Newspaper Page Text
A SPIRIVA HandiHaler
(tintrnniiim bromide inhalation powder)
SPIRIVA® HandiHaler®
(trotroprum bromide inhalation powder)
For Oral Inhalation Only
Brief Summary of Prescribing Information
INDICATIONS AND USAGE
SPIRIVA rtanaiHater (tiotropium bromide inhalation oowder) is indicated for the long-term, once-daily
maintenance treatment of broncftospasm associated with chronic obstructive Dulmonary disease
(COPO) including chrome bronchitis and emphysema
CONTRAINDICATIONS
SPIRIVA HandiHaler (tiotropium Dromide inhalation powder! s contraindicated m patients with a histcry ol
hypersensitivity to atropine or its derivatives including ipratropium, cr to any component of this product
WARNINGS
SPIRIVA HandiHaler (tiotropium bromide inhalation powder) is intended as a once-caiiy maintenance
treatment for COPO and is not indicated for the initial treatment of acute episodes of bronchospasm
i.e rescue therapy
immediate hypersensitivity reactions, including angioedema may occur after administration of SPIRIVA
if suen a reaction occurs, therapy with SPIRIVA should be stooped at once and alternative treatments
should be considered
inhaled medicines, including SPIRIVA may cause paradoxical bronchospasm if this occurs, treatment
with SPIRIVA should be stopped and other treatments considerec
PRECAUTIONS
General
As an antichoimergic drug. SPtRiVA (tiotropium bromide «MMon powder) may potentially worsen
symptoms ana signs associated with narrow-angie glaucoma, prostatic hyperplasia cr biaflder-neck
obstruction anc should be usee 'with caution m patients with any of these conditions
As a predominantly renaily excreted drug, patients with moderate to severe renal impairment
(creatinine clearance of <SO ml/mm) treated with SPIRIVA should be monitored closely ;see
CLINICAL PHARMACOLOGY. Pharmacokinetics, Special Populations Renally-impaired Patients)
information for Patients
It is important tor patients to understand how to correctly administer SPIRIVA capsules using the
HandiHaler mnalation device isee Patient's Instructions for Use SPIRIVA caosules should only be
administered via the HandiHaler device and the HandiHaler device should not be used for administering
other medications
Capsules should always be stored in sealed blisters and only removed immediately before use. The
blister stop should be carefully opened to expose only one capsule at a time Open the blister foil as far
as the STOP hoe to remove only one capsule at a time The drug should be used immediately after the
packaging over an individual capsule is opened, or else its effectiveness may be reduced Capsules that
are inadvertently exposed to air <i.e., not intended for immediate usei should be discarded
Eye pair, or discomfort, blurred vision visual halos or colored images m association with red eyes from
conjunctival congestion and comeal edema may be signs of acute narrow-angle glaucoma. Should any
ot these signs and symptoms develop, consult a physician immediately Miotic eye drops atone are not
considered to be effective treatment
Care must be taken not tc allow the powder tc enter mto the eyes as this may cause biumng of vision
and pupu dilation
SPIRIVA HandiHaler is a once-daily maintenance oronchodilator aid should not be used for immediate
relief ot breathing problems, i.e.. as a rescue medication
Drug Interactions
SPIRIVA has been used concomitantly with other drugs commonly used m COPO without meases in
adverse drug reactions These include sympathomimetic oronchodilators methyixantnmes. and oral ana
•nnaied steroids However the co-aommistration of SPIRIVA with other anticholinergic-containing drugs
(e g. ipratropmmi nas not been studied and •$ therefore not recommended
Drug/Laboratory Test Interactions
None known.
Carcinogenesis. Mutagenesis. Impairment ot Fertility
No evidence of tumongenicity was oOserved m a 104-week mnalaticn study m rats at tiotropium dcses
up tc 0 059 mg/kg/day. nan 83-week inhalation study m female mice at coses up to C 145 mg/kg/day
and m a 101-week mnalation stucy m male mice at doses up to 0 002 mg/kg/oay These doses
correspond to 25. 35. and 0 5 times the Recommended Human Da.ly Dose (RHODi on a mg/m basis,
respectively Tnese dose multiples may be over-estimated due to difficulties in measurma depositee
coses m animal inhalation studies.
Tiotropium bromide demonstrated no evidence ot mutagenicity or ciastogeniaty m the following assays:
the bacterial gene mutation assay the V 79 Chinese hamster cell mutagenesis assay the chromosomal
aberration assays m human lymphocytes -n vitro and mouse mcronucieus formation m vivo, and the
unscheduled DNA synthesis m primary rat nepatocytes m vitro assay
in rats decreases in the number ot corpora lutea and the percentage of implants were noted at
innatation tiotropium doses of 0 078 mg/kg/day or greater (approximately 35 times the RHDD on a
mg/m- basis) No such effects were observed at 0.009 mg/kgdav (approximately 4 times than the
RHDD on a mg/m basis) The fertility index, however, was not affected at mnalation doses up to 1 689
mg/kgday (approximately 760 times the RHDD on a mgm bass) These oose multiples may be ever
estimated due to difficulties m measunng depositee doses m animal 1003131100 studies
Pregnancy
Pregnancy Category C
No evidence ot structural alterations was observed m rats and rabbits at inhalation tiotropium doses ot
up to 1 .471 and 0.007 mg/kg/day respectively These doses correspond to approximately 660 and
6 times the recommended human daily dose (RHDD) or a mgm basis. However in rats fetal
resorption utter loss, decreases m the number of iive pups at birth aid the mean pup wetgnts and a
delay in pup sexual maturation were observed at mhaiatw tiotropium doses of >0 078 mg/kg
(approximately 35 times the RHDD on a mg/m bass) m rabbits, an increase m post-implantation loss
was observed at an mnalation cose of 0 4 mg/kgoay (approximately 360 times the RHDD on a mgm
basisi Such effects were not observed at mnalation doses of 0 009 anc up to 0 088 mgkgoay m rats
and rabbits respectively These doses correspond to approximately 4 and 80 times the RHDD on a
mgm- bass respectively These dose multiples may be over-estimated due to difficulties in measuring
deposited doses m animal mnalation studies
There are no adequate and well-con trolled studies m pregnant women SPIRIVA should be usee during
pregnancy only if the potentai benefit justifies the potential nsk to the fetus.
Use m Labor and Delivery
The safety and effectiveness of SPIRIVA has not been studied during labor and delivery
Nursing Mothers
Ckmcal data from nursing women exposed to tiotropium are not available Based on lactatmg rodent
studies, tiotropium is excreted mto breast milk. It is not known whether tiotropium g excreted m human
mdk. but because many drugs are excreted m human milk and given these findings m rats, caution
should be exercised if SPIRIVA is administered tc a nursing woman
only
5P2775368
Copyright ©2006. Boehnnger ingelheim Pharmaceuticals. Inc. All rights reserved
Pediatric Use
SP'RiVA HandiHaler is approved for use in the maintenance treatment of bronchcspasm associated
with chronic obstructive pulmonary disease, including chronic bronchitis anc emphysema 'his
disease does not normally occur m children The safety and effectiveness of SPIRIVA in pediatr c
patients have not been established
Genatnc Use
Of the total number of patients wno received SPIRIVA m the i-year clinical tnais 426 were <65 years
375 were 65-74 years and 105 were >75 years of age Within each age supgroup there were no
differences between the proportion of patients with adverse events in the SPIRIVA and the comparator
groups for most events Dry mouth increased with age m the SP'RiVA group (differences from placebo
were 9 0%. 17 1% and 16 2% in the aforementioned age subgroups) A highei frequency of
constipation and urinary tract infections with increasing ace was observed in the SPIRIVA giouo m te
piacebo-controllec studies The differences from placebo for constioatior were 0%. 1 8%. and 7 8% tor
each of the age groups The differences from placebo for unnary tract rfections were -0.6%. 4.6% and
4 5%. No overall differences m effectiveness were observed among these groups Based on available
data, no adiustment of SPIRIVA dosage m geriatric patients is warranted
AOVERSE REACTIONS
Of the 2.663 patients in the four 1 -year and two 6-mcnth controlled clinical trials.' 308 were treated
with SPIRIVA (tiotropium bromide mnalation powder at the recommended dose ot 18 meg once a day
Patients with narrow angle glaucoma, or symptomatic prostatic hypertrophy or bladder outlet
obstruction were excluded from these tnais.
The most commonly reported adverse drug reaction was dry mouth Dry mouth was usually mild and
often resolved during continued treatment Other reactions reported m individual patients and consistent
with possible antichoimergic effects included constipation increased neart rate oiurreo vision
glaucoma urinary difficulty and unnary retention
Four multicenter 1-year, controlled studies evaluated SPIRIVA in patients with COPD Table 1 shows all
adverse events that occurred with a frequency of >3% in the SPIRIVA group in the 1-year
piacebc-controlled tnais where the rates m the SPIRIVA group exceeded placebo by >l%. The frequency
ot corresponding events in the ipratropium-controlled trials is included for companson.
Table 1: Adverse Experience Incidence (% Patients) in One-Year-COPO Clinical Tnais
Body System (Event) Placebo-Controlled Tnais Ipratropium-Controlled Tnais
SPIRIVA Placebo SPIRIVA Ipratropium
Body as a Whole
Accidents 13 n 5 8
Chest Pam T.on-specific) 7 5 5 2
Edema. Dependent 5 4 3 5
Gastrointestinal System Disorders
Abdominal Pam 5 3 6 6
Constipation 4 ;
Dry Mouth 16 3 12 6 ~~
Dyscepsus 6 5 ; 1
Vomiting 4 2 ] 2
Musculoskeletal System
Myalgia 4 3 4 3
Resistance Mechanism Disorders
infection 4 3 i 3
Moniliasis 4 ; 3 2
Respiratory System (upper)
Epistaxrs 4 2
Pharyngitis 9 7 7 3
Rhinitis 6 5 3 2
Sinusitis '1 9 3 2
Upper Respiratory Tract infection 4i 37 43 35
Skin and Appendage Disorders
Rash 4 2 2 2
Unnary System
Urinary Tract Infection 7 5 4 2
Arthritis coughing, and mfiuenza-uke symptoms occurred at a rate of >3% in the SPIRIVA treatment
group but were <l% m excess of me placebo group
Other events that occurred m tne SPIRIVA group at a frequency of 1 -3% in the piacebc-contrcliec tnais
where tne rates exceeded that in the piaceDo group include: Body as a Whole allergic reaction, leg pain
Central ana Peripheral Nervous System dysphoma. paresthesia: Gastrointestinal System DisoiCeis.
gastrointestinal disorder not otherwise specified (NOS), gastroesophageal reflux, stomatitis (including
ulcerative stomatitis): Metaoohc anc Nutritional Disorders . hypercholesterolemia, hyperglycemia.
Musculoskeletal System Disorders skeletal pain: Cardiac Events: angina pectoris (including aggravated
angina pectons). Psychiatric Disorder depression infections herpes zoster Respiratory System
Disorder (Upper) laryngitis Vision Disorder cataract in addition, among the adverse everts observed
m the dmicai trials with an incidence of <l% were airiai fibniiatton supraventricular tachycardia
angioedema. and unnary retention
in the 1 -year trials, the incidence ot dry mouth, constipation, and unnary tract infection increased with
age (see PRECAUTIONS, Genatnc Use)
Two multicenter. 6-month, controlled studies evaluatec SPIRIVA m parents with COPO. The aoveree
events anc the incidence rates were similar to those seen m the 1 -year controlled tnais
The following adverse reactions have oeen identified during worldwide post-appcvai use of SPIRIVA
dizziness, epistaxis hoarseness, palpitations, pruritus tachycardia tnroat rotation and urticaria
DOSAGE AND ADMINISTRATION
The recommended dosage ol SPIRIVA HandiHaler (tiotropium bromide inhalation powder) is the
inhalation of the contents ot one SPIRIVA capsule, once-daily. with the HandiHaler mnalation device (see
Patient s Instructions tor Use'
Nc dosage adjustment s required for genatnc. heoaticaily-impairec or renaiiy-impaired oatients
However patients with moderate to severe renal impairment given SPIRIVA should be monitored closely
(see CLINICAL PHARMACOLOGY. Pharmacokinetics. Special Populations and PRECAUTIONS.
SPIRIVA capsules are tor inhalation only and must not be swallowed
HOW SUPPLIED
The following packages are available
carton containing 6 SPIRIVA capsules (1 blister card) and 1 HandiHaler inhalation device
(NDC 0597-0075-06)
carton containing 30 SPtRiVA capsules (5 blister cards) and 1 HandiHaler inhalation device
(NDC 0597-0075-37)
SV-BS (10/05)
59873AJ5/3 October 2005
®Boehringer
Ingelheim
(09/06) 5V12385Q
(Continued from page 7)
Still, the poinsettia remains Ecke
Ranch's signature product and, though
sold only six weeks a year, is the world's
top-selling potted flowering plant. Each
year, the company’s 1,000 employees in
the United States, Guatemala and Mexico
breed and produce more than 50 million
poinsettia cuttings in 60 varieties under
LOO acres of greenhouses.
"We can't rest on our laurels,” says
Paul 111, whose grandfather and father
died in 1991 and 2002, respectively, and
entrusted the family business to him. “At
the end of the day, you have to have more
chan heritage and name recognition. You
have to have a good product. I'm reminded
of that with every shipment."
Visit www.ecke.com for more
information.
Online Extras
View more photos of the Paul Ecke
Ranch at AmericanProfile.com
SPECIAL OFFER-
There’s Still Time!
The experts at Pro Flowers will deliver
a bright red poinsettia just in time
for Christmas! There’s nothing like a
classic red poinsettia. Pro Flowers has
dressed it up in a decorative copper
colored tin to warm the home and
the hearts of your loved ones.
Overall gift measures approximately 15 inches tall.
Call (800) 416-1959 and mention
“API” or go to www.profiowers.com/API.
Not available tor same-day or international delivery.
IVoKlf mens
www.americanprofiie.com •
Page 14