Kaletra and Norvir: drug-drug interaction updates

December 19, 2019 The KALETRA (lopinavir and ritonavir) capsule, tablet and oral solution label was updated to include the following drug-drug interaction changes. Similar changes were made to the NORVIR (ritonavir) capsules, tablets, oral powder and oral solution labels. Below is a summary of the changes to the KALETRA label. Section 4: CONTRAINDICATIONS Addition of apalutamide to the list of drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening reactions Section 7: DRUG INTERACTIONS 7.1  Potential for KALETRA to Affect Other Drugs Addition of language stating “These examples are a guide and not considered a comprehensive list of all possible drugs that may interact with lopinavir/ritonavir. The healthcare provider should consult appropriate references for comprehensive information. 7.3  Established and Other Potentially Significant Drug Interactions, Table 12, Established and Other Potentially Significant Drug Interactions was updated as follows Anticancer drugs: Apalutamide is contraindicated due to potential for loss of virologic response and possible resistance to KALETRA or to the class of protease inhibitors Avoid co-administration of encorafenib or ivosidenib with KALETRA due to potential risk of serious adverse events such as QT interval prolongation. If co-administration of encorafenib with KALETRA cannot be avoided, modify dose as  recommended in encorafenib USPI. If co-administration of ivosidenib with KALETRA cannot be avoided, reduce ivosidenib dose to 250 mg once daily. GnRH Receptor Antagonists: elagolix Concomitant use of elagolix 200 mg twice daily and KALETRA for more than 1 month is not recommended due to potential risk of adverse events such as bone loss and hepatic transaminase elevations. Limit concomitant use of elagolix 150 mg once daily and KALETRA to 6 months      Kinase Inhibitors: fostamatinib Monitor for toxicities of fostamatinib metabolite R406 such as hepatotoxicity and neutropenia. Fostamatinib dose reduction may be required.

The updated labels will soon be available at Drugs@FDA or DailyMed Kimberly Struble Division of Antivirals Food and Drug Administration Elizabeth Thompson Division of Antivirals Food and Drug Administration Michael Stanfield Jr. Division of Antivirals Food and Drug Administration