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section title)
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Hypersensitivity reactions including rash, urticaria, pruritus, chills, chest
and throat tightness, lip and
throat swelling, and hypotension were reported in
27 (4.5%)
of 606 healthy subjects during
or after the administration of raxibacumab in clinical
trials. Two subjects experienced anaphylaxis
during the raxibacumab infusion [see Adverse Reactions (6.1)].
Some subjects
with hypersensitivity or anaphylaxis required interruption or discontinuation of the
raxibacumab infusion as well as additional appropriate treatment that included steroids, diphenhydramine,
H2 blockers,
and/or intravenous fluids [see
Adverse Reactions (6.1)].
Due to the risk of anaphylaxis, administer
raxibacumab injection in monitored
settings where appropriate
equipment, medication (including epinephrine) and personnel trained
to manage hypersensitivity,
anaphylaxis, and shock are available. Monitor patients closely
during the infusion and for
a period of time after administration.
If hypersensitivity reactions or anaphylaxis occur, interrupt or stop the raxibacumab infusion immediately and
treat appropriately.
Premedicate with diphenhydramine within 1 hour
prior to administering raxibacumab to reduce the risk of occurrence
and/or severity of a hypersensitivity reaction [see Dosage and Administration
(2.1), Adverse Reactions (6.1)]. Diphenhydramine
premedication does not
prevent anaphylaxis and may mask
or delay the onset of symptoms of hypersensitivity.
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In the three
pre-licensure clinical trials (Trials
1, 2, and 3), the safety of
raxibacumab was
evaluated in 326 healthy subjects treated with
a dose of 40 mg/kg in 3 clinical trials: a
drug interaction trial with ciprofloxacin (Trial
1), a repeat-dose trial of
20 subjects with the second raxibacumab dose administered ?4 months
after the first dose (Trial 2), and a placebo-controlled trial evaluating single doses with a subset of subjects receiving 2 raxibacumab
doses 14 days apart (Trial 3).
Raxibacumab was administered to 86 healthy subjects in Trial
1. In Trial 3, 240 healthy subjects received
raxibacumab (217 received
1 dose and 23 received 2 doses) and 80 subjects received
placebo.
Trial 4 was
a post-marketing trial
in healthy subjects designed to evaluate the effect
of a single 40 mg/kg infusion of raxibacumab on the immunogenicity of a concurrently administered 3-dose subcutaneous (SC) regimen
of Anthrax Vaccine Adsorbed (AVA) [N=286] compared
with an AVA-alone regimen [N=286].
In the combination arm, the first dose
of AVA was administered immediately following the
raxibacumab infusion (Day 1), while the second and third doses were administered
on Days 15 and 29 The mean age
of subjects was 36 years in both arms, 52% of subjects
in the
AVA arm and 50% in the AVA
+ raxibacumab arm were female, 75% and 77% in the two
arms, respectively, were white, while
21% and 20%, respectively, were
African American.
Adverse Reactions
Leading to Discontinuation or Interruption of Raxibacumab Infusion
Four subjects
(1.2%) in Trials 1, 2 and 3 had their infusion of raxibacumab
discontinued for hypersensitivity
and anaphylaxis: 2 subjects (neither
of whom received diphenhydramine premedication) discontinued due to urticaria
(mild), and 1 subject each discontinued for
clonus (mild) and dyspnea (moderate).
In Trial 4, six (2.1%) subjects required discontinuation of the raxibacumab
infusion and 3 (1.0%) subjects required infusion
interruption due to hypersensitivity or anaphylaxis [see
Warnings and Precautions (5.1)].
Most
Frequently Reported Adverse Reactions
Trials 1, 2, and -3
In Trials 1,
2, and 3, the most frequently reported adverse reactions
were rash, pain in
extremity, pruritus, and somnolence
(Table 3).
(Title
of Table 3 updated)
Trial 4
Eleven (3.8%)
of 286 subjects who received
raxibacumab, all of whom received
diphenhydramine premedication, experienced hypersensitivity
manifesting as urticaria, pruritus, lip and throat
swelling, chest and throat tightness,
hypotension, and diffuse erythema;
2 (0.7%) of these subjects had anaphylaxis. Raxibacumab infusion was discontinued or interrupted
in 9/11 subjects. Hypersensitivity
reactions and anaphylaxis occurred
during administration of raxibacumab
prior to administration of the first dose
of AVA [see Warnings
and Precautions (5.1)].
Common adverse reactions, other than hypersensitivity,
occurring at a frequency of ?1.5% in
raxibacumab-exposed subjects
are presented in Table
4.
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added section)
Co-administration of 40 mg/kg raxibacumab intravenously
(Day 1) with a SC AVA regimen (Days 1, 15, and 29)
did not affect the immunogenicity
of AVA [see Clinical
Pharmacology (12.3)].
PCI
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Hypersensitivity Reactions
and Anaphylaxis
Inform patients
that hypersensitivity reactions, including anaphylaxis,
have occurred with the
administration of raxibacumab. Inform patients of
the signs and symptoms of hypersensitivity and anaphylaxis and instruct patients to seek immediate medical care if they experience
such symptoms during or following administration of
raxibacumab.
Prophylactic administration of diphenhydramine is recommended within 1
hour prior to administering raxibacumab to reduce the
risk of occurrence and/or the severity
of
hypersensitivity reactions [see Warnings and Precautions
(5.1)].
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What is the most important information I should know
about RAXIBACUMAB?
RAXIBACUMAB can cause serious side effects, including:
• Serious allergic reactions. Tell your healthcare
provider right away if you have any of the following symptoms while
receiving RAXIBACUMAB or after receiving RAXIBACUMAB:
o rash
o itching
o chest tightness or shortness
of breath
o swelling of the lips, throat, or tongue
o hives
o chills
o throat tightness or trouble breathing
o feeling dizzy or lightheaded
What is RAXIBACUMAB?
• RAXIBACUMAB is a prescription medicine used along with
antibiotic medicines to treat people with inhalational
anthrax. RAXIBACUMAB can also be used to prevent inhalational
anthrax disease when there are no other
treatment options.
• Your healthcare provider should give you a medicine called
diphenhydramine (BENADRYL) before you receive
RAXIBACUMAB to
help reduce your chances of developing an allergic reaction from
RAXIBACUMAB.
The most common side effects of RAXIBACUMAB include:
o rash
o pain in your arms or legs
o sleepiness
o injection site reactions, including redness and pain
o headache
Medicines are sometimes prescribed for purposes other
than those listed in a patient information leaflet. This patient
information leaflet summarizes the most important
information about RAXIBACUMAB. If you would like more information, talk to your
healthcare provider.
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