Módulo 1 – Curso pós-graduado – VIH e Envelhecimento

Drug-drug Interactions and Polypharmacy in Older HIV Persons

Polymedication and drug metabolism in aging patients

Autor: Marta Boffito, MD PhD (Chelsea and Westminster Hospital, London, UK)

New information about drug interactions

There has been new information about drug interactions with antiretrovirals, presented in several scientific meetings.

The interaction between dolutegravir (DTG) and metformin was first reported at the 2014 Glasgow conference.7 The authors found that administration of 50 mg DTG once daily or twice daily, especially, led to an increase of metformin levels above the safety threshold.The intake of 50 mg once daily (OD) produced a 66% increase in maximum serum concentration (Cmax) of metformin, a problematic level in older age groups.The mechanism of interaction is related to the blockade by DTG of organic cation transporter 2 (OCT-2) in renal tubular cells. These proteins are responsible for the metformin transport during its renal elimination.

At the 2015 Conference on Retroviruses and Opportunistic Infections (CROI), they were also presented data on the interaction between ledispavir/sofosbuvir with antiretrovirals.8 The authors found:

  • Slight increases of ledipasvir and sofosbuvir metabolite (GS-331 007) with ATV;
  • A slight reduction in sofosbuvir as a result of interaction with darunavir (DRV),;
  • A remarkable increased concentration of TDF with protease inhibitor ritonavir-boosted, particularly ATV or DRV, in co-administration with ledispavir/sofosbuvir,.

In this case, it is recommended to avoid co-administration, or monitor for toxicity of ritonavir. In the case of TDF, it is advisable to monitor renal function. Since treatment with ledipasvir / sofosbuvir lasts for three months, it is not necessary to change the antiretroviral treatment. However, the risk of toxicity may be higher in older individuals with a suboptimal tolerability to TDF.

Another aspect that has gained importance is the interaction between antiretroviral drugs and substances of abuse. The website of the University of Liverpool recommends caution since the inhibition of CYP3A4 or other metabolic pathways can create situations of lethal toxicity.

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