Pharmacokinetics and Dosing Recommendations of Tenofovir Disoproxil Fumarate in Hepatic or Renal Impairment

Kearney, Brian P.; Yale, Kitty; Shah, Jaymin; Zhong, Lijie; Flaherty, John F.

doi:10.2165/00003088-200645110-00005

Cited by 77 publications

(52 citation statements)

References 11 publications

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“…Tenofovir has been shown to exhibit relatively better efficacy and safety, but its prolonged application has been found to cause nephrotoxicity in patients. 36,37 Tenofovir was approved by the FDA on October 26, 2001 (Table 1). …”

Section: Sharmamentioning

confidence: 99%

Anti-HIV-1 drug toxicity and management strategies

Sharma¹

2011

NBHIV

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Section: Sharmamentioning

confidence: 99%

Anti-HIV-1 drug toxicity and management strategies

Sharma¹

2011

NBHIV

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“…As such, the modest EVG exposure changes are not considered to be clinically relevant and do not necessitate dose modifications for EVG/co. Further, based on the lack of expected/observed changes in the PK of the nucleoside reverse transcriptase inhibitors (NRTIs) emtricitabine (FTC) and tenofovir (TFV) (15) with liver impairment, no dose modifications for the EVG/COBI/ FTC/TDF single-tablet regimen are necessary for patients with moderate or mild liver impairment.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and Safety of Boosted Elvitegravir in Subjects with Hepatic Impairment

Custodio

Rhee

Shen

et al. 2014

Antimicrob Agents Chemother

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Elvitegravir (EVG), an HIV strand transfer integrase inhibitor, is metabolized primarily via cytochrome P450 3A4 (CYP3A) and secondarily via glucuronidation. The pharmacokinetics (PK) and safety of cobicistat (COBI)-boosted EVG (EVG/co) were evaluated in subjects with impaired liver function. The enrolled subjects had stable moderate liver impairment (n ‫؍‬ 10; Child-PughTurcotte [CPT] class B) or were healthy controls (n ‫؍‬ 10) matched for age (؎5 years), gender, and body mass index (؎15%). EVG/co (150/150 mg) was administered once daily for 10 days, followed by pharmacokinetic (PK) sampling. Safety was assessed throughout the study. EVG and COBI exposures were compared between the impairment and control groups, with a >100% increase considered clinically relevant. EVG and COBI protein binding was also measured. All enrolled subjects completed the study. The treatment-emergent adverse event (AE) incidences were comparable between the groups; all study drug-related AEs were mild. The geometric mean ratio (90% confidence interval [CI]) for EVG area under the concentration-time curve over the dosing interval (AUC tau ) and maximum observed plasma concentration (C max ) were 135% (103%, 177%) and 141% (109%, 183%), respectively. The corresponding values for COBI were 99.8% (76.0%, 131%) and 86.1% (65.4%, 113%), respectively, indicating no clinically relevant change in exposure. No correlations were observed between the EVG and COBI exposures versus CPT score. The EVG-and COBI-free fractions were similar between groups. EVG and COBI do not require dose adjustment in moderate or mild liver impairment, as no clinically relevant PK changes were observed for EVG or COBI in this special population. No PK or safety data are available for EVG or COBI in subjects with severe hepatic impairment.

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“…Some practical questions regarding the management of HIV-infected patients undergoing cART are briefly summarized in the box. An increased time between tenofovir administration has been recommended in subjects with a severe kidney and also liver function impairment, where the potent antiviral activity of this compound has been successfully exploited also in these difficult-to-treat patients [142]. To conclude, a strategic approach to HIV infection management should enable all individuals living with HIV to aspire to a long life expectancy, with minimized end-organ compromise caused by both the virus, the cART, and underlying or concurrent diseases and/or treatments.…”

Section: Discussionmentioning

confidence: 99%

Kidney failure during HIV disease treated with tenofovir, multiple concurrent diseases and drug therapies

Manfredi¹,

Calza

Colangeli

et al. 2012

RHC

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A significant case report of a HIV infected patient in his fifties who experienced an excellent virological and immunological response to antiretroviral therapy (which has been modified just to prevent or avoid some adverse events), but developed a severe, sudden acute kidney failure while under a polypharmacy due to some underlying and overwhelming disorders (i.e. arterial hypertension, non-insulin-dependent diabetes mellitus, a recent acute heart infarction with remarkable remnants, and finally an anecdotal muscle-joint pain with self-prescription of non-steroideal anti-inflammatory drugs), represents the key point for a debate around the increasing frequency of "polypharmacy" in the field of HIV infection, even when HIV resistance to antiretroviral is not a concern. The continuing increase of mean age of HIV-infected population, plus the existing, sometimes unmodifiable risk factors for cardiovascular, dysmetabolic, and renal disorders, plus the adjunct of anecdotal illnesses prompting the resort to different drugs and medications, either prescribed for HIV infection itself, or taken for concurrent or subsequent diseases, or self-prescribed occasionally due to an intercurrent, trivial disorders per se, may prompt a complicated scenario culminating with a lifethreatening acute renal failure of tubular origin. Our report gives us the opportunity to revise and discuss the expected interactions between antiretroviral therapy and the even growing exposure to multiple different drug and drug classes, which may be responsible for relevant drug interactions and direct or adjunctive end-organ impairment, up to life-threatening conditions, which may be avoided or prevented by considering carefully all comorbidites and co-treatments potentially administered to HIV infected patients, thirty years after the discovery of AIDS.

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Pharmacokinetics and Dosing Recommendations of Tenofovir Disoproxil Fumarate in Hepatic or Renal Impairment

Cited by 77 publications

References 11 publications

Anti-HIV-1 drug toxicity and management strategies

Anti-HIV-1 drug toxicity and management strategies

Pharmacokinetics and Safety of Boosted Elvitegravir in Subjects with Hepatic Impairment

Kidney failure during HIV disease treated with tenofovir, multiple concurrent diseases and drug therapies

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