Table 1. Study Design, DDIs, DDI-Associated Adverse Outcomes, and Mechanisms Reported by the Reviewed Studies.
| Source | Study design | Study quality score | Drugs involved in potential DDIs | DDIs mechanism | DDI-associated adverse clinical outcomes and/or ADRs |
|---|---|---|---|---|---|
| Anmella et al,16 2020 | Case series | 4 | Acetazolamide, hydroxychloroquine, lopinavir-ritonavir, paroxetine, risperidone, and topiramate | PK | Behavioral disturbances |
| Case series | 4 | Acetazolamide, hydroxychloroquine, lopinavir and ritonavir, venlafaxine | PK | Mild QT-interval prolongation (443 ms) | |
| Bartiromo et al,17 2020 | Case report | 5 | Darunavir-cobicistat, hydroxychloroquine, and tacrolimus | PK | Tacrolimus trough levels found to be extremely high (90.5 ng/mL), intermittent abdominal pain, nausea and vomiting |
| Borba et al,18 2020 | Original investigation | 1 | Acetazolamide, ceftriaxone, and chloroquine | PK | Rhabdomyolysis, myocarditis, severe arrhythmias, QT-interval prolongation |
| Original investigation | 1 | Acetazolamide, ceftriaxone, chloroquine, and oseltamivir | PK | Rhabdomyolysis, myocarditis, severe arrhythmias, QT-interval prolongation | |
| Crescioli et al,19 2021 | Observational study | 3 | Amiodarone, acetazolamide, darunavir-cobicistat, and hydroxychloroquine | PK and PD | QT-interval prolongation |
| Observational study | 3 | Acetazolamide, citalopram, hydroxychloroquine, and lopinavir and ritonavir | PK and PD | QT-interval prolongation | |
| Observational study | 3 | Acetazolamide, darunavir-cobicistat, and hydroxychloroquine | PK and PD | Diarrhea, vomiting | |
| Observational study | 3 | Acetazolamide, haloperidol, hydroxychloroquine, levomepromazine, lopinavir-ritonavir, and zuclopenthixol | PK and PD | QT-interval prolongation | |
| Observational study | 3 | Acetazolamide, haloperidol, hydroxychloroquine, and lopinavir-ritonavir | PK and PD | QT-interval prolongation | |
| Observational study | 3 | Acetazolamide, hydroxychloroquine, and lopinavir-ritonavir | PK and PD | QT-interval prolongation | |
| Observational study | 3 | Acetazolamide, hydroxychloroquine, and lopinavir-ritonavir | PK and PD | QT-interval prolongation, vomiting | |
| Observational study | 3 | Acetazolamide, hydroxychloroquine, and sertraline | PK and PD | QT-interval prolongation | |
| Observational study | 3 | Citalopram and hydroxychloroquine | PK and PD | QT-interval prolongation | |
| Observational study | 3 | Darunavir-cobicistat, haloperidol, and hydroxychloroquine | PK and PD | QT-interval prolongation | |
| Observational study | 3 | Darunavir-cobicistat and hydroxychloroquine | PK and PD | QT-interval prolongation | |
| Observational study | 3 | Darunavir-cobicistat, hydroxychloroquine, lopinavir-ritonavir, and tocilizumab | PK and PD | Hypertransaminasemia | |
| Observational study | 3 | Darunavir-cobicistat, hydroxychloroquine, and tocilizumab | PK and PD | Psychosis, agitation, delirium, aggressiveness | |
| Observational study | 3 | Darunavir-cobicistat and tacrolimus | PK and PD | Nausea, vomiting, abdominal pain, drug level modification | |
| Observational study | 3 | Hydroxychloroquine and lopinavir-ritonavir | PK and PD | QT-interval prolongation, hypokalemia | |
| Observational study | 3 | Hydroxychloroquine and lopinavir-ritonavir | PK and PD | QT-interval prolongation | |
| Observational study | 3 | Hydroxychloroquine and magnesium sulfate | PK and PD | QT-interval prolongation, hypokalemia | |
| Observational study | 3 | Hydroxychloroquine and risperidone | PK and PD | QT-interval prolongation, atrial flutter, hemiplegia, hypokalemia, major depression | |
| Observational study | 3 | Hydroxychloroquine and trazodone | PK and PD | QT-interval prolongation | |
| Dajti et al,20 2020 | Case report | 5 | DRV/c, hydroxychloroquine, prednisone, and tacrolimus | PK | Increased tacrolimus levels |
| Gautret et al,21 2021 | Letter | 5 | Acetazolamide and hydroxychloroquine | PK | QT-interval prolongation (>60 ms), discontinuation of treatment |
| Ghani et al,22 2020 | Case series | 4 | Apixaban, enoxaparin, hydroxychloroquine, and corticosteroids | PK | A large intraparenchymal hemorrhage and cerebral edema |
| Case series | 4 | Apixaban, hydroxychloroquine, corticosteroids, and unfractionated heparin | PK | Scattered subarachnoid hemorrhages, a subdural hematoma | |
| Case series | 4 | Hydroxychloroquine, corticosteroids, and unfractionated heparin | PK | Acute subarachnoid and intraparenchymal hemorrhages within the posterior fossa | |
| Li et al,23 2020 | Observational study | 3 | Ganciclovir, lopinavir-ritonavir, oseltamivir, peramivir, penciclovir, rubavirin, and umifenovir | PK | Increase in D-dimer, hematologic abnormalities |
| Macías et al,24 2020 | Cross-sectional study | 4 | Amiodarone and lopinavir-ritonavir | PK | Orthostatic syncope |
| Martínez-López-de-Castro et al,25 2021 | Cohort, retrospective and single-center study | 3 | Alprazolam and lopinavir-ritonavir | PK | Psychiatric disorders |
| Cohort, retrospective and single-center study | 3 | Aripiprazole, digoxin, fentanyl, lithium, lopinavir-ritonavir, and tacrolimus | PK | Alteration of the concentration of blood levels | |
| Cohort, retrospective and single-center study | 3 | Acetazolamide and hydroxychloroquine | PK | Cutaneous reactions | |
| Cohort, retrospective and single-center study | 3 | Acetazolamide and lopinavir-ritonavir | PK | Gastrointestinal disorders | |
| Cohort, retrospective and single-center study | 3 | Hydroxychloroquine and lopinavir-ritonavir | PK | Hyperglycemia | |
| Cohort, retrospective and single-center study | 3 | Hydroxychloroquine and lopinavir-ritonavir | PK | Cutaneous reactions | |
| Cohort, retrospective and single-center study | 3 | Hydroxychloroquine and lopinavir-ritonavir | PK | Gastrointestinal disorders | |
| Cohort, retrospective and single-center study | 3 | Hydroxychloroquine and lopinavir-ritonavir | PK | Psychiatric disorders | |
| Cohort, retrospective and single-center study | 3 | Hydroxychloroquine and tacrolimus | PK | Alteration of the concentration of blood levels | |
| Cohort, retrospective and single-center study | 3 | Interferon beta and metamizole | PK | Hematologic toxicity | |
| Cohort, retrospective and single-center study | 3 | Lopinavir-ritonavir and methylprednisolone or prednisone | PK | Hyperglycemia | |
| Cohort, retrospective and single-center study | 3 | Lopinavir-ritonavir and midazolam or diazepam | PK | Increased sedative effect | |
| Cohort, retrospective and single-center study | 3 | Lopinavir-ritonavir and propofol | PK | Increased triglyceride level | |
| Cohort, retrospective and single-center study | 3 | Lopinavir-ritonavir and simvastatin | PK | Liver toxicity | |
| Cohort, retrospective and single-center study | 3 | Lopinavir-ritonavir and valproate | PK | Seizures | |
| Meriglier et al,26 2021 | Observational study | 2 | Darunavir-ritonavir and hydroxychloroquine | PK | Diarrhea grade I and II; ECG abnormalities; hepatic enzyme elevation |
| Observational study | 2 | Hydroxychloroquine and lopinavir-ritonavir | PK | Diarrhea grade I and II; ECG abnormalities; severe nausea | |
| Meziyerh et al,27 2020 | Case report | 5 | Everolimus, hydroxychloroquine, and lopinavir-ritonavir | PK | Dyspnea or tachypnea, everolimus plasma concentrations increased |
| Nham et al,28 2020 | Case report | 5 | Ceftriaxone, levofloxacin, and lopinavir-ritonavir | PK | Severe thrombocytopenia with epistaxis and petechiae |
| Ramireddy et al,29 2020 | Original research | 3 | Acetazolamide and hydroxychloroquine | PK | QT-interval prolongation |
| Skroza et al,30 2020 | Case report | 5 | Ceftriaxone, enoxaparin, hydroxychloroquine, and lopinavir-ritonavir | PK | Urticarial vasculitis attributable to adverse drug reaction |
| Szekely et al,31 2020 | Original research | 2 | Chloroquine, letrozole, and memantine | PK | Extreme QT-interval prolongation (720 ms), torsades de pointes |
| Teoli et al,32 2021 | Case report | 5 | Remdesivir and tramadol | PK | Severe pain localized in the legs |
| Thammathiwat et al,33 2021 | Case report | 5 | Darunavir-ritonavir and tacrolimus | PK | Tacrolimus levels turned significantly high, acute kidney injury, lymphopenia, Pio2/Fio2 was lowered, tacrolimus withdrawn for 10 d |
| Treon et al,34 2020 | Letter | 5 | Acetazolamide, hydroxychloroquine, and ibrutinib | PK | Wide QRS complex tachyarrhythmia |
| Yekedüz et al,35 2020 | Case report | 5 | Antidiabetics and hydroxychloroquine | PK | Hypoglycemia |
Abbreviations: ADRs, adverse drug reactions; DDIs, drug-drug interactions; DRV/c, darunavir-cobicistat; ECG, electrocardiography; Fio2, fraction of inspired oxygen; PD, pharmacodynamic; Pio2, inspired oxygen tension; PK, pharmacokinetic.