Drug-Drug Interaction

SLT ANTICONVUL/SLT ANTINEOPLASTIC SYSTEMIC ENZYME INHIB

MECHANISM OF ACTION
Carbamazepine, phenobarbital, and phenytoin may induce the metabolism of dasatinib,(1) imatinib, (2) lapatinib,(3) nilotinib,(4) pazopanib,(5) sorafenib,(6) and sunitinib(7) by CYP P-450-3A4.

DISCUSSION
In a study in healthy subjects, concurrent rifampin (600 mg daily), another CYP P-450-3A4 inducer, decreased the maximum concentration (Cmax) and area-under-curve (AUC) of a single dose of dasatinib by 81% and 82%, respectively.(1)

CLINICAL EFFECTS
Concurrent use of carbamazepine, phenobarbital, or phenytoin may decrease the levels and effectiveness of dasatinib,(1) imatinib, (2) lapatinib,(3) nilotinib,(4) pazopanib,(5) sorafenib,(6) or sunitinib.(7)

SEVERITY LEVEL
2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

PATIENT MANAGEMENT
The US manufacturer of dasatinib states that alternative agents with less enzyme induction potential should be used in place of CYP P-450-3A4 inducers such as carbamazepine, phenobarbital, or phenytoin. If concurrent use is warranted, consider increasing the dose of dasatinib.(1)

PREDISPOSING FACTORS
None determined.

REFERENCES

1. Sprycel (dasatinib) US prescribing information. Bristol-Myers Squibb .Sprycel (dasatinib) US prescribing information. Bristol-Myers Squibb Company June, 2009.
2. Gleevec (imatinib mesylate) US prescribing information. Novartis .Gleevec (imatinib mesylate) US prescribing information. Novartis Pharmaceuticals Corporation September, 2008.
3. Tykerb (lapatinib) US prescribing information. GlaxoSmithKline January 29, .Tykerb (lapatinib) US prescribing information. GlaxoSmithKline January 29, 2010.
4. Tasigna (nilotinib) US prescribing information. Novartis Pharmaceuticals .Tasigna (nilotinib) US prescribing information. Novartis Pharmaceuticals Corporation August, 2009.
5. Votrient (pazopanib) US prescribing information. GlaxoSmithKline October, .Votrient (pazopanib) US prescribing information. GlaxoSmithKline October, 2009.
6. Nexavar (sorafenib) US prescribing information. Bayer Pharmaceuticals .Nexavar (sorafenib) US prescribing information. Bayer Pharmaceuticals Corporation November, 2007.
7. Sutent (sunitinib malate) US prescribing information. Pfizer Inc. October, .Sutent (sunitinib malate) US prescribing information. Pfizer Inc. October, 2008.