Overview
11 DESCRIPTION Fostemsavir tromethamine is a prodrug of temsavir, an HIV-1 gp120-directed attachment inhibitor. The chemical name of fostemsavir tromethamine is (3-((4-benzoyl-1-piperazinyl)(oxo)acetyl)-4-methoxy-7-(3-methyl-1 H -1,2,4-triazol-1-yl)-1 H -pyrrolo[2,3-c]pyridin-1-yl)methyl dihydrogen phosphate, 2-amino-2-(hydroxymethyl)-1,3-propanediol (1:1).
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action RUKOBIA is an HIV-1 antiretroviral agent [see Microbiology ( 12.4 )]. 12.2 Pharmacodynamics Cardiac Electrophysiology At therapeutic doses, RUKOBIA does not prolong the QT interval to any clinically relevant extent. At 4 times the recommended dose, the mean (upper 90% confidence interval) QTcF increase was 11.2 milliseconds (13.3 milliseconds). The observed increase in QTcF was temsavir concentration-dependent [see Warnings and Precautions ( 5.2 )] . Exposure-Response Relationship In the Phase 3 trial evaluating the recommended dosing regimen of RUKOBIA (600 mg twice daily) in subjects with multidrug resistant HIV-1 infection on their failing regimen, no relationship was observed between plasma temsavir C trough and change in plasma HIV-1...
Indications
- 1 INDICATIONS AND USAGE RUKOBIA, in combination with other antiretroviral(s), is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in heavily treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen due to resistance, intolerance, or safety considerations [see Clinical Studies ( 14 )]. RUKOBIA, a human immunodeficiency virus type 1 (HIV-1) gp120-directed attachment inhibitor, in combination with other antiretroviral(s), is indicated for the treatment of HIV-1 infection in heavily treatment-experienced...
Common Doses
- Refer to label
Dosage
2 DOSAGE AND ADMINISTRATION The recommended dosage of RUKOBIA is one 600-mg tablet taken orally twice daily with or without food [see Clinical Pharmacology ( 12.3 )] . Swallow tablets whole. Do not chew, crush, or split tablets. One tablet taken twice daily with or without food. ( 2 )
Contraindications
- 4 CONTRAINDICATIONS 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 Interactions ( 7 ), Clinical Pharmacology ( 12.
Side Effects
- 6 ADVERSE REACTIONS 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, contact ViiV Healthcare at 1-877-844-8872 or FDA at 1-800-FDA-1088 or www.fda.
Interactions
- 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 transporting polypeptide (OATP)1B1/3 inhibition [see Drug Interactions ( 7.3 )] .