Date of report: 31 Jan 2020
Reported case interaction between
 Cobicistat and Vinblastine

FLS Science

Drugs suspected to be involved in the DDI

Drug A
Cobicistat (Perpetrator)
Daily Dose
150 (mg)
Dose adjustment performed
No
Administration Route
Oral
Start date
Unknown
End date
Unknown
Drug B
Vinblastine (Victim)
Daily Dose
11 every 2 w (mg)
Dose adjustment performed
No
Administration Route
Intravenous
Start date
Unknown
End date
Unknown

Complete list of drugs taken by the patient

Antiretroviral treatment
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir-DF
Complete list of all comedications taken by the patient, included that involved in the DDI
vinblastin 11 mg every 2 weeks doxorubin 46 mg every 2 weeks bleomycin 18.6 mg every 2 weeks dacarbazine 700 mg every 2 weeks

Clinical case description

Gender
Female
Age
46
eGFR (mL/min)
>60
Liver function impairment
No
Description
HIV infected woman initiated on ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy protocol for the treatment of Hodgkin's lymphoma while on antiretroviral treatment with elvitegravir/c, emtricitabine, tenofovir-DF. After the first chemotherapy cycle, the patient complained of slight paresthesia of the legs which progressed to serious sensory-motor lower and upper limbs peripheral neuropathies after the third chemotherapy cycle. A neuro-meningeal lymphoma was excluded by performing a lumbar puncture. An electromyogram confirmed the diagnosis of evolutive axonal four limbs sensory-motor peripheral polyneuropathy. This complication was suspected to result from a drug-drug interaction between cobicistat (strong CYP3A4 Inhibitor) and vinblastine (substrate of CYP3A4). Severe neutoxicity has indeed been reported in patients treated concomitantly with vinblastine and ritonavir, another strong CYP4A4 inhibitor (Cingolani A te al. AIDS 2010; Corona G et al. AIDS 2013; Cheung MC et al. Clin Lymphoma Myeloma Leuk 2010). Vinblastine was replaced by etoposide and antiretroviral treatment was changed to darunavir/r, abacavir, lamivudine. After 2 weeks, neuropathies were reduced although they persisted for 6 months. This case has been published: Bidon D et al. AIDS 2015; 29:1117-1121.

Outcome

Toxicity

Drug Interaction Probability Scale (DIPS)

Score
7 - Probable

Editorial Comment

Coadministration may increase vinblastine concentrations (due to inhibition of CYP3A4 and P-gp), resulting in the potential for increased incidence of adverse events. Severe neutoxicity has been reported in patients treated concomitantly with vinblastine and ritonavir, another strong CYP4A4 inhibitor (Cingolani A te al. AIDS 2010; Corona G et al. AIDS 2013; Cheung MC et al. Clin Lymphoma Myeloma Leuk 2010).