UGT1A1 is an enzyme that breaks down medicines and also removes a substance called bilirubin from the body. Bilirubin is made in the body when red blood cells break down through a natural process.
Some people have a genetic tendency to make low levels of UGT1A1; these people may need a lower dose of certain medications because the low level of UGT1A1 puts them at risk for unusually high levels of some medications, or the low level of UGT1A1 means that their bilirubin levels get unusually high when they take certain medicines.
Some medicines may interfere with UGT1A1’s ability to do its job at getting rid of bilirubin. One such medicine is atazanavir. Atazanavir stops UGT1A1 from removing bilirubin from the body. As a result, people who take atazanavir may have higher levels of bilirubin in their blood, which can lead to yellowing of the eyes and skin. The medical word for this is “jaundice.” Although this effect may cause some people to worry about their appearance, this effect is usually not harmful and goes away when atazanavir is stopped. Like many medicines, how well atazanavir works and its side effects can be different from person to person.
Patients can be divided into 3 genotype metabolizer categories based on the function of UGT1A1; this information is used by clinicians to help guide drug therapy decisions.
- Poor metabolizers – These patients have decreased UGT1A1 enzyme (30% of normal function) and may require different medicines or different doses of medicines. This genotype is generally indicative of Gilbert syndrome (for more information, please see http://ghr.nlm.nih.gov/condition/gilbert-syndrome). About 15 in 100 people fall into this category.
- Drugs that may need to be avoided:
- Atazanavir. Consider using an alternative regimen that does not contain atazanavir, particularly if jaundice would be of concern to the patient.
- Another drug, irinotecan, may require a dose adjustment if used at doses above 250 mg/m2/dose. At St. Jude, we do not routinely use such high doses; therefore dose adjustment based on UGT1A1 function is usually not required.
- Drugs that may need to have their doses decreased:
- Belinostat: If belinostat is used in a patient who is a UGT1A1 poor metabolizer, a dose reduction from the normal dose may be necessary.
- Drugs that may need to be avoided:
- Normal metabolizers – These patients have normal working UGT1A1 enzyme. No changes to prescribing are needed based on this result. About 50 in 100 people fall in this category.
- Intermediate metabolizers – These patients have slightly reduced UGT1A1 enzyme function. Currently, there are no known changes to prescribing are needed based on this result. About 40 in 100 people fall in this category.
More information for patients
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