Adult Dosing
HIV-1 infection in treatment-naive adults
Pediatric Dosing
- Safety and effectiveness in pediatric patients have not been established
[Outline]
Renal Dose Adjustment (Based on CrCl)
- <70 mL/min: Avoid use
- CrCL below 50 mL/min: Discontinue therapy
Hepatic Dose Adjustment
- Mild-to-moderate impairment (Child-Pugh Class A or B): No dose adjustments
- Severe impairment (Child-Pugh Class C): Dose adjustments not defined
- Women are more prone to lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, with the use of nucleoside analogs such as tenofovir or in combination with other antiretroviral [US Black Box Warning]; obesity and prolonged nucleoside therapy may be the associated risk factors
- Discontinue therapy on developing clinical or lab findings suggestive of lactic acidosis or pronounced hepatotoxicity including hepatomegaly and steatosis even in the absence of marked transaminase elevations
- Test all patients with HIV-1 for the presence of chronic hepatitis B virus (HBV) before initiating antiretroviral therapy. This combination drug is not approved for the treatment of chronic HBV infection and the safety and efficacy of this drug have not been established in patients co-infected with HBV and HIV-1
- Patients who are co-infected with HBV and HIV-1 and have discontinued emtricitabine or tenofovir are susceptible for development of severe acute exacerbations of hepatitis B [US Black Box Warning]
- Exacerbations of hepatitis B were associated with liver decompensation and liver failure in certain patients infected with HBV and treated with emtricitabine. Closely monitor hepatic function with both clinical and lab follow-up for at least several months after discontinuation of therapy in patients who are co-infected with HIV-1 and HBV. If required, initiate appropriate anti-hepatitis B therapy [US Black Box Warning]
- New onset or worsening renal impairment may occur during therapy. Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has occurred with the use of tenofovir
- Monitor estimated CrCl, urine glucose, and urine protein in all patients prior to initiating and during therapy; additionally monitor serum phosphorus in patients with or at risk for renal impairment. Avoid treatment in patients with creatinine clearance <50 mL/min and with concurrent use of a nephrotoxic agent or in patients with recent use of a nephrotoxic agent
- Should not be coadministered with antiretroviral agents containing any of the same active components, with products containing lamivudine, with adefovir dipivoxil, or with products containing ritonavir
- Decreases in bone mineral density (BMD) and cases of osteomalacia reported with tenofovir. Monitor bone mineral density (BMD) for HIV-1 infected patients having a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss. Tenofovir component is associated with significant increases in biochemical markers of bone metabolism (serum bone-specific alkaline phosphatase, serum osteocalcin, serum C-telopeptide, and urinary N-telopeptide). Tenofovir component is also associated with higher serum parathyroid hormone levels and 1,25 Vitamin D levels
- Fat redistribution and accumulation including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and cushingoid appearance may occur in patients receiving antiretroviral therapy
- Immune reconstitution syndrome including autoimmune disorders such as Graves’ disease, polymyositis, and Guillain-Barré syndrome may occur in patients treated with combination antiretroviral therapy. Patients may develop opportunistic infections during the initial phase of combination antiretroviral treatment, which may necessitate further evaluation and treatment
- Cobicistat may cause modest increases in serum creatinine and declines in CrCl without affecting renal glomerular function; serum creatinine >0.4 mg/dL from baseline should be closely monitored for renal safety
Cautions: Use cautiously in
- Risk factors for liver disease
- Elderly patients
- HBV co-infection
- Long-term nucleoside treatment
- Obesity
- Osteopenia or osteoporosis
- Hx of pathologic fracture
Pregnancy Category:B
Breastfeeding: Traces of emtricitabine and tenofovir have been detected in human milk; because of both the potential for HIV transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breastfeed while receiving therapy. According to CDC recommendations HIV infected mothers should not breastfeed their infants to avoid risking postnatal transmission of HIV.
Elvitegravir
- Integrase inhibitor; inhibits the strand transfer activity of HIV-1 integrase required for viral replication thus preventing the integration of HIV-1 DNA into host genomic DNA, blocking the formation of the HIV-1 provirus and propagation of the viral infection
- Metabolized by CY3A4; undergoes glucuronidation via UGT1A1/3 enzymes
- Excreted in feces (94.8%) and urine (6.7%)
- Half-life: 12.9 hrs
Cobicistat
- Selective CYP3A4 inhibitor; inhibits CYP3A-mediated metabolism and enhances the systemic exposure of CYP3A substrates, such as elvitegravir
- Metabolized by CYP3A4 and CYP2D6
- Excreted in feces (86.2%) and urine (8.2%)
- Half-life: 3.5 hrs
Emtricitabine
- Synthetic nucleoside cytidine analog; phosphorylated to emtricitabine 5'-triphosphate and inhibits the activity of the HIV-1 RT by competing with the natural substrate deoxycytidine 5'-triphosphate and by being incorporated into nascent viral DNA which results in chain termination
- Not significantly metabolized
- Primarily excreted in urine through glomerular filtration and active tubular secretion
Tenofovir disoproxil fumarate
- Acyclic nucleoside phosphonate diester analog of adenosine monophosphate; undergoes hydrolysis and subsequent phosphorylations to form tenofovir diphosphate which inhibits HIV-1 RT by competing with the natural substrate deoxyadenosine 5'-triphosphate
- Not significantly metabolized; converted intracellularly by hydrolysis to tenofovir, then phosphorylated to active tenofovir diphosphate
- Excreted in urine via filtration and active secretion
US Trade Name(s)
US Availability
Stribild (elvitegravir/cobicistat/emtricitabine/tenofovir)
- TAB: 150 mg/150 mg/200 mg/300 mg
Canadian Trade Name(s)
Canadian Availability
UK Trade Name(s)
UK Availability
Australian Trade Name(s)
Australian Availability
[Outline]
