GIST Support Wiki

 
Gleevec Interactions

GLEEVEC IS METABOLIZED IN THE LIVER BY CYP3A4. This is the basis for most interactions, if CYP3A4 is affected by other drugs or foods. A pharmacist can use computer programs available to pharmacists to check whether other drugs would interact with Gleevec.

The NCCN Task Force Report on GIST Management includes a table of Gleevec interactions on pages S12-S13. Download the pdf at the above link to read this. This table does not name every possible interaction.

The Gleevec prescribing information from Novartis also details some interactions. Go to Gleevec.com and click "prescribing information" at the top of the screen.



Contents

GRAPEFRUIT, POMEGRANATE, OTHER CITRUS FRUIT

Due to the metabolism of Gleevec, Novartis recommends that grapefruit and grapefruit juice be avoided by patients taking Gleevec.

The new NCCN Task Force Report mentions grapefruit juice and names a quantity of 200-250 ml as increasing blood levels of Gleevec. That is over 3/4 cup of juice. A smaller quantity might not raise Gleevec levels much.

Grapefruit juice INHIBITS the liver enzyme (CYP3A4) that processes Gleevec. If you eat a lot of grapefruit then Gleevec stays in your blood LONGER. It does not decrease the effectiveness of Gleevec, as it raises the blood levels of Gleevec. This could potentially increase side effects. However, if you have no trouble with side effects, then it would not seem that popping the occasional strawberry, grapefruit section, or 1/4 cup of pomegranate juice would hurt...

Tangelos are a hybrid of grapefruit and mandarin orange: Some doctors say to stay away from Tangelos. There have been several studies, one being the USDA Agricultural Research Service, "....have so far shown that unlike grapefruit, interactions with STATINS are not likely with tangelos, even though it is derived from a grapefruit crossed with a tangerine. This is apparently because the furocoumarins in grapefruit are not expressed in tangelo. "

http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=175058

POMEGRANATE juice also affects CYP3A, but not in exactly the same way as grapefruit. For some medical papers discussing pomegranate efects on drug disposition see this PubMed search.


ST. JOHN'S WORT

ON THE OTHER HAND, St. John's wort does the opposite, increasing enzyme activity to get Gleevec out of the body faster. Therefore, it is a clear no-no since it decreases blood levels of Gleevec, thereby decreasing the drug's effectiveness.


STATIN DRUGS

Gleevec raises the level of statins in the blood. Patients who take statins with Gleevec need to be very cautious, as very serious side effects such as muscle damage (rhabdomyolysis) may result from excess statins. Statin dose should be reduced when taking Gleevec. Discuss this with your pharmacist and doctors.


MILK THISTLE

Caution! Milk thistle decreases the activity of CYP3A4, which is the major enzyme responsible for the metabolism of Gleevec and Sutent. DO NOT take milk thistle while on these drugs and check with your doctor if on other drugs.