Table 5.
Antivirals for mpox treatmenta
| Antivirals | Pharmacokinetics | Contraindications | Warning and precautions | Adverse reactions | Use in specific populations |
|---|---|---|---|---|---|
| Tecovirimat (TPOXX®) |
Absorption: median Tmax ≈ 6 h; food increased the absorption of orally administered tecovirimat by 39% Distribution: human plasma protein binding ≈ 77–82%; VD ≈ 383 L (200 mg intravenously), 1030 L (600 mg orally) Metabolism: hydrolysis; UGT1A1, UGT1A4 Excretion Cl ≈ 13 L/h (200 mg intravenously); 31 L/h (600 mg oral); t½ ≈ 21 h (200 mg intravenously), 19 h (600 mg oral); urine excretion (oral) ≈ 73% (mostly as metabolites); fecal excretion ≈ 23% (mostly as tecovirimat) |
Tecovirimat injection (not capsule) is contraindicated in patients with creatinine clearance below 30 mL/min |
Coadministration with repaglinide may lead to hypoglycemia Tecovirimat may reduce serum concentrations of tacrolimus and sirolimus, and a dose increase of these drugs may be required |
Oral (capsule): headache, nausea, abdominal pain, and vomiting (incidence ≥ 2%) Injection: injection site reactions, headache (incidence ≥ 4%) |
Use in pregnancy: human data are not available. Animal reproduction studies did not report any embryofetal developmental toxicity Pediatric use: no clinical studies are available due to ethical reasons. The dose is calculated based on weight Geriatric use: dose adjustment is not needed in patients ≥ 65 years of age Renal impairment: Tecovirimat capsules do not require dose adjustment in renally impaired patients. Tecovirimat injections also do not require dose adjustment in patients with mild (creatinine clearance 60–89 mL/min) or moderate (creatinine clearance 30–59 mL/min) renal impairment; however, it is contraindicated in patients with severe renal impairment Hepatic impairment: Dose adjustment is not required in patients with mild, moderate, or severe hepatic impairment |
| Brincidofovir (TEMBEXA®) |
Absorption: bioavailability ≈ 16.8% (oral suspension); 13.4% (tablet) Tmaxb ≈ 6 h; AUC∞ and Cmax decreased by 31% and 49%, respectively, when Brincidofovir tablet is taken with food Distribution: human plasma protein binding > 99.9%; VD ≈1230 L Metabolism Hydrolysis; CYP4F2 Metabolites Cidofovir and cidofovir diphosphate (active) Excretion Cl ≈ 44.1 L/h; t½ ≈ 19.3 h; Urine excretion ≈ 51% (mostly as metabolites); fecal excretion ≈ 40% (mostly as metabolites) |
– |
Serum transaminases (ALT or AST) and bilirubin may increase. Monitor hepatic parameters before and during brincidofovir treatment. Monitor brincidofovir-associated GI symptoms; if severe, do not provide the second and final dose Intravenous cidofovir should not be coadministered with brincidofovir May cause embryo-fetal toxicity Crushing or diving the tablets is not recommended due to its potential carcinogenicity May irreversibly impair male fertility Brincidofovir has drug interactions with several antiretroviral agents (protease inhibitors, cobicistat, and fostemsavir). ART regimen or dosing may need modification |
Diarrhea, nausea, vomiting, and abdominal pain (incidence ≥ 2%) |
Use in pregnancy: embryotoxicity has been reported in animal studies. Not recommended during pregnancy Pediatric use: the safety profiles are similar in adult and pediatric populations Geriatric use: dose adjustment is not required. The safety profiles are similar in patients older and younger than 65 years Renal impairment: dose adjustment is not required in renally impaired patients or patients with end-stage renal diseases receiving dialysis Hepatic impairment: liver function test is recommended before starting therapy and during the therapy. Dose adjustment is not required in mild, moderate, or severe hepatic impairment Lactation: brincidofovir is excreted in the milk (animal studies) |
| Cidofovir | AUCc ≈ 40.8 μg.h/mL; Cmaxc ≈ 19.6 μg/mL; VDc ≈ 410 mL/kg; clearancec ≈ 148 mL/min/1.73 m2; renal clearance ≈ 98.6 mL/min/1.73 m2 (usually administered with probenecid, which may increase plasma levels of other drugs) |
Contraindicated in patients with creatinine clearance ≤ 55 mL/min, serum creatinine > 1.5 mg/dL, or a urine protein ≥ 100 mg/dL Contraindicated in patients taking nephrotoxic drugs; must be stopped 7 days prior to starting the therapy Patients with cidofovir hypersensitivity |
Dose-dependent nephrotoxicity. A renal function test must be performed prior to each dose administration Neutrophil count should be monitored due to the risk of developing neutropenia Coadministration of cidofovir and tenofovir disoproxil fumarate is not recommended |
Neutropenia, headache, iritis, impaired hearing, dyspnea, nausea, vomiting, diarrhea, pancreatitis, alopecia, rash, proteinuria, asthenia, fever, chills | Data regarding cidofovir use in different age groups, sex, and race are not available |
mpox monkeypox, Tmax time to reach Cmax, VD volume of distribution, UGT1A1 uridine diphosphate (UDP)-glucuronosyl transferase family 1 member A1, UGT1A4 uridine diphosphate (UDP)-glucuronosyl transferase family 1 member A4, Cl clearance, ALT alanine transaminase, AST aspartate transaminase, AUC∞ area under the unbound plasma concentration-time curve extrapolated to infinity, Cmax maximum concentration, CYP4F2 cytochrome P450 family 4 subfamily F member 2, t½ terminal half-life, ART antiretroviral therapy, GI gastrointestinal
aDisclaimer: Table 5 is for general information only and does not constitute professional advice. Please consult the relevant up-to-date guidelines, package inserts, and authoritative texts before making a clinical decision
bAdministered under fasted conditions
c5 mg/kg cidofovir administered with probenecid