Risperidone Indinavir

A 34-year-old man with AIDS took risperidone 4 mg/ day for a Tourette-like tic disorder. Ritonavir and indinavir were added, and 1 week later he developed significantly impaired swallowing, speaking, and breathing, and worsening of his existing tremors. 

The authors hypothesized that inhibition of CYP2D6 and CYP3A4 by ritonavir and indinavir may have resulted in accumulation of the active moiety of risperidone. 

Kelly DV, Beique LC, Bowmer MI. Extrapyramidal symptoms with ritonavir/indinavir plus risperidone. Ann Pharmacother 2002 36(5) 827-30. 

An interaction of risperidone with ritonavir and indinavir has been reported (160). 

The neuroleptic malignant syndrome, ataxia and severe lethai leading to a coma, and extrapyramidal adverse effects have been seen in patients given risperidone with indinavir and ritonavir. 

Indinavir inhibits the cytochrome P450 isoenzyme CYP3A4 and ritonavir inhibits CYP2D6 and CYP3A4, which are the main isoenzymes involved in the metabolism of risperidone. Therefore eoncurrent use would be expected to raise risperidone levels. The symptoms reported in the cases above may have all been due to increased risperidone levels. ... 

Lee SI, Klesmer J, Hirsch BE. Neuroleptic malignant syndrome associated with the use of risperidone, ritonavir and indinavir a case report. Psychosomatics (2000) 41, 453-4. 

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