Potential Interaction Between Ritonavir and Carbamazepine

Kato, Yasuhiro; Fujii, Teruhisa; Mizoguchi, Nobuyuki; Takata, Noboru; Ueda, Kazuhiro; Feldman, Mitchell D.; Kayser, Steven R.

doi:10.1592/phco.20.9.851.35206

Cited by 38 publications

(20 citation statements)

References 15 publications

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“…In addition, 14 case studies (class IV) described patients whose AED concentrations changed after ARV therapy was initiated (Honda et al., 1999; Berbel Garcia et al., 2000; Burman & Orr, 2000; Hugen et al., 2000; Kato et al., 2000; Mateu‐de Antonio et al., 2001; Robertson et al., 2005; Bates & Herman, 2006; Motoya et al., 2006; Saraga et al., 2006; Bonora et al., 2007). In some cases, this provides some confirmatory patient data supporting the significance of the human volunteer data.…”

Section: Analysis Of the Evidencementioning

confidence: 99%

Antiepileptic drug selection for people with HIV/AIDS: Evidence‐based guidelines from the ILAE and AAN

Birbeck

French²,

Perucca

et al. 2012

Epilepsia

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Summary A joint panel of the American Academy of Neurology (AAN) and the International League Against Epilepsy (ILAE) convened to develop guidelines for selection of antiepileptic drugs (AEDs) among people with HIV/AIDS. The literature was systematically reviewed to assess the global burden of relevant comorbid entities, to determine the number of patients who potentially utilize AEDs and antiretroviral agents (ARVs), and to address AED–ARV interactions. Key findings from this literature search included the following: AED–ARV administration may be indicated in up to 55% of people taking ARVs. Patients receiving phenytoin may require a lopinavir/ritonavir dosage increase of approximately 50% to maintain unchanged serum concentrations (Level C). Patients receiving valproic acid may require a zidovudine dosage reduction to maintain unchanged serum zidovudine concentrations (Level C). Coadministration of valproic acid and efavirenz may not require efavirenz dosage adjustment (Level C). Patients receiving ritonavir/atazanavir may require a lamotrigine dosage increase of approximately 50% to maintain unchanged lamotrigine serum concentrations (Level C). Coadministration of raltegravir/atazanavir and lamotrigine may not require lamotrigine dosage adjustment (Level C). Coadministration of raltegravir and midazolam may not require midazolam dosage adjustment (Level C). Patients may be counseled that it is unclear whether dosage adjustment is necessary when other AEDs and ARVs are combined (Level U). It may be important to avoid enzyme‐inducing AEDs in people on ARV regimens that include protease inhibitors or nonnucleoside reverse transcriptase inhibitors because pharmacokinetic interactions may result in virologic failure, which has clinical implications for disease progression and development of ARV resistance. If such regimens are required for seizure control, patients may be monitored through pharmacokinetic assessments to ensure efficacy of the ARV regimen (Level C).

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Section: Analysis Of the Evidencementioning

confidence: 99%

Antiepileptic drug selection for people with HIV/AIDS: Evidence‐based guidelines from the ILAE and AAN

Birbeck

French²,

Perucca

et al. 2012

Epilepsia

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“…Compared to pre-overlap levels, efavirenz AUC and minimum (Cmin) and maximum (Cmax) concentrations were reduced by approximately 17% to 43% while carbamazepine AUC decreased by 27%. Though the majority of drug-drug interactions result in reduced plasma concentrations, carbamazepine toxicity may occur secondary to inhibition of CYP3A4 when used with low dose ritonavir[4,14]. Since most studies were performed in healthy volunteers, extrapolation of these findings to patients with HIV infection and epilepsy is difficult because the clinical implications of these interactions have not been adequately studied.…”

Section: Discussionmentioning

confidence: 99%

Virologic outcomes of HAART with concurrent use of cytochrome P450 enzyme-inducing antiepileptics: a retrospective case control study

Okulicz

Grandits

French³

et al. 2011

AIDS Res Ther

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BackgroundTo evaluate the efficacy of highly-active antiretroviral therapy (HAART) in individuals taking cytochrome P450 enzyme-inducing antiepileptics (EI-EADs), we evaluated the virologic response to HAART with or without concurrent antiepileptic use.MethodsParticipants in the US Military HIV Natural History Study were included if taking HAART for ≥6 months with concurrent use of EI-AEDs phenytoin, carbamazepine, or phenobarbital for ≥28 days. Virologic outcomes were compared to HAART-treated participants taking AEDs that are not CYP450 enzyme-inducing (NEI-AED group) as well as to a matched group of individuals not taking AEDs (non-AED group). For participants with multiple HAART regimens with AED overlap, the first 3 overlaps were studied.ResultsEI-AED participants (n = 19) had greater virologic failure (62.5%) compared to NEI-AED participants (n = 85; 26.7%) for the first HAART/AED overlap period (OR 4.58 [1.47-14.25]; P = 0.009). Analysis of multiple overlap periods yielded consistent results (OR 4.29 [1.51-12.21]; P = 0.006). Virologic failure was also greater in the EI-AED versus NEI-AED group with multiple HAART/AED overlaps when adjusted for both year of and viral load at HAART initiation (OR 4.19 [1.54-11.44]; P = 0.005). Compared to the non-AED group (n = 190), EI-AED participants had greater virologic failure (62.5% vs. 42.5%; P = 0.134), however this result was only significant when adjusted for viral load at HAART initiation (OR 4.30 [1.02-18.07]; P = 0.046).ConclusionsConsistent with data from pharmacokinetic studies demonstrating that EI-AED use may result in subtherapeutic levels of HAART, EI-AED use is associated with greater risk of virologic failure compared to NEI-AEDs when co-administered with HAART. Concurrent use of EI-AEDs and HAART should be avoided when possible.

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“…Carbemazepine is a potent inducer of CYP3A enzymes, usually auto-inducing its metabolism and requiring upward titration at some point after a therapeutic level is attained. HIV treatment failure as a result of lowered levels of ARVs may be possible in patients treated with carbemazepine (Hugen et al, 2000), and carbemazepine toxicity may result from concurrent use of CYP3A inhibitors, such as efavirenz and ritonavir (Burnam & Orr, 2000;Dato et al, 2000), so caution should be used when concomitant prescription is necessary. Despite these complexities, we have used it with good success in patients by extensive monitoring of levels and careful ARV selection.…”

Section: Bipolar Disordermentioning

confidence: 99%

Issues in co-morbid severe mental illnesses in HIV infected individuals

Angelino

Treisman

2008

International Review of Psychiatry

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Patients with comorbid HIV and serious mental illnesses pose particular difficulties for clinicians. Presentation of several mental disturbances can be similar, and often significanlty complicate the management of advancing HIV disease. In this article, we will review the assessment and management of four serious mental conditions in HIV-infected patients: delirium, dementia, schizophrenia and bipolar disorder.

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Potential Interaction Between Ritonavir and Carbamazepine

Cited by 38 publications

References 15 publications

Antiepileptic drug selection for people with HIV/AIDS: Evidence‐based guidelines from the ILAE and AAN

Antiepileptic drug selection for people with HIV/AIDS: Evidence‐based guidelines from the ILAE and AAN

Virologic outcomes of HAART with concurrent use of cytochrome P450 enzyme-inducing antiepileptics: a retrospective case control study

Issues in co-morbid severe mental illnesses in HIV infected individuals

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