Approved Drug Label (PDF)
Boxed Warning
Effective
6/27/2025, Box Warning in supplement 17 has been removed.
5
Warnings and Precautions
5.1 Infusion Reactions
Additions and/or revisions underlined:
Hypotension,
including shock and cardiac arrest, wheezing, dyspnea, urticaria, muscular and
chest pain may occur with rapid TYZAVAN administration (e.g., over several
minutes). The reactions may be more severe in pediatric patients [see Use in Specific Populations (8.4)].
Rapid
intravenous administration of TYZAVAN may also be associated with “vancomycin
infusion reactions” which manifests as pruritus and erythema that involves
the face, neck and upper body or pain and muscle spasm of the chest and
back.
There
have been reports that the frequency of infusion-related reactions (including
hypotension, flushing, erythema, urticaria, and pruritus) increases with the
concomitant administration of anesthetic agents.
Infusion-related
adverse reactions are related to both the concentration and the rate of
administration of TYZAVAN. Infusion-related adverse reactions may occur,
however, at any rate or concentration. Administer TYZAVAN over a period of 60
minutes or greater to reduce the risk of infusion-related adverse reactions. In
selected patients in need of fluid restriction, a concentration up to 10 mg/mL
may be used; use of such higher concentrations may increase the risk of
infusion-related adverse reactions. Administer TYZAVAN as a 60-minute
infusion prior to administration of intravenous anesthetic agents
when feasible to minimize infusion-related adverse reactions. Stop the
infusion if a reaction occurs because this usually results in prompt
cessation of these reactions.
6
Adverse Reactions
Addition of the following
to the bulleted line listing:
Phlebitis
and Other Administration Site Reactions [see
Warnings and Precautions (5.8)].
6.1 Clinical
Trials Experience
Additions and/or revisions underlined:
…
Immune System Disorders: Hypersensitivity
reactions including anaphylaxis and “vancomycin infusion reactions”
8
Use in Specific Populations
8.1 Pregnancy
Additions
and/or revisions underlined:
Risk
Summary
…
The
background risk of major birth defects and miscarriage for the indicated population
is unknown.
…
Data
…
Animal
reproduction studies conducted in pregnant rabbits (gestation days 6 to 19) administered
intravenous NADA at 1680 mg/kg (32 times the maximum daily human dose or
greater based on AUC levels of NADA) resulted in fetal scoliosis and a spectrum
of cardiovascular malformations. Increased incidence of delayed or incomplete
ossifications of the metacarpals/metatarsals/phalanges and increased
ossification (fused jugal/maxilla bones) were also observed in rabbits at 1680
mg/kg without maternal toxicity. No adverse developmental outcomes were
observed in rabbits administered intravenous NADA at 560 mg/kg (11 times the
maximum daily human dose based on AUC levels of NADA). In reproduction studies
in pregnant rats (gestation days 6 to 17) administered intravenous NADA at
3780 mg/kg (20 times the maximum daily human dose based on AUC levels of
NADA) no fetal adverse effects were observed. Maternal toxicity, including
increased incidence of litter loss, was observed in rats at 3780 mg/kg [see Clinical Pharmacology (12.3)].
…
8.4
Pediatric Use
Additions and/or revisions underlined:
TYZAVAN is indicated in pediatric patients (1 month
and older) for the treatment of septicemia, infective endocarditis, skin and
skin structure infections, bone infections and lower respiratory tract
infections for whom appropriate dosing with this formulation can be achieved [see Indications and Usage (1.1 to 1.5) and
Dosage and Administration (2.1, 2.3)].
Because
of the limitations of the available strengths and administration requirements
(i.e., administration of fractional doses is not recommended) of TYZAVAN, and
to avoid unintentional overdose, this product is not recommended for use if a
dose of Vancomycin Injection that does not equal 500 mg, 750 mg, 1 g, 1.25 g,
1.5 g, 1.75 g and 2 g is required, and an alternative formulation of vancomycin
should be considered [see Dosage and
Administration (2.1, 2.3)].
More
severe infusion related reactions related to vancomycin administration may
occur in pediatric patients. In pediatric patients, monitor vancomycin serum
concentration and renal function when administering TYZAVAN [see Dosage and Administration (2.3) and Warnings and Precautions (5.1)]. Concomitant administration of vancomycin and
intravenous anesthetic agents has been associated with erythema and
histamine-like flushing in all patients including pediatric patients [see Warnings and Precautions (5.1)].
Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Potential Risk of Exposure to Excipients During
Early Pregnancy
(Additions
and/or revisions underlined)
If use of vancomycin is needed during the first or second
trimester of pregnancy, use other available formulations of vancomycin.
This formulation of Vancomycin Injection contains the excipients polyethylene glycol
(PEG 400) and N-acetyl D-alanine (NADA). In a rabbit reproduction study, fetal spinal
malformations occurred when the excipient PEG 400 was administered at
dose exposures approximately 8 times the exposure at the maximum daily human
dose. In a separate rabbit reproduction study, fetal spinal and cardiovascular
malformations occurred when the excipient NADA was administered at dose
exposures approximately 32 times the exposure at the maximum daily human dose.
The active ingredient vancomycin is not known to be associated with embryo-
fetal toxicity [see Use in Specific
Populations (8.1)].
5.5 Severe Dermatologic Reactions
(Newly
Added Subsection)
Severe dermatologic reactions such as toxic epidermal
necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic
symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and linear
IgA bullous dermatosis (LABD) have been reported in association with the use of
vancomycin. Cutaneous signs or symptoms reported include skin rashes, mucosal
lesions, and blisters.
Discontinue
Vancomycin Injection at the first appearance of signs and symptoms of TEN, SJS,
DRESS, AGEP, or LABD.
6
Adverse Reactions
(Additions
and/or revisions underlined)
The following clinically
significant adverse reactions are described elsewhere in the labeling:
6.2 Postmarketing Experience
(Additions
and/or revisions underlined)
The following
adverse reactions have been identified during postmarketing use of vancomycin.
Because these reactions are reported
voluntarily from a population of uncertain size, it is not possible to reliably estimate their
frequency or establish a causal relationship to drug exposure.
Skin and Subcutaneous Tissue Disorders: Drug reaction
with eosinophilia and systemic symptoms (DRESS), acute generalized
exanthematous pustulosis (AGEP) [see Warnings and
Precautions (5.5)].
8
Use in Specific Populations
8.1 Pregnancy
(Additions and/or revisions underlined)
Risk Summary
This formulation
of Vancomycin Injection is not recommended for use during the first or
second trimester of pregnancy because it contains the excipients, PEG 400
and NADA, which caused fetal malformations in animal reproduction studies (see Data). Advise pregnant women of the
potential risk to the fetus. If therapy with Vancomycin Injection is
needed during the first or second trimester
of pregnancy, use other available formulations of vancomycin, free of
PEG 400 and NADA.
The available
data on use of this formulation of Vancomycin Injection (with the excipients PEG 400 and NADA) in
pregnant women are insufficient to evaluate for a drug-associated risk
of major birth defects, miscarriage,
or other adverse maternal or fetal outcomes. Available published data on
vancomycin (without the excipients PEG 400 and NADA) use in pregnancy
during the second and third trimesters have not shown an association with adverse pregnancy related outcomes (see Data). There are no available data on first trimester use of vancomycin
in pregnant women to assess the risk of major birth defects or miscarriage.
Vancomycin alone did not show adverse developmental effects when administered
intravenously to pregnant rats and rabbits during organogenesis at doses less than or equal to the recommended maximum
human dose based on body surface area (see Data).
Reproduction
studies in rabbits with intravenous doses of PEG 400 at approximately 8
times the maximum daily human dose based
on systemic exposures of PEG 400
during organogenesis resulted in fetal spinal malformations.
Reproduction studies in rabbits and rats using intravenous doses of NADA at
approximately 32 and 20 times the maximum daily human dose,
respectively, based on systemic exposures of NADA resulted in maternal
toxicity and fetal spinal and cardiovascular malformations in rabbits, and
maternal toxicity with no adverse embryo-fetal effects in rats…
Data
Human
Data
Available data from
postmarketing cases on use of this formulation of vancomycin injection
(with the excipients PEG 400 and NADA) in pregnant women are insufficient
to evaluate for a drug- associated risk of major birth defects,
miscarriage, or other adverse maternal or infant outcomes.
There are no
available data on first trimester use of vancomycin (without the excipients PEG
400 and NADA); however, available published data on use in pregnancy during the
second and third trimesters have not shown an association with adverse
pregnancy related outcomes.
Animal
Data
Animal reproduction studies conducted in rabbits administered intravenous PEG 400 at 2000 mg/kg
(approximately 8 times the maximum daily human dose, based on AUC
levels of PEG 400) during organogenesis
(gestation days 6 to 19) resulted in fetal scoliosis (thoracic and lumbar)
and increased incidence of delayed or incomplete ossification of the pubes,
epiphyses, and talus bones. No maternal
toxicity was observed up to the maximum dose
tested.
Similarly,
in animal reproduction studies conducted in pregnant rabbits (gestation days 6
to 19) and pregnant rats (gestation days 6 to 17) administered intravenous NADA
at 1680 and 3780 mg/kg, respectively (at 32 times or greater
based on AUC levels of NADA) resulted in fetal scoliosis and a spectrum
of cardiovascular anomalies in rabbits and no adverse effects on fetuses in
rats. Increased incidence of delayed or incomplete ossifications of the
metacarpals/metatarsals/phalanges and increased ossification (fused jugal/maxilla
bones) were observed in rabbits at 1680 mg/kg. Minor non adverse fetal
skeletal abnormalities were observed in rats at 3780 mg/kg which was also
associated with maternal toxicity including increased incidence of litter loss [see Clinical Pharmacology
(12.3)]..
No animal
studies have been conducted to evaluate the potential reproductive and
embryo-fetal effects of Vancomycin Injection (with the excipients PEG 400
and NADA).
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION
(Additions
and/or revisions underlined)
Potential Risk of Exposure to Excipients
During Early Pregnancy
Advise patients to
notify their healthcare provider if they are pregnant prior to treatment with
this formulation of vancomycin [see Boxed Warning, Warnings and
Precautions (5.1) and Use in Specific
Populations (8.1)].
Severe Dermatologic Reactions
Advise patients about the signs
and symptoms of serious skin manifestations. Instruct patients to stop
Vancomycin Injection immediately and promptly report the first signs or
symptoms of skin rash, mucosal lesions or blisters to their healthcare provider
[see Warnings and Precautions (5.5)].
Approved Drug Label (PDF)
5
Warnings and Precautions
5.5 Severe Dermatologic Reactions
(Newly added information)
Severe
dermatologic reactions such as toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and linear IgA bullous dermatosis (LABD) have been reported in association with the use of vancomycin. Cutaneous signs or symptoms
reported include skin rashes, mucosal
lesions, and blisters.
Discontinue Vancomycin Injection at the first appearance of signs and symptoms of TEN, SJS, DRESS,
AGEP, or LABD.
6
Adverse Reactions
6.2 Post Marketing Experience
(Additions and/or revisions underlined)
The following adverse reactions have been identified during post marketing use of vancomycin. Because these reactions are reported
voluntarily from a population of uncertain
size, it is not possible
to reliably estimate
their frequency or establish
a causal relationship to drug exposure.
Skin and Subcutaneous Tissue Disorders: Drug reaction with eosinophilia and systemic symptoms
(DRESS), acute generalized exanthematous pustulosis (AGEP) [see Warnings and Precautions (5.5)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
Patient Counseling Information
(Newly
added information)
Severe
Dermatologic Reactions
Advise patients
about the signs and symptoms
of serious skin manifestations. Instruct patients to stop Vancomycin Injection immediately and promptly
report the first signs or symptoms of skin rash, mucosal
lesions or blisters, [see Warnings and Precautions (5.5)].
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