Lorbrena and Rifampin Oral, Intravenous

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Using lorlatinib together with rifAMPin is not recommended. RifAMPin may significantly reduce the blood levels of lorlatinib, which may make the medication less effective in treating your cancer. In addition, combining these medications may increase the risk of liver problems. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

CONTRAINDICATED: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of lorlatinib, which has been found to be metabolized primarily by CYP450 3A4 and UGT1A4 in vitro. In addition to the potential for diminished efficacy of lorlatinib, the risk of serious hepatotoxicity may be increased due to activation of the pregnane X receptor (PXR) by both lorlatinib and CYP450 3A4 inducers. When a single 100 mg oral dose of lorlatinib was administered to 12 healthy volunteers on day 8 of treatment with the potent CYP450 3A4 inducer rifampin (600 mg once daily for 8 days), mean lorlatinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 76% and 85%, respectively. The AUC of the two active metabolites also decreased--one by 92% and the other by 59%. Severe hepatotoxicity was reported in 10 of the 12 subjects, with Grade 4 alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations occurring in 50% of subjects, Grade 3 elevations in 33% of subjects, and Grade 2 elevations in 8% of subjects. ALT or AST elevations occurred within 3 days and returned to within normal limits within 7 to 34 days (median 15 days). The median time to recovery was 18 days in subjects with Grade 3 or 4 elevations and 7 days in subjects with Grade 2 elevations.

MANAGEMENT: Concomitant use of lorlatinib with potent CYP450 3A4 inducers is considered contraindicated. Lorlatinib should not be initiated until after discontinuation of potent CYP450 3A4 inducers for at least 3 plasma half-lives.

Lorbrena

Generic Name: lorlatinib

Brand name: Lorbrena

Synonyms: n.a.

What is Lorbrena?

Rifampin Oral, Intravenous

Generic Name: rifampin

Brand name: Rifadin, Rifadin IV, Rimactane

Synonyms: Rifampin

What is Rifampin Oral, Intravenous?