Table 1.
Drug Information for FDA-Approved Therapies Under Consideration for Patients With COVID-19
| Generic Name (Brand Name) | Dose | Dose Adjustment | Contraindications/Adverse Effects (Listed in Alphabetic Order) | Potential Drug Interactions |
|---|---|---|---|---|
| IL-6 Inhibitors | ||||
| Tocilizumab (Actemra) [19] | Cytokine Release Syndrome • <30 kg–12 mg/kg IV • ≥30 kg–8 mg/kg IV (maximum 800 mg per IV infusion. Up to 3 additional doses 8 hours apart.) Giant cell arteritis/RA •162 mg SQ every 7 to 14 days Optimal dosage for COVID-19 unknown but doses of 4–8 mg/kg IV (maximum 800 mg/dose) that may be repeated in patients with suboptimal response are being studied in clinical trials |
No dose adjustments recommended in renal dysfunction Hepatic dysfunction: • ALT or AST >1−3× ULN: 4 mg/kg • ALT or AST >3−5× ULN: dose every other week • ALT or AST >5× UNL: discontinue |
• GI perforation • Hepatotoxicity • Hypersensitivity • Increased risk of infections including TB, IFI, opportunistic infections, and reactivation of HBV or VZV • Major adverse cardiovascular events • Neutropenia • Thrombocytopenia • Transaminitis |
• May increase or decrease metabolism of CYP450 substrates • Live vaccines should be avoided |
| Sarilumab (Kevzara) [20] | RA • 200 mg SQ every 2 weeks Optimal dosage for COVID-19 unknown but doses of 200 mg SQ and alternative IV dosing regimens are being studied in clinical trials |
No dose adjustments recommended in renal dysfunction Hepatic dysfunction: • ALT >3−5× ULN: interrupt therapy, may result once ALT <3× ULN • ALT >5× ULN: discontinue Neutropenia: • ANC 500–1000 cells/mm3: interrupt therapy, may resume once ANC >1000 cells/mm3 • ANC <500 cells/mm3: discontinue Thrombocytopenia: • Platelets 50 000–100 000 cells/mm3: interrupt therapy, may resume once platelets >100 000 cells/mm3 • Platelets <50 000 cells/mm3: discontinue |
• GI perforation • Hepatotoxicity • Hyperlipidemia • Hypersensitivity • Increased risk of infections including TB, IFI, opportunistic infections, and reactivation of HBV or VZV • Neutropenia • Thrombocytopenia • Transaminitis |
|
| Siltuximab (Sylvant) [21] | Castleman Disease • 11 mg/kg IV every 3 weeks Optimal dosage for COVID-19 unknown but doses of 11 mg/kg per day are being studied in clinical trials |
No dose adjustments recommended in renal or hepatic dysfunction Therapy should be delayed in patients with the following: • ANC <1000 cells/mm3 • Platelets <50 000 cells/mm3 • Hemoglobin ≥17 g/dL |
• Hepatotoxicity • Hypersensitivity • Increased hemoglobin • Increased risk of infections including TB, IFI, opportunistic infections, and reactivation of HBV or VZV • Neutropenia • Thrombocytopenia • Transaminitis |
|
| JAK Inhibitors | ||||
| Sunitinib (Sutent) [68] | GI stromal tumor, pancreatic neuroendocrine tumor, renal cell carcinoma • 37.5–50 mg PO every 24 hours, 4 weeks on, 2 weeks off Optimal dosage for COVID-19 unknown |
No dose adjustments recommended in renal or hepatic dysfunction Therapy should be modified or discontinued in patients with the following: • EF >20% but <50% below baseline without signs of HF • Signs or symptoms of HF • Severe hypertension • Dermatologic toxicities • Grade 3 or 4 hepatotoxicity • Thrombotic microangiopathy • Reversible posterior leukoencephalopathy syndrome • Nephrotic syndrome • Proteinuria (≥3 g/day) |
• Cardiotoxicity (including HR, cardiomyopathy, myocardial ischemia, and MI) • Embryo-fetal toxicity • Erythema multiforme • Hand-foot skin reaction • Hemorrhage • Hepatotoxicity • Hypertension • Necrotizing fasciitis • Neutropenia • Osteonecrosis of the jaw • Proteinuria/nephrotic syndrome • QTc prolongation • Stevens-Johnson syndrome (SJS) • Thrombotic microangiopathy • Toxic epidermal necrolysis (TEN) |
• Strong CYP3A4 inhibitors may increase sunitinib plasma concentration • Strong CYP3A4 inducers may decrease sunitinib plasma concentration |
| Erlotinib (Tarceva) [69] | Pancreatic Cancer • 100 mg PO every 24 hours Nonsmall Cell Lung Cancer • 150 mg PO every 24 hours Optimal dosage for COVID-19 unknown |
No dose adjustments recommended in renal or hepatic dysfunction Therapy should be delayed in patients with grade 3 or 4 renal toxicity or renal failure associated with hepatorenal syndrome or dehydration Concomitant administration with CYP3A4 inducers: increase by 50 mg Concomitant administration with CYP3A4 inhibitors: decrease by 50 mg | • Bullous and exfoliative skin disorders • Cardiovascular events (including cerebrovascular accidents, myocardial ischemia, and MI) • GI perforation • Hepatotoxicity • Interstitial lung disease • Microangiopathic hemolytic anemia • Ocular toxicity • Renal dysfunction and/or failure • Embryo-fetal toxicity |
• CYP3A4 and CYP1A2 inhibitor increase erlotinib plasma concentrations • CYP3A4 inducers decrease erlotinib plasma concentrations • Acid suppressive therapy |
| Ruxolitinib (Jakafi) [70] | Polycythemia vera • 50 mg PO every 24 hours Myelofibrosis • 20–50 mg PO every 24 hours Optimal dosage for COVID-19 unknown but doses of 10 mg PO every 12 hours × 14 days, then 5 mg PO every 12 hours × 2 days, then 5 mg PO every 24 hours × 1 day are being studied in clinical trials |
Therapy should be modified or discontinued in patients with the following: • Bleeding • CrCl <60 mL/min and platelets <150 000 cells/mm3 • Hepatic impairment (Child-Pugh class A, B, C) and platelets <150 000 cells/mm3 |
• Acute relapse of myelofibrosis symptoms • Anemia • Dizziness • Fatigue • Headache • Hyperlipidemia • Increased risk of infections including TB, IFI, opportunistic infections, and reactivation of HBV or VZV • Neutropenia • Nonmelanoma skin cancer • Thrombocytopenia |
• Strong CYP3A4 inhibitors, fluconazole |
| Fedratinib (Inrebic) [71] | Myelofibrosis • 400 mg PO every 24 hours Optimal dosage for COVID-19 unknown |
Renal dysfunction: • CrCl 15–29 mL/min: decrease dose to 200 mg every 24 hours Hepatic dysfunction: • Total bilirubin >3× ULN and any AST value: avoid use |
• Anemia • Encephalopathy including Wernicke’s • GI toxicity, • Hepatotoxicity, • Increased amylase and/or lipase • Neutropenia • Thrombocytopenia |
• Strong CYP3A inhibitors and inducers |
| Baricitinib (Olumiant) [72] | RA • 2 mg PO every 24 hours Optimal dosage for COVID-19 unknown but doses of 2–4 mg PO every 24 hours are being studied in clinical trials |
Renal dysfunction: • CrCl 30–60 mL/min: decrease dose to 1 mg every 24 hours • CrCl <30 mL/min: discontinue No dose adjustments recommended in hepatic dysfunction |
• Anemia • GI perforations • Hepatotoxicity • Hyperlipidemia • Increased risk of infections including TB, IFI, opportunistic infections, and reactivation of HBV or VZV • Lymphopenia • Malignancy • Neutropenia • Thrombosis |
• Live vaccines should be avoided • Organic Anion Transporter 3 (OAT3) inhibitors (eg, probenecid) |
| IL-1 Receptor Antagonists | ||||
| Anakinra (Kineret) [81] | Neonatal-Onset Multisystem Inflammatory Disease • 1–2 mg SQ every 24 hours (maximum dose 8 mg/kg per day) RA • 100 mg SQ every 24 hours Approved only for SQ administration in USA. Optimal dosage for COVID-19 unknown but multiple SQ and IV doses are being studied in clinical trials |
Renal dysfunction: • CrCl <30 mL/min or ESRD: administer every 48 hours No dose adjustments recommended in hepatic dysfunction |
• Cross-sensitivity to Escherichia coli-derived proteins • Hypersensitivity reactions including anaphylaxis • Increased risk of infections including TB, IFI, opportunistic infections, and reactivation of HBV or VZV • Injection site reactions • Malignancy • Neutropenia • Thrombocytopenia |
• Use with TNF-α inhibitors may increase risk of serious infections • Live vaccinations should be avoided |
| VEGF Inhibitors | ||||
| Bevacizumab (Avastin) [127] | Metastatic Colorectal Cancer • 5–7.5 mg/kg IV every 2 to 3 weeks Nonsmall Cell Lung Cancer • 15 mg/kg IV every 3 weeks Renal Cell Carcinoma • 10 mg/kg IV every 2 weeks Cervical Cancer • 15 mg/kg IV every 3 weeks Glioblastoma • 10 mg/kg IV every 2 weeks Ovarian, Fallopian Tube, or Peritoneal Cancer • 10–15 mg/kg IV every 2 to 3 weeks Do not administer for 28 days following major surgery Optimal dosage for COVID-19 unknown but doses of 7.5 mg/kg IV and 500 mg IV are being studied in clinical trials |
No dose adjustments recommended in renal or hepatic dysfunction Therapy should be modified or discontinued in patients with the following: • Nephrotic syndrome • Proteinuria (≥2 g/day) • Fistula formation involving any internal organ • GI perforation (any grade) • HF • Grade 3 or 4 hemorrhage • Hypertensive crisis • Hypertensive encephalopathy • Infusion reaction • Posterior reversible encephalopathy syndrome • Thromboembolic events • Wound healing complications |
• Delayed wound healing • Fetal toxicity • Fistula formation • GI perforations • Hemorrhage • HF • Hypertension • Ocular toxicity • Ovarian failure • Posterior reversible encephalopathy syndrome • Proteinuria/nephrotic syndrome • Thromboembolic events |
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| TNF-α Inhibitors | ||||
| Adalimumab (Humira) [105] | RA, psoriatic arthritis, ankylosing spondylitis • 40 mg SQ every 2 weeks Plaque psoriasis, uveitis • 80 mg SQ on day 1, then 1 week later, 40 mg SQ every 2 weeks Crohn disease, ulcerative colitis, hidradenitis suppurativa • 160 mg SQ × 1, then 2 weeks later, 80 mg SQ × 1, then 2 weeks later, 40 mg SQ every 2 weeks Optimal dosage for COVID-19 unknown |
No dose adjustments recommended in renal or hepatic dysfunction | • Demyelinating disease • HF • Hypersensitivity • Increased risk of infections including TB, IFI, opportunistic infections, and reactivation of HBV or VZV • Malignancy • Neurologic reactions • Pancytopenia |
• Use with TNF-α inhibitors may increase risk of serious infections • Live vaccines should be avoided |
Abbreviations: ALT, alanine aminotransferase; ANC, absolute neutrophil count; AST, aspartate aminotransferase; COVID-19, coronavirus disease 2019; CrCl, creatinine clearance; CYP, cytochrome P450; EF, ejection fraction; ESRD, end-stage renal disease; FDA, US Food and Drug Administration; GI, gastrointestinal; HBV, hepatitis B virus; HF, heart failure; IFI, invasive fungal infections (including candidiasis and aspergillosis); IL, interleukin; IV, intravenous; JAK, Janus kinase; MI, myocardial infarction; OI, opportunistic infections (including pneumocystis); PO, by mouth; RA, rheumatoid arthritis; SQ, subcutaneous; TB, tuberculosis; TNF, tumor necrosis factor; ULN, upper limit of normal; VEGF, vascular endothelial growth factor; VZV, varicella zoster virus.