Structure Mechanism of action Production Administration Monitoring Side effects Toxicology

1. JSS SCIENCE AND TECHNOLOGY UNIVERSITY
Sri Jayachamarajendra College of Engineering
JSS TI Campus, Mysuru 570006
PHARMACEUTICAL BIOTECHNOLOGY
BT550
“Cetuximab: Structure, Mechanism of action, Application,
Side effects”
MANASAY
5TH SEMESTER
BIOTECHNOLOGY
01JST18BT012

2. CETUXIMAB
•Drug type: Cetuximab is an anti-cancer ("anti-neoplastic") targeted
therapy. This medication is classified as a "monoclonal antibody" and
"Epidermal Growth Factor Receptor (EGFR) Inhibitor.
•Trade name: Erbitux®
•Other name: C225
•Half life: 114 hours (range 75-188 hours)
•Clearance rate: Female patients had 25% lower intrinsic clearance than
male patients.
Manufacture
•Eli lilly and company
•Merck KGaA
Sales
•Cetuximab is given by intravenous therapy and costs up to $30,000 for
eight weeks of treatment per patient.
•Merck KGaA had 887 million euros ($1.15 billion) in Erbitux sales in
2012, from head and neck as well as bowel cancer, while Bristol-Myers
Squibb generated $702 million in sales from the drug.
•Erbitux was the eighth best-selling cancer drug of 2013, with sales of
$1.87 billion

3. Cetuximab is used for treatment of
Metastatic Colorectal Cancer (cancer spread
beyond the colon or rectum)
Non-small Cell Lung Cancer
Squamous Cell Cancer of the Head and Neck
Squamous Cell Skin Cancer

4. Structure
•Recombinant, human/mouse
chimeric monoclonal antibody
•Binds specifically to the
extracellular domain of the human
epidermal growth factor receptor
(EGFR).
•Composed of the Fv regions of a
murine anti-EGFR antibody with
human IgG1 heavy and kappa light
chain constant regions .
•Molecular weight : 152 kDa
•Chemical formula
C6484H10042N1732O2023S36
•Produced in mammalian (murine
myeloma) cell culture.

5. ERBITUX (cetuximab) injection for
intravenous use, is a sterile,
preservative-free, clear, colorless
solution, which may contain a small
amount of visible, white, amorphous
cetuximab particulates in a single-dose
vial.
Each 1 mL of solution contains :
•2 mg of cetuximab
•sodium chloride (8.48 mg)
•sodium phosphate dibasic
heptahydrate (1.88 mg)
•sodium phosphate monobasic
monohydrate (0.41 mg)
•Water for Injection
•USP at pH of 7.0 to 7.4.

6. Mechanism of Action

7.  Cell culture and harvesting
 Purification
 Gene construct
 Cell banking system
 Control of steps
 Biochemical characterisation
 Control of drug substance
 Product development and finished product
 Process validation
Production

8. Storage and handling
 Store vials under refrigeration at 2 C to 8 C
 Do not freeze or shake
 Increased particulate formation may occur at temperatures at or
below 0 C
 Discard any remaining solution in the infusion container after 8
hours at controlled room temperature or after 12 hours at 2 C
to 8C.
 Discard any unused portion of the vial.

9. Administration
•The administration of the drug is via
IV infusion with a loading dose
lasting over 2 hours, weekly
maintenance dose over 1 hour.
•Do not shake or dilute.
•Administer via infusion pump or
syringe pump.
•Following the infusion, an
observation period of 1 hour is
recommended; longer observation
time following an infusion reaction
may be necessary.
•Dosing prescribed as initial loading
dose 400 mg/m2 infused over 120
minutes and maintenance dose of 250
mg/m2 infused over 60 minutes for
both colorectal cancer, metastatic,
and head and neck cancer (squamous
cell)

10. Monitoring
 Vital signs during infusion and observe for at
least 1-hour post-infusion.
 Patients developing dermatologic toxicities
should be monitored for the development of
complications.
 Periodic monitoring of serum magnesium,
calcium, and potassium are recommended to
continue over an interval consistent with the
half-life (8 weeks); monitor closely (during
and after treatment) for cetuximab plus
radiation therapy.

11. Side Effects:
 Generalized weakness, fatigue,
 Weight loss and poor appetite
 Diarrhea, Nausea and Vomiting
 Abdominal pain, Constipation
 Inflammation of the mouth
 Low magnesium level
 Low blood counts.white cells may
temporarily decrease (neutropenia).
 Difficulty breathing, Cough
 Liver problems (hepatotoxicity and
elevated liver enzymes)
 Headache
 Nail changes - inflammation of the skin
surrounding a fingernail or toenail

12. Toxicity
 Cardiopulmonary arrest
 Infusion reactions
 Dermatologic toxicity
 Interstitial lung disease
 Electrolyte abnormality

13. THANK YOU