Date of report 14 May 2024

Reported case interaction between
Ritonavir and Levonorgestrel

A 25-year-old female well-controlled on tenofovir alafenamide, emtricitabine and darunavir/ritonavir presented elevated transaminases during a routine clinic appointment, consistent with drug induced liver injury (DILI). Blood tests demonstrated ALT at 535 IU/L and AST at 380 IU/L, with a subsequent rise of ALT to 1115 IU/L in 24 h, prompting admission. Viral hepatitis and autoimmune screens were negative apart from the antinuclear antibody (ANA), which had been previously investigated and attributed to HIV. Drug history revealed that the patient took levonorgestrel progesteron-only emergency contraception (POEC) 3 days prior to admission. She had attended a community pharmacy for emergency contraception and disclosed her antiretroviral treatment. She was advised to take 3 mg (double the normal 1.5 mg dose) of levonorgestrel POEC due to a potential interaction with ritonavir (listed as an inducer of POEC in the contraception prescribing resources with the recommendation to double the POEC dose). Investigations found that the most probable cause of DILI in this patient was a drug-drug interaction between levonorgestrel and with ritonavir. Ritonavir inhibits CYP4A5 and does induce certain CYPs and UGT. POEC undergoes glucuronidation but is mainly metabolized by CYP3A4 thus the net effect of ritonavir is an increase in POEC exposure. This case prompted the revision of the contraception prescribing resources which no longer recommend to double POEC in presence of ritonavir.

This case was published by Oddie PD et al. in Int J STD & AIDS 2023.