Cobicistat Tablets

TYBOST is a CYP3A inhibitor indicated to increase systemic exposure of atazanavir or darunavir (once daily dosing regimen) in combination with other antiretroviral agents in the treatment of HIV-1 infection [see DOSAGE AND ADMINISTRATION].

Limitations Of Use

• TYBOST is not interchangeable with ritonavir to increase systemic exposure of darunavir 600 mg twice daily, fosamprenavir, saquinavir, or tipranavir due to lack of exposure data. The use of TYBOST is not recommended with darunavir 600 mg twice daily, fosamprenavir, saquinavir, or tipranavir [see WARNINGS AND PRECAUTIONS].
• Complex or unknown mechanisms of drug interactions preclude extrapolation of ritonavir drug interactions to certain TYBOST interactions. TYBOST and ritonavir when administered with either atazanavir or darunavir may result in different drug interactions when used with concomitant medications [see WARNINGS AND PRECAUTIONS , DRUG INTERACTIONS and CLINICAL PHARMACOLOGY].

Included as part of the "PRECAUTIONS" Section

The following adverse reaction is described in greater detail in another section of the labeling:

• New Onset or Worsening Renal Impairment When Used with Tenofovir Disoproxil Fumarate [see WARNINGS AND PRECAUTIONS]

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 to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of TYBOST is based on Week 144 data from a Phase 3 trial, Study 114, in which 692 HIV-1 infected, antiretroviral treatment-naive subjects received:

• TYBOST coadministered with atazanavir and tenofovir DF/emtricitabine(administered as TRUVADA) (N=344) or;
• ritonavir coadministered with atazanavir and tenofovir DF/emtricitabine (administered as TRUVADA) (N=348).

The most common adverse reactions (Grades 2-4) and reported in >5% of subjects in the TYBOST group were jaundice (6%) and rash (5%). The proportion of subjects who discontinued study treatment due to adverse events, regardless of severity, was 11% in both the TYBOST and ritonavir groups. Table 3 displays the frequency of adverse reactions (Grades 2-4) occurring in at least 2% of subjects in the TYBOST group in Study 114.

Table 3 Selected Adverse Reactionsa (Grades 2-4) Reported in ≥2% of HIV-1 Infected Treatment-Naive Adults in the TYBOST Coadministered with Atazanavir Group in Study 114 (Week 144 Analysis)

Selected adverse reactions of at least moderate severity (≥Grade 2) occurring in less than 2% of subjects receiving TYBOST coadministered with atazanavir and TRUVADA are listed below. These events have been included because of the investigator’s assessment of potential causal relationship and were considered serious or have been reported in more than one subject treated with TYBOST and with greater frequency compared with ritonavir.

Gastrointestinal Disorders: vomiting, upper abdominal pain

General Disorders and Administration Site Conditions: fatigue

Musculoskeletal and Connective Tissue Disorders: rhabdomyolysis

Psychiatric Disorders: depression, abnormal dreams, insomnia

Renal and Urinary Disorders: nephropathy, Fanconi syndrome acquired, nephrolithiasis

Refer to the prescribing information for atazanavir or darunavir for information regarding adverse reactions with these drugs.

The frequency of laboratory abnormalities (Grades 3-4) occurring in at least 2% of subjects in the TYBOST group in Study 114 is presented in Table 4.

Table 4 Laboratory Abnormalities (Grades 3-4) in ≥2% of HIV-1 Infected Treatment-Naive Adults in the TYBOST Coadministered with Atazanavir Group in Study 114 (Week 144 Analysis)

TYBOST causes increases in serum creatinine and decreases in estimated creatinine clearance due to inhibition of tubular secretion of creatinine without affecting actual renal glomerular function [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]. In Study 114, increases in serum creatinine and decreases in estimated creatinine clearance occurred early in treatment with TYBOST, after which they stabilized. The mean (± SD) change in estimated glomerular filtration rate (eGFR) by Cockcroft-Gault method after 144 weeks of treatment was .15.1 ± 16.5 mL/min in the TYBOST group and .8.0 ± 16.8 mL/min in the ritonavir group.

Changes from baseline in total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides are presented in Table 5. In both groups, mean values for serum lipids remained within the study reference range for each laboratory test. The clinical significance of these changes is unknown.

Table 5 Lipid Values, Mean Change from Baseline, Reported in HIV-1 Infected Treatment-Naive Adults Receiving TYBOST Coadministered with Atazanavir + TRUVADA or Ritonavir Coadministered with Atazanavir

Read the entire FDA prescribing information for Tybost (Cobicistat Tablets)