Recommendations on avoiding drug-drug interactions, data on recovery after ventilation

Advice on avoiding drug-drug interactions (DDIs) when prescribing nirmatrelvir-ritonavir for patients with COVID-19 was provided by an Ideas and Opinions article published by Annals of Internal Medicine on March 1.

The authors recommend using the NIH COVID-19 treatment guidelines or the University of Liverpool's website on COVID-19 drug interactions for this purpose but also suggest that clinicians understand the metabolic pathways that lead to these interactions. “Ritonavir inhibition of CYP3A4, and also the transporter P-glycoprotein, means that significant DDIs can be expected with comedications that are predominantly metabolized by CYP3A4 and/or have a narrow therapeutic index (such as tacrolimus) or are sensitive substrates of P-glycoprotein (such as digoxin),” they wrote. Another risk is that strong enzyme inducers (such as rifampicin, carbamazepine, enzalutamide, and St. John's wort) can reduce the efficacy of nirmatrelvir-ritonavir, they added. The authors offered four options for dealing with potential interactions: “1) preemptive pausing of the comedication therapy; 2) monitoring or dose adjustment of comedications (not usually feasible); 3) patient counseling with symptom-driven withdrawal of medications where appropriate, such as with antihypertensives; or 4) choice of an alternative treatment of SARS-CoV-2 infection.”

Two recent studies looked at long-term outcomes in COVID-19 patients who underwent tracheostomy and mechanical ventilation. An analysis of patients discharged to long-term acute care hospitals after respiratory failure, published by CHEST on Feb. 24, compared 37 with COVID-19 to 128 with another diagnosis. It found that the COVID-19 patients had a higher adjusted ventilator liberation rate (91.4% vs. 56.0%) as well as greater improvement in functional status and shorter length of stay. “We believe that COVID patients represent a unique population in the post-acute care settings. Allowing time for rehabilitation and ventilator liberation attempts can help them to achieve a recovery beyond what is seen in the general [long-term acute care hospital] population,” the authors said. The other study, published by Critical Care Medicine on Feb. 21, followed 81 COVID-19 patients with tracheostomy and percutaneous endoscopic gastrostomy (PEG) placement for 90 days, finding that 9.9% had died, 2.7% still had the tracheostomy, 32.9% still had the PEG, and 58.9% were at home.

Finally, the New England Journal of Medicine published an analysis of the omicron variant in South Africa on Feb. 23 and The Lancet published a systematic review of the duration of COVID-19 vaccine effectiveness on Feb. 21.