Included as part of the PRECAUTIONS section.
Monitor nasal mucosa adjacent to the SINUVA Sinus Implant
for any signs of bleeding (epistaxis), irritation, infection, or perforation.
Avoid use in patients with nasal ulcers or trauma.
Glaucoma, cataracts, and clinically significant elevation
of intraocular pressure were not observed in patients from the treatment group
of one randomized controlled clinical study (N = 53) who underwent bilateral
placement of SINUVA Sinus Implants. Close monitoring is warranted in patients
with a change in vision or with a history of increased intraocular pressure, glaucoma,
Hypersensitivity reactions, including rash, pruritus, and
angioedema have been reported with use of corticosteroids.
Persons who are using drugs that suppress the immune
system are more susceptible to infections than healthy individuals. Chickenpox
and measles, for example, can have a more serious or even fatal course in
susceptible children or adults using corticosteroids. In such children or
adults who have not had these diseases or who are not properly immunized,
particular care should be taken to avoid exposure. How the dose, route, and
duration of corticosteroid administration affect the risk of developing a
disseminated infection is not known.
The contribution of the underlying disease and/or prior
corticosteroid treatment to the risk is also not known. If exposed to
chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be
indicated. If exposed to measles, prophylaxis with pooled intramuscular
immunoglobulin (IG) may be indicated (See the respective package inserts for
complete VZIG and IG prescribing information). If chickenpox develops,
treatment with antiviral agents may be considered. Corticosteroids should be
used with caution, if at all, in patients with active or quiescent tuberculosis
infection of the respiratory tract; untreated systemic fungal, bacterial,
viral, or parasitic infections; or ocular herpes simplex.
Hypercorticism And Adrenal Suppression
Hypercorticism and adrenal suppression were not evaluated
as part of the SINUVA Sinus Implant clinical program.
Since individual sensitivity to effects of cortisol
production exists, physicians should consider this information when prescribing
SINUVA Sinus Implant. Particular care should be taken in observing patients
postoperatively or during periods of stress for evidence of inadequate adrenal response.
It is possible that systemic corticosteroid effects such
as hypercorticism and adrenal suppression may appear in patients, particularly
when systemic mometasone furoate is administered at higher than recommended doses
over prolonged periods of time. If such effects occur, consider sinus implant
Carcinogenesis, Mutagenesis, Impairment Of Fertility
In a 2-year carcinogenicity study in Sprague Dawley rats,
mometasone furoate demonstrated no statistically significant increase of tumors
at inhalation doses up to 67 mcg/kg (approximately 14 times the MRHD on an AUC
basis). In a 19-month carcinogenicity study in Swiss CD-1 mice, mometasone
furoate demonstrated no statistically significant increase in the incidence of tumors
at inhalation doses up to 160 mcg/kg (approximately 9 times the MRHD on an AUC basis).
Mometasone furoate increased chromosomal aberrations in
an in vitro Chinese hamster ovary cell assay, but did not have this effect in
an in vitro Chinese hamster lung cell assay. Mometasone furoate was not
mutagenic in the Ames test or mouse lymphoma assay, and was not clastogenic in
an in vivo mouse micronucleus assay, a rat bone marrow chromosomal aberration assay,
or a mouse male germ-cell chromosomal aberration assay. Mometasone furoate also
did not induce unscheduled DNA synthesis in vivo in rat hepatocytes.
In reproductive studies in rats, impairment of fertility
was not produced by subcutaneous doses up to 15 mcg/kg (approximately 8 times
the MRHD on an AUC basis).
Use In Specific Populations
There are no randomized clinical studies of SINUVA Sinus
Implant or mometasone furoate in pregnant women. The active pharmaceutical
ingredient, mometasone furoate is systemically available when administered
topically or when inhaled. In animal reproduction studies, subcutaneous
administration of mometasone furoate to pregnant mice, rats, or rabbits caused increased
fetal malformations and decreased fetal survival and growth following
administration of doses that produced exposures approximately 1/3 to 8 times
the maximum recommended human dose (MRHD) on a mcg/m² or AUC basis [see Data].
However, experience with oral corticosteroids suggests that rodents are more
prone to teratogenic effects from corticosteroid exposure than humans.
The estimated background risk of major birth defects and
miscarriage for the indicated population is unknown. In the U.S. general
population, the estimated risk of major birth defects and miscarriage in clinically
recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
In an embryofetal development study with pregnant mice
dosed throughout the period of organogenesis, mometasone furoate produced cleft
palate at an exposure approximately one-third of the MRHD (on a mcg/m² basis
with maternal subcutaneous doses of 60 mcg/kg and above) and decreased fetal
survival at an exposure approximately equivalent to the MRHD (on a mcg/m² basis
with a maternal subcutaneous dose of 180 mcg/kg). No toxicity was observed with
a dose that produced an exposure approximately one-tenth of the MRHD (on a
mcg/m² basis with maternal topical dermal doses of 20 mcg/kg and above).
In an embryofetal development study with pregnant rats
dosed throughout the period of organogenesis, mometasone furoate produced fetal
umbilical hernia at exposures approximately 6 times the MRHD (on a mcg/m² basis
with maternal topical dermal doses of 600 mcg/kg and above) and delays in fetal
ossification at exposures approximately 3 times the MRHD (on a mcg/m² basis
with maternal topical dermal doses of 300 mcg/kg and above).
In another reproductive toxicity study, pregnant rats
were dosed with mometasone furoate throughout pregnancy or late in gestation.
Treated animals had prolonged and difficult labor, fewer live births, lower
birth weight, and reduced early pup survival at an exposure that was approximately
8 times the MRHD (on an area under the curve (AUC) basis with a maternal subcutaneous
dose of 15 mcg/kg). There were no findings with an exposure approximately 4
times the MRHD (on an AUC basis with a maternal subcutaneous dose of 7.5
Embryofetal development studies were conducted with
pregnant rabbits dosed with mometasone furoate by either the topical dermal
route or oral route throughout the period of organogenesis. In the study using
the topical dermal route, mometasone furoate caused multiple malformations in fetuses
(e.g., flexed front paws, gallbladder agenesis, umbilical hernia, hydrocephaly)
at an exposure approximately 3 times the MRHD (on a mcg/m² basis with maternal
topical dermal doses of 150 mcg/kg and above). In the study using the oral
route, mometasone furoate caused increased fetal resorptions and cleft palate
and/or head malformations (hydrocephaly and domed head) at an exposure
approximately ½ of the MRHD (on AUC basis with a maternal oral dose of 700
mcg/kg). At an exposure approximately 2 times the MRHD (on an AUC basis with a maternal
oral dose of 2800 mcg/kg), most litters were aborted or resorbed. No effects
were observed at an exposure approximately 1/10 of the MRHD (on an AUC basis
with a maternal oral dose of 140 mcg/kg).
There are no available data on the presence of SINUVA
Sinus Implant in human milk, the effects on the breastfed child or the effects
on milk production. Systemic absorption of a single inhaled 400 mcg mometasone
dose was less than 1%. It is not known if mometasone furoate is excreted in
human milk. Other inhaled corticosteroids, similar to mometasone furoate, are
present in human milk. The developmental and health benefits of breastfeeding
should be considered along with the mother's clinical need for the SINUVA Sinus
Implant and any potential adverse effects on the breastfed infant from the
SINUVA Sinus Implant.
The safety and effectiveness of the SINUVA Sinus Implant
have not been established in children or adolescents less than 18 years of age.
A total of 33 patients 65 years of age or older received
the SINUVA Sinus Implant in 2 controlled randomized clinical trials. Clinical
studies did not include sufficient numbers of subjects aged 65 and over to
determine whether they respond differently from younger subjects.
Concentrations of mometasone furoate appear to increase
with severity of hepatic impairment [see CLINICAL PHARMACOLOGY].