Drug Dosing in Hospitalized Obese Patients With COVID-19

Abstract and Introduction

Abstract

Obesity is highly prevalent in hospitalized patients admitted with COVID-19. Evidence based guidelines are available for COVID-19-related therapies but dosing information specific to patients with obesity is lacking. Failure to account for the pharmacokinetic alterations that exist in this population can lead to underdosing, and treatment failure, or overdosing, resulting in an adverse effect. The objective of this manuscript is to provide clinicians with guidance for making dosing decisions for medications used in the treatment of patients with COVID-19. A detailed literature search was conducted for medications listed in evidence-based guidelines from the National Institutes of Health with an emphasis on pharmacokinetics, dosing and obesity. Retrieved manuscripts were evaluated and the following prioritization strategy was used to form the decision framework for recommendations: clinical outcome data > pharmacokinetic studies > adverse effects > physicochemical properties. Most randomized controlled studies included a substantial number of patients who were obese but few had large numbers of patients more extreme forms of obesity. Pharmacokinetic data have described alterations with volume of distribution and clearance but this variability does not appear to warrant dosing modifications. Future studies should provide more information on size descriptors and stratification of data according to obesity and body habitus.

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Table 1. Characteristics of weight in subjects included in randomized controlled trials evaluating tocilizumab
Study	N	Dose	Weight descriptor for tocilizumab arm	Main results
BACC Bay Stone [27]	243	8 mg/kg, max 800 mg	BMI = 29.9 (26–34.2) kg/m²	No difference in mechanical ventilation or death
CORIMUNO-19 Hermine [28]	131	8 mg/kg, option for additional 400 mg dose at 72 h	Weight = 80 (70–90) kg BMI = 27.9 (23.3–30.8) kg/m²	No improvement in need for mechanical ventilation on day 4 or survival free from mechanical ventilation
COVACTA Rosas [29]	438	8 mg/kg, max 800 mg, option to repeat dose in 8–24 h	Weight = 89 ± 24 kg	No difference in clinical status
COVINTOC Soin [30]	180	6 mg/kg, max 480 mg, option to repeat dose in 12 h	Not reported	No improvement in progression of disease
EMPACTA Salama [31]	340	8 mg/kg, max 800 mg, option to repeat dose in 8–24 h	Weight = 90 ± 24 kg BMI = 32 ± 7.9 kg/m²	Reduction in progression to the composite of mechanical ventilation or death
RCT-TCZ-COVID-19 Salvarani [32]	126	8 mg/kg, max 800 mg followed by 2nd dose after 12 h	BMI ≥ 30 kg/m² = 28%	No difference in clinical worsening
RECOVERY [33]	1350	800 mg if > 90 kg, 600 mg if > 65 and ≤ 90 kg, 400 mg if > 40 and ≤ 65 kg, 8 mg/kg if ≤ 40 kg, option to repeat dose in 12–24 h	Not reported	Improvement in 28-day survival
REMAP-CAP, 2021 [34]	865	8 mg/kg, max 800 mg, option to repeat dose in 12–24 h	BMI = 30.5 (26.9–34.9) kg/m²	Improvement in respiratory and cardiovascular organ support-free days
REMDACTA Rosas [35]	649	8 mg/kg, max 800 mg, option to repeat dose in 8–24 h	Weight = 94 ± 27 kg	No difference in time to discharge
TOCIBRAS Veiga [36]	129	8 mg/kg, max 800 mg	Obesity = 23%	No improvement in clinical status at day 15
Wang [37]	65	400 mg, option to repeat dose at 24 h	Not reported	No difference in cure rate

Table 1. Characteristics of weight in subjects included in randomized controlled trials evaluating tocilizumab

Study

Dose

Weight descriptor for tocilizumab arm

Main results

BACC Bay
Stone [27]

243

8 mg/kg, max 800 mg

BMI = 29.9 (26–34.2) kg/m²

No difference in mechanical ventilation or death

CORIMUNO-19
Hermine [28]

131

8 mg/kg, option for additional 400 mg dose at 72 h

Weight = 80 (70–90) kg
BMI = 27.9 (23.3–30.8) kg/m²

No improvement in need for mechanical ventilation on day 4 or survival free from mechanical ventilation

COVACTA
Rosas [29]

438

8 mg/kg, max 800 mg, option to repeat dose in 8–24 h

Weight = 89 ± 24 kg

No difference in clinical status

COVINTOC
Soin [30]

180

6 mg/kg, max 480 mg, option to repeat dose in 12 h

Not reported

No improvement in progression of disease

EMPACTA
Salama [31]

340

8 mg/kg, max 800 mg, option to repeat dose in 8–24 h

Weight = 90 ± 24 kg
BMI = 32 ± 7.9 kg/m²

Reduction in progression to the composite of mechanical ventilation or death

RCT-TCZ-COVID-19
Salvarani [32]

126

8 mg/kg, max 800 mg followed by 2nd dose after 12 h

BMI ≥ 30 kg/m² = 28%

No difference in clinical worsening

RECOVERY
[33]

1350

800 mg if > 90 kg, 600 mg if > 65 and ≤ 90 kg, 400 mg if > 40 and ≤ 65 kg, 8 mg/kg if ≤ 40 kg, option to repeat dose in 12–24 h

Not reported

Improvement in 28-day survival

REMAP-CAP,
2021 [34]

865

8 mg/kg, max 800 mg, option to repeat dose in 12–24 h

BMI = 30.5 (26.9–34.9) kg/m²

Improvement in respiratory and cardiovascular organ support-free days

REMDACTA
Rosas [35]

649

8 mg/kg, max 800 mg, option to repeat dose in 8–24 h

Weight = 94 ± 27 kg

No difference in time to discharge

TOCIBRAS
Veiga [36]

129

8 mg/kg, max 800 mg

Obesity = 23%

No improvement in clinical status at day 15

Wang [37]

400 mg, option to repeat dose at 24 h

Not reported

No difference in cure rate

Drug Dosing in Hospitalized Obese Patients With COVID-19

Abstract and Introduction

Abstract

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References

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