Approved Drug Label (PDF)
4
Contraindications
(additions
underlined)
…
Use
of a LABA, including STIOLTO RESPIMAT, without an inhaled corticosteroid is contraindicated
in patients with asthma .STIOLTO RESPIMAT
is not indicated for the treatment of asthma.
STIOLTO
RESPIMAT is contraindicated in patients with a hypersensitivity to tiotropium,
ipratropium, olodaterol, or any component of this product.
In
clinical trials and postmarketing experience with tiotropium, immediate
hypersensitivity reactions, including angioedema (including swelling of the
lips, tongue, or throat), itching, or rash have been reported. Hypersensitivity reactions were also reported
in clinical trials with STIOLTO RESPIMAT.
5
Warnings and Precautions
5.1 Serious Asthma-Related Events – Hospitalizations, Intubations, Death
(additions
underlined)
The safety and efficacy of STIOLTO RESPIMAT in
patients with asthma have not been established. STIOLTO RESPIMAT is not
indicated for the treatment of asthma.
Use of long-acting beta2-adrenergic agonists (LABA)
as monotherapy [without inhaled corticosteroids (ICS)] for asthma is associated
with an increased risk of asthma-related death. Available data from controlled
clinical trials also suggest that use of LABA as monotherapy increases the risk
of asthma-related hospitalization in pediatric and adolescent patients. These
findings are considered a class effect of LABA monotherapy. When LABA are used
in fixed-dose combination with ICS, data from large clinical trials do not show
a significant increase in the risk of serious asthma-related events
(hospitalizations, intubations, death) compared with ICS alone.
…
6
Adverse Reactions
(additions
underlined)
LABA,
such as olodaterol, one of the active components in STIOLTO RESPIMAT, as
monotherapy (without an inhaled corticosteroid) for asthma, increase the
risk of asthma-related events. STIOLTO RESPIMAT is not indicated for the
treatment of asthma.
…
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
(additions
underlined)
…
Serious
Asthma-Related Events
Inform
patients that LABA, such as STIOLTO RESPIMAT, when used as monotherapy
[without an inhaled corticosteroid], increase the risk of serious
asthma-related events, including asthma-related death. STIOLTO RESPIMAT is
not indicated for the treatment of asthma.
…
PATIENT INFORMATION
(
Medication Guide replaced with a Patient
Package Insert, please refer to label for more information)
Approved Drug Label (PDF)
6
Adverse Reactions
6.1 Clinical Trials Experience in Chronic Obstructive Pulmonary Disease
Additions and/or revisions are
underlined)
…
COPD
Exacerbation Reduction Trial
In a
one year trial (Trial 5) of 7880 patients to compare rates of COPD
exacerbations, 3939 patients were treated with STIOLTO RESPIMAT and 3941
patients were treated with tiotropium 5 mcg inhalation spray. The safety
profile of STIOLTO RESPIMAT was similar to that of tiotropium 5 mcg inhalation
spray and consistent with that documented in the STIOLTO RESPIMAT primary
safety database.
8
Use in Specific Populations
8.1 Pregnancy
(Additions and/or revisions are
underlined)
Risk Summary
There are no adequate and well-controlled clinical
studies with STIOLTO RESPIMAT or its individual components, tiotropium bromide
and olodaterol, in pregnant women to inform of drug-associated risk of
adverse pregnancy-related outcomes. Animal reproduction studies were
conducted with the individual components of STIOLTO RESPIMAT, tiotropium
bromide and olodaterol. There are
clinical considerations with the use of STIOLTO RESPIMAT in pregnant women.
STIOLTO RESPIMAT should be used during pregnancy only if the potential benefit
justifies the potential risk to the fetus. Based on animal reproduction
studies, no structural abnormalities were observed when tiotropium was
administered by inhalation to pregnant rats and rabbits during the period of
organogenesis at doses 790 and 8 times, respectively, the maximum recommended
human daily inhalation dose (MRHDID). Increased post-implantation loss was
observed in rats and rabbits administered tiotropium at maternally toxic doses
430 times and 40 times the MRHDID, respectively [see Data]. Based on
animal studies, olodaterol was not teratogenic when administered to pregnant
rats or rabbits during organogenesis at inhalation doses of approximately 2731
or 1353 times the MRHDID (on an AUC basis), in rats or rabbits, respectively.
The estimated background risk of major birth
defects and miscarriage for the indicated population is unknown. 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.
Clinical Considerations
Labor
and Delivery
There are no adequate and well-controlled
human studies that have investigated the effects of STIOLTO RESPIMAT on preterm
labor or labor at term. Because of the potential for beta-agonist interference
with uterine contractility, use of STIOLTO RESPIMAT during labor should be
restricted to those patients in whom the benefits clearly outweigh the risks.
Data
Animal Data
Animal reproduction studies with the
combination of tiotropium and olodaterol are not available; however, studies
are available with the individual components.
Tiotropium
In 2 separate embryo-fetal development
studies, pregnant rats and
rabbits received tiotropium during the period of organogenesis at doses
up to approximately 790 and 8 times
the MRHDID, respectively (on a mcg/m2 basis at inhalation doses of 1471
and 7 mcg/kg/day in rats and rabbits, respectively). No evidence of
structural abnormalities was observed in rats or rabbits. However, in rats,
tiotropium caused fetal resorption, litter loss, decreases in the number of
live pups at birth and the mean pup weights, and a delay in pup sexual
maturation at tiotropium doses of approximately 40 times the MRHDID (on
a mcg/m2 basis at a maternal inhalation dose of 78 mcg/kg/day). In rabbits,
tiotropium caused an increase in post-implantation loss at a tiotropium dose
of approximately 430 times the MRHDID (on a mcg/m2 basis at a
maternal inhalation dose of 400 mcg/kg/day). Such effects were not observed at
approximately 5 and 95 times the MRHDID, respectively (on a mcg/m2 basis
at inhalation doses of 9 and 88 mcg/kg/day in rats and rabbits, respectively).
Olodaterol
Olodaterol was not teratogenic in rats at
inhalation doses approximately 2731 times the MRHDID (on an AUC
basis at a maternal inhalation dose of 1054 mcg/kg/day). No significant
effects occurred in rabbits at inhalation doses approximately 1353 times the
MRHDID in adults (on an AUC basis at a maternal inhalation dose of 974
mcg/kg/day). Placental transfer of olodaterol was observed in pregnant
rats.
Olodaterol has been shown to be teratogenic in
New Zealand rabbits at inhalation doses approximately 7130 times the MRHDID
in adults (on an AUC basis at a maternal inhalation dose of 2489
mcg/kg/day). Olodaterol exhibited the following fetal toxicities: enlarged or small
heart atria or ventricles, eye abnormalities, and split or distorted sternum.
8.2 Lactation
(Additions and/or revisions are underlined)
Risk Summary
There are no data on the presence of
tiotropium or olodaterol in human milk, the effects on the breastfed
infant, or the effects on milk production. Tiotropium, olodaterol, and/or their metabolites
are present in the milk of lactating rats, however, due to
species-specific differences in lactation physiology, the clinical relevance of
these data are not clear [see Data]. The developmental and health
benefits of breastfeeding should be considered along with the mother’s clinical
need for STIOLTO RESPIMAT and any potential adverse effects on the breastfed
child from STIOLTO RESPIMAT or from the underlying maternal condition.
Data
The distributions of tiotropium bromide or
olodaterol into milk were investigated in separate studies after a single
intravenous administration of 10 mg/kg or 0.4 ?mol/kg, respectively, to
lactating rats. Tiotropium, olodaterol, and/or their metabolites are present in
the milk of lactating rats at concentrations above those in plasma.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17. PATIENT COUNSELING INFORMATION
(Additions and/or revisions are
underlined)
…
Immediate
Hypersensitivity Reactions
Inform
patients that anaphylaxis, angioedema (including swelling of the lips, tongue,
or throat), urticaria, rash, bronchospasm, or itching, may occur after
administration of STIOLTO RESPIMAT. Advise patient to immediately discontinue
treatment and consult a physician should any of these signs or symptoms
develop.
…
MEDICATION GUIDE
(Format changed, please refer to
label)
Other
INSTRUCTIONS FOR USE
(Additions and/or revisions are
underlined)
…
How
to store your STIOLTO RESPIMAT inhaler
Store STIOLTO RESPIMAT at room
temperature between 68°F to 77°F (20°C to 25°C).
Do not freeze
your STIOLTO RESPIMAT cartridge and inhaler.
If STIOLTO RESPIMAT has not been
used for more than 3 days, release 1 puff towards the ground.
If STIOLTO RESPIMAT has not been
used for more than 21 days, repeat steps 4 to 6 under the “Prepare for first
use” until a mist is visible. Then repeat steps 4 to 6 three more times.
Keep your STIOLTO RESPIMAT cartridge, inhaler, and all medicines out of the reach of children.
…
When
to get a new STIOLTO RESPIMAT inhaler
The
scale on your inhaler will show the number
of puffs you have, if used as indicated (2 puffs 1 time each day).
The dose indicator will show you approximately how much medicine is left.
When the dose indicator
enters the red area of the scale, it will show you approximately how many puffs are left before you need
a refill or new prescription.
When the dose indicator
reaches the end of the red scale, your STIOLTO RESPIMAT is empty and automatically locks. At this point, the clear
base cannot be turned any further.
…
Answers
to Common Questions
It is difficult to insert the cartridge deep
enough:
Did
you accidentally turn the clear base before inserting the cartridge? Open the cap, press the dose-release button,
then insert the cartridge.
Did
you insert the cartridge with the wide end first? Insert the cartridge with the narrow end
first.
I cannot press the dose-release
button:
Did
you turn the clear base? If
not, turn the clear base in a continuous movement until it clicks (half a
turn).
Is
the dose indicator on the STIOLTO RESPIMAT pointing to 0 (zero)? The STIOLTO RESPIMAT inhaler is locked after the
labeled number of puffs have been used. Prepare and use your new
STIOLTO RESPIMAT inhaler.
I cannot turn the clear base:
Did
you turn the clear base already? If
the clear base has already been turned, follow steps “Open” and “Press” under
“Daily use” to get your medicine.
Is
the dose indicator on the STIOLTO RESPIMAT pointing to 0 (zero)? The STIOLTO RESPIMAT inhaler is locked after the
labeled number of puffs have been used. Prepare and use your new
STIOLTO RESPIMAT inhaler.
The dose indicator on the STIOLTO
RESPIMAT reaches 0 (zero) too soon:
you use STIOLTO RESPIMAT as indicated (2 puffs
1 time each day)? STIOLTO RESPIMAT will deliver the labeled
number of puffs if used at 2 puffs 1 time each day.
Did
you turn the clear base before you inserted the cartridge? The dose indicator counts each turn of the
clear base regardless whether a cartridge has been inserted or not.
you
spray in the air often to check whether the STIOLTO RESPIMAT is working?
After you
have prepared STIOLTO RESPIMAT, no test-spraying is required if used daily.
…
Get Email Alerts |
Guide
