All About Gleevec (Glivec)

General Information | Response Rate & Related Exon Mutations
Dosage | Side Effects | Drug Interactions

Drug Interactions

Other drugs affect Gleevec | Gleevec affects other drugs
Long list of inhibitors and inducers | Drug interaction glossary

Other drugs affect Gleevec drug concentrations

In addition to the intended affects, many drugs have an effect on how quickly other drugs are metabolized by the liver. This is one type of drug interaction, but not the only type.
Gleevec is metabolized (broken down) by the liver. The enzyme most responsible for this is called CYP3A4 (one part of the "cytochrome P450" family of liver enzymes). The next most important enzyme for metabolizing Gleevec is CYP2D6.

Drugs that inhibit the activity/production of these two enzymes (but especially CYP3A4) slow down the metabolism of Gleevec. This results in a higher concentration of Gleevec in the blood. The could result in more side effects from Gleevec; similar to taking a higher dose of Gleevec. This would be more of a concern for patients already taking a high dose of Gleevec especially if they were already having significant Gleevec side effects.
For patients on a lower dose of Gleevec that were having few or no side effects, then taking a drug that might "inhibit" CYP3A4 or CYP2D6 would probably have less effects, and perhaps not even be noticed.

Drugs that may alter Gleevec plasma concentrations NOTE: Sutent is also metabolized by CYP3A4 and is affected by drugs that induce or inhibit CYP3A4. (This is a "short list")
Major Inducers of CYP3A4	Major Inhibiters of CYP3A4
Reduce Gleevec levels	Increase Gleevec levels
May result in sub-therapeutic levels of Gleevec	May result in above normal levels of Gleevec
May be more of a concern for lower doses of Gleevec	May be more of a concern for higher doses of Gleevec
CYP3A4 inducers (short list) long list	CYP3A4 inhibitors (short list) long list
St. John’s Wart Phenytoin Dexamethasone Carbamazepine Rifampin Phenobarbital	Ketoconazole Itraconazole Erythromycin Clarithromycin Grapefruit juice

People also metabolize drugs at different rates. Given the vast amount of differences that can occur, it is critical to clinically monitor patients and adjust dosages of medicines as needed. This is a job for your doctor, but patients also need to keep their doctor informed of side effects. How you feel may be just as important as whether or not the drug you are taking appears on the CYP3A4 or CYP2D6 INHIBITOR lists.

A different situation exists when taking a drug that could INDUCE CYP3A4 or CYP2D6. In this case, the drug might cause Gleevec to be metabolized faster, possibility resulting in AN INEFFECTIVE AMOUNT OF GLEEVEC IN THE BLOOD. In the worst case scenario, you could stop responding to Gleevec. The danger of this type of interaction is probably higher for patients taking a lower dose of Gleevec since they are closer to the minimum therapeutic levels of Gleevec, and taking a drug that increases Gleevec metabolism might result in Gleevec levels being below the minimum needed to keep GIST (or CML) under control. Patients on higher doses of Gleevec are not immune to this problem either, as at least one drug, phenytoin, reduced plasma levels of Gleevec by 75% in a CML patient.
Your body will be more likely to give you some indication of a problem with the drugs on the inhibitor list, due to an increase in side effects. Drugs that induce CYP3A4 or CYP2D6 may be less likely to produce side effects, since they tend to lower the concentration of Gleevec in the blood.

More information can be found at: www.drug-interactions.com

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