Use of SYMTUZA in Patients with Renal Impairment

SUMMARY

• SYMTUZA should not be initiated in patients who have an estimated glomerular filtration rate according to the Cockcroft-Gault formula for creatinine clearance (eGFR_CG) below 30 mL/min.¹
• SYMTUZA should be discontinued in patients with eGFR_CG that declines below 30 mL/min during treatment.¹
• No dosage adjustment of SYMTUZA is required in patients with an eGFR_CG of 30 mL/min or greater.¹
• Due to extensive protein binding, it is unlikely that darunavir (DRV) or cobicistat (COBI) would be removed by hemodialysis (HD) or peritoneal dialysis (PD).¹
• Emtricitabine (FTC) can be removed by HD, which removes approximately 30% of the dose over a 3 hour dialysis period starting within 1.5 hours of FTC dosing.¹
• Tenofovir (TFV) is removed by HD with an extraction coefficient of approximately 54%.¹
• It is not known if FTC or TFV can be removed by PD.¹
• There are no studies conducted with the single-tablet regimen (STR) SYMTUZA in patients undergoing HD or PD.
• A case report of a patient undergoing HD who was receiving DRV 800 mg + COBI 150 mg QD found no significant difference in trough levels on days with and without HD.²
• The pharmacokinetics (PK) of the single-tablet regimen (STR) elvitegravir (EVG) 150 mg/COBI 150 mg/FTC 200 mg/tenofovir alafenamide (TAF) 10 mg (which contains 3 of the 4 components of SYMTUZA) was evaluated in adult patients with mild or moderate renal impairment or end-stage renal disease (ESRD) receiving HD.^3,4
  • In both patient populations, the PK of COBI and TAF were consistent with historical data in HIV-infected patients with normal renal function.
  • Increases in both FTC and TFV exposures were observed, but no increase in adverse effects was reported.

CLINICAL STUDIES with symtuza

• The phase 3 registrational trials AMBER and EMERALD included 202 patients with estimated glomerular filtration rate (eGFR) 70 to <90 mL/min, 55 patients with eGFR 50 to <70 mL/min, and 3 patients with eGFR <50 mL/min who received SYMTUZA. The data from these subjects did not suggest any safety concerns.⁵

CLINICAL STUDIES with components of symtuza

Kobayashi et al (2021)² described in a case report from Japan the PK of DRV and COBI in a male patient in his 40s who was undergoing HD.

• The patient was receiving DRV 800 mg + COBI 150 mg + doravirine 100 mg once daily after breakfast. Drug concentrations for PK analysis were obtained on days 47, 54, and 82.
• Drug concentrations were measured at 4 timepoints:
  • A) trough on the day of HD
  • B) before HD (1-hour post-dose)
  • C) after HD (5 hours post-dose)
  • D) trough on the day after HD
• Data for DRV and COBI are presented in Table: PK of DRV and COBI Before and After Hemodialysis.
• Trough concentrations of DRV and COBI did not differ significantly on days with and without HD (P=0.44 and P=0.96, respectively).

Data from STR EVG/COBI/FTC/TAF Studies

• The PK of COBI, FTC, and TFV were evaluated in studies using the STR EVG 150 mg/COBI 150 mg/FTC 200 mg/TAF 10 mg in virologically suppressed HIV-1 infected adult patients with mild or moderate renal impairment (estimated CrCL between 30-69 mL/min by Cockcroft-Gault method), and in patients with ESRD (estimated CrCL of less than 15 mL per minute by Cockcroft-Gault method) receiving chronic HD who were enrolled in 2 respective open-label trials, Gilead study GS-US-292-0112 and Gilead study GS-US-292-1825.^3,4
  • In both patient populations, the PK of COBI and TAF were consistent with historical data in HIV-infected patients with normal renal function.^3,4
  • However, the PK of FTC and TFV were affected (see Table: PK of FTC and TFV in Adults with Normal Renal Function Compared to Patients with Renal Impairment and Patients with ESRD Receiving Chronic Hemodialysis).^3,4
  • Increases in FTC and TFV exposures were observed in patients with mild-moderate renal impairment.³
    • A comparison of FTC adverse reactions performed by baseline CrCL found no significant differences existed.
    • Exposure to TFV in patients with mild-moderate renal impairment was higher than historical data in patients with normal renal function, but was below that reported in patients receiving tenofovir disoproxil fumarate (TDF)-containing regimens.
  • Increases in FTC and TFV exposures were observed in patients undergoing HD, but the overall safety profile was not affected.⁴
    • TFV exposure was less than that achieved in HD patients receiving TDF.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 17 June 2025.