Drug-Drug Interactions (DDI) amidst the Pandemic and Opportunities for Objective DDI Monitoring via Oral Fluid Testing

Clinical Update
November 2020

Drug-Drug Interactions (DDI) amidst the Pandemic and Opportunities for Objective DDI Monitoring via Oral Fluid Testing

The Coronavirus Disease 19 (COVID-19) pandemic has introduced many different challenges to the world this year. Economic, technologic, and healthcare issues have arisen to the forefront, where solutions to unexpected healthcare problems have been needed.  For example, patients with preexisting or new health conditions have been tentative to seek medical care because of fear of contracting COVID-19 or because of lack of transportation access.1  During the initial quarantine period around the middle of March, many patients were encouraged to stay home despite having medical conditions that needed professional evaluation.2  Outpatient ambulatory medical visits declined by ~60% from early March until late April, but have steadily increased through the end of October 2020.3  Telemedicine and other virtual technologies have increased to help ameliorate access to care problems, but continuity of  care still remains an issue for some patients.  However, increases in outpatient visits have not all returned to pre-pandemic levels for some specialties, such as Behavioral Health and Pulmonology, which are still down about 14% and 20%, respectively.3  Some patients may not have seen their provider for quite some time this year or are seeing them only virtually.  For these patients and possibly others, providers could benefit from objective laboratory data about their patient’s recent medication use, especially among patients who are at higher risk for drug-drug interactions and potential adverse events. 

Discussions related to drug-drug interactions amidst the pandemic first made news as new therapeutics and repurposed older medications were being considered either prophylactically or for treatment of COVID-19.  For example, hydroxychloroquine, an anti-malarial drug that was surrounded by controversy throughout the pandemic, drew significant concern for risk of cardiac adverse effects that can be worsened secondary to DDIs.4  A published meta-analysis demonstrated risk for DDIs between medications prescribed in the treatment of common comorbid conditions, such as hypertension and diabetes, and those therapeutics used in the treatment of patients with severe cases of COVID-19.5  This principle also applies to medications used in the treatment of behavioral health disorders.  For example, steroids used in the treatment of COVID-19 may impact mood in patients, or may have decreased efficacy in individuals that are being prescribed metabolic enzyme inducers such as carbamazepine.  Additionally, some medications prescribed in this patient population can also contribute to adverse cardiac effects with COVID-19 therapeutics.6  Assessment for risk of DDIs involving drugs used to treat COVID-19 should certainly remain top of mind, but it should not be forgotten that lapses in continuity of care can contribute to DDIs. 

Anxiety from fears of contracting COVID-19 as well as economic hardships from loss of income can shift how patients use medications, both from an illicit and legitimate prescription drug use perspective.  From February 16, 2020 until April 25, 2020 U.S. prescription drug claims decreased for the cholesterol medicines, atorvastatin, blood pressure medicine, lisinopril, and thyroid medicine, levothyroxine by 9.1%, 15.3%, and 20.0%, respectively.7 The health impact of this data is unknown at this time, but it does lend itself to the possibility of significant shifts in acute and maintenance medication use, which may contribute to adverse health outcomes for some patients.  Internal data from Aegis’ InterACT Rx testing completed in 2020 from 1/1-10/31 (Total Samples: 80,829) demonstrates significant ongoing risk for interactions between concurrently ingested substances:


As of November 2020 COVID-19 continues to circulate in the community and while outpatient visits are rising closer to their pre-pandemic levels, providers may still have new challenges assessing their patients’ health status.  Some patients may have stopped taking medications or started taking new prescriptions unbeknownst to their provider.  To better meet provider needs during the pandemic, InterACT Rx testing capabilities have been expanded to allow for testing in oral fluid specimens.  This will allow for objective assessment of very recent substance ingestion using definitive testing methodologies as well as identification of DDIs between detected substances.  Moreover, oral fluid collection procedures do not have to occur in person and can be monitored through virtual platforms, or can be performed in a less invasive manner in-office.  Data captured from oral fluid drug-drug interaction testing could be helpful for providers who have patients at high risk of adverse drug events or those who have been disproportionately affected by the pandemic.     

NOTICE: The information above is intended as a resource for health care providers. Providers should use their independent medical judgment based on the clinical needs of the patient when making determinations of who to test, what medications to test, testing frequency, and the type of testing to conduct.



1. Vervoort D, Luc JG, Percy E, et al.  Assessing the collateral damage of the novel coronavirus: a call to action for the post-COVID-19 era.  Ann Thorac Surg 2020; 110: 757-760. doi: 10.1016/j.athoracsur.2020.04.015.
2. Mattioli AV, Puviani MB, Nasi M, and Farinetti A. COVID-19 pandemic: the effects of quarantine on cardiovascular risk.  Eur J Clin Nutr 2020; 74: 852-855.
3. Mehrotra A, Chernew M, Linetsky D, et al.  The impact of the COVID-19 pandemic on outpatient care: visits return to prepandemic levels, but not for all providers and patients (Commonwealth Fund, Oct. 2020). https://doi.org/10.26099/41xy-9m57.
4. Hossen MS, Barek MA, Jahan N, Safiqul Islam M. A Review on Current Repurposing Drugs for the Treatment of COVID-19: Reality and Challenges. SN Compr Clin Med. 2020 Aug 31:1-13. doi: 10.1007/s42399-020-00485-9. Epub ahead of print. PMID: 32904710; PMCID: PMC7457893.
5. Charles A, Ingolf C. Meta-analysis on outcome-worsening comorbidities of COVID-19 and related potential drug-drug interactions. Pharmacol Res. 2020 Oct 12:105250. doi: 10.1016/j.phrs.2020.105250. Epub ahead of print. PMID: 33059010; PMCID: PMC7550259.
6. Hernández-Gómez A, Andrade-González N, Lahera G, Vieta E. Recommendations for the care of patients with bipolar disorder during the COVID-19 pandemic. J Affect Disord. 2020 Sep 28;279:117-121. doi: 10.1016/j.jad.2020.09.105. Epub ahead of print. PMID: 33045553.
7. Vaduganathan M, Meijgaard J, Mehra MR, et al. Prescription fill patterns for commonly used drugs during the COVID-19 pandemic in the United States. JAMA 2020; 323: 2524-2526. doi:10.1001/jama.2020.9184.