Date of report: 28 Jul 2020
Reported case interaction between
Ritonavir and Paclitaxel
Ritonavir and Paclitaxel
Drugs suspected to be involved in the DDI
Drug A
Ritonavir
(Perpetrator)
Daily Dose
100
(mg)
Dose adjustment performed
No
Administration Route
Oral
Start date
Unknown
End date
Unknown
Drug B
Paclitaxel
(Victim)
Daily Dose
Unknown
Dose adjustment performed
No
Administration Route
Intravenous
Start date
Unknown
End date
Unknown
Complete list of drugs taken by the patient
Antiretroviral treatment
Abacavir/Lamivudine
Darunavir (with Ritonavir or Cobicistat)
Complete list of all comedications taken by the patient, included that involved in the DDI
Paclitaxel, Carboplatin
Clinical case description
Gender
Male
Age
60
eGFR (mL/min)
60-30
Liver function impairment
No
Description
This is about an HIV-infected patient successfully treated with ABC/3TC/DRV/r who was diagnosed with metastatic gastric cancer for which palliative treatment with paclitaxel/carboplatin was indicated.
The HIV physician and oncologist were aware of a potential interaction between DRV/r and paclitaxel (see Liverpool site) but a switch to an integrase inhibitor was not chosen due to concern about a psychiatric history in this patient. Rilpivirine was considered but not attractive due to expected use of PPIs around the chemotherapy cycles.
As the Liverpool site recommended close monitonring of toxicity and uncertainty whether paclitaxel levels would go up or down, the DRV/r regimen was continued and the patient was monitored according to usual toxicity evaluation by the oncologist.
The 1st cycle of chemotherapy was administered in normal dose and no toxicity occurred. The 2nd cycle was also given in normal dose. Three days later the patient became ill, got fever, mucositis, positive blood culture for E coli, and two days later died. Obduction showed extensive mucositis, no perforation
Outcome
Toxicity
Drug Interaction Probability Scale (DIPS)
Score
2 - Possible
Editorial Comment
Paclitaxel is primarily metabolized by CYP2C8 and to a lesser extent 3A4. Darunavir/cobicistat could potentially increase paclitaxel exposure (inhibition of CYP3A4). Monitor paclitaxel induced toxicity.
This case report suggests that there was a DDI leading to extensive mucositis (increased paclitaxel toxicity) that resulted in death. This is indeed possible but not substantiated (there were no levels done), and complicated by E coli bacteraemia.