RUKOBIA (fostemsavir tromethamine)

Fostemsavir is a prodrug of temsavir, its active moiety. Fostemsavir was generally not detectable in plasma following oral administration. However, temsavir was readily absorbed ( Table 4 ). Following oral administration, increases in plasma temsavir exposure (C max and AUC tau ) appeared dose proportional or slightly greater than dose proportional, over the range of 600 mg to 1,800 mg of RUKOBIA. The pharmacokinetics of temsavir following administration of RUKOBIA are similar between healthy an...

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. A total of 620 subjects with HIV-1 infection received at least one dose of RUKOBIA as part of a controlled clinical trial. The primary safety assessment of RUKOBIA is based on 96 weeks of data from a Phase 3 partially randomized, international, multicenter, double-blind, placebo-controlled trial (BRIGH...

The following adverse reactions are discussed in greater detail in other sections of the labeling:

• Immune reconstitution syndrome [see Warnings and Precautions ( 5.1 )] .
• QTc prolongation [see Warnings and Precautions ( 5.2 )] .
• Elevations in hepatic transaminases in patients with hepatitis B or C virus co-infection [see Warnings and Precautions ( 5.3 )]. The most common adverse reaction (all grades) observed in ≥5% of subjects was nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, con...

RUKOBIA is contraindicated in patients:

• with previous hypersensitivity to fostemsavir or any of the components of RUKOBIA.
• coadministered strong cytochrome P450 (CYP)3A inducers, as significant decreases in temsavir (the active moiety of fostemsavir) plasma concentrations may occur which may result in loss of virologic response. These drugs include, but are not limited to [see Drug Interaction...

• Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapies. ( 5.1 )
• QTc prolongation: Use RUKOBIA with caution in patients with a history of QTc prolongation or with relevant pre-existing cardiac disease or who are taking drugs with a known risk of Torsade de Pointes. ( 5.2 )
• Elevations in hepatic transaminases in patients with hepatitis B (HBV) or C (HCV) virus co-infection: Elevations in hepatic transaminases were observed in a greater ...

7 DRUG INTERACTIONS

• See full prescribing information for complete list of significant drug interactions. ( 4 , 7 )
• Doses of oral contraceptives should not contain more than 30 mcg of ethinyl estradiol per day. ( 7.3 ) 7.1 Potential for RUKOBIA to Affect Other Drugs Temsavir may increase plasma concentrations of grazoprevir or voxilaprevir to a clinically relevant extent due to organic anion tr...