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

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.

• Authors: Dominique Levêque, Raoul Santucci, Julien Pavillet, Raoul Herbrecht, Jean Pierre Bergerat
• Journal: Pharmacy world & science : PWS (Pharm World Sci) Vol. 31 Issue 6 Pg. 619-21 (Dec 2009) ISSN: 1573-739X [Electronic] Germany
• PMID: 19757141 (Publication Type: Case Reports, Journal Article)

Chemical References

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

Topics

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