TYBOST SIDE EFFECTS
- Generic Name: cobicistat tablets
- Brand Name: Tybost
- Drug Class: CYP450 Inhibitors
SIDE EFFECTS
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
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.
Adverse Reactions From Clinical Trials Experience In Adults
The safety of TYBOST is based on Week 144 data from a Phase 3 trial, Trial 114, in which 692 HIV-1 infected, antiretroviral treatment-naïve subjects received:
- TYBOST coadministered with atazanavir and TDF/emtricitabine (administered as TRUVADA) (N=344) or
- ritonavir coadministered with atazanavir and TDF/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 Trial 114.
Table 1- Selected Adverse Reactionsa (Grades 2−4) Reported in ≥2% of HIV-1 Infected Treatment-Naïve Adults in the TYBOST Coadministered with Atazanavir Group in Trial 114 (Week 144 Analysis)
| TYBOST Coadministered with Atazanavir + TRUVADA N=344 |
Ritonavir Coadministered with Atazanavir + TRUVADA N=348 |
|
| Jaundice | 6% | 3% |
| Rashb | 5% | 4% |
| Ocular icterus | 4% | 2% |
| Nausea | 2% | 2% |
| Diarrhea | 2% | 1% |
| Headache | 2% | 1% |
| a. Frequencies of adverse reactions are based on Grades 2−4 adverse events attributed to study drugs. b. Rash events include dermatitis allergic, drug hypersensitivity, pruritus generalized, eosinophilic pustular folliculitis, rash, rash generalized, rash macular, rash maculo-papular, rash morbilliform, rash papular, and urticaria. |
||
Less Common Adverse Reactions
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.
Laboratory Abnormalities
The frequency of laboratory abnormalities (Grades 3−4) occurring in at least 2% of subjects in the TYBOST group in Trial 114 is presented in Table 2.
Table 2- Laboratory Abnormalities (Grades 3−4) in ≥2% of HIV-1 Infected Treatment-Naïve Adults in the TYBOST Coadministered withs Atazanavir Group in Trial 114 (Week 144 Analysis)
| TYBOST + Atazanavir + TRUVADA | Ritonavir + Atazanavir + TRUVADA | |
| Laboratory Parameter Abnormality | N=344 | N=348 |
| Total Bilirubin (>2.5 × ULN) | 73% | 66% |
| Creatine Kinase (≥10.0 × ULN) | 8% | 9% |
| Urine RBC (Hematuria) (>75 RBC/HPF) | 6% | 3% |
| ALT (>5.0 × ULN) | 6% | 3% |
| AST (>5.0 × ULN) | 4% | 3% |
| GGT (>5.0 × ULN) | 4% | 2% |
| Serum Amylasea (>2.0 × ULN) | 4% | 2% |
| Urine Glucose (Glycosuria) (≥1000 mg/dL) | 3% | 3% |
| Neutrophils (<750/mm3) | 3% | 2% |
| Serum Glucose (Hyperglycemia) (>250 mg/dL) | 2% | 2% |
| a. For subjects with serum amylase >1.5 × upper limit of normal, lipase test was also performed. The frequency of increased lipase (Grades 3−4) occurring in the TYBOST (N=46) and ritonavir (N=35) groups was 7% and 3%, respectively. | ||
Increase in Serum Creatinine
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. In Trial 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.
Serum Lipids
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 3- Lipid Values, Mean Change from Baseline, Reported in HIV-1 Infected Treatment-Naïve Adults Receiving TYBOST Coadministered with Atazanavir + TRUVADA or Ritonavir Coadministered with Atazanavir + TRUVADA in Trial 114 (Week 144 Analysis)
| TYBOST + Atazanavir + TRUVADA | Ritonavir + Atazanavir + TRUVADA | |||
| Baseline | Week 144 | Baseline | Week 144 | |
| mg/dL | Change from baselinea | mg/dL | Change from baselinea | |
| Total Cholesterol (fasted) | 163 [N=219] |
+11 [N=219] |
165 [N=227] |
+13 [N=227] |
| HDL-cholesterol (fasted) | 43 [N=218] |
+7 [N=218] |
43 [N=228] |
+6 [N=228] |
| LDL-cholesterol (fasted) | 102 [N=218] |
+11 [N=218] |
104 [N=228] |
+16 [N=228] |
| Triglycerides (fasted) | 130 [N=219] |
+14 [N=219] |
131 [N=227] |
+14 [N=227] |
| a. The change from baseline is the mean of within-patient changes from baseline for patients with both baseline and Week 144 values. Analysis excludes subjects receiving an HMG-CoA reductase inhibitor drug. | ||||
Adverse Reactions From Clinical Trials Experience In Pediatric Subjects
The safety of TYBOST was evaluated in HIV-1 infected virologically suppressed pediatric subjects between the ages of 12 to less than 18 years through Week 48 in an open-label clinical trial (Trial 128) of TYBOST coadministered with atazanavir (N=14) or darunavir (N=7) plus two nucleoside reverse transcriptase inhibitors. In this trial, the safety profile of TYBOST was similar to that in adults.
SRC: NLM .