Uveitis associated with concurrent administration of rifabutin and lopinavir/ritonavir (Kaletra)

Hc, Lin; Lü, Peng; Ch, Chang

doi:10.1038/sj.eye.6703016

Cited by 11 publications

(6 citation statements)

References 11 publications

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“…Co-administration of rifamycin and PI leads to a reduction in the plasma concentration of IP [5]. These interactions may lead to an increased risk of TB drug toxicity [31,32], failure of HIV treatment, and potential development of drug resistance [29].…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of plasma lopinavir and ritonavir in tuberculosis–HIV co-infected African adult patients also receiving rifabutin 150 or 300 mg three times per week

Ouédraogo

Matteelli

Sulis

et al. 2020

Ann Clin Microbiol Antimicrob

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Background: To evaluate the pharmacokinetic of plasma lopinavir (LPV) and ritonavir (RTV) when co-administered with three times weekly (TPW) rifabutin (RBT) at a dose of either 150 or 300 mg in African tuberculosis (TB) and HIV co-infected adult patients. Methods: This is a pharmacokinetic study conducted in Ouagadougou among patients treated with a standard dosage of LPV/RTV 400/100 mg twice daily and RBT 150 mg TPW (arm A = 9 patients) or rifabutin 300 mg TPW (arm B = 7 patients) based regimens. Patients were recruited from the Bogodogo and Kossodo district hospitals in Ouagadougou from May 2013 to December 2015. Study inclusion criteria were that the patients were between 18 and 60 years of age, HIV-1 infected with pulmonary tuberculosis confirmed or suspected. Subsequent blood samples for pharmacokinetic monitoring were collected at 1, 2, 3, 4, 6, 8 and 12 h after combined drug ingestion for plasma drug monitoring using HPLC/MS assays. Results: The medians LPV C max and T max were respectively, 20 μg/mL and 4 h for the RBT 150 mg group (arm A) and 7.7 μg/mL and 3 h for the RBT 300 mg group (arm B). The AUC 0-12 of LPV was 111.8 μg h/mL in patients belonging to arm A versus 69.9 μg/mL for those in arm B (p = 0.313). The C 0 of LPV was lower than 4 μg/mL in three patients receiving RBT 300 mg. Of note, the RTV plasma concentrations were nearly halved among patients on RBT 300 mg compared to those on lower RBT doses. The AUC 0-12 of RTV in arm A was 12.7 μg h/mL versus 6.6 μg h/ml in arm B (p = 0.313). Conclusion: In our study, the pharmacokinetic of LPV and RTV was found to be highly variable when coadministrated with RBT 150 mg or 300 mg three times per week. There is a need for specific large study to verify clinical and virological effects of this variation, especially when coadministrated with RBT of 300 mg TPW, and to prevent viral resistance in response to under-dosing of LPV.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of plasma lopinavir and ritonavir in tuberculosis–HIV co-infected African adult patients also receiving rifabutin 150 or 300 mg three times per week

Ouédraogo

Matteelli

Sulis

et al. 2020

Ann Clin Microbiol Antimicrob

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“…Ritonavir is a potent inhibitor of CYP3A and has been demonstrated that it can exacerbate the adverse reactions of rifabutin [13,14]. Subsequently, recent guidelines have proposed the use of intermittently administered rifabutin 150 mg 3 times per week or 150 mg daily with close monitoring of adverse effects when used in the combination with ritonavir.…”

Section: Discussionmentioning

confidence: 99%

Rifabutin Low Dose-Induced Intermediate Uveitis in a Patient with Acquired Immunodeficiency Syndrome

Palacio¹,

Cabrini²,

Ben³

et al. 2017

AJMCR

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Intermediate uveitis is a relatively rare manifestation of Rifabutin induced uveitis. Rifabutin toxicity is unusual at doses of 300 mg daily or less. The purpose of this study is to report the case of an HIV+ patient with unilateral rifabutin induced intermediate uveitis after 4 months of treatment with low dose rifabutin (150 mg daily) in combination with ritonavir and fluconazole. The uveitis resolved after drug discontinuance and the use topical corticosteroids.

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“…Coadministration of PIs and rifabutin will reduce the clearance of rifabutin 11 and increase the incidence of rifabutin toxicities, including uveitis. 12 Nelfinavir, a PI, is metabolized by multiple CYP enzymes, including CYP3A and CYP2C19. Coadministration of rifabutin with nelfinavir may increase the area under the concentration–time curve of rifabutin to 207%, compared with adminis tration of rifabutin alone.…”

Section: Discussionmentioning

confidence: 99%

Bilateral uveitis associated with concurrent administration of rifabutin and nelfinavir

Cheng

Chang

et al. 2015

Taiwan Journal of Ophthalmology

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Rifabutin-associated uveitis has been recognized as a dosage-dependent side effect. Previous studies have reported that clarithromycin or fluconazole may elevate concentrations of rifabutin through inhibition of metabolism through the cytochrome P-450 pathway. Nelfinavir is a protease inhibitor widely used in the treatment of human immunodeficiency virus (HIV) infection. The interactions between protease inhibitors and rifabutin have not been reported in clinical practice. Therefore, we present a case of bilateral uveitis associated with coadministration of rifabutin and nelfinavir. Uveitis did not subside until discontinuation of rifabutin. To our knowledge, this is the first report of uveitis with concurrent administration of rifabutin and nelfinavir. Our finding reminds us that rifabutin dosage should be reduced when it is administered with protease inhibitors.

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Uveitis associated with concurrent administration of rifabutin and lopinavir/ritonavir (Kaletra)

Cited by 11 publications

References 11 publications

Pharmacokinetics of plasma lopinavir and ritonavir in tuberculosis–HIV co-infected African adult patients also receiving rifabutin 150 or 300 mg three times per week

Pharmacokinetics of plasma lopinavir and ritonavir in tuberculosis–HIV co-infected African adult patients also receiving rifabutin 150 or 300 mg three times per week

Rifabutin Low Dose-Induced Intermediate Uveitis in a Patient with Acquired Immunodeficiency Syndrome

Bilateral uveitis associated with concurrent administration of rifabutin and nelfinavir

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