Paralytic ileus possibly associated with interaction between ritonavir/lopinavir and vincristine.
METHODS
A French Caucasian man aged 39 with HIV infection was treated with abacavir/lamivudine and ritonavir/lopinavir. The patient (normal renal and liver functions) was diagnosed with a Burkitt lymphoma for which he was treated with cyclophosphamide day 1 to 5; doxorubicin day 1; methotrexate day 10; and vincristine day 1 and 8. At day 12, he suffered from abdominal pain associated with constipation. Paralytic ileus was diagnosed by study imaging. Ileus lasted 10 days necessitating parenteral feeding. Later on, a further cycle of chemotherapy with etoposide replacing vincristine was given and was well tolerated.


CONCLUSIONS
We speculate that an interaction between ritonavir/lopinavir and vincristine was responsible for this severe toxicity. Vincristine is transported by P-gp and is metabolized via CYP3A5. Ritonavir is a potent CYP3A5 isoenzyme and P-gp inhibitor. Lopinavir is also a P-gp inhibitor. Ritonavir and lopinavir might have delayed vincristine elimination. Clinicians should be aware of this possible interaction.
Levêque
Dominique
D
Department of Pharmacy Pharmacology, Hôpital de Hautepierre, Strasbourg, France. dominique.leveque@chru-strasbourg.fr
Santucci
Raoul
R
Pavillet
Julien
J
Herbrecht
Raoul
R
Bergerat
Jean Pierre
JP
D015746:Abdominal Pain / Q000139:chemically induced; D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects* / Q000493:pharmacokinetics; D002051:Burkitt Lymphoma / Q000150:complications / Q000188:drug therapy*; D003248:Constipation / Q000139:chemically induced; D004347:Drug Interactions; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects*; D006801:Humans; D007418:Intestinal Pseudo-Obstruction / Q000139:chemically induced*; D061466:Lopinavir; D008297:Male; D011744:Pyrimidinones / Q000009:adverse effects*; D019438:Ritonavir / Q000009:adverse effects*; D014750:Vincristine / Q000009:adverse effects* / Q000493:pharmacokinetics
D000972:Antineoplastic Agents, Phytogenic; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D014750:Vincristine; D019438:Ritonavir