Friday, May 8, 2020

Tocilizumab Administration Guide


TOCILIZUMAB 400 MG  / 20 ML (20 MG/ML)
ACTEMRA®
FRIDGE item
NOT in HKGU Formulary
ROUTE
DILUTION
INFUSION RATE
INTRAVENOUS
Dilute to final volume
of 100 ml NS 2,3
Infused over 1 hr 2,3
(using a dedicated IV line) 3
Allow diluted solution for infusion to reach room temperature prior to administration 3
DILUENT
NS 1 
STABILITY
·       For vials: Store at 2-8ºC. DO NOT freeze. Keep container in outer carton to protect from light 1
·       For prepared infusion solution: Physically and chemically stable in 0.9% NaCl at 30ºC for 24 hrs (provided aseptic techniques applied). 1
·       Only solutions which are clear to opalescent, colourless to pale yellow and free of visible particles must be infused. 1,3
DOSING
·       Limited data available; dosing used in clinical trials includes the following: 3
§  4-8 mg/kg (usual dose: 400 mg/dose; max: 800 mg/dose) as a single dose; may repeat dose in ≥12 hours in patients who remain febrile within 24 hours of initial dose (NIH 2020c).
§  8 mg/kg (max: 800 mg/dose) as a single dose; may repeat dose in 8-12 hours if signs/symptoms worsen or do not improve (Genentech 2020).
§  8 mg/kg (max: 800 mg/dose) every 12 hours for 2 doses (NIH 2020a).
§  8 mg/kg as a single dose (NIH 2020b; NIH 2020e).

HOWEVER, LATEST SLIDE available from ID Team, HQE @ 28.08.2020:
Dose recommended: 8 mg/kg single dose (MAX: 800 mg/dose).

·       Tocilizumab may reduce the serum concentration of chloroquine and ritonavir (component of Kaletra). 4

·       The renal dosing recommendations are based upon the best available evidence and clinical expertise: 3

CrCl (mL/min)
Suggested Renal Adjustment
≥30
No dosage adjustment necessary.
<30
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, based on tocilizumab's molecular weight (148 kDa), it is unlikely to be significantly renally eliminated (expert opinion).

ADVERSE REACTIONS
>10%
1-10%
o Increased serum cholesterol (20%)
o Increased ALT (≤36%)
o Increased AST (≤22%)
o Infusion-related reaction (4-20%)
o Hypertension (6%)
o Peripheral edema (<2%)
o Skin rash (2%)
o Leukopenia (<2%)
o Thrombocytopenia (1%)
o Increased serum bilirubin (<2%)
o Herpes simplex infection (<2%)
o  Headache (7%)
o  Nasopharyngitis (7%)
o  URTI (7%)
o  Conjunctivitis (<2%)
o Hypothyroidism (<2%)
o Increased LDL (9%)
o Nephrolithiasis (<2%)
o Gastric ulcer (<2%)
o Oral mucosa ulcer (2%)
o Stomatitis (<2%)
o Upper abdominal pain (2%)
o Weight gain (<2%)
o Bronchitis (3%)
o Cough (<2%)
o Dyspnea (<2%)
REFERENCES
1.     Product Leaflet (Actemra - Roche).
2.     COVID-19 treatment and drug doses [Sarawak General Hospital, updated 23.03.2020]
3.     UptoDate: Tocilizumab: Drug information [Accessed online on 8 May 2020]
4.     UptoDate: Drug Interaction Checker [Accessed online on 8 May 2020]
Prepared by J. Ho [8 May 2020]

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