Fostemsavir Tromethamine: uses, dosing, side effects & brands

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.gov/medwatch. 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 (BRIGHTE) conducted in 371 heavily treatment-experienced adult subjects [see Clinical Studies ( 14 )] . In the randomized cohort, 203 subjects received at least one dose of blinded RUKOBIA 600 mg twice daily and 69…

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 ( 12.3 )] : o Androgen receptor inhibitor: Enzalutamide o Anticonvulsants: Carbamazepine, phenytoin o Antimycobacterial: Rifampin o Antineoplastic: Mitotane o Herbal product: St John’s wort ( Hypericum perforatum ) • Hypersensitivity to fostemsavir or any of the components of the formulation. ( 4 ) • Coadministration with strong cytochrome P450 (CYP)3A inducers as significant decreases in temsavir plasma concentrations may occur, which may result in loss of virologic response. ( 4 )

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 )] . When RUKOBIA was coadministered with oral contraceptives, temsavir increased concentrations of ethinyl estradiol ( Table 3 ) [see Drug Interactions ( 7.3 ), Clinical Pharmacology ( 12.3 )] . 7.2 Potential for Other Drugs to Affect RUKOBIA Coadministration of RUKOBIA with rifampin, a strong CYP3A4 inducer, significantly decreases temsavir plasma concentrations. The use of RUKOBIA with drugs that are strong inducers of CYP3A4 can significantly decrease temsavir plasma concentrations which may lead to loss of virologic response [see Contraindications ( 4 ), Drug Interactions ( 7.3 ), Clinical Pharmacology ( 12.3 )] . 7.3 Established and Other Potentially Significant Drug Interactions Information regarding potential drug interactions with RUKOBIA is provided in Table 3 . These recommendations are based on either drug interaction trials or predicted interactions due to the expected magnitude of interaction and potential for serious adverse events or loss of efficacy [see Contraindications ( 4 ), Warnings and Precautions ( 5.4 ), Clinical Pharmacology ( 12.3 )] . Table 3. Established and Other Potentially Significant Drug Interactions a ↑ = Increase; ↓ = Decrease; HCV = Hepatitis C virus. a This table is not all inclusive. b See Clinical Pharmacology ( 12.3 ) for magnitude of interaction. Concomitant Drug Class: Drug Name Effect on Concentration of Temsavir and/or Concomitant Drug Clinical Comment Androgen receptor inhibitor: Enzalutamide ↓Temsavir Coadministration is contraindicated due to potential for loss of therapeutic effect to RUKOBIA [see Contraindications ( 4 )] . Anticonvulsants: Carbamazepine Phenytoin ↓Temsavir Antimycobacterial: Rifampin b ↓Temsavir Antineoplastic: Mitotane ↓Temsavir Herbal product: St John’s wort ( Hypericum perforatum ) ↓Temsavir Hepatitis C virus direct-acting antivirals: Grazoprevir Voxilaprevir ↑Grazoprevir ↑Voxilaprevir Coadministration may increase exposures of grazoprevir or voxilaprevir; however, the magnitude of increase in exposure is unknown. Increased exposures of grazoprevir may increase the risk of ALT elevations. Use an alternative HCV regimen if possible. Oral contraceptive: Ethinyl estradiol b ↑Ethinyl estradiol Ethinyl estradiol daily dose should not exceed 30 mcg . Caution is advised particularly in patients with additional risk factors for thromboembolic events. Statins: Rosuvastatin b Atorvastatin Fluvastatin Pitavastatin Simvastatin ↑Rosuvastatin ↑Atorvastatin ↑Fluvastatin ↑Pitavastatin ↑Simvastatin Use the lowest possible starting dose for statins and monitor for statin-associated adverse events. 7.4 Drugs that Prolong QT Interval Coadministration of RUKOBIA with a drug with a known risk of Torsade de Pointes may increase the risk of Torsade de Pointes [see Warnings and Precautions ( 5.2 ), Clinical Pharmacology ( 12.2 )] . Use RUKOBIA with caution when coadministered with drugs with a known risk of Torsade de Pointes. 7.5 Drugs without Clinically Significant Interactions with RUKOBIA Based on drug interaction study results, the following drugs can be coadministered with RUKOBIA without a dose adjustment: atazanavir/ritonavir, buprenorphine/naloxone, cobicistat, darunavir/cobicistat, darunavir/ritonavir with and without etravirine, etravirine, famotidine, maraviroc, methadone, norethindrone, raltegravir, ritonavir, rifabutin with and without ritonavir, tenofovir disoproxil fumarate [see Clinical Pharmacology ( 12.3 )] .