Question

My bilirubin levels are 80 mmol/L on atazanavir – what can I do?

11 July 2012. Related: All topics, Side effects.

In the section on yellowing from bilirubin/atazanavir you mention that levels are dangerous when four times higher than normal and that drugs should be changed after that. Mine is at 80 mmol/l.

I drink 3 litres of water a day as suggested by my doctor but I still have significant yellowing in my eyes. Other than this side-effect I tolerate this regime better than any other I’ve been on.

Can you tell me what type of damage/ danger these high levels bring?

Before I considering changing regime is there anything I can try to lessen the effects?

More water? Being out in the sun? Cutting out alcohol? time of eating/taking meds? anything else that might help?

Answer

Answer: Simon Collins

Hi

Thanks for your question and for allowing us to post the answer online.

The increased bilirubin caused by atazanavir is apparently just a dye. It is not causing toxicity at levels higher than 5 times the upper limit of normal (5xULN). I have modified the online text to make this clearer.

The 5xULN is used for modifying treatment because, by this level, the yellowing eyes and skin, is likely to be cosmetically more difficult to live with.
Drinking additional water is unlikely to help as this type of bilirubin is insoluble in water. The dye only affects fatty tissue – ie the eyes and skin.

This may be related to your genetics. Some genes (in the UGT1A1 enzyme) have been linked to higher atazanavir levels because they slow down how atazanavir is cleared from your body. While testing for this gene is difficult – it is really a research tool – you can test you atazanavir levels and look at whether you can safely modify the dose. For the 5-10% of people with this gene, a lower atazanavir dose is easy can safe.

Ask your doctor for a drug level test. This is sometimes called TDM (therapeutic drug monitoring). The lab will take a blood sample and will need to know the time you took your last dose.

Also, are you currently using 100 mg with a 300 mg dose of atazanavir? Although this is the recommended dose, using TDM you can find a dose that is individualised to your own metabolism.

Some people are able to use a 400 mg atazanavir dose, without needing ritonavir, and lots of other options are available, but only confirming the dose with TDM results after as well as before the change.

As you are tolerating the combination better than other drugs, these other things you can do are easy (if you live in the UK) and important.

This link is to a medical review of increased bilirubin related to atazanavir (sorry that the language is technical).

This link is to information about genetics and side effects and this one is to TDM and drug levels.

This article reports the use of TDM specifically for people using atazanavir (again, sorry it is technical, but perhaps also take this to your doctor).