Pronunciation
(oh mah lye ZOO
mab)
Index Terms
rhuMAb-E25
Dosage Forms
Excipient
information presented when available (limited, particularly for generics);
consult specific product labeling.
Solution
Reconstituted, Subcutaneous [preservative free]:
Xolair: 150 mg
(1 ea)
Brand Names:
U.S.
Xolair
Pharmacologic
Category
Monoclonal
Antibody, Anti-Asthmatic
Pharmacology
Asthma:
Omalizumab is an IgG monoclonal antibody (recombinant DNA derived) which
inhibits IgE binding to the high-affinity IgE receptor on mast cells and
basophils. By decreasing bound IgE, the activation and release of mediators in
the allergic response (early and late phase) is limited. Serum free IgE levels
and the number of high-affinity IgE receptors are decreased. Long-term
treatment in patients with allergic asthma showed a decrease in asthma
exacerbations and corticosteroid usage.
Chronic
idiopathic urticaria: Omalizumab binds to IgE and lowers free IgE levels.
Subsequently, IgE receptors (FcεRI) on cells down-regulate. The mechanism by
which these effects of omalizumab result in an improvement of chronic
idiopathic urticaria symptoms is unknown.
Absorption
Slow following
SubQ injection
Distribution
Vd:
78 ± 32 mL/kg
Metabolism
Degradation of
IgG and omalizumab:IgE complexes by reticuloendothelial system and endothelial
cells in the liver
Excretion
Primarily via
hepatic degradation; intact IgG may be secreted in bile
Onset of Action
Response to
therapy: ~12 to 16 weeks (87% of patients had measurable response in 12 weeks)
Time to Peak
7-8 days
Half-Life
Elimination
26 days (asthma
patients); 24 days (chronic idiopathic urticaria patients)
Use: Labeled
Indications
Asthma: Treatment
of moderate to severe persistent asthma in adults and patients 6 years and
older who have a positive skin test or in vitro reactivity to
a perennial aeroallergen and whose symptoms are inadequately controlled with
inhaled corticosteroids.
Guideline
recommendations:
The 2007
National Asthma Education and Prevention Program asthma guidelines recommend
use be considered as adjunctive therapy in patients with severe persistent asthma
who have allergies and in patients with severe persistent asthma that is
inadequately controlled with a combination of a high-dose inhaled
corticosteroid and a long-acting beta2-agonist (NAEPP 2007).
The Global
Initiative for Asthma suggests use be considered as adjunctive therapy in
patients with moderate or severe allergic asthma that is uncontrolled with a
combination of a medium- to high-dose inhaled corticosteroid and a long-acting
beta2-agonist (GINA 2016).
Chronic
idiopathic urticaria: Treatment of chronic idiopathic urticaria in adults
and adolescents 12 years and older who remain symptomatic despite H1 antihistamine
treatment.
Contraindications
Severe
hypersensitivity reaction to omalizumab or any component of the formulation
Dosing: Adult
Asthma: SubQ: Dose
and frequency based on body weight and pretreatment total IgE
serum levels. Dosing should be adjusted during therapy for significant changes
in body weight. Dosing should not be adjusted based on total
IgE levels taken during treatment or <1 year following interruption of
therapy. If therapy has been interrupted for ≥1 year, total IgE levels may be
re-evaluated for dosage determination.
Pretreatment
serum IgE ≥30 to 100 units/mL:
30 to 90 kg: 150
mg every 4 weeks
>90 to 150
kg: 300 mg every 4 weeks
Pretreatment
serum IgE >100 to 200 units/mL:
30 to 90 kg: 300
mg every 4 weeks
>90 to 150
kg: 225 mg every 2 weeks
Pretreatment
serum IgE >200 to 300 units/mL:
30 to 60 kg: 300
mg every 4 weeks
>60 to 90 kg:
225 mg every 2 weeks
>90 to 150
kg: 300 mg every 2 weeks
Pretreatment
serum IgE >300 to 400 units/mL:
30 to 70 kg: 225
mg every 2 weeks
>70 to 90 kg:
300 mg every 2 weeks
>90 kg: Do
not administer dose
Pretreatment
serum IgE >400 to 500 units/mL:
30 to 70 kg: 300
mg every 2 weeks
>70 to 90 kg:
375 mg every 2 weeks
>90 kg: Do
not administer dose
Pretreatment
serum IgE >500 to 600 units/mL:
30 to 60 kg: 300
mg every 2 weeks
>60 to 70 kg:
375 mg every 2 weeks
>70 kg: Do
not administer dose
Pretreatment
serum IgE >600 to 700 units/mL:
30 to 60 kg: 375
mg every 2 weeks
>60 kg: Do
not administer dose
Chronic
idiopathic urticaria: SubQ: 150 or 300 mg every 4 weeks. Dosing is not
dependent on serum IgE (free or total) level or body weight.
Dosing:
Geriatric
Refer to adult
dosing.
Dosing:
Pediatric
Asthma:
Children 6 to
<12 years: SubQ:
Pretreatment
serum IgE ≥30 to 100 units/mL:
20 to 40 kg: 75
mg every 4 weeks
>40 to 90 kg:
150 mg every 4 weeks
>90 to 150
kg: 300 mg every 4 weeks
Pretreatment
serum IgE >100 to 200 units/mL:
20 to 40 kg: 150
mg every 4 weeks
>40 to 90 kg:
300 mg every 4 weeks
>90 to 125
kg: 225 mg every 2 weeks
>125 to 150
kg: 300 mg every 2 weeks
Pretreatment
serum IgE >200 to 300 units/mL:
20 to 30 kg: 150
mg every 4 weeks
>30 to 40 kg:
225 mg every 4 weeks
>40 to 60 kg:
300 mg every 4 weeks
>60 to 90 kg:
225 every 2 weeks
>90 to 125
kg: 300 mg every 2 weeks
>125 to 150
kg: 375 mg every 2 weeks
Pretreatment
serum IgE >300 to 400 units/mL:
20 to 30 kg: 225
mg every 4 weeks
>30 to 40 kg:
300 mg every 4 weeks
>40 kg to 70
kg: 225 mg every 2 weeks
>70 to 90 kg:
300 mg every 2 weeks
>90 kg: Do
not administer
Pretreatment
serum IgE >400 to 500 units/mL:
20 to 25 kg: 225
mg every 4 weeks
>25 to 30 kg:
300 mg every 4 weeks
>30 to 50 kg:
225 mg every 2 weeks
>50 to 70 kg:
300 mg every 2 weeks
>70 to 90 kg:
375 mg every 2 weeks
>90 kg: Do
not administer
Pretreatment
serum IgE >500 to 600 units/mL:
20 to 30 kg: 300
mg every 4 weeks
>30 to 40 kg:
225 mg every 2 weeks
>40 to 60 kg:
300 mg every 2 weeks
>60 to 70 kg:
375 mg every 2 weeks
>70 kg: Do
not administer
Pretreatment
serum IgE >600 to 700 units/mL:
20 to 25 kg: 300
mg every 4 weeks
>25 to 40 kg:
225 mg every 2 weeks
>40 to 50 kg:
300 mg every 2 weeks
>50 to 60 kg:
375 mg every 2 weeks
>60 kg: Do
not administer
Pretreatment
serum IgE >700 to 900 units/mL:
20 to 30 kg: 225
mg every 2 weeks
>30 to 40 kg:
300 mg every 2 weeks
>40 to 50 kg:
375 mg every 2 weeks
>50 kg: Do
not administer
Pretreatment
serum IgE >900 to 1,100 units/mL:
20 to 25 kg: 225
mg every 2 weeks
>25 to 30 kg:
300 mg every 2 weeks
>30 to 40 kg:
375 mg every 2 weeks
>40 kg: Do
not administer
Pretreatment
serum IgE >1,100 to 1,200 units/mL:
20 to 30 kg: 300
mg every 2 weeks
>30 kg: Do
not administer
Pretreatment
serum IgE >1,200 to 1,300 units/mL:
20 to 25 kg: 300
mg every 2 weeks
>25 to 30 kg:
375 mg every 2 weeks
>30 kg: Do
not administer
Adolescents ≥12
years: SubQ: Refer to adult dosing.
Chronic
idiopathic urticaria: Adolescents ≥12 years: SubQ: Refer to adult dosing.
Dosing: Renal
Impairment
There are no
dosage adjustments provided in the manufacturer’s labeling.
Dosing: Hepatic
Impairment
There are no
dosage adjustments provided in the manufacturer’s labeling.
Dosing:
Adjustment for Toxicity
Severe
hypersensitivity reaction or anaphylaxis: Discontinue treatment.
Fever,
arthralgia, and rash: Discontinue treatment if this constellation of symptoms
occurs.
Reconstitution
Reconstitute
using SWFI only; add SWFI 1.4 mL to upright vial using a 1-inch, 18-gauge
needle on a 3 mL syringe and swirl gently for ~1 minute to evenly wet the
powder; do not shake. Then gently swirl the upright vial for 5 to 10 seconds
approximately every 5 minutes until dissolved; generally takes 15 to 20 minutes
to dissolve completely. If it takes >20 minutes to dissolve completely,
continue to swirl the upright vial for 5 to 10 seconds every 5 minutes until no
gel-like particles are visible in the solution; do not use if contents are not
completely dissolved after 40 minutes. After reconstitution, solution is
somewhat viscous and will appear clear or slightly opalescent. It is acceptable
if there are a few small bubbles or foam around edge of vial. Invert the vial
for 15 seconds so the solution drains toward the stopper. Remove all of the
solution by inserting a new 3 mL syringe with a 1-inch, 18-gauge needle into
the inverted vial. Replace the 18-gauge needle with a 25-gauge needle for
subcutaneous injection, and expel any air, bubbles, or excess solution to
obtain the resulting dose of 150 mg per 1.2 mL; or discard 0.6 mL from the
syringe to obtain the resulting dose of 75 mg per 0.6 mL.
Administration
For SubQ
injection only; doses >150 mg should be divided over more than one injection
site (eg, 225 mg or 300 mg administered as two injections, 375 mg administered
as three injections). Injections may take 5 to 10 seconds to administer
(solution is slightly viscous). Administer only under direct medical
supervision and observe patient for a minimum of 2 hours following
administration of any dose given.
Storage
Prior to
reconstitution, store under refrigeration at 2°C to 8°C (36°F to 46°F); product
may be shipped at room temperature. Following reconstitution, protect from
direct sunlight. May be stored for up to 8 hours if refrigerated or 4 hours if
stored at room temperature ≤30°C (≤86°F).
Drug
Interactions
Belimumab:
Monoclonal Antibodies may enhance the adverse/toxic effect of Belimumab. Avoid
combination
Loxapine: Agents
to Treat Airway Disease may enhance the adverse/toxic effect of Loxapine. More
specifically, the use of Agents to Treat Airway Disease is likely a marker of
patients who are likely at a greater risk for experiencing significant
bronchospasm from use of inhaled loxapine. Management: This is specific to the
Adasuve brand of loxapine, which is an inhaled formulation. This does not apply
to non-inhaled formulations of loxapine. Avoid combination
Test
Interactions
Total IgE levels
are elevated for up to 1 year following treatment. Total serum IgE may be
retested after interruption of therapy for 1 year or more.
Adverse
Reactions
Asthma:
>10%: Local:
Injection site reaction (45%; severe 12%; includes bruising, redness, warmth,
burning, stinging, itching, hive formation, pain, indurations, mass, and
inflammation). Most reactions occurred within 1 hour, lasted <8 days, and
decreased in frequency with additional dosing.
1% to 10%:
Cardiovascular:
Pulmonary embolism (≤3%), venous thrombosis (≤3%), myocardial infarction (2%),
unstable angina pectoris (2%)
Central nervous
system: Pain (7%), dizziness (3%), fatigue (3%)
Dermatologic:
Dermatitis (2%), pruritus (2%)
Neuromuscular
& skeletal: Arthralgia (8%), leg pain (4%), arm pain (2%), bone fracture
(2%)
Otic: Otalgia
(2%)
Chronic
idiopathic urticaria:
>10%: Central
nervous system: Headache (6% to 12%)
1% to 10%:
Cardiovascular:
Peripheral edema (≥2%)
Central nervous
system: Anxiety (≥2%), migraine (≥2%)
Dermatologic:
Alopecia (≥2%)
Gastrointestinal:
Toothache (≥2%)
Genitourinary:
Urinary tract infection (≥2%)
Infection:
Fungal infection (≥2%)
Local: Injection
site reaction (3%)
Neuromuscular
& skeletal: Arthralgia (3%), limb pain (≥2%), musculoskeletal pain (≥2%),
myalgia (≥2%)
Respiratory:
Nasopharyngitis (9%), sinusitis (5%), upper respiratory tract infection (3%),
asthma (≥2%), oropharyngeal pain (≥2%), sinus headache (≥2%), cough (2%), viral
upper respiratory tract infection (≤2%)
Miscellaneous:
Fever (≥2%)
All indications: <1%
(Limited to important or life-threatening): Alopecia, anaphylaxis, antibody
development, arthritis, chest tightness, eosinophilic granulomatosis with
polyangiitis (formerly known as Churg-Strauss), lymphadenopathy, malignant
neoplasm, pulmonary hypertension, syncope, thrombocytopenia, transient ischemic
attacks
ALERT: U.S.
Boxed Warning
Anaphylaxis:
Anaphylaxis,
presenting as bronchospasm, hypotension, syncope, urticaria, and/or angioedema
of the throat or tongue, has been reported to occur after administration of
omalizumab. Anaphylaxis has occurred as early as after the first dose of
omalizumab but also has occurred beyond 1 year after beginning regularly
administered treatment. Because of the risk of anaphylaxis, observe patients
closely for an appropriate period of time after omalizumab administration.
Health care providers administering omalizumab should be prepared to manage
anaphylaxis that can be life-threatening. Inform patients of the signs and
symptoms of anaphylaxis and instruct them to seek immediate medical care if
symptoms occur.
Warnings/Precautions
Concerns related
to adverse effects:
• Cardiovascular
effects: Cerebrovascular events, including transient ischemic attack and
ischemic stroke, have been reported.
• Eosinophilia
and vasculitis: In rare cases, patients may present with systemic eosinophilia,
sometimes presenting with clinical features of vasculitis consistent with
eosinophilic granulomatosis with polyangiitis (formerly known as
Churg-Strauss), a condition which is often treated with systemic corticosteroid
therapy. Health care providers should be alert to eosinophilia, vasculitic
rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy
presenting in their patients. A causal association between omalizumab and these
underlying conditions has not been established.
•
Fever/arthralgia/rash: Reports of a constellation of symptoms including fever,
arthritis or arthralgia, rash, and lymphadenopathy have been reported with
postmarketing use (symptoms resemble those seen in patients experiencing serum
sickness, although circulating immune complexes or a skin biopsy consistent
with a Type III hypersensitivity reaction were not seen with these cases).
Onset of symptoms generally occurred 1 to 5 days following the first or
subsequent doses. Discontinue therapy in any patient reporting this
constellation of signs/symptoms.
•
Hypersensitivity/anaphylactoid reactions: [US Boxed Warning]:
Anaphylaxis, including delayed-onset anaphylaxis, has been reported following
administration; anaphylaxis may present as bronchospasm, hypotension, syncope,
urticaria, and/or angioedema of the throat or tongue. Anaphylaxis has occurred
after the first dose and in some cases >1 year after initiation of regular
treatment. Due to the risk, patients should be observed closely for an
appropriate time period after administration and should receive treatment only
under direct medical supervision. Healthcare providers should be prepared to
administer appropriate therapy for managing potentially life-threatening
anaphylaxis. Patients should be instructed on identifying signs/symptoms of
anaphylaxis and to seek immediate care if they arise. In postmarketing
reports, anaphylaxis usually occurred with the first or second dose and with a
time to onset of ≤60 minutes; however, reactions have been reported with
subsequent doses (after 39 doses) and with a time to onset of up to 4 days
after administration. A case-control study showed that patients with a history
of anaphylaxis to foods, medications, or other causes were at an increased risk
of anaphylaxis. Discontinue therapy following any severe reaction.
• Malignant
neoplasms: Have been reported rarely with use in short-term studies; impact of
long-term use is not known.
Disease-related
concerns:
• Parasitic
infections: Use with caution and monitor patients at high risk for parasitic
(helminth) infections; risk of infection may be increased; appropriate duration
of continued monitoring following therapy discontinuation has not been
established.
Concurrent drug
therapy issues:
• Corticosteroid
therapy: Gradually taper systemic or inhaled corticosteroid therapy; do not
discontinue corticosteroids abruptly following initiation of omalizumab
therapy. The combined use of omalizumab and corticosteroids in patients with
chronic idiopathic urticaria has not been evaluated.
• Drug-drug
interactions: Potentially significant interactions may exist, requiring dose or
frequency adjustment, additional monitoring, and/or selection of alternative
therapy. Consult drug interactions database for more detailed information.
Other
warnings/precautions:
• Appropriate
use: Therapy has not been shown to alleviate acute asthma exacerbations; do not
use to treat acute bronchospasm, status asthmaticus, or other allergic
conditions. Do not use to treat forms of urticaria other than chronic
idiopathic urticaria.
• Dosing/IgE
levels: Dosing for asthma is based on body weight and pretreatment total IgE
serum levels. IgE levels remain elevated up to 1 year following treatment;
therefore, levels taken during treatment or for up to 1 year following
treatment cannot and should not be used as a dosage guide. Dosing in chronic
idiopathic urticaria is not dependent on serum IgE (free or total) level or
body weight.
Monitoring
Parameters
Anaphylactic/hypersensitivity
reactions, baseline serum total IgE; FEV1, peak flow, and/or other
pulmonary function tests; monitor for signs of infection
Pregnancy
Considerations
Adverse events
have not been observed in animal reproduction studies. IgG molecules are known
to cross the placenta. Information related to the use of omalizumab in
pregnancy is available from case reports of women with severe asthma
(Kupryś-Lipińska 2014) or chronic idiopathic urticaria (some also with asthma)
(Cuervo-Pardo 2016; Ghazanfar 2015). In addition, preliminary data from the
Xolair Pregnancy Registry (EXPECT) has been published. Based on data collected
from 191 women September 2006 through November 2012, the incidence of the
adverse events monitored (major congenital malformations, prematurity, low
birth weight, small for gestational age) are within the rates of those reported
for women with severe asthma (Namazy 2015). The pregnancy registry has closed;
however, new cases of exposure may be reported to the manufacturer (Genentech
888-835-2555).
Uncontrolled
asthma is associated with adverse events on pregnancy (increased risk of
perinatal mortality, pre-eclampsia, preterm birth, low-birth-weight infants).
Optimal control of asthma prior to and during pregnancy is recommended (GINA
2016; NAEPP 2005).
Patient
Education
• Discuss
specific use of drug and side effects with patient as it relates to treatment.
(HCAHPS: During this hospital stay, were you given any medicine that you had
not taken before? Before giving you any new medicine, how often did hospital
staff tell you what the medicine was for? How often did hospital staff describe
possible side effects in a way you could understand?)
• Patient may
experience headache, nausea, loss of strength and energy, pharyngitis,
rhinitis, common cold symptoms (children), abdominal pain (children), vomiting
(children), or nosebleed (children). Have patient report immediately to
prescriber signs of infection, signs of severe cerebrovascular disease (change
in strength on one side is greater than the other, difficulty speaking or
thinking, change in balance, or vision changes), signs of DVT (edema, warmth,
numbness, change in color, or pain in the extremities), burning or numbness
feeling, bone pain, severe injection site irritation, angina, jaw pain, arm
pain, passing out, shortness of breath, difficulty breathing, joint pain,
muscle rigidity, muscle pain, joint edema, swollen glands, rash, or coughing up
blood (HCAHPS).
• Educate
patient about signs of a significant reaction (eg, wheezing; chest tightness;
fever; itching; bad cough; blue skin color; seizures; or swelling of face,
lips, tongue, or throat). Note: This is not a comprehensive
list of all side effects. Patient should consult prescriber for additional
questions.
Intended Use and
Disclaimer: Should not be printed and given to patients. This information is
intended to serve as a concise initial reference for health care professionals
to use when discussing medications with a patient. You must ultimately rely on
your own discretion, experience, and judgment in diagnosing, treating, and
advising patients.
