Date of report: 03 Feb 2020
Reported case interaction between
Cobicistat and Ranolazine

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
Jan. 1, 2014
End date
Ongoing
Drug B
Ranolazine (Victim)
Daily Dose
1000 (mg)
Dose adjustment performed
No
Administration Route
Oral
Start date
Nov. 1, 2018
End date
Jan. 31, 2019

Complete list of drugs taken by the patient

Antiretroviral treatment
Darunavir (with Ritonavir or Cobicistat)
Emtricitabine/Tenofovir-AF
Complete list of all comedications taken by the patient, included that involved in the DDI
Aspirin 81 mg once daily (5 years), cilostazol 50 once daily (5 years), clopidogrel 75 mg once daily (5 years), atorvastatin 40 mg once daily (5 years), tiotropium 18 ug once daily (2 years), ondansetron 8 mg twice daily (<2months), pantoprazole 40 mg once daily (<2months), tramadol 50 mg once daily (1 year), ranolazine 500 mg twice daily (2 months)

Clinical case description

Gender
Male
Age
64
eGFR (mL/min)
>60
Liver function impairment
No
Description
In early January 2019, a 64 year old man was admitted to the hospital with left-sided chest pain, dizziness and near syncope. The patient also reported persistent and severe episodes of nausea, vomiting, dyspepsia and anorexia for the past 2 months. Electrocadiography revealed first-degree atrioventricular block (AV). During the hospitalization, the pharmacist identified the drug-drug interaction between ranolazine and darunavir/cobicistat which led to the interruption of ranolazine. The patient's chest pain, nausea and dizziness resolved in a couple of days after stopping ranolazine. Gastrointestinal and AV block events are known side effects of ranolazine. In the present case, these side effects occurred likely due to cobicistat inhibition of ranolazine metabolism leading to an increased exposure. This case has been published by Dougherty JA et al. Ann Pharmacother 2019; 53:966-7.

Outcome

Toxicity

Drug Interaction Probability Scale (DIPS)

Score
8 - Probable

Editorial Comment

Ranolazine levels have been shown to be significantly increased by ketoconazole another strong CYP4A4 inhibitor (Jerling M et al. J Clin Pharmacol 2005). Ranolazine product label contra-indicated the coadministration with strong CYP3A4 inhibitors.