Sir, as we are aware, many patients are dentally anxious and undergo treatment under intravenous sedation using midazolam. What may be less common knowledge is that numerous drugs used in the management of HIV interact with midazolam.

Curative treatment of HIV with antiretroviral therapy is currently not yet possible; however, drug regimens known as combined antiretroviral therapy aim to reduce morbidity and transmission of disease, whilst increasing survival. A combination of drugs are used, commonly two or three, which are from at least two different drug classes.1

Classes of drugs used in the management of HIV include:

  • Nucleotide reverse transcriptase inhibitors (NRTI)

  • Non-nucleotide reverse transcriptase inhibitors (NNRTI)

  • Integrase strand transfer inhibitors (INSTI)

  • Protease inhibitors (PI)

  • Fusion inhibitors (FI)

  • Post-attachment inhibitors

  • Pharmacokinetic enhancers

  • Integrase inhibitors

  • CCR5 antagonists.1,2

Saquinavir is a protease inhibitor and a study found that the clearance of intravenous midazolam was reduced by 56% in patients taking this drug. Furthermore, the elimination half-life was increased from 4.1 to 9.5 hours.3 Hence, sedation is likely to be prolonged. Other medications used in the management of HIV include but are not limited to: ritonavir, atazanavir, fosamprenavir, tipranavir, darunavir, cobicistat, lopinavir and letermovir. These are all listed in the BNF as having severe interactions with midazolam.

It is therefore necessary for both sedationists and referrers to be aware of these interactions in order to be able to accurately advise patients of the safe treatment options available to them. Furthermore, this highlights the importance of checking for drug interactions in the BNF.

Given that these drugs are listed as having severe interactions with midazolam, should we consider referring patients taking them for anaesthetist-led sedation?