Serum concentrations of vinblastine may be increased when co-administered with ritonavir resulting in the potential for increased incidence of adverse events.

Coadministration is expected to increase vinblastine concentrations. Consideration should be given to temporarily withholding the ritonavir-containing antiretroviral regimen in patients who develop significant hematologic or gastrointestinal side effects when ritonavir is administered concurrently with vinblastine. Clinicians should be aware that if the ritonavir-containing regimen is withheld for a prolonged period, consideration should be given to altering the regimen to not include a CYP3A or P-gp inhibitor in order to control HIV-1 viral load.

A case was reported of a 60-year-old HIV positive woman treated with emtricitabine/tenofovir and atazanavir/ritonavir who developed Hodgkin’s lymphoma. She was started on an ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) chemotherapy regimen. Eight days after initialising ABVD, she presented with neutropenia, fever, and severe hypokalemia, due to proximal tubular renal dysfunction. Her next cycle of ABVD had a 50% dose reduction of doxorubicin and dacarbazine, yet she was readmitted for febrile neutropenia and hypokalemia, leading the authors to suspect a drug-drug interaction with her ARV medication. Atazanavir/ritonavir was switched to dolutegravir, and no further episodes of neutropenia/hypokalemia occurred in subsequent ABVD cycles. The authors hypothesise a drug-drug interaction occurred via inhibition of CYP3A4 and P-gp by ritonavir.

In order to better define the interaction between combination antiretroviral therapy and vinblastine (a substrate of CYP3A4), clinical charts were reviewed of all HIV infected patients in a centre in Rome who received a diagnosis of Hodgkin’s lymphoma as coadministration of potent inhibitors of CYP3A4, such as ritonavir, may decrease vinblastine metabolism and consequently increase vinblastine-related myelosuppression. It was found that the use of protease inhibitors was independently associated with WHO grade III-IV neutropaenia.  Moreover, an inverse correlation between dosage of ritonavir and mean nadir neutrophil count was found.  The concomitant administration of vinblastine-containing chemotherapy regimens with protease inhibitors can lead to higher levels of neutropaenia than those of different classes of drugs such as NNRTIs or integrase inhibitors.