, and anything that slows the pulse. And state whether you have asthma or chronic obstructive pulmonary disease, heart rhythm disturbances, and any planned operations.
