How to use omalizumab:

Use omalizumab as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Omalizumab comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it
again each time you get omalizumab refilled.
Omalizumab is usually given as an injection at your doctor's office, hospital, or clinic.
If you miss a dose of omalizumab or you are unable to keep your doctor's appointment, contact your doctor right
away.
Ask your health care provider any questions you may have about how to use omalizumab.
Metabolism and Pharmacokinetic Profile
The metabolism and pharmacokinetic profile of omalizumab has been previously reviewed in detail.
25
After a single
subcutaneous dose in adult and adolescents with asthma, omalizumab is absorbed slowly over several days, reaching
peak serum concentrations after an average of seven to eight days.
25,26
The pharmacokinetics of omalizumab are
linear at doses above 0.5 mg per kg. Measurements of omalizumab serum concentrations reflect the combination of
free omalizumab and that bound to IgE. Serum free IgE levels reduce in a dose-dependent manner within one hour of
the first dose of omalizumab and levels are maintained between doses, whereas concentrations of total IgE (ie, the
sum of free and omalizumab bound IgE) are increased. Information about drug distribution is limited to reports from
intravenous administration of radiolabeled omalizumab in cynomolgus monkeys.
27
These studies suggest that most of
the drug remains in the central intravascular compartment, with little accumulation in tissues. Elimination of
omalizumab appears to involve IgG clearance processes as well as clearance via specific binding and complex
formation with its target ligand, IgE. Liver elimination of IgG includes degradation in the reticulo-endothelial system
and endothelial cells. Intact IgG is also excreted in bile. In patients with asthma, the omalizumab serum elimination
half-life averages 26 days, with apparent clearance rates averaging 2.4 1.1 mL per kg per day. In addition, doubling
of body weight approximately doubles clearance rates. The half-life of omalizumab is variable, with values ranging
from one to four weeks.
25
After discontinuation of omalizumab, free and total IgE concentrations approach baseline
slowly. In a dose-ranging study involving patients with ragweed seasonal allergic rhinitis, average free IgE
concentrations returned to baseline within eight weeks of the last omalizumab infusion.
28
Total IgE concentrations
generally take longer to approach baseline after stopping therapy.
28,29
One year after discontinuation of omalizumab
dosing, circulating IgE levels return to baseline pre-treatment levels with no observed rebound.
26
Analyses of
population pharmacokinetics of omazulamab suggest that no dose adjustments are necessary for the age range 6 to 76
years, race, ethnicity, gender or Body Mass Index. There are no pharmacokinetic or pharmacodynamic data in
patients with renal or hepatic impairment
Doubling of body weight approximately doubles clearance rates. The half-life of omalizumab is variable, with values
ranging from one to four weeks. After discontinuation of omalizumab, free and total IgE concentrations approach
baseline slowly.
Elimination :The metabolism of omalizumab is determined by its IgG1 framework, and specific binding to IgE.
Liver is one site of elimination for IgG, includingdegradation in the liver reticulo-endothelial system and endothelial
cells. The omalizumab:IgE complexes are believed to clear via interactions with Fcgamma-Rs at rates that are
generally faster than IgG clearance. Relative clearance of free omalizumab, free IgE, and complexes is summarized
as: free IgE clearance > >omalizumab:IgE clearance >omalizumab clearance.
Omalizumab appears to be eliminated through one fast pathway as IgE complex and by slower hepatic elimination as
free omalizumab. In therapeutic dosing, omalizumab concentrations in blood are markedly higher than the
concentrations of IgE. Thus, the slowpathway greatly dominated during therapeutic dosing but the faster pathway has
a greater role at subtherapeutic doses.
The elimination of omalizumab is dose-dependent. Clearance of omalizumab is low (around 0.181 l/day) and the
half-life is long; around 35-40 days or even longer. The partial accumulation ratio from day 112 to day 336 was 1.1-
1.4
Omalizumab concentrations in blood are markedly higher than the concentrations of IgE.
The slow pathway greatly dominated during therapeutic dosing but the faster pathway has a greater role at
subtherapeutic doses.
The patient's pretreatment serum total IgE level (IU/mL) and body weight (lb or kg) are used to determine doses (mg)
and dosing frequency. Refer to the dosing calculator and dosing tables below for the appropriate dose. Doses of more
than 150 mg are divided among more than 1 injection site to limit injections to not more than 150 mg per site.
Patients whose pretreatment serum total IgE level or body weight is outside the limits of the dosing table (<30 or
>700 IU/mL and <66 or >330 lb, respectively) should not be dosed.
XOLAIR is administered subcutaneously every 4 weeks: 150mg/dose or 300 mg per dose, or every 2 weeks at 225,
300, or 375 mg per dose. Because the solution is slightly viscous, the injection may take 5 to 10 seconds to
administer.
Anaphylaxis usually occurred within two hours of receiving a omalizumab subcutaneous injection.
Anaphylaxis may occur after any dose of omalizumab including the first dose.
Anaphylaxis has occurred as early as after the first dose of omalizumab, but also has occurred beyond 1 year after
beginning regularly administered treatment.
Malignant neoplasm was observed in 20 of 4127 (0.5%) patients treated with XOLAIR compared with 5 of 2236
(0.2%) control patients in clinical studies.
The observed malignancies in patients treated with XOLAIR were a variety of types, with breast, non-melanoma
skin, prostate, melanoma, and parotid occurring more than once, and 5 other types occurring once each
The majority of patients were observed for less than 1 year
The impact of longer exposure to XOLAIR or use in patients at higher risk of malignancy is unknown.
An injection site reaction refers to swelling, redness or soreness.
The injection site reaction most commonly occurs within an hour of the Xolair injection, but may occur up to a day or
so later.