Xarelto liver damage: a new threat for Atrial Fibrillation patients

Cirrhosis of the liver (trichrome stain) - Photo by: Ed Uthman - Source: Flickr Creative CommonsCirrhosis of the liver (trichrome stain) - Photo by: Ed Uthman - Source: Flickr Creative Commons

Xarelto liver damage can be a serious threat associated with this drug, and recent findings indicate that this drug could be even more dangerous that it was thought to be.

One of the most controversial medications of the last few years is Xarelto (rivaroxaban), a new generation blood-thinner from the Novel Oral Anticoagulants category (NOACs), produced by Johnson & Johnson and Bayer AG. Rivaroxaban is used to prevent the risk of pulmonary embolism and stroke in patients suffering from atrial fibrillation, and to reduce the chance of formation of blood clots in patients who underwent knee or hip replacement surgery. The central issue that contributed to Xarelto’s negative reputation is the lack of a proper antidote to reverse its potentially fatal side effects. Just like its counterparts Pradaxa and Eliquis in fact, Xarelto can cause severe internal bleedings and gastrointestinal hemorrhages that if not properly treated, can seriously harm a patient or even cause his death. However, unlike other commonly available anticoagulants such as Warfarin, the lack of reversing agents such as Vitamin K or fresh platelet transfusion make Xarelto a dangerous drug whenever an uncontrollable bleeding event occurs.

However, a recently published post-marketing investigation showed that rivaroxaban side effects may include other life-threatening adverse reactions such as the risk of liver damage and liver failure. Although several studies in the past highlighted a concerning association between Xarelto and liver damage, a new study published in the British Journal of Clinical Pharmacology last August showed an alarming number of adverse event reports, including many acute liver failure events (ALF) . The analysis included the results extracted from three large international pharmacovigilance databases, and searched for rivaroxaban adverse reactions that caused any form of hepatic damage. Researchers from the Italian University of Bologna explained in their paper that “the disproportionality signal for rivaroxaban calls for further comparative population-based studies to characterize and quantify the actual drug-induced liver injury (DILI) risk of NOACs”.

 

How Xarelto damages your liver?

Liver damage is the third most reported adverse reaction associated with Xarelto, just after gastrointestinal bleeding and internal hemorrhage. Xarelto liver injuries can be spotted when the plasma levels of the liver enzymes AST and ALT (transaminase) increase over the upper limit of normal (ULN). Findings from a 4 RECORD analysis, showed that how of the 6183 patients treated with Xarelto, 2.33% of them had elevated transaminase levels, up to three times higher than the ULN. The record is also called Regulation of Coagulation in Major Orthopedic Surgery Reducing the Risk of Deep Venous Thrombosis and Pulmonary Embolism. More studies pointed to a potential hepatotoxicity of this drug, clearly indicating that Xarelto’s safety profile may need a prompt re-evaluation from the US Food and Drugs Administration (FDA).

The possible rivaroxaban liver injuries could further pose the patient’s lives at risk. Almost 70% of the drug dose administered orally is, in fact, eliminated in the bile or urines after an intense liver metabolization. Whenever the liver is injured, and its function is reduced, however, the actual quantity of circulating drug may increase, as one of main selling points of Xarelto is its lack of blood monitoring. Unlike Warfarin, it was widely advertised in internet and TV ads how there’s no need to check Xarelto levels to adjust its dosage appropriately. For this reason, if the liver fails to eliminate the medication, it will slowly accrue without no one noticing, actually increasing the risk of an uncontrollable bleeding event.

Xarelto’s drug label does not include any warnings regarding symptomatic liver damage, although it’s mandatory that physicians as well as patients and should be adequately informed about this serious threat.

 

Article by Dr. Claudio Butticè, PharmD.

REFERENCES

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