Paralytic ileus possibly associated with interaction between ritonavir/lopinavir and vincristine

Pharm World Sci. 2009 Dec;31(6):619-21. doi: 10.1007/s11096-009-9323-y. Epub 2009 Sep 10.

Abstract

Case description: 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.

Conclusion: 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.

Publication types

  • Case Reports

MeSH terms

  • Abdominal Pain / chemically induced
  • Adult
  • Antineoplastic Agents, Phytogenic / adverse effects*
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Burkitt Lymphoma / complications
  • Burkitt Lymphoma / drug therapy*
  • Constipation / chemically induced
  • Drug Interactions
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Protease Inhibitors / adverse effects*
  • Humans
  • Intestinal Pseudo-Obstruction / chemically induced*
  • Lopinavir
  • Male
  • Pyrimidinones / adverse effects*
  • Ritonavir / adverse effects*
  • Vincristine / adverse effects*
  • Vincristine / pharmacokinetics

Substances

  • Antineoplastic Agents, Phytogenic
  • HIV Protease Inhibitors
  • Pyrimidinones
  • Lopinavir
  • Vincristine
  • Ritonavir