Managing drug interactions in HIV-infected adults with comorbid illness

Hughes, Christine; Tseng, Alice; Cooper, Ryan

doi:10.1503/cmaj.131626

Cited by 39 publications

(32 citation statements)

References 51 publications

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“…19 In addition, the chemical structure of doravirine 20 does not contain the chelating motifs that render HIV integrase strand transferase inhibitors susceptible to divalent cation binding by cations present in antacid salts, with a subsequent loss of bioavailability. 21,22 Along with the data from the current trial, these properties support that doravirine is unlikely to interact with acid-reducing agents or cationcontaining antacids.…”

Section: Discussionsupporting

confidence: 66%

A Study to Evaluate Doravirine Pharmacokinetics When Coadministered With Acid‐Reducing Agents

Khalilieh

Yee

Sánchez

et al. 2019

The Journal of Clinical Pharma

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Doravirine is a novel non-nucleoside reverse transcriptase inhibitor indicated for the treatment of human immunodeficiency virus type 1 infection. Because of potential concomitant administration with acid-reducing agents, a drug-interaction trial was conducted to evaluate the potential impact of these types of medications on doravirine pharmacokinetics. In an open-label, 3-period, fixed-sequence trial, healthy adult participants received the following:period 1,a single dose of doravirine 100 mg;period 2,coadministration of a single dose of doravirine 100 mg and an antacid (1600 mg aluminum hydroxide, 1600 mg magnesium hydroxide, and 160 mg simethicone); period 3, 40 mg pantoprazole once daily on days 1-5 coadministered with a single dose of doravirine 100 mg on day 5. There was a minimum 10-day washout between periods. Plasma samples for pharmacokinetic evaluation were collected, and safety was assessed. Fourteen participants (8 male, 6 female) were enrolled, and 13 completed the trial. Geometric mean ratios (90% confidence intervals) for doravirine AUC 0-inf ,C max ,and C 24 for doravirine + antacid/doravirine were 1.01 (0.92-1.11), 0.86 (0.74-1.01), and 1.03 (0.94-1.12), respectively, and for doravirine + pantoprazole/doravirine were 0.83 (0.76-0.91), 0.88 (0.76-1.01), and 0.84 (0.77-0.92), respectively. Doravirine was generally well tolerated administered alone or with either of the acid-reducing agents. Coadministration of an aluminum/magnesium-containing antacid or pantoprazole did not have a clinically meaningful effect on doravirine pharmacokinetics, supporting the use of acid-reducing agents with doravirine.

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Section: Discussionsupporting

confidence: 66%

A Study to Evaluate Doravirine Pharmacokinetics When Coadministered With Acid‐Reducing Agents

Khalilieh

Yee

Sánchez

et al. 2019

The Journal of Clinical Pharma

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“…Carbonato de calcio 21,41,42,43,44 Hidróxido de aluminio 21,41,42,43,44 Hidróxido de magnesio 21,41,42,43,44 RAL 2: Riesgo alto Los antiácidos pueden producir quelación y disminuir la absorción de RAL y con ello, disminuir sus concentraciones plasmáticas hasta 67%. Administrar con al menos una hora de diferencia entre RAL y los antiácidos…”

Section: Antiácidounclassified

“…Fumarato ferroso 21,41,42,43,44,45 Carbonato de calcio 21,41,42,43,44,45 Hidróxido de aluminio 21,41,42,43,44,45 Hidróxido de magnesio 21,41,42,43,44,45 Sofosbuvir 20, 35,59 EFV No hay cambios en la Cp de ledipasvir/sofosbuvir y sofosbuvir con el EFV. No se requiere ajuste en la dosis…”

Section: Antiácidounclassified

Relevancia clínica de las interacciones medicamentosas en pacientes infectados con el virus de la inmunodeficiencia humana: actualización 2015-2017

Pino-Marín

et al. 2019

Rev. chil. infectol.

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“…Being potent inhibitors of CYP3A4 enzyme, LPV/RTV can exert uniquely powerful inhibiting effects of CYP3A4 substrate drugs, potentially increased blood concentrations of substrate drugs which may leads to a number of clinically significant DDIs (Food and Drug Administration, 2020;Francis et al, 2020). Contrastingly, CYP3A4 inducer drugs may expedite the hepatic clearance of LPV/RTV and may cause therapeutic failure leading to reduced virologic control (Hughes et al, 2015). Being acting as substrates of a transporter protein called permeability glycoprotein (P-gp) (Liu et al, 2017) known as efflux transporter, the pharmacokinetics (PK) effects of LPV/RTV may also be affected by the co-prescription with substrate, inhibitor or inducer drugs of P-gp and were predicted to cause potential clinically significant DDIs.…”

Section: Introductionmentioning

confidence: 99%

Potential clinically significant life-threatening drug–drug interactions of lopinavir and ritonavir used in the treatment of COVID-19

Biswas

Michaelis

2020

Exp Results

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Potential clinically significant life-threatening drug–drug interactions (DDIs) of lopinavir (LPV) and ritonavir (RTV) used in the treatment of COVID-19 is not systematically reviewed. It was aimed to identify severe DDI pairs of LPV/RTV from international resources predicted to cause life-threatening adverse drug reactions (ADRs). Severe DDI pairs predicted to cause life-threatening ADRs were identified from the FDA and Liverpool COVID-19 prescribing information of LPV/RTV. In total, 62 severe DDI pairs were identified from the FDA and Liverpool COVID-19 resources predicted to cause life-threatening ADRs in patients with COVID-19. Of these, seven unique DDI pairs (11.3%; 95% CI 3%–19%) were identified from the FDA only whereas 45 unique DDI pairs (72.6%; 95% CI 61%–84%) were identified from the Liverpool COVID-19 drug interactions resource. Of interest, only 10 DDI pairs (16.1%; 95% CI 7%–25%) were recognized by both of these drug interaction resources. Clinicians should not entirely rely on any individual DDI resource for checking life threatening ADRs of LPV/RTV in patients with COVID-19.

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Managing drug interactions in HIV-infected adults with comorbid illness

Cited by 39 publications

References 51 publications

A Study to Evaluate Doravirine Pharmacokinetics When Coadministered With Acid‐Reducing Agents

A Study to Evaluate Doravirine Pharmacokinetics When Coadministered With Acid‐Reducing Agents

Relevancia clínica de las interacciones medicamentosas en pacientes infectados con el virus de la inmunodeficiencia humana: actualización 2015-2017

Potential clinically significant life-threatening drug–drug interactions of lopinavir and ritonavir used in the treatment of COVID-19

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