Liverpool HIV Interactions

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Potential Interaction

Lopinavir/ritonavir (LPV/r)

Prednisone

Quality of Evidence: Very Low

Summary:

Prednisone is converted to the active metabolite prednisolone by 11-B-hydroxydehydrogenase. Prednisolone is then metabolized by CYP3A4. Coadministration is expected to decrease lopinavir concentrations and increase concentrations of prednisone. Consider alternative corticosteroids, particularly for long term use. Pharmacokinetics of prednisolone were determined following administration of prednisone (20 mg single dose) in three groups of ten HIV+ subjects receiving either lopinavir/ritonavir or efavirenz or no antiretrovirals. Prednisolone AUC was significantly lower (40% decrease) in the presence of efavirenz versus lopinavir/ritonavir and was higher in the subjects taking lopinavir/ritonavir than in subjects on no antiretrovirals (30% increase), but this was not significant. Prednisolone concentrations may fluctuate widely when patients on efavirenz switch to lopinavir/ritonavir or vice versa.

Description:

Coadministration is expected to decrease lopinavir concentrations and increase concentrations of prednisone. Coadministration with systemic corticosteroids that induce CYP3A may result in loss of therapeutic effect and development of resistance to lopinavir. Consider alternative corticosteroids. Coadministration with corticosteroids whose exposures are significantly increased by strong CYP3A inhibitors can increase the risk for Cushing’s syndrome and adrenal suppression. Alternative corticosteroids including beclomethasone and prednisolone (whose PK and/or PD are less affected by strong CYP3A inhibitors relative to other studied steroids) should be considered, particularly for long-term use.

Kaletra Prescribing Information, AbbVie Inc, October 2020.

The influence of antiretroviral medications on the pharmacokinetics of prednisolone (a CYP3A4 substrate) was investigated in three groups of ten HIV-infected subjects receiving either lopinavir/ritonavir or efavirenz or no antiretrovirals. Each subject received a single prednisone dose (20 mg) followed by serial blood sampling for determining prednisolone pharmacokinetics. Prednisolone AUC was significantly lower in the presence of efavirenz versus lopinavir/ritonavir (GMR=0.60, p=0.01) and was higher in the subjects taking lopinavir/ritonavir than in subjects on no antiretrovirals, but this was not significant (30% increase; p>0.05). The authors conclude that prednisolone concentrations may fluctuate widely when patients on efavirenz switch to lopinavir/ritonavir or vice versa.
Influence of antiretroviral drugs on the pharmacokinetics of prednisolone in HIV-infected individuals. Busse KH, Formentini E, Alfaro RM, Kovacs JA, Penzak SR. J Acquir Immune Defic Syndr, 2008, 48(5): 561-566.

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