Date of report 31 Oct 2019
Reported case interaction between
Cobicistat and PACLITAXEL
Cobicistat and PACLITAXEL
Drugs suspected to be involved in the DDI
Complete list of drugs taken by the patient
Paliperidone 6 mg BID, mirtazapine 30 mg QD, lorazepam 2 mg QD, levomepromazine 25 mg QD, and alprazolam 0.5 mg PRN (bipolar disorder), transdermal fentanyl 25 mcg/h transdermal patch and pancreatine supplements.
Clinical case description
50 year-old patient, 77 kg, smoker, no enolic habit, ex-drug user (no drug use since 2002), HIV infected since 1987 on ART. HCV was treated in June 2018, with sustained virologic response. Since February 2019 on ART with dolutegravir 50 mg QD and darunavir/cobicistat 800/150 mg QD. A locally advanced pancreas head cancer was diagnosed in July 2019. He started chemotherapy in August 2019 with gemcitabine 1640 mg and (paclitaxel albumin) 205 mg (dose adjusted at 80%), days +1,+8 and +15 every 28 days. On September 18th chemotherapy dose was adjusted to 60% due to patient fragility. According to the treating physician, chemotherapy was acceptably well tolerated: nadir value of neutrophils 2,3 x10^9/L and platelets 63 x 10^9/L in October 2019. He had had mucositis (grade1 G1), diarrhea (G1), asthenia, cellulitis of the leg and was admitted due to biliary focus sepsis in September. In August 2019 he had an HIV viral load of 63 c/mL and CD4 432 cells/mm3 (18%). On October 24th viral load was <50 c/mL and CD4 861 cells/ mm3.
Clinical Outcome
Editorial Comment
Paclitaxel is predominantly metabolized by CYP2C8 and to a lesser extent by CYP3A4. The literature reports several cases of paclitaxel associated toxicities in patients on PI/ritonavir regimens (Mir O et al. BJCP 2010) due to ritonavir inhibition of both CYP2C8 and CYP3A4 mediated metabolism resulting in higher exposure of paclitaxel. Of interest, cobicistat has no inhibitory effect on CYP2C8 thus boosting by cobicistat might represent an advantage as the main metabolic pathway of paclitaxel is not inhibited thereby mitigating the magnitude of the interaction.
University of Liverpool Recommendation
These drugs should not be coadministered