Ritonavir-containing products: reports of interaction with levothyroxine leading to reduced thyroxine levels

Monitor thyroid-stimulating hormone (TSH) in patients treated with levothyroxine for at least the first month after starting and ending ritonavir treatment.

Advice for healthcare professionals:

  • reduced thyroxine levels have been reported in patients concomitantly taking ritonavir-containing products and levothyroxine
  • monitor thyroid-stimulating hormone (TSH) in patients treated with levothyroxine for at least the first month after the start and end of ritonavir treatment
  • report suspected adverse drug reactions resulting from interactions on a Yellow Card

Review of interaction between ritonavir and levothyroxine

An EU review has assessed evidence for an interaction between ritonavir and levothyroxine following a signal of reduced thyroxine concentrations and increased TSH plasma concentrations in patients concomitantly taking these medicines. Some of the cases reported were symptomatic, including cases of hypothyroidism.

This interaction has been added to the Summaries of Product Characteristics and Patient Information Leaflets for ritonavir-containing medicines and levothyroxine.

Levothyroxine has a narrow therapeutic index and if ritonavir is stopped, any previous modifications to levothyroxine dose may have significant consequences for thyroxine levels. Induction of metabolism (glucuronidation) of levothyroxine by ritonavir is a possible mechanism for this interaction.

Monitor TSH during ritonavir changes

TSH should be monitored in patients receiving concomitant treatment with ritonavir and levothyroxine for at least the first month after starting and ending ritonavir treatment. The duration of the monitoring proposed is based on the pharmacokinetics of the drug—the half-life of thyroxine being 6–7 days.

About ritonavir and levothyroxine

Ritonavir is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infected patients (adults and children of 2 years of age and older). Ritonavir is also indicated for the treatment of chronic hepatitis C as part of a fixed-dose combination of ritonavir/ombitasvir/paritaprevir. The potential for an interaction with levothyroxine is already known for antivirals used in chronic hepatitis C treatment because paritaprevir and ombitasvir are inhibitors of uridine diphosphoglucuronate-glucuronosyltransferase 1A1.

Levothyroxine is indicated for the control of hypothyroidism.

Report drug interactions and access the latest safety information on the Yellow Card app

MHRA encourages the reporting of any suspected side effects, especially from interactions with medicines, food, or complimentary remedies such as herbals medicines. Remember only a suspicion is needed to report – if in doubt, please complete a Yellow Card.

Your report helps the MHRA to monitor the safety of medicines in the UK and identify potential side effects and adverse reactions. By reporting a Yellow Card, you can prevent future harms to other patients – see our Yellow Card patient leaflet for more. Personal details are kept safe, secure, and confidential.

Healthcare professionals, patients, and caregivers can report suspected side effects via the Yellow Card website or via the Yellow Card app. Download the app today via iTunes Yellow Card for iOS devices or via PlayStore Yellow Card for Android devices.

You can also use the app to access the latest safety information from MHRA about medicines and medical devices on the Newsfeed. Search for medicines to see details of Yellow Card reports others have made. Medicines of interest can also be added to a Watch List to receive news and alerts about new side effects and safety advice as it emerges.

Further information

Pharmacovigilance Risk Assessment Committee recommendations on signals. Adopted at the 5-8 February 2018 PRAC meeting.

Article citation: Drug Safety Update volume 12, issue 3: October 2018: 2.

Published 11 October 2018