Included as part of the PRECAUTIONS section.
Oral Use Only
FIRVANQ™ must be given orally for treatment of C.
difficile-associated diarrhea and staphylococcal enterocolitis. Orally
administered vancomycin is not effective for treatment of other types of
Parenteral administration of vancomycin is not effective
for treatment of C. difficile-associated diarrhea and staphylococcal
enterocolitis. If parenteral vancomycin therapy is desired, use an intravenous
preparation of vancomycin and consult the package insert accompanying that
Potential For Systemic Absorption
Significant systemic absorption has been reported in some
patients (e.g., patients with renal insufficiency and/or colitis) who have
taken multiple oral doses of vancomycin hydrochloride for C. difficile-associated
diarrhea. In these patients, serum vancomycin concentrations reached
therapeutic levels for the treatment of systemic infections. Some patients with
inflammatory disorders of the intestinal mucosa also may have significant
systemic absorption of vancomycin. These patients may be at risk for the
development of adverse reactions associated with higher doses of FIRVANQ™;
therefore, monitoring of serum concentrations of vancomycin may be appropriate
in some instances, e.g., in patients with renal insufficiency and/or colitis or
in those receiving concomitant therapy with an aminoglycoside antibacterial
Nephrotoxicity (e.g., reports of renal failure, renal
impairment, blood creatinine increased) has occurred following oral vancomycin
hydrochloride therapy in randomized controlled clinical trials, and can occur
either during or after completion of therapy. The risk of nephrotoxicity is
increased in patients over 65 years of age [see ADVERSE REACTIONS and Use
In Specific Populations].
In patients over 65 years of age, including those with
normal renal function prior to treatment, renal function should be monitored
during and following treatment with FIRVANQ™ to detect potential vancomycin
Ototoxicity has occurred in patients receiving
vancomycin. It may be transient or permanent. It has been reported mostly in
patients who have been given high intravenous doses, who have an underlying
hearing loss, or who are receiving concomitant therapy with another ototoxic
agent, such as an aminoglycoside. Serial tests of auditory function may be
helpful in order to minimize the risk of ototoxicity [see ADVERSE REACTIONS].
Potential For Microbial Overgrowth
Use of FIRVANQ™ may result in the overgrowth of
non-susceptible bacteria. If superinfection occurs during therapy, appropriate
measures should be taken.
Development Of Drug-Resistant Bacteria
Prescribing FIRVANQ™ in the absence of a proven or
strongly suspected bacterial infection is unlikely to provide benefit to the
patient and increases the risk of the development of drug resistant bacteria.
Hemorrhagic Occlusive Retinal Vasculitis (HORV)
Hemorrhagic occlusive retinal vasculitis, including
permanent loss of vision, occurred in patients receiving intracameral or
intravitreal administration of vancomycin during or after cataract surgery. The
safety and efficacy of vancomycin administered by the intracameral or
intravitreal route have not been established by adequate and well-controlled
studies. Vancomycin is not indicated for prophylaxis of endophthalmitis.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
No long-term carcinogenesis studies in animals have been
At concentrations up to 1000 mcg/mL, vancomycin had no
mutagenic effect in vitro in the mouse lymphoma forward mutation assay or the
primary rat hepatocyte unscheduled DNA synthesis assay. The concentrations
tested in vitro were above the peak plasma vancomycin concentrations of 20 to
40 mcg/mL usually achieved in humans after slow infusion of the maximum
recommended dose of 1 g. Vancomycin had no mutagenic effect in vivo in the
Chinese hamster sister chromatid exchange assay (400 mg/kg IP) or the mouse
micronucleus assay (800 mg/kg IP).
No definitive fertility studies have been conducted.
Use In Specific Populations
There are no available data on FIRVANQ™ use in pregnant
women to inform a drug associated risk of major birth defects or miscarriage.
Available published data on vancomycin use in pregnancy during the second and
third trimesters have not shown an association with adverse pregnancy related
outcomes (see Data). Vancomycin 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).
All pregnancies have a background risk of birth defect,
loss or other adverse outcomes. In the U.S. general population, the estimated
background risk of major birth defects and miscarriage in clinically recognized
pregnancies is 2 to 4% and 15 to 20%, respectively.
A published study evaluated hearing loss and
nephrotoxicity in infants of pregnant intravenous drug users treated with
vancomycin for suspected or documented methicillin-resistant S. aureus in
the second or third trimester. The comparison groups were 10 non-intravenous
drug-dependent patients who received no treatment, and 10 untreated intravenous
drug-dependent patients served as substance abuse controls. No infant in the
vancomycin exposed group had abnormal sensorineural hearing at 3 months of age
A published prospective study assessed outcomes in 55
pregnant women with a positive Group B Streptococcus culture and a
high-risk penicillin allergy with resistance to clindamycin or unknown
sensitivity who were administered vancomycin at the time of delivery.
Vancomycin dosing ranged from the standard 1 g intravenously every 12 hours to
20 mg/kg intravenous every 8 hours (maximum individual dose 2 g). No major
adverse reactions were recorded either in the mothers or their newborns. None
of the newborns had sensorineural hearing loss. Neonatal renal function was not
examined, but all of the newborns were discharged in good condition.
Vancomycin did not cause fetal malformations when
administered during organogenesis to pregnant rats (gestation days 6 to 15) and
rabbits (gestation days 6 to 18) at the equivalent recommended maximum human
dose (based on body surface area comparisons) of 200 mg/kg/day IV to rats or
120 mg/kg/day IV to rabbits. No effects on fetal weight or development were
seen in rats at the highest dose tested or in rabbits given 80 mg/kg/day
(approximately 1 and 0.8 times the recommended maximum human dose based on body
surface area, respectively). Maternal toxicity was observed in rats (at doses
120 mg/kg and above) and rabbits (at 80 mg/kg and above).
There are insufficient data to inform the levels of
vancomycin in human milk. However, systemic absorption of vancomycin following
oral administration is expected to be minimal [see CLINICAL PHARMACOLOGY].
There are no data on the effects of FIRVANQ™ on the breastfed infant or milk
production. The developmental and health benefits of breastfeeding should be
considered along with the mother's clinical need for FIRVANQ™ and any potential
adverse effects on the breastfed infant from FIRVANQ™ or from the underlying
FIRVANQ™ is indicated in pediatric patients less than 18
years of age for the treatment of C. difficile-associated diarrhea and
enterocolitis caused by S. aureus (including methicillin-resistant
strains) [see INDICATIONS AND USAGE and DOSAGE AND ADMINISTRATION].
In clinical trials, 54% of vancomycin
hydrochloride-treated subjects were > 65 years of age. Of these, 40% were
between the ages of > 65 and 75, and 60% were > 75 years of age.
Clinical studies with vancomycin hydrochloride in C.
difficile-associated diarrhea have demonstrated that geriatric subjects are
at increased risk of developing nephrotoxicity following treatment with oral
vancomycin hydrochloride, which may occur during or after completion of
therapy. In patients over 65 years of age, including those with normal renal
function prior to treatment, renal function should be monitored during and
following treatment with vancomycin hydrochloride to detect potential
vancomycin induced nephrotoxicity [see WARNINGS AND PRECAUTIONS, ADVERSE
REACTIONS and Clinical Studies].
Patients over 65 years of age may take longer to respond
to therapy compared to patients 65 years of age and younger [see Clinical
Studies]. Clinicians should be aware of the importance of appropriate
duration of vancomycin hydrochloride treatment in patients over 65 years of age
and not discontinue or switch to alternative treatment prematurely.