Poltixa: composition and dosage form
One film-coated tablet contains 2.5 mg or 5 mg of apixaban. It is taken with or without food, with water, and this medicine carries a proviso rare among anticoagulants: anyone who cannot swallow the tablet whole is allowed to crush it.
The procedure is this: the crushed tablet is suspended in water, in 5% aqueous glucose solution or in apple juice, or mixed with apple purée and given by mouth at once. It may also be suspended in 60 ml of water or the same glucose solution and given through a nasogastric tube. In those media the crushed tablets stay stable for up to 4 hours. By way of comparison: with capsule anticoagulants, opening the capsule is expressly forbidden because it changes absorption — here that problem does not arise.
How Poltixa works
Apixaban is a potent, reversible, direct and highly selective inhibitor of the active site of factor Xa. The word "direct" matters here: unlike the heparins, it does not need antithrombin III in order to work. It inhibits both free factor Xa and the factor bound to a clot, and along with them the activity of prothrombinase.
From there the logic is simple. Factor Xa stands on the path to the formation of thrombin, so inhibiting it stops thrombin from forming, and without thrombin no clot is built. Apixaban has no direct effect on platelet aggregation but indirectly inhibits the part of it that thrombin sets off. In preclinical models the medicine prevented both venous and arterial thrombosis at doses at which haemostasis was preserved.
Indications
There are three indications, and they are shared unequally between the two strengths of the tablet. The 2.5 mg dose covers all three: prevention of venous thromboembolism in adults after elective hip or knee replacement, prevention of stroke and systemic embolism in non-valvular atrial fibrillation, and treatment of deep vein thrombosis and pulmonary embolism together with prevention of their recurrence.
The 5 mg dose has two indications — atrial fibrillation and venous thrombosis with pulmonary embolism; orthopaedic prophylaxis is not on its list. Prescribing it in atrial fibrillation requires at least one risk factor: a previous stroke or transient ischaemic attack, age 75 or over, arterial hypertension, diabetes, or symptomatic heart failure of NYHA class II or higher.
Method of administration and dosage
The chief peculiarity of apixaban is that the dose here is set by the indication, not by the patient. The very same characteristics — age, body weight, the state of the kidneys — decide everything in one indication and mean nothing in the rest.
| Indication | Dose | What changes it |
| After hip replacement | 2.5 mg twice a day, 32—38 days | nothing: neither age, nor body weight, nor mild or moderate reduction in kidney function alters the dose |
| After knee replacement | 2.5 mg twice a day, 10—14 days | the same; the first dose is given 12 to 24 hours after the operation, and the doctor weighs an earlier start against the risk of post-operative bleeding |
| Non-valvular atrial fibrillation | 5 mg twice a day, long term | the one indication where the patient decides: with two features out of three — age 80 or over, body weight 60 kg or less, serum creatinine 1.5 mg/dl or higher — the dose falls to 2.5 mg twice a day |
| Treatment of deep vein thrombosis and pulmonary embolism | 10 mg twice a day for 7 days, then 5 mg twice a day | nothing; this is the only regimen with a dose change inside the course, and it is tied to the timetable, not to the patient |
| Prevention of recurrent thrombosis | 2.5 mg twice a day | nothing; one moves to this dose after six months of treatment |
A missed dose is taken as soon as it is remembered, and thereafter twice a day as before. Switching from a parenteral anticoagulant to apixaban and back is done at the time of the next scheduled dose, without the medicines overlapping. The product information separately permits what is rarely permitted with anticoagulants: during catheter ablation the medicine need not be interrupted, and for cardioversion treatment may be started or continued — though for those who were not previously on anticoagulants it is worth ruling out a clot in the left atrium by imaging before cardioversion. Children and adolescents under 18 are not prescribed the medicine: there is no data.
Contraindications
The first group is self-evident for an anticoagulant: hypersensitivity to the active substance or to an excipient, active clinically significant bleeding, and liver disease running with coagulopathy and a clinically relevant risk of bleeding. The second is any condition regarded in itself as a risk factor for major bleeding: gastrointestinal ulceration now or recently, a malignant tumour carrying a high risk of bleeding, recent injury to the brain or spinal cord, surgery on the brain, spine or eye, recent intracranial haemorrhage, oesophageal varices, arteriovenous malformations, aneurysms and serious vascular abnormalities of the brain and spinal cord.
The third group is combinations. Concurrent treatment with any other anticoagulant is contraindicated: unfractionated heparin, low-molecular-weight heparins, heparin derivatives, oral agents such as warfarin, rivaroxaban and dabigatran. There are two exceptions and both are technical: the moment of switching from one therapy to another, and unfractionated heparin given in the doses needed to keep a central venous or arterial catheter patent, or during catheter ablation for atrial fibrillation.
Special warnings and precautions
Stopping an anticoagulant is itself a risk. The product information puts it plainly: interrupting the medicine because of active bleeding, elective surgery or an invasive procedure raises the likelihood of thrombosis, so restarting must not be delayed, and if the medicine was interrupted for any reason, treatment is brought back as soon as possible.
- with spinal and epidural anaesthesia and with puncture of those spaces there is a risk of a haematoma capable of causing prolonged or irreversible paralysis, so such patients need frequent neurological assessment;
- in patients with severe renal impairment, at a creatinine clearance of 15 to 29 ml/min, the blood concentration of apixaban is raised and the risk of bleeding grows — caution is needed here;
- the medicine is not recommended for patients on dialysis;
- in severe hepatic impairment the medicine is not recommended; in mild and moderate impairment, Child-Pugh classes A and B, it is used with caution, and liver function tests are done before treatment begins;
- in antiphospholipid syndrome direct oral anticoagulants are not recommended: in patients with triple positivity, thrombotic recurrences on them occur more often;
- taking it together with antidepressants of the SSRI and SNRI groups, non-steroidal anti-inflammatory drugs, acetylsalicylic acid and P2Y12 inhibitors calls for caution — all of them raise the risk of bleeding in their own right.
The situation with acute coronary syndrome and percutaneous coronary intervention deserves attention of its own: experience with apixaban at the dose intended for atrial fibrillation alongside antiplatelet drugs in such patients is limited, and the decision is taken individually once haemostasis has been achieved. One more practical detail: routine monitoring of coagulation is not required with this medicine, and in that it differs from the vitamin K antagonists, where measuring the international normalised ratio regularly is part of the treatment.
Interaction with other medicines
Apixaban is metabolised by the CYP3A4 system and carried by P-glycoprotein, so only substances acting on both routes at once matter. Strong inhibitors of both — ketoconazole, for instance — double the exposure: with it the area under the curve rose 2-fold and the maximum concentration 1.6-fold, and the medicine is not recommended in patients treated systemically with such agents. Strong inducers work the other way: rifampicin reduced the area under the curve by about 54% and the maximum concentration by 42%; in the same series are phenytoin, carbamazepine, phenobarbital and St John's wort.
Everything that inhibits only one of the two routes, by contrast, does not change the dose. Amiodarone, clarithromycin, diltiazem, fluconazole, naproxen, quinidine and verapamil raise the concentration of apixaban to some degree, but no dose adjustment is needed with them. Nor were significant interactions found with antiplatelet drugs: neither acetylsalicylic acid at 325 mg a day, nor clopidogrel, nor its combination with aspirin, nor prasugrel lengthened bleeding time or deepened the inhibition of platelet aggregation beyond their own effect. That does not remove the need for caution — the bleeding risk still adds up — but it means that pharmacokinetics has nothing to do with it here.
Pregnancy and breastfeeding
There is no data on the use of apixaban in pregnant women. Animal studies showed no direct or indirect harmful effect on reproduction, but as a precaution its use in pregnancy is to be avoided. No effect on fertility was seen in animal studies either.
With breastfeeding the picture is clearer and more troubling. Whether apixaban passes into human milk is unknown, but in rats the ratio of the concentration in milk to that in plasma proved high — about 8 by maximum concentration and about 30 by area under the curve — which points to active transport into the milk. A risk to the child cannot be ruled out, so a decision is made on what to stop, the feeding or the treatment, weighing the benefit of each.
Adverse effects
An anticoagulant's main adverse reaction is single and obvious — bleeding, and it can happen anywhere. The practical consequence matters more than the list: an unexplained fall in haemoglobin or blood pressure should be taken as a reason to look for the source of bleeding rather than to wait for visible blood.
Of the rest, the more frequent are anaemia, nosebleeds, bruises and haematomas, blood in the urine, gastrointestinal and rectal bleeding, and nausea. Less often described are a fall in platelet count, hypersensitivity reactions, skin rash and itching, bleeding into the eye, haemoptysis, and bleeding from the gums and after procedures. The most dangerous is intracranial haemorrhage: it is rare, but it is precisely that which explains why an anticoagulant is prescribed only when the risk of thrombosis outweighs the risk of bleeding. Any severe bleeding, and the appearance of neurological symptoms during treatment, calls for immediate medical help.
Overdose
The medicine itself has no specific antidote, and an overdose means an increased risk of bleeding. Where bleeding occurs, treatment is stopped, the source is looked for and, if needed, surgical haemostasis is performed or fresh frozen plasma transfused. In controlled studies healthy volunteers took up to 50 mg a day for 3 to 7 days with no clinically significant adverse reactions.
Beyond that there are two practical options. The first is activated charcoal, and its effect has been measured: charcoal given 2 and 6 hours after 20 mg of apixaban reduced the mean area under the curve by 50% and 27% respectively, and the half-life fell from 13.4 hours to 5.3 and 4.9 hours. In other words, charcoal helps even several hours later. The second is an agent that reverses the action of factor Xa inhibitors, available where bleeding is life-threatening or uncontrolled; prothrombin complex concentrates or recombinant factor VIIa are also considered.
How to get a prescription for Poltixa online
With apixaban the dose is set by the indication: in joint replacement and in venous thrombosis it depends neither on age, nor on body weight, nor on moderate reduction of kidney function, while in atrial fibrillation those same features decide everything — two out of three and the dose halves. The doctor therefore needs to know exactly what the medicine is being prescribed for. 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 diagnosis and its date: atrial fibrillation, a past thrombosis, a pulmonary embolism, or joint surgery either planned or already done — both the dose and the duration depend on it. If it is atrial fibrillation, you must give your age, your body weight and your serum creatinine with the date of the test: those are precisely the three features. Provide your creatinine clearance and say whether you are on dialysis. Describe liver disease and any clotting disorder. List the bleeds, ulcers, operations on the brain, spine and eye, and head injuries you have had. Name your medicines separately: other anticoagulants, aspirin and clopidogrel, painkillers from the non-steroidal anti-inflammatory group, antidepressants, antifungals, HIV medicines, rifampicin, carbamazepine and St John's wort. And state any planned operations and dental procedures.
