تیوتروپیوم بروماید
Tiotropium Bromide (Spiriva)
تیوتروپیوم بروماید

نام ژنریک

Tiotropium Bromide

شکل دارویی

اشكال دارويي:


Inhaler: 18 mcg/capsule

موارد مصرف

موارد و مقدار مصرف


درمان نگهدارنده اسپاسم برونش در COPD، شامل برونشيت مزمن و آمفيزم


بزرگسالان: يك كپسول (mcg 18) يك بار در روز با استفاده از Handihaler از راه دهان استنشاق مي‌شود.

موارد منع مصرف

موارد منع مصرف و احتياط


موارد منع مصرف: حساسيت به آتروپين و مشتقات آن، ايپراتروپيوم و يا هر يك از اجزاي فرمولاسيون دارو.


موارد احتياط: بارداري، دوران شيردهي، كليرانس كراتينين كمتر يا برابر با ml/min 50، گلوكوم زاويه بسته، BPH، انسداد گردن مثانه.

عوارض جانبی دارو

عوارض جانبي


اعصاب مرکزي: افسردگي، گزگز اندامها.


قلبي ـ عروقي: آنژين صدري، درد سينه، ادم.


چشم، حلق و بيني: آب مرواريد، تغيير صدا، خونريزي بيني، گلوكوم، لارنژيت، فارنژيت، رينيت، سينوزيت.


دستگاه گوارش: درد شكمي، يبوست، خشكي دهان، سوء‌هاضمه، رفلاكس معده به مري، استوماتيت، استفراغ.


ادراري ـ تناسلي: عفونت ادراري.


متابوليك: هايپركلسترولمي، هايپرگليسمي.


عضلاني ـ اسكلتي: آرتريت، درد پا، درد عضلاني، درد اسكلتي.


تنفسي: سرفه، عفونت دستگاه تنفسي فوقاني.


پوست: راش.


ساير عوارض: واكنشهاي آلرژيك، كانديدياز، سندرم شبه آنفلوانزا، هرپس زوستر، انواع عفونت.


مسموميت و درمان


تظاهرات باليني: مسموميت باعث خشكي دهان، كونژنكتيويت دو طرفه، تغيير وضعيت ذهني، لرزش، درد شكمي و يبوست شديد مي‌شود.


درمان:‌ حمايتي است.

موارد قابل توجه

-

تداخل دارویی

تداخل دارويي


ساير داروهاي آنتي‌كولينرژيك ممكن است خطر بروز عوارض جانبي را افزايش دهند.

مکانیزم اثر

تداخل دارويي


ساير داروهاي آنتي‌كولينرژيك ممكن است خطر بروز عوارض جانبي را افزايش دهند.

فارماكوكینتیك

فارماكوكينتيك


جذب: از دستگاه گوارش به مقدار ناچيزي جذب مي‌شود. فراهمزيستي مطلق دارو پس از استنشاق پودر، 5/19% مي‌باشد. شروع اثر دارو 30 دقيقه، اوج اثر پس از 3 ساعت و مدت اثر بيش از 24 ساعت مي‌باشد.


پخش: دارو به مقدار زيادي به بافتها متصل مي‌شود. اتصال پروتئيني 72% مي‌باشد.


متابوليسم: مقدار كمي از دارو توسط آنزيمهاي كبدي CYP2D6 و CYP3A4 متابوليزه مي‌شود.


دفع: حدود 14% از دوز استنشاقي در ادرار و مابقي در مدفوع دفع مي‌شود. نيمه‌ عمر دارو 6-5 روز مي‌باشد.

سایر اطلاعات

طبقه‌بندي فارماكولوژيك: آنتي‌كولينرژيك طولاني اثر.


طبقه‌بندي درماني: برونكوديلاتور (گشاد كننده برونش).


طبقه‌بندي مصرف در بارداري: رده C


نام‌هاي تجاري: Spiriva


ملاحظات اختصاصي


1- تيوتروپيوم براي درمان نگهدارنده COPD به كار مي‌رود و در درمان اسپاسم برونشي حاد مؤثر نيست.


2- بيمار را از نظر واكنشهاي حساسيتي (به ويژه آنژيوادم) و برونكواسپاسم متناقض پايش كنيد.


نكات قابل توصيه به بيمار


1- دارو در درمان حملات حاد اسپاسم برونشي كمك كننده نيست.


2- كپسول‌ها فقط براي مصرف استنشاقي (با استفاده از دستگاه Handihaler) است و نبايد بلعيده شود.


3- روش استفاده از Handihaler را به طور كامل براي بيمار شرح دهيد.


4- در صورت بروز واكنشهاي ازدياد حساسيت (به ويژه آنژيوادم) مصرف دارو را قطع نموده و با پزشك خود تماس بگيريد.


5- در صورت بروز درد چشمي، تاري‌ديد، لكه‌هاي بينايي، تصاوير رنگي غير طبيعي يا قرمزي چشمها، سريعاً پزشك را مطلع نماييد.


6- هر كپسول بايد فقط قبل استفاده از بليستر خارج شود و نبايد آنها را در محيط بيرون نگهداري نمود.


7- بسته دارو بايد در دماي 25 درجه سانتي‌گراد و دور از حرارت و رطوبت بيش از حد نگهداري شود.


مصرف در كودكان: ايمني و اثربخشي دارو تأييد نشده است.


مصرف در شيردهي: ترشح دارو در شير مشخص نيست. با احتياط مصرف شود.


مصرف در بارداري: با احتياط بايد مصرف شود.


اثر بر آزمايشهاي تشخيصي


ممكن است باعث افزايش سطح كلسترول و گلوكز خون شود.

Tiotropium Bromide (Spiriva)

SPIRIVA®
HandiHaler® (tiotropium bromide) Inhalation Powder

DRUG DESCRIPTION

SPIRIVA HandiHaler consists of a capsule dosage form containing a dry powder formulation of tiotropium intended for oral inhalation only with the HandiHaler device.

Each light green, hard gelatin SPIRIVA capsule contains 18 mcg tiotropium (equivalent to 22.5 mcg tiotropium bromide monohydrate) blended with lactose monohydrate (which may contain milk proteins) as the carrier.

The dry powder formulation within the SPIRIVA capsule is intended for oral inhalation only.

The active component of SPIRIVA HandiHaler is tiotropium. The drug substance, tiotropium bromide monohydrate, is an anticholinergic with specificity for muscarinic receptors. It is chemically described as (1α, 2β, 4 β, 5α, 7β)-7-[(Hydroxydi-2-thienylacetyl)oxy]-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.02,4]nonane bromide monohydrate. It is a synthetic, non-chiral, quaternary ammonium compound. Tiotropium bromide is a white or yellowish white powder. It is sparingly soluble in water and soluble in methanol.

The structural formula is:

SPIRIVA® HandiHaler® (tiotropium bromide) Structural Formula Illustration

Tiotropium bromide (monohydrate) has a molecular mass of 490.4 and a molecular formula of C19H22NO4S2Br •H2O.

The HandiHaler device is an inhalation device used to inhale the dry powder contained in the SPIRIVA capsule. The dry powder is delivered from the HandiHaler device at flow rates as low as 20 L/min. Under standardized in vitro testing, the HandiHaler device delivers a mean of 10.4 mcg tiotropium when tested at a flow rate of 39 L/min for 3.1 seconds (2 L total). In a study of 26 adult patients with COPD and severely compromised lung function [mean FEV1 1.02 L (range 0.45 to 2.24 L); 37.6% of predicted (range 16% to 65%)], the median peak inspiratory flow (PIF) through the HandiHaler device was 30.0 L/min (range 20.4 to 45.6 L/min). The amount of drug delivered to the lungs will vary depending on patient factors such as inspiratory flow and peak inspiratory flow through the HandiHaler device, which may vary from patient to patient, and may vary with the exposure time of the SPIRIVA capsule outside the blister pack.

What are the possible side effects of tiotropium inhalation (Spiriva)?

Stop using tiotropium inhalation and get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • tongue swelling or redness;
  • sores or white patches of your mouth, lips, or tongue; or
  • urinating less than usual or not at all.

Less serious side effects may include:

  • dry mouth, cough, hoarseness;
  • blurred vision;
  • trouble...

Read All Potential Side Effects and See Pictures of Spiriva »

What are the precautions when taking tiotropium bromide (Spiriva)?

Before using tiotropium, tell your doctor or pharmacist if you are allergic to it or to ipratropium; or to atropine or other belladonna-type drugs; or if you have any other allergies. This product may contain inactive ingredients (such as milk proteins), which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, glaucoma (narrow-angle), difficulty urinating (for example, due to enlarged prostate).

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Older adults may be more sensitive to the side effects of this...

Read All Potential Precautions of Spiriva »

Last reviewed on RxList: 9/7/2011
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

SPIRIVA HandiHaler (tiotropium bromide inhalation powder) is indicated for the long-term, once-daily, maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. SPIRIVA HandiHaler is indicated to reduce exacerbations in COPD patients.

DOSAGE AND ADMINISTRATION

DO NOT SWALLOW SPIRIVA CAPSULES

FOR USE WITH HANDIHALER DEVICE ONLY

FOR ORAL INHALATION ONLY

SPIRIVA capsules must not be swallowed as the intended effects on the lungs will not be obtained. The contents of the SPIRIVA capsules are only for oral inhalation and should only be used with the HandiHaler device [see OVERDOSAGE].

The recommended dose of SPIRIVA HandiHaler is two inhalations of the powder contents of one SPIRIVA capsule, once-daily, with the HandiHaler device [see PATIENT INFORMATION].

For administration of SPIRIVA HandiHaler, a SPIRIVA capsule is placed into the center chamber of the HandiHaler device. The SPIRIVA capsule is pierced by pressing and releasing the green piercing button on the side of the HandiHaler device. The tiotropium formulation is dispersed into the air stream when the patient inhales through the mouthpiece [see PATIENT INFORMATION].

No dosage adjustment is required for geriatric, hepatically-impaired, or renally-impaired patients. However, patients with moderate to severe renal impairment given SPIRIVA HandiHaler should be monitored closely for anticholinergic effects [see WARNINGS AND PRECAUTIONS, Use In Specific Populations and CLINICAL PHARMACOLOGY].

HOW SUPPLIED

Dosage Forms And Strengths

SPIRIVA HandiHaler consists of SPIRIVA capsules and a HandiHaler device. SPIRIVA capsules contain 18 mcg dry powder formulation of tiotropium in a light green, hard gelatin capsule with TI 01 printed on one side and Boehringer Ingelheim company logo on the other side.

Storage And Handling

SPIRIVA HandiHaler consists of SPIRIVA capsules and the HandiHaler device. SPIRIVA capsules contain 18 mcg of tiotropium and are light green, with the Boehringer Ingelheim company logo on the SPIRIVA capsule cap and TI 01 on the SPIRIVA capsule body, or vice versa.

The HandiHaler device is gray colored with a green piercing button. It is imprinted with SPIRIVA HandiHaler (tiotropium bromide inhalation powder), the Boehringer Ingelheim company logo, and the Pfizer company logo. It is also imprinted to indicate that SPIRIVA capsules should not be stored in the HandiHaler device and that the HandiHaler device is only to be used with SPIRIVA capsules.

SPIRIVA capsules are packaged in an aluminum/aluminum blister card and joined along a perforated-cut line. SPIRIVA capsules should always be stored in the blister and only removed immediately before use. The drug should be used immediately after the packaging over an individual SPIRIVA capsule is opened.

The following packages are available:

  • carton containing 5 SPIRIVA capsules (1 unit-dose blister card) and 1 HandiHaler inhalation device (NDC 0597-0075-75)
  • carton containing 30 SPIRIVA capsules (3 unit-dose blister cards) and 1 HandiHaler inhalation device (NDC 0597-0075-41)
  • carton containing 90 SPIRIVA capsules (9 unit-dose blister cards) and 1 HandiHaler inhalation device (NDC 0597-0075-47)
Storage

Store at 25°C (77°F); excursions permitted to 15°–30°C (59°–86°F) [see USP Controlled Room Temperature].

The SPIRIVA capsules should not be exposed to extreme temperature or moisture. Do not store SPIRIVA capsules in the HandiHaler device.

Distributed by: Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT 06877 USA. Marketed by: Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT 06877 USA and Pfizer Inc New York, NY 10017 USA. Revised: 2011

Last reviewed on RxList: 9/7/2011
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

The following adverse reactions are described, or described in greater detail, in other sections:

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

6-Month to 1-Year Trials

The data described below reflect exposure to SPIRIVA HandiHaler in 2663 patients. SPIRIVA HandiHaler was studied in two 1-year placebo-controlled trials, two 1-year active-controlled trials, and two 6-month placebo-controlled trials in patients with COPD. In these trials, 1308 patients were treated with SPIRIVA HandiHaler at the recommended dose of 18 mcg once a day. The population had an age ranging from 39 to 87 years with 65% to 85% males, 95% Caucasian, and had COPD with a mean pre-bronchodilator forced expiratory volume in one second (FEV1) percent predicted of 39% to 43%. Patients with narrow-angle glaucoma, or symptomatic prostatic hypertrophy or bladder outlet obstruction were excluded from these trials. An additional 6-month trial conducted in a Veteran's Affairs setting is not included in this safety database because only serious adverse events were collected.

The most commonly reported adverse drug reaction was dry mouth. Dry mouth was usually mild and often resolved during continued treatment. Other reactions reported in individual patients and consistent with possible anticholinergic effects included constipation, tachycardia, blurred vision, glaucoma (new onset or worsening), dysuria, and urinary retention.

Four multicenter, 1-year, placebo-controlled and active-controlled trials evaluated SPIRIVA HandiHaler in patients with COPD. Table 1 shows all adverse reactions that occurred with a frequency of ≥ 3% in the SPIRIVA HandiHaler group in the 1-year placebo-controlled trials where the rates in the SPIRIVA HandiHaler group exceeded placebo by ≥ 1%. The frequency of corresponding reactions in the ipratropium-controlled trials is included for comparison.

Table 1 : Adverse Reactions (% Patients) in One-Year COPD Clinical Trials

Body System (Event) Placebo-Controlled Trials Ipratropium-Controlled Trials
SPIRIVA
(n = 550)
Placebo
(n = 371)
SPIRIVA
(n = 356)
Ipratropium
(n = 179)
Body as a Whole
Chest Pain (non-specific) 7 5 5 2
Edema, Dependent 5 4 3 5
Gastrointestinal System Disorders
Dry Mouth 16 3 12 6
Dyspepsia 6 5 1 1
Abdominal Pain 5 3 6 6
Constipation 4 2 1 1
Vomiting 4 2 1 2
Musculoskeletal System
Myalgia 4 3 4 3
Resistance Mechanism Disorders
Infection 4 3 1 3
Moniliasis 4 2 3 2
Respiratory System (Upper)
Upper Respiratory Tract Infection 41 37 43 35
Sinusitis 11 9 3 2
Pharyngitis 9 7 7 3
Rhinitis 6 5 3 2
Epistaxis 4 2 1 1
Skin and Appendage Disorders
Rash 4 2 2 2
Urinary System
Urinary Tract Infection 7 5 4 2

Arthritis, coughing, and influenza-like symptoms occurred at a rate of ≥ 3% in the SPIRIVA HandiHaler treatment group, but were < 1% in excess of the placebo group.

Other reactions that occurred in the SPIRIVA HandiHaler group at a frequency of 1% to 3% in the placebo-controlled trials where the rates exceeded that in the placebo group include: Body as a Whole: allergic reaction, leg pain; Central and Peripheral Nervous System: dysphonia, paresthesia; Gastrointestinal System Disorders: gastrointestinal disorder not otherwise specified (NOS), gastroesophageal reflux, stomatitis (including ulcerative stomatitis); Metabolic and Nutritional Disorders: hypercholesterolemia, hyperglycemia; Musculoskeletal System Disorders: skeletal pain; Cardiac Events: angina pectoris (including aggravated angina pectoris); Psychiatric Disorder: depression; Infections: herpes zoster; Respiratory System Disorder (Upper): laryngitis; Vision Disorder: cataract. In addition, among the adverse reactions observed in the clinical trials with an incidence of < 1% were atrial fibrillation, supraventricular tachycardia, angioedema, and urinary retention.

In the 1-year trials, the incidence of dry mouth, constipation, and urinary tract infection increased with age [see Use In Specific Populations].

Two multicenter, 6-month, controlled studies evaluated SPIRIVA HandiHaler in patients with COPD. The adverse reactions and the incidence rates were similar to those seen in the 1-year controlled trials.

4-Year Trial

The data described below reflect exposure to SPIRIVA HandiHaler in 5992 COPD patients in a 4-year placebo-controlled trial. In this trial, 2986 patients were treated with SPIRIVA HandiHaler at the recommended dose of 18 mcg once a day. The population had an age range from 40 to 88 years, was 75% male, 90% Caucasian, and had COPD with a mean pre-bronchodilator FEV1 percent predicted of 40%. Patients with narrow-angle glaucoma, or symptomatic prostatic hypertrophy or bladder outlet obstruction were excluded from these trials. When the adverse reactions were analyzed with a frequency of ≥ 3% in the SPIRIVA HandiHaler group where the rates in the SPIRIVA HandiHaler group exceeded placebo by ≥ 1%, adverse reactions included (SPIRIVA HandiHaler, placebo): pharyngitis (12.5%, 10.8%), sinusitis (6.5%, 5.3%), headache (5.7%, 4.5%), constipation (5.1%, 3.7%), dry mouth (5.1%, 2.7%), depression (4.4%, 3.3%), insomnia (4.4%, 3.0%), and arthralgia (4.2%, 3.1%).

Additional Adverse Reactions

Other adverse reactions not previously listed that were reported more frequently in COPD patients treated with SPIRIVA HandiHaler than placebo include: dehydration, skin ulcer, stomatitis, gingivitis, oropharyngeal candidiasis, dry skin, skin infection, and joint swelling.

Postmarketing Experience

Adverse reactions have been identified during worldwide post-approval use of SPIRIVA HandiHaler. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These adverse reactions are: application site irritation (glossitis, mouth ulceration, and pharyngolaryngeal pain), dizziness, dysphagia, hoarseness, intestinal obstruction including ileus paralytic, intraocular pressure increased, oral candidiasis, palpitations, pruritus, tachycardia, throat irritation, and urticaria.

Read the Spiriva (tiotropium bromide) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

Sympathomimetics, Methylxanthines, Steroids

SPIRIVA HandiHaler has been used concomitantly with short-acting and long-acting sympathomimetic (beta-agonists) bronchodilators, methylxanthines, and oral and inhaled steroids without increases in adverse drug reactions.

Anticholinergics

There is potential for an additive interaction with concomitantly used anticholinergic medications. Therefore, avoid coadministration of SPIRIVA HandiHaler with other anticholinergic-containing drugs as this may lead to an increase in anticholinergic adverse effects [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS].

Cimetidine, Ranitidine

No clinically significant interaction occurred between tiotropium and cimetidine or ranitidine [see CLINICAL PHARMACOLOGY].

Last reviewed on RxList: 9/7/2011
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Not for Acute Use

SPIRIVA HandiHaler is intended as a once-daily maintenance treatment for COPD and is not indicated for the initial treatment of acute episodes of bronchospasm (i.e., rescue therapy).

Immediate Hypersensitivity Reactions

Immediate hypersensitivity reactions, including angioedema (including swelling of the lips, tongue, or throat), itching, or rash may occur after administration of SPIRIVA HandiHaler. If such a reaction occurs, therapy with SPIRIVA HandiHaler should be stopped at once and alternative treatments should be considered. Given the similar structural formula of atropine to tiotropium, patients with a history of hypersensitivity reactions to atropine should be closely monitored for similar hypersensitivity reactions to SPIRIVA HandiHaler. In addition, SPIRIVA HandiHaler should be used with caution in patients with severe hypersensitivity to milk proteins.

Paradoxical Bronchospasm

Inhaled medicines, including SPIRIVA HandiHaler, may cause paradoxical bronchospasm. If this occurs, treatment with SPIRIVA HandiHaler should be stopped and other treatments considered.

Worsening of Narrow-Angle Glaucoma

SPIRIVA HandiHaler should be used with caution in patients with narrow-angle glaucoma. Prescribers and patients should be alert for signs and symptoms of acute narrow-angle glaucoma (e.g., eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema). Instruct patients to consult a physician immediately should any of these signs or symptoms develop.

Worsening of Urinary Retention

SPIRIVA HandiHaler should be used with caution in patients with urinary retention. Prescribers and patients should be alert for signs and symptoms of prostatic hyperplasia or bladder-neck obstruction (e.g., difficulty passing urine, painful urination). Instruct patients to consult a physician immediately should any of these signs or symptoms develop.

Renal Impairment

As a predominantly renally excreted drug, patients with moderate to severe renal impairment (creatinine clearance of ≤ 50 mL/min) treated with SPIRIVA HandiHaler should be monitored closely for anticholinergic side effects [see CLINICAL PHARMACOLOGY].

Patient Counseling Information

See FDA-approved Patient Labeling

Instructions for Administering SPIRIVA HandiHaler

It is important for patients to understand how to correctly administer SPIRIVA capsules using the HandiHaler device [see PATIENT INFORMATION]. Patients should be instructed that SPIRIVA capsules should only be administered via the HandiHaler device and the HandiHaler device should not be used for administering other medications. The contents of SPIRIVA capsules are for oral inhalation only and must not be swallowed.

SPIRIVA capsules should always be stored in sealed blisters. Only one SPIRIVA capsule should be removed immediately before use or its effectiveness may be reduced. Additional SPIRIVA capsules that are exposed to air (i.e., not intended for immediate use) should be discarded.

Paradoxical Bronchospasm

Patients should be informed that SPIRIVA HandiHaler can produce paradoxical bronchospasm. If paradoxical bronchospasm occurs, patients should discontinue SPIRIVA HandiHaler.

Urinary Retention

Difficulty passing urine and dysuria may be symptoms of new or worsening prostatic hyperplasia or bladder outlet obstruction. Patients should be instructed to consult a physician immediately should any of these signs or symptoms develop.

Visual Effects

Eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema may be signs of acute narrow-angle glaucoma. Patients should be told to consult a physician immediately should any of these signs and symptoms develop. Miotic eye drops alone are not considered to be effective treatment.

Patients should be told that care must be taken not to allow the powder to enter into the eyes as this may cause blurring of vision and pupil dilation.

Acute Exacerbation

Patients should understand that SPIRIVA HandiHaler is a once-daily maintenance bronchodilator and should not be used for immediate relief of breathing problems (i.e., as a rescue medication).

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

No evidence of tumorigenicity was observed in a 104-week inhalation study in rats at tiotropium doses up to 0.059 mg/kg/day, in an 83-week inhalation study in female mice at doses up to 0.145 mg/kg/day, and in a 101-week inhalation study in male mice at doses up to 0.002 mg/kg/day. These doses correspond to approximately 25, 35, and 0.5 times the recommended human daily inhalation dose (RHDID) on a mg/m² basis, respectively. These dose multiples may be over-estimated due to difficulties in measuring deposited doses in animal inhalation studies.

Tiotropium bromide demonstrated no evidence of mutagenicity or clastogenicity in the following assays: the bacterial gene mutation assay, the V79 Chinese hamster cell mutagenesis assay, the chromosomal aberration assays in human lymphocytes in vitro and mouse micronucleus formation in vivo, and the unscheduled DNA synthesis in primary rat hepatocytes in vitro assay.

In rats, decreases in the number of corpora lutea and the percentage of implants were noted at inhalation tiotropium doses of 0.078 mg/kg/day or greater (approximately 35 times the RHDID on a mg/m² basis). No such effects were observed at 0.009 mg/kg/day (approximately 4 times than the RHDID on a mg/m² basis). The fertility index, however, was not affected at inhalation doses up to 1.689 mg/kg/day (approximately 760 times the RHDID on a mg/m² basis). These dose multiples may be over-estimated due to difficulties in measuring deposited doses in animal inhalation studies.

Use In Specific Populations

Pregnancy

Teratogenic Effects, Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. SPIRIVA HandiHaler should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

No evidence of structural alterations was observed in rats and rabbits at inhalation tiotropium doses of up to approximately 660 and 6 times the recommended human daily inhalation dose (RHDID) on a mg/m² basis, respectively. 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 inhalation tiotropium doses of approximately 35 times the RHDID on a mg/m² basis. In rabbits, tiotropium caused an increase in post-implantation loss at an inhalation dose of approximately 360 times the RHDID on a mg/m² basis. Such effects were not observed at inhalation doses of approximately 4 and 80 times the RHDID on a mg/m² basis, respectively. These dose multiples may be over-estimated due to difficulties in measuring deposited doses in animal inhalation studies.

Labor and Delivery

The safety and effectiveness of SPIRIVA HandiHaler has not been studied during labor and delivery.

Nursing Mothers

Clinical data from nursing women exposed to tiotropium are not available. Based on lactating rodent studies, tiotropium is excreted into breast milk. It is not known whether tiotropium is excreted in human milk, but because many drugs are excreted in human milk and given these findings in rats, caution should be exercised if SPIRIVA HandiHaler is administered to a nursing woman.

Pediatric Use

SPIRIVA HandiHaler is approved for use in the maintenance treatment of bronchospasm associated with COPD and for the reduction of COPD exacerbations. COPD does not normally occur in children. The safety and effectiveness of SPIRIVA HandiHaler in pediatric patients have not been established.

Geriatric Use

Of the total number of patients who received SPIRIVA HandiHaler in the 1-year clinical trials, 426 were < 65 years, 375 were 65 to 74 years, and 105 were ≥ 75 years of age. Within each age subgroup, there were no differences between the proportion of patients with adverse events in the SPIRIVA HandiHaler and the comparator groups for most events. Dry mouth increased with age in the SPIRIVA HandiHaler group (differences from placebo were 9.0%, 17.1%, and 16.2% in the aforementioned age subgroups). A higher frequency of constipation and urinary tract infections with increasing age was observed in the SPIRIVA HandiHaler group in the placebo-controlled studies. The differences from placebo for constipation were 0%, 1.8%, and 7.8% for each of the age groups. The differences from placebo for urinary tract infections were –0.6%, 4.6%, and 4.5%. No overall differences in effectiveness were observed among these groups. Based on available data, no adjustment of SPIRIVA HandiHaler dosage in geriatric patients is warranted [see CLINICAL PHARMACOLOGY].

Renal Impairment

Patients with moderate to severe renal impairment (creatinine clearance of ≤ 50 mL/min) treated with SPIRIVA HandiHaler should be monitored closely for anticholinergic side effects [see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY].

Hepatic Impairment

The effects of hepatic impairment on the pharmacokinetics of tiotropium were not studied.

Last reviewed on RxList: 9/7/2011
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

High doses of tiotropium may lead to anticholinergic signs and symptoms. However, there were no systemic anticholinergic adverse effects following a single inhaled dose of up to 282 mcg tiotropium in 6 healthy volunteers. In a study of 12 healthy volunteers, bilateral conjunctivitis and dry mouth were seen following repeated once-daily inhalation of 141 mcg of tiotropium.

Accidental Ingestion

Acute intoxication by inadvertent oral ingestion of SPIRIVA capsules is unlikely since it is not well-absorbed systemically.

A case of overdose has been reported from postmarketing experience. A female patient was reported to have inhaled 30 capsules over a 2.5 day period, and developed altered mental status, tremors, abdominal pain, and severe constipation. The patient was hospitalized, SPIRIVA HandiHaler was discontinued, and the constipation was treated with an enema. The patient recovered and was discharged on the same day.

No mortality was observed at inhalation tiotropium doses up to 32.4 mg/kg in mice, 267.7 mg/kg in rats, and 0.6 mg/kg in dogs. These doses correspond to 7300, 120,000, and 850 times the recommended human daily inhalation dose on a mg/m² basis, respectively. These dose multiples may be over-estimated due to difficulties in measuring deposited doses in animal inhalation studies.

CONTRAINDICATIONS

SPIRIVA HandiHaler is contraindicated in patients with a hypersensitivity to ipratropium or tiotropium. In clinical trials and postmarketing experience with SPIRIVA HandiHaler, immediate hypersensitivity reactions, including angioedema (including swelling of the lips, tongue, or throat), itching, or rash have been reported.

Last reviewed on RxList: 9/7/2011
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Mechanism of Action

Tiotropium is a long-acting, antimuscarinic agent, which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors, M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of M3-receptors at the smooth muscle leading to bronchodilation. The competitive and reversible nature of antagonism was shown with human and animal origin receptors and isolated organ preparations. In preclinical in vitro as well as in vivo studies, prevention of methacholine-induced bronchoconstriction effects was dose-dependent and lasted longer than 24 hours. The bronchodilation following inhalation of tiotropium is predominantly a site-specific effect.

Pharmacodynamics

Cardiovascular Effects

In a multicenter, randomized, double-blind trial that enrolled 198 patients with COPD, the number of subjects with changes from baseline-corrected QT interval of 30 to 60 msec was higher in the SPIRIVA HandiHaler group as compared with placebo. This difference was apparent using both the Bazett (QTcB) [20 (20%) patients vs 12 (12%) patients] and Fredericia (QTcF) [16 (16%) patients vs 1 (1%) patient] corrections of QT for heart rate. No patients in either group had either QTcB or QTcF of > 500 msec. Other clinical studies with SPIRIVA HandiHaler did not detect an effect of the drug on QTc intervals.

The effect of SPIRIVA HandiHaler on QT interval was also evaluated in a randomized, placebo- and positive-controlled crossover study in 53 healthy volunteers. Subjects received SPIRIVA HandiHaler 18 mcg, 54 mcg (3 times the recommended dose), or placebo for 12 days. ECG assessments were performed at baseline and throughout the dosing interval following the first and last dose of study medication. Relative to placebo, the maximum mean change from baseline in study-specific QTc interval was 3.2 msec and 0.8 msec for SPIRIVA HandiHaler 18 mcg and 54 mcg, respectively. No subject showed a new onset of QTc > 500 msec or QTc changes from baseline of ≥ 60 msec.

Pharmacokinetics

Tiotropium is administered by dry powder inhalation. In common with other inhaled drugs, the majority of the delivered dose is deposited in the gastrointestinal tract and, to a lesser extent, in the lung, the intended organ. Many of the pharmacokinetic data described below were obtained with higher doses than recommended for therapy.

Absorption

Following dry powder inhalation by young healthy volunteers, the absolute bioavailability of 19.5% suggests that the fraction reaching the lung is highly bioavailable. It is expected from the chemical structure of the compound (quaternary ammonium compound) that tiotropium is poorly absorbed from the gastrointestinal tract. The effect of food on tiotropium's bioavailability has not been studied. Oral solutions of tiotropium have an absolute bioavailability of 2% to 3%. Maximum tiotropium plasma concentrations were observed 5 minutes after inhalation.

Distribution

Tiotropium shows a volume of distribution of 32 L/kg indicating that the drug binds extensively to tissues. The human plasma protein binding for tiotropium is 72%. At steady state, peak tiotropium plasma levels in COPD patients were 17 to 19 pg/mL when measured 5 minutes after dry powder inhalation of an 18 mcg dose and decreased in a multi-compartmental manner. Steady-state trough plasma concentrations were 3 to 4 pg/mL. Local concentrations in the lung are not known, but the mode of administration suggests substantially higher concentrations in the lung. Studies in rats have shown that tiotropium does not readily penetrate the blood-brain barrier.

Metabolism

The extent of metabolism appears to be small. This is evident from a urinary excretion of 74% of unchanged substance after an intravenous dose to young healthy volunteers. Tiotropium, an ester, is nonenzymatically cleaved to the alcohol N-methylscopine and dithienylglycolic acid, neither of which binds to muscarinic receptors.

In vitro experiments with human liver microsomes and human hepatocytes suggest that a fraction of the administered dose (74% of an intravenous dose is excreted unchanged in the urine, leaving 25% for metabolism) is metabolized by cytochrome P450-dependent oxidation and subsequent glutathione conjugation to a variety of Phase II metabolites. This enzymatic pathway can be inhibited by CYP450 2D6 and 3A4 inhibitors, such as quinidine, ketoconazole, and gestodene. Thus, CYP450 2D6 and 3A4 are involved in the metabolic pathway that is responsible for the elimination of a small part of the administered dose. In vitro studies using human liver microsomes showed that tiotropium in supra-therapeutic concentrations did not inhibit CYP450 1A1, 1A2, 2B6, 2C9, 2C19, 2D6, 2E1, or 3A4.

Elimination

The terminal elimination half-life of tiotropium was between 5 and 6 days following inhalation. Total clearance was 880 mL/min after an intravenous dose in young healthy volunteers with an inter-individual variability of 22%. Intravenously administered tiotropium was mainly excreted unchanged in urine (74%). After dry powder inhalation, urinary excretion was 14% of the dose, the remainder being mainly non-absorbed drug in the gut which was eliminated via the feces. The renal clearance of tiotropium exceeds the creatinine clearance, indicating active secretion into the urine. After chronic once-daily inhalation by COPD patients, pharmacokinetic steady state was reached after 2 to 3 weeks with no accumulation thereafter.

Drug Interactions

An interaction study with tiotropium (14.4 mcg intravenous infusion over 15 minutes) and cimetidine 400 mg three times daily or ranitidine 300 mg once daily was conducted. Concomitant administration of cimetidine with tiotropium resulted in a 20% increase in the AUC0-4h, a 28% decrease in the renal clearance of tiotropium and no significant change in the Cmax and amount excreted in urine over 96 hours. Co-administration of tiotropium with ranitidine did not affect the pharmacokinetics of tiotropium.

Specific Populations

Geriatric Patients

As expected for drugs predominantly excreted renally, advanced age was associated with a decrease of tiotropium renal clearance (326 mL/min in COPD patients < 58 years to 163 mL/min in COPD patients > 70 years), which may be explained by decreased renal function. Tiotropium excretion in urine after inhalation decreased from 14% (young healthy volunteers) to about 7% (COPD patients). Plasma concentrations were numerically increased with advancing age within COPD patients (43% increase in AUC0-4 after dry powder inhalation), which was not significant when considered in relation to inter- and intra-individual variability [see DOSAGE AND ADMINISTRATION and Use In Specific Populations].

Renal Impairment

Since tiotropium is predominantly renally excreted, renal impairment was associated with increased plasma drug concentrations and reduced drug clearance after both intravenous infusion and dry powder inhalation. Mild renal impairment (creatinine clearance of 50 to 80 mL/min), which is often seen in elderly patients, increased tiotropium plasma concentrations (39% increase in AUC0-4 after intravenous infusion). In COPD patients with moderate to severe renal impairment (creatinine clearance of < 50 mL/min), the intravenous administration of tiotropium resulted in doubling of the plasma concentrations (82% increase in AUC0-4), which was confirmed by plasma concentrations after dry powder inhalation. Patients with moderate to severe renal impairment (creatinine clearance of ≤ 50 mL/min) treated with SPIRIVA HandiHaler should be monitored closely for anticholinergic side effects [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS, and Use In Specific Populations].

Hepatic Impairment

The effects of hepatic impairment on the pharmacokinetics of tiotropium were not studied.

Animal Toxicology and Pharmacology

Reproductive Toxicology Studies

No evidence of fetal structural alteration was observed in rats and rabbits at inhalation tiotropium doses of up to 1.471 and 0.007 mg/kg/day, respectively. These doses correspond to approximately 660 and 6 times the RHDID on a mg/m² basis, respectively. However, in rats, 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 were observed at inhalation tiotropium doses of ≥ 0.078 mg/kg (approximately 35 times the RHDID on a mg/m² basis). In rabbits, an increase in post-implantation loss was observed at an inhalation dose of 0.4 mg/kg/day (approximately 360 times the RHDID on a mg/m² basis). Such effects were not observed at inhalation doses of 0.009 and up to 0.088 mg/kg/day in rats and rabbits, respectively. These doses correspond to approximately 4 and 80 times the RHDID on a mg/m² basis, respectively. These dose multiples may be over-estimated due to difficulties in measuring deposited doses in animal inhalation studies.

Clinical Studies

The SPIRIVA HandiHaler (tiotropium bromide inhalation powder) clinical development program consisted of six Phase 3 studies in 2663 patients with COPD (1308 receiving SPIRIVA HandiHaler): two 1-year, placebo-controlled studies, two 6-month, placebo-controlled studies and two 1-year, ipratropium-controlled studies. These studies enrolled patients who had a clinical diagnosis of COPD, were 40 years of age or older, had a history of smoking greater than 10 pack-years, had a forced expiratory volume in one second (FEV1) less than or equal to 60% or 65% of predicted, and a ratio of FEV1/FVC of less than or equal to 0.7.

In these studies, SPIRIVA HandiHaler, administered once-daily in the morning, provided improvement in lung function (FEV1), with peak effect occurring within 3 hours following the first dose.

Two additional trials evaluated exacerbations: a 6-month, randomized, double-blind, placebo-controlled, multicenter clinical trial of 1829 COPD patients in a US Veterans Affairs setting and a 4-year, randomized, double-blind, placebo-controlled, multicenter, clinical trial of 5992 COPD patients. Long-term effects on lung function and other outcomes were also evaluated in the 4-year multicenter trial.

6-Month to 1-Year Effects on Lung Function

In the 1-year, placebo-controlled trials, the mean improvement in FEV1 at 30 minutes was 0.13 liters (13%) with a peak improvement of 0.24 liters (24%) relative to baseline after the first dose (Day 1). Further improvements in FEV1 and forced vital capacity (FVC) were observed with pharmacodynamic steady state reached by Day 8 with once-daily treatment. The mean peak improvement in FEV1, relative to baseline, was 0.28 to 0.31 liters (28% to 31%), after 1 week (Day 8) of once-daily treatment. Improvement of lung function was maintained for 24 hours after a single dose and consistently maintained over the 1-year treatment period with no evidence of tolerance.

In the two 6-month, placebo-controlled trials, serial spirometric evaluations were performed throughout daytime hours in Trial A (12 hours) and limited to 3 hours in Trial B. The serial FEV1 values over 12 hours (Trial A) are displayed in Figure 1. These trials further support the improvement in pulmonary function (FEV1) with SPIRIVA HandiHaler, which persisted over the spirometric observational period. Effectiveness was maintained for 24 hours after administration over the 6-month treatment period.

Figure 1: Mean FEV1 Over Time (prior to and after administration of study drug) on Days 1 and 169 for Trial A (a Six-Month Placebo-Controlled Study)* Day 1

Mean FEV1 Over Time on Day 1 - Illustration

Day 169

Mean FEV1 Over Time on Day 169 - Illustration

*Means adjusted for center, treatment, and baseline effect. On Day 169, a total of 183 and 149 patients in the SPIRIVA HandiHaler and placebo groups, respectively, completed the trial. The data for the remaining patients were imputed using the last observation or least favorable observation carried forward.

Results of each of the 1-year ipratropium-controlled trials were similar to the results of the 1-year placebo-controlled trials. The results of one of these trials are shown in Figure 2.

Figure 2 : Mean FEV1 Over Time (0 to 6 hours post-dose) on Days 1 and 92, Respectively for One of the Two Ipratropium-Controlled Studies* Day 1

Mean FEV1 Over Time (0 to 6 hours post-dose) on Days 1 - Illustration

Day 92

Mean FEV1 Over Time (0 to 6 hours post-dose) on Days 92

*Means adjusted for center, treatment, and baseline effect. On Day 92 (primary endpoint), a total of 151 and 69 patients in the SPIRIVA HandiHaler and ipratropium groups, respectively, completed through 3 months of observation. The data for the remaining patients were imputed using the last observation or least favorable observation carried forward.

A randomized, placebo-controlled clinical study in 105 patients with COPD demonstrated that bronchodilation was maintained throughout the 24-hour dosing interval in comparison to placebo, regardless of whether SPIRIVA HandiHaler was administered in the morning or in the evening.

Throughout each week of the one-year treatment period in the two placebo-controlled trials, patients taking SPIRIVA HandiHaler had a reduced requirement for the use of rescue short-acting beta2-agonists. Reduction in the use of rescue short-acting beta2-agonists, as compared to placebo, was demonstrated in one of the two 6-month studies.

4-Year Effects on Lung Function

A 4-year, randomized, double-blind, placebo-controlled, multicenter clinical trial involving 5992 COPD patients was conducted to evaluate the long-term effects of SPIRIVA HandiHaler on disease progression (rate of decline in FEV1). Patients were permitted to use all respiratory medications (including short-acting and long-acting beta-agonists, inhaled and systemic steroids, and theophyllines) other than inhaled anticholinergics. The patients were 40 to 88 years of age, 75% male, and 90% Caucasian with a diagnosis of COPD and a mean pre-bronchodilator FEV1 of 39% predicted (range = 9% to 76%) at study entry. There was no difference between the groups in either of the co-primary efficacy endpoints, yearly rate of decline in pre- and post-bronchodilator FEV1, as demonstrated by similar slopes of FEV1 decline over time (Figure 3).

SPIRIVA HandiHaler maintained improvements in trough (pre-dose) FEV1 (adjusted means over time: 87 to 103 mL) throughout the 4 years of the study (Figure 3).

Figure 3 : Trough (pre-dose) FEV1 Mean Values at Each Time Point

Trough (pre-dose) FEV1 Mean Values at Each Time Point - Illustration

Repeated measure ANOVA was used to estimate means. Means are adjusted for baseline measurements. Baseline trough FEV1 (observed mean) = 1.12. Patients with ≥ 3 acceptable pulmonary function tests after Day 30 and non-missing baseline value were included in the analysis.

Exacerbations

The effect of SPIRIVA HandiHaler on COPD exacerbations was evaluated in two clinical trials: a 4-year clinical trial described above and a 6-month clinical trial of 1829 COPD patients in a Veterans Affairs setting. In the 6-month trial, COPD exacerbations were defined as a complex of respiratory symptoms (increase or new onset) of more than one of the following: cough, sputum, wheezing, dyspnea, or chest tightness with a duration of at least 3 days requiring treatment with antibiotics, systemic steroids, or hospitalization. The population had an age ranging from 40 to 90 years with 99% males, 91% Caucasian, and had COPD with a mean pre-bronchodilator FEV1 percent predicted of 36% (range = 8% to 93%). Patients were permitted to use respiratory medications (including short-acting and long-acting beta-agonists, inhaled and systemic steroids, and theophyllines) other than inhaled anticholinergics. In the 6-month trial, the co-primary endpoints were the proportion of patients with COPD exacerbation and the proportion of patients with hospitalization due to COPD exacerbation. SPIRIVA HandiHaler significantly reduced the proportion of COPD patients who experienced exacerbations compared to placebo (27.9% vs 32.3%, respectively; Odds Ratio (OR) (tiotropium/placebo) = 0.81; 95% CI = 0.66, 0.99; p = 0.037). The proportion of patients with hospitalization due to COPD exacerbations in patients who used SPIRIVA HandiHaler compared to placebo was 7.0% vs 9.5%, respectively; OR = 0.72; 95% CI = 0.51, 1.01; p = 0.056.

Exacerbations were evaluated as a secondary outcome in the 4-year multicenter trial. In this trial, COPD exacerbations were defined as an increase or new onset of more than one of the following respiratory symptoms (cough, sputum, sputum purulence, wheezing, dyspnea) with a duration of three or more days requiring treatment with antibiotics and/or systemic (oral, intramuscular, or intravenous) steroids. SPIRIVA HandiHaler significantly reduced the risk of an exacerbation by 14% (Hazard Ratio (HR) = 0.86; 95% CI = 0.81, 0.91; p < 0.001) and reduced the risk of exacerbation-related hospitalization by 14% (HR = 0.86; 95% CI = 0.78, 0.95; p < 0.002) compared to placebo. The median time to first exacerbation was delayed from 12.5 months (95% CI = 11.5, 13.8) in the placebo group to 16.7 months (95% CI = 14.9, 17.9) in the SPIRIVA HandiHaler group.

Last reviewed on RxList: 9/7/2011
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

SPIRIVA® HandiHaler®
(speh REE vah)
(tiotropium bromide) inhalation powder

Do NOT swallow SPIRIVA capsules.

Important Information: Do not swallow SPIRIVA capsules. SPIRIVA capsules should only be used with the HandiHaler device and inhaled through your mouth (oral inhalation).

Read the information that comes with your SPIRIVA HandiHaler before you start using it and each time you refill your prescription. There may be new information. This leaflet does not take the place of talking with your doctor about your medical condition or your treatment.

What is SPIRIVA HandiHaler?

SPIRIVA HandiHaler is a prescription medicine that you use one time every day (a maintenance medicine) to control symptoms of chronic obstructive pulmonary disease (COPD). SPIRIVA HandiHaler helps make your lungs work better for 24 hours. SPIRIVA HandiHaler relaxes your airways and helps keep them open. You may start to feel like it is easier to breathe on the first day, but it may take longer for you to feel the full effects of the medicine. SPIRIVA HandiHaler works best and may help make it easier to breathe when you use it every day.

SPIRIVA HandiHaler also reduces the likelihood of flare-ups and worsening of COPD symptoms (COPD exacerbations). A COPD exacerbation is defined as an increase or new onset of more than one COPD symptom such as cough, mucus, shortness of breath, and wheezing that requires medicine beyond your rescue medicine.

SPIRIVA HandiHaler is not a rescue medicine and should not be used for treating sudden breathing problems. Your doctor may give you other medicine to use for sudden breathing problems.

SPIRIVA HandiHaler has not been studied in children.

Who should not take SPIRIVA HandiHaler?

Do not use SPIRIVA HandiHaler if you:

  • are allergic to tiotropium. See the end of this leaflet for a complete list of ingredients.
  • have had an allergic reaction to ipratropium (Atrovent®).

Allergic reactions may include itching, rash, or swelling of the lips, tongue, or throat (trouble swallowing).

What should I tell my doctor before using SPIRIVA HandiHaler?

Before taking SPIRIVA HandiHaler, tell your doctor about all your medical conditions, including if you:

  • have kidney problems.
  • have glaucoma. SPIRIVA HandiHaler may make your glaucoma worse.
  • have an enlarged prostate, problems passing urine, or a blockage in your bladder. SPIRIVA HandiHaler may make these problems worse.
  • are pregnant or plan to become pregnant. It is not known if SPIRIVA HandiHaler could harm your unborn baby.
  • are breast-feeding or plan to breast-feed. It is not known if SPIRIVA HandiHaler passes into breast milk. You and your doctor will decide if SPIRIVA HandiHaler is right for you while you breast-feed.
  • have a severe allergy to milk proteins. Ask your doctor if you are not sure.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines and eye drops, vitamins, and herbal supplements. Some of your other medicines or supplements may affect the way SPIRIVA HandiHaler works. SPIRIVA HandiHaler is an anticholinergic medicine. You should not take other anticholinergic medicines while using SPIRIVA HandiHaler, including ipratropium. Ask your doctor or pharmacist if you are not sure if one of your medicines is an anticholinergic.

Know the medicines you take. Keep a list of your medicines with you to show your doctor and pharmacist when you get a new medicine.

How should I take SPIRIVA HandiHaler?

  • Use SPIRIVA HandiHaler exactly as prescribed. Use SPIRIVA HandiHaler one time every day.
  • Read the “Instructions for Use” at the end of this leaflet before you use SPIRIVA HandiHaler. Talk with your doctor if you do not understand the instructions.
  • Do not swallow SPIRIVA capsules.
  • Only use SPIRIVA capsules with the HandiHaler device.
  • Do not use the HandiHaler device to take any other medicine.
  • SPIRIVA HandiHaler comes as a powder in a SPIRIVA capsule that fits the HandiHaler device. Each SPIRIVA capsule, containing only a small amount of SPIRIVA powder, is one full dose of medicine.
  • Separate one blister from the blister card. Then take out one of the SPIRIVA capsules from the blister package right before you use it.
  • After the capsule is pierced, take a complete dose of SPIRIVA HandiHaler by breathing in the powder by mouth two times, using the HandiHaler device (take 2 inhalations from one SPIRIVA capsule). See the “Instructions for Use” at the end of this leaflet.
  • Throw away any SPIRIVA capsule that is not used right away after it is taken out of the blister package. Do not leave the SPIRIVA capsules open to air; they may not work as well.
  • If you miss a dose, take it as soon as you remember. Do not use SPIRIVA HandiHaler more than one time every 24 hours.
  • If you use more than your prescribed dose of SPIRIVA HandiHaler, call your doctor or a poison control center.

What should I avoid while using SPIRIVA HandiHaler?

Do not let the powder from the SPIRIVA capsule get into your eyes. Your vision may get blurry and the pupil in your eye may get larger (dilate). If this happens, call your doctor.

What are the possible side effects of SPIRIVA HandiHaler?

SPIRIVA HandiHaler can cause serious side effects. If you get any of the following side effects, stop taking SPIRIVA HandiHaler and get medical help right away.

  • Allergic reaction. Symptoms may include: itching, rash, swelling of the lips, tongue, or throat (trouble swallowing).
  • Sudden narrowing and blockage of the airways into the lungs (bronchospasm). Your breathing suddenly gets worse.
  • New or worsened increased pressure in the eyes (acute narrow-angle glaucoma). Symptoms of acute narrow-angle glaucoma may include: eye pain, blurred vision, seeing halos (visual halos) or colored images along with red eyes.
  • New or worsened urinary retention. Symptoms of blockage in your bladder and/or enlarged prostate may include: difficulty passing urine, painful urination.

Other side effects with SPIRIVA HandiHaler include:

These are not all the possible side effects with SPIRIVA HandiHaler. Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How do I store SPIRIVA HandiHaler?

  • Do not store SPIRIVA capsules in the HandiHaler device.
  • Store SPIRIVA capsules in the sealed blister package at room temperature between 68oF–77oF (20o–25oC).
  • Keep SPIRIVA capsules away from heat and cold (do not freeze).
  • Store SPIRIVA capsules in a dry place. Throw away any unused SPIRIVA capsules that have been open to air.

Ask your doctor or pharmacist if you have any questions about storing your SPIRIVA capsules.

Keep SPIRIVA HandiHaler, SPIRIVA capsules, and all medicines out of the reach of children.

General information about SPIRIVA HandiHaler

Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflets. Do not use SPIRIVA HandiHaler for a purpose for which it has not been prescribed. Do not give SPIRIVA HandiHaler to other people even if they have the same symptoms that you have. It may harm them.

For more information about SPIRIVA HandiHaler, talk with your doctor. You can ask your doctor or pharmacist for information about SPIRIVA HandiHaler that is written for health professionals.

For more information about SPIRIVA HandiHaler, you may call Boehringer Ingelheim Pharmaceuticals, Inc. at 1-800-542-6257 or (TTY) 1-800-459-9906.

What are the ingredients in SPIRIVA HandiHaler?

Active ingredient: tiotropium

Inactive ingredient: lactose monohydrate

What is COPD (Chronic Obstructive Pulmonary Disease)?

COPD is a serious lung disease that includes chronic bronchitis, emphysema, or both. Most COPD is caused by smoking. When you have COPD, your airways become narrow. So, air moves out of your lungs more slowly. This makes it hard to breathe.

Instructions for Use

SPIRIVA® HandiHaler®
(speh REE vah)
(tiotropium bromide inhalation powder)

Do not swallow SPIRIVA capsules.

Do not swallow SPIRIVA capsules - Illustration

Important Information about using your SPIRIVA HandiHaler

  • Do not swallow SPIRIVA capsules.
  • SPIRIVA capsules should only be used with the HandiHaler device and inhaled through your mouth (oral inhalation).
  • Do not use your HandiHaler device to take any other medicine.

First read the Patient Information, then read these Instructions for Use before you start to use SPIRIVA HandiHaler and each time you refill your prescription. There may be new information.

Becoming familiar with your HandiHaler device and SPIRIVA capsules:

Your SPIRIVA HandiHaler comes with SPIRIVA capsules in blister packaging and a HandiHaler device. Use the new HandiHaler device provided with your medicine.

The parts of your HandiHaler device include: (See Figure A)

  1. dust cap (lid)
  2. mouthpiece
  3. mouthpiece ridge
  4. base
  5. green piercing button
  6. center chamber
  7. air intake vents

Figure A

The parts of your HandiHaler - Illustration

Each SPIRIVA capsule is packaged in a blister. (See Figure B)

Figure B

SPIRIVA capsule is packaged in a blister - Illustration

  • Each SPIRIVA capsule contains only a small amount of powder. (See Figure C) This is 1 full dose.
  • Do not open the SPIRIVA capsule or it may not work.

Figure C

Capsule contains only a small amount of powder - Illustration

Taking your full daily dose of medicine requires 4 main steps.

Step 1. Opening your HandiHaler device:

After removing your HandiHaler device from the pouch:

  • Open the dust cap (lid) by pressing the green piercing button. (See Figure D)

Figure D

Open the dust cap - Illustration

  • Pull the dust cap (lid) upwards away from the base to expose the mouthpiece. (See Figure E)

Figure E

Pull the dust cap (lid) upwards - Illustration

  • Open the mouthpiece by pulling the mouthpiece ridge up and away from the base so the center chamber is showing. (See Figure F)

Figure F

Open the mouthpiece by pulling the mouthpiece ridge up -  Illustration

Step 2. Inserting the SPIRIVA capsule into your HandiHaler device:

Each day, separate only 1 of the blisters from the blister card by tearing along the perforated line. (See Figure G)

Figure G

Each day, separate only 1 of the blisters - Illustration

Remove the SPIRIVA capsule from the blister:

  • Do not cut the foil or use sharp instruments to take out the SPIRIVA capsule from the blister.
  • Bend 1 of the blister corners with an arrow and separate the aluminum foil layers.
  • Peel back the printed foil until you see the whole SPIRIVA capsule. (See Figure H)
  • If you have opened more than 1 blister to the air, the extra SPIRIVA capsule should not be used and should be thrown away

Figure H

Peel back the printed foil - Illustration

Place the SPIRIVA capsule in the center chamber of your HandiHaler device. (See Figure I)

Figure I

Place the SPIRIVA capsule in the center chamber of your HandiHaler - Illustration

Close the mouthpiece firmly against the gray base until you hear a click. Leave the dust cap (lid) open. (See Figure J)

Figure J

Leave the dust cap (lid) open - Illustration

Step 3. Piercing the SPIRIVA capsule:

  • Hold your HandiHaler device with the mouthpiece pointed up. (See Figure K)
  • Press the green piercing button once until it is flat (flush) against the base, then release. This is how you make holes in the SPIRIVA capsule so that you get your medicine when you breathe in.
  • Do not press the green button more than one time.
  • Do not shake your HandiHaler device.
  • The piercing of the SPIRIVA capsule may produce small gelatin pieces. Some of these small pieces may pass through the screen of your HandiHaler device into your mouth or throat when you breathe in your medicine. This is normal. The small pieces of gelatin should not harm you.

Figure K

Hold your HandiHaler device with the mouthpiece pointed up - Illustration

Step 4. Taking your full daily dose (2 inhalations from the same SPIRIVA capsule):

Breathe out completely in 1 breath, emptying your lungs of any air. (See Figure L)

Important: Do not breathe into your HandiHaler device.

Figure L

Breathe out completely - Illustration

With your next breath, take your medicine:

  • Hold your head in an upright position while you are looking straight ahead. (See Figure M)
  • Raise your HandiHaler device to your mouth in a horizontal position. Do not block the air intake vents.
  • Close your lips tightly around the mouthpiece.
  • Breathe in deeply until your lungs are full. You should hear or feel the SPIRIVA capsule vibrate (rattle). (See Figure M)
  • Hold your breath for a few seconds and, at the same time, take your HandiHaler device out of your mouth.
  • Breathe normally again.

The rattle tells you that you breathed in correctly. If you do not hear or feel a rattle, see the section, “If you do not hear or feel the SPIRIVA capsule rattle as you breathe in your medicine.”

Figure M

Breathe in deeply - Illustration

Figure N

Breathe out completely - Illustration

To get your full daily dose, you must again, breathe out completely (See Figure N) and for a second time, breathe in (See Figure O) from the same SPIRIVA capsule.

Important: Do not press the green piercing button again.

Remember: To get your full medicine dose each day, you must breathe in 2 times from the same SPIRIVA capsule. Make sure you breathe out completely each time before you breathe in from your HandiHaler device.

Figure O

For a second time, breathe in - Illustration

Caring for and storing your SPIRIVA HandiHaler:

  • After taking your daily dose, open the mouthpiece and tip out the used SPIRIVA capsule into your trash can, without touching it.
  • Remove any SPIRIVA capsule pieces or SPIRIVA powder buildup by turning your HandiHaler device upside down and gently, but firmly, tapping it. (See Figure P) Then, close the mouthpiece and dustcap for storage.
  • Do not store your HandiHaler device and SPIRIVA capsules (blisters) in a damp moist place. Always store SPIRIVA capsules in the sealed blisters.

Figure P

Remove any SPIRIVA capsule pieces or SPIRIVA powder - Illustration

If you do not hear or feel the SPIRIVA capsule rattle as you breathe in your medicine:

Do not press the green piercing button again.

Hold your HandiHaler device with the mouthpiece pointed up and tap your HandiHaler device gently on a table. (See Figure Q)

Check to see that the mouthpiece is completely closed. Breathe out completely before deeply breathing in again with the mouthpiece in your mouth. (See Figure O)

If you still do not hear or feel the SPIRIVA capsule rattle after repeating the above steps:

  • Throw away the SPIRIVA capsule.
  • Open the base by lifting the green piercing button and check the center chamber for pieces of the SPIRIVA capsule. SPIRIVA capsule pieces in the center chamber can cause a SPIRIVA capsule not to rattle.
  • Turn your HandiHaler device upside down and gently, but firmly, tap to remove the SPIRIVA capsule pieces. Call your doctor for instructions.

Figure Q

Tap your HandiHaler device gently - Illustration

Cleaning your HandiHaler device:

Clean your HandiHaler device as needed. (See Figure R)

  • It takes 24 hours to air dry your HandiHaler device after you clean it.
  • Do not use cleaning agents or detergents.
  • Do not place your HandiHaler device in the dishwasher for cleaning.

Cleaning Steps:

  • Open the dust cap and mouthpiece
  • Open the base by lifting the green piercing button.
  • Look in the center chamber for SPIRIVA capsule pieces or powder buildup. If seen, tap out.
  • Rinse your HandiHaler device with warm water, pressing the green piercing button a few times so that the center chamber and the piercing needle is under the running water. Check that any powder buildup or SPIRIVA capsule pieces are removed.
  • Dry your HandiHaler device well by tipping the excess water out on a paper towel. Air-dry afterwards, leaving the dust cap, mouthpiece, and base open by fully spreading it out so that it dries completely.
  • Do not use a hair dryer to dry your HandiHaler device.
  • Do not use your HandiHaler device when it is wet. If needed, you may clean the outside of the mouthpiece with a clean damp cloth.

Figure R

Clean your HandiHaler device as needed - Illustration

Helpful Hints to help ensure that you are properly taking your full daily dose of SPIRIVA HandiHaler:

  • Press the green piercing button 1 time; Breathe in 2 times; Breathe out completely before each of the 2 inhalations.
  • Always use the new HandiHaler device provided with your medicine.
  • Keep your HandiHaler device with the mouthpiece pointed up when pressing the green piercing button.
  • Press the green piercing button 1 time to pierce the SPIRIVA capsule.
  • Do not breathe out into your HandiHaler device.
  • Keep your HandiHaler device in a horizontal position and keep your head upright, looking straight ahead, when breathing in.
  • Check the center chamber of your HandiHaler device for SPIRIVA capsule pieces or powder build-up. If pieces or powder are seen, tap out before use.
  • Clean your HandiHaler as needed and dry thoroughly.

For more information, ask your doctor or pharmacist, or go to www.spiriva.com or call 1-800-XXX-XXX.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Last reviewed on RxList: 9/7/2011
This monograph has been modified to include the generic and brand name in many instances.

>

PATIENT INFORMATION

SPIRIVA® HandiHaler®
(speh REE vah)
(tiotropium bromide) inhalation powder

Do NOT swallow SPIRIVA capsules.

Important Information: Do not swallow SPIRIVA capsules. SPIRIVA capsules should only be used with the HandiHaler device and inhaled through your mouth (oral inhalation).

Read the information that comes with your SPIRIVA HandiHaler before you start using it and each time you refill your prescription. There may be new information. This leaflet does not take the place of talking with your doctor about your medical condition or your treatment.

What is SPIRIVA HandiHaler?

SPIRIVA HandiHaler is a prescription medicine that you use one time every day (a maintenance medicine) to control symptoms of chronic obstructive pulmonary disease (COPD). SPIRIVA HandiHaler helps make your lungs work better for 24 hours. SPIRIVA HandiHaler relaxes your airways and helps keep them open. You may start to feel like it is easier to breathe on the first day, but it may take longer for you to feel the full effects of the medicine. SPIRIVA HandiHaler works best and may help make it easier to breathe when you use it every day.

SPIRIVA HandiHaler also reduces the likelihood of flare-ups and worsening of COPD symptoms (COPD exacerbations). A COPD exacerbation is defined as an increase or new onset of more than one COPD symptom such as cough, mucus, shortness of breath, and wheezing that requires medicine beyond your rescue medicine.

SPIRIVA HandiHaler is not a rescue medicine and should not be used for treating sudden breathing problems. Your doctor may give you other medicine to use for sudden breathing problems.

SPIRIVA HandiHaler has not been studied in children.

Who should not take SPIRIVA HandiHaler?

Do not use SPIRIVA HandiHaler if you:

  • are allergic to tiotropium. See the end of this leaflet for a complete list of ingredients.
  • have had an allergic reaction to ipratropium (Atrovent®).

Allergic reactions may include itching, rash, or swelling of the lips, tongue, or throat (trouble swallowing).

What should I tell my doctor before using SPIRIVA HandiHaler?

Before taking SPIRIVA HandiHaler, tell your doctor about all your medical conditions, including if you:

  • have kidney problems.
  • have glaucoma. SPIRIVA HandiHaler may make your glaucoma worse.
  • have an enlarged prostate, problems passing urine, or a blockage in your bladder. SPIRIVA HandiHaler may make these problems worse.
  • are pregnant or plan to become pregnant. It is not known if SPIRIVA HandiHaler could harm your unborn baby.
  • are breast-feeding or plan to breast-feed. It is not known if SPIRIVA HandiHaler passes into breast milk. You and your doctor will decide if SPIRIVA HandiHaler is right for you while you breast-feed.
  • have a severe allergy to milk proteins. Ask your doctor if you are not sure.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines and eye drops, vitamins, and herbal supplements. Some of your other medicines or supplements may affect the way SPIRIVA HandiHaler works. SPIRIVA HandiHaler is an anticholinergic medicine. You should not take other anticholinergic medicines while using SPIRIVA HandiHaler, including ipratropium. Ask your doctor or pharmacist if you are not sure if one of your medicines is an anticholinergic.

Know the medicines you take. Keep a list of your medicines with you to show your doctor and pharmacist when you get a new medicine.

How should I take SPIRIVA HandiHaler?

  • Use SPIRIVA HandiHaler exactly as prescribed. Use SPIRIVA HandiHaler one time every day.
  • Read the “Instructions for Use” at the end of this leaflet before you use SPIRIVA HandiHaler. Talk with your doctor if you do not understand the instructions.
  • Do not swallow SPIRIVA capsules.
  • Only use SPIRIVA capsules with the HandiHaler device.
  • Do not use the HandiHaler device to take any other medicine.
  • SPIRIVA HandiHaler comes as a powder in a SPIRIVA capsule that fits the HandiHaler device. Each SPIRIVA capsule, containing only a small amount of SPIRIVA powder, is one full dose of medicine.
  • Separate one blister from the blister card. Then take out one of the SPIRIVA capsules from the blister package right before you use it.
  • After the capsule is pierced, take a complete dose of SPIRIVA HandiHaler by breathing in the powder by mouth two times, using the HandiHaler device (take 2 inhalations from one SPIRIVA capsule). See the “Instructions for Use” at the end of this leaflet.
  • Throw away any SPIRIVA capsule that is not used right away after it is taken out of the blister package. Do not leave the SPIRIVA capsules open to air; they may not work as well.
  • If you miss a dose, take it as soon as you remember. Do not use SPIRIVA HandiHaler more than one time every 24 hours.
  • If you use more than your prescribed dose of SPIRIVA HandiHaler, call your doctor or a poison control center.

What should I avoid while using SPIRIVA HandiHaler?

Do not let the powder from the SPIRIVA capsule get into your eyes. Your vision may get blurry and the pupil in your eye may get larger (dilate). If this happens, call your doctor.

What are the possible side effects of SPIRIVA HandiHaler?

SPIRIVA HandiHaler can cause serious side effects. If you get any of the following side effects, stop taking SPIRIVA HandiHaler and get medical help right away.

  • Allergic reaction. Symptoms may include: itching, rash, swelling of the lips, tongue, or throat (trouble swallowing).
  • Sudden narrowing and blockage of the airways into the lungs (bronchospasm). Your breathing suddenly gets worse.
  • New or worsened increased pressure in the eyes (acute narrow-angle glaucoma). Symptoms of acute narrow-angle glaucoma may include: eye pain, blurred vision, seeing halos (visual halos) or colored images along with red eyes.
  • New or worsened urinary retention. Symptoms of blockage in your bladder and/or enlarged prostate may include: difficulty passing urine, painful urination.

Other side effects with SPIRIVA HandiHaler include:

These are not all the possible side effects with SPIRIVA HandiHaler. Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How do I store SPIRIVA HandiHaler?

  • Do not store SPIRIVA capsules in the HandiHaler device.
  • Store SPIRIVA capsules in the sealed blister package at room temperature between 68oF–77oF (20o–25oC).
  • Keep SPIRIVA capsules away from heat and cold (do not freeze).
  • Store SPIRIVA capsules in a dry place. Throw away any unused SPIRIVA capsules that have been open to air.

Ask your doctor or pharmacist if you have any questions about storing your SPIRIVA capsules.

Keep SPIRIVA HandiHaler, SPIRIVA capsules, and all medicines out of the reach of children.

General information about SPIRIVA HandiHaler

Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflets. Do not use SPIRIVA HandiHaler for a purpose for which it has not been prescribed. Do not give SPIRIVA HandiHaler to other people even if they have the same symptoms that you have. It may harm them.

For more information about SPIRIVA HandiHaler, talk with your doctor. You can ask your doctor or pharmacist for information about SPIRIVA HandiHaler that is written for health professionals.

For more information about SPIRIVA HandiHaler, you may call Boehringer Ingelheim Pharmaceuticals, Inc. at 1-800-542-6257 or (TTY) 1-800-459-9906.

What are the ingredients in SPIRIVA HandiHaler?

Active ingredient: tiotropium

Inactive ingredient: lactose monohydrate

What is COPD (Chronic Obstructive Pulmonary Disease)?

COPD is a serious lung disease that includes chronic bronchitis, emphysema, or both. Most COPD is caused by smoking. When you have COPD, your airways become narrow. So, air moves out of your lungs more slowly. This makes it hard to breathe.

Instructions for Use

SPIRIVA® HandiHaler®
(speh REE vah)
(tiotropium bromide inhalation powder)

Do not swallow SPIRIVA capsules.

Do not swallow SPIRIVA capsules - Illustration

Important Information about using your SPIRIVA HandiHaler

  • Do not swallow SPIRIVA capsules.
  • SPIRIVA capsules should only be used with the HandiHaler device and inhaled through your mouth (oral inhalation).
  • Do not use your HandiHaler device to take any other medicine.

First read the Patient Information, then read these Instructions for Use before you start to use SPIRIVA HandiHaler and each time you refill your prescription. There may be new information.

Becoming familiar with your HandiHaler device and SPIRIVA capsules:

Your SPIRIVA HandiHaler comes with SPIRIVA capsules in blister packaging and a HandiHaler device. Use the new HandiHaler device provided with your medicine.

The parts of your HandiHaler device include: (See Figure A)

  1. dust cap (lid)
  2. mouthpiece
  3. mouthpiece ridge
  4. base
  5. green piercing button
  6. center chamber
  7. air intake vents

Figure A

The parts of your HandiHaler - Illustration

Each SPIRIVA capsule is packaged in a blister. (See Figure B)

Figure B

SPIRIVA capsule is packaged in a blister - Illustration

  • Each SPIRIVA capsule contains only a small amount of powder. (See Figure C) This is 1 full dose.
  • Do not open the SPIRIVA capsule or it may not work.

Figure C

Capsule contains only a small amount of powder - Illustration

Taking your full daily dose of medicine requires 4 main steps.

Step 1. Opening your HandiHaler device:

After removing your HandiHaler device from the pouch:

  • Open the dust cap (lid) by pressing the green piercing button. (See Figure D)

Figure D

Open the dust cap - Illustration

  • Pull the dust cap (lid) upwards away from the base to expose the mouthpiece. (See Figure E)

Figure E

Pull the dust cap (lid) upwards - Illustration

  • Open the mouthpiece by pulling the mouthpiece ridge up and away from the base so the center chamber is showing. (See Figure F)

Figure F

Open the mouthpiece by pulling the mouthpiece ridge up -  Illustration

Step 2. Inserting the SPIRIVA capsule into your HandiHaler device:

Each day, separate only 1 of the blisters from the blister card by tearing along the perforated line. (See Figure G)

Figure G

Each day, separate only 1 of the blisters - Illustration

Remove the SPIRIVA capsule from the blister:

  • Do not cut the foil or use sharp instruments to take out the SPIRIVA capsule from the blister.
  • Bend 1 of the blister corners with an arrow and separate the aluminum foil layers.
  • Peel back the printed foil until you see the whole SPIRIVA capsule. (See Figure H)
  • If you have opened more than 1 blister to the air, the extra SPIRIVA capsule should not be used and should be thrown away

Figure H

Peel back the printed foil - Illustration

Place the SPIRIVA capsule in the center chamber of your HandiHaler device. (See Figure I)

Figure I

Place the SPIRIVA capsule in the center chamber of your HandiHaler - Illustration

Close the mouthpiece firmly against the gray base until you hear a click. Leave the dust cap (lid) open. (See Figure J)

Figure J

Leave the dust cap (lid) open - Illustration

Step 3. Piercing the SPIRIVA capsule:

  • Hold your HandiHaler device with the mouthpiece pointed up. (See Figure K)
  • Press the green piercing button once until it is flat (flush) against the base, then release. This is how you make holes in the SPIRIVA capsule so that you get your medicine when you breathe in.
  • Do not press the green button more than one time.
  • Do not shake your HandiHaler device.
  • The piercing of the SPIRIVA capsule may produce small gelatin pieces. Some of these small pieces may pass through the screen of your HandiHaler device into your mouth or throat when you breathe in your medicine. This is normal. The small pieces of gelatin should not harm you.

Figure K

Hold your HandiHaler device with the mouthpiece pointed up - Illustration

Step 4. Taking your full daily dose (2 inhalations from the same SPIRIVA capsule):

Breathe out completely in 1 breath, emptying your lungs of any air. (See Figure L)

Important: Do not breathe into your HandiHaler device.

Figure L

Breathe out completely - Illustration

With your next breath, take your medicine:

  • Hold your head in an upright position while you are looking straight ahead. (See Figure M)
  • Raise your HandiHaler device to your mouth in a horizontal position. Do not block the air intake vents.
  • Close your lips tightly around the mouthpiece.
  • Breathe in deeply until your lungs are full. You should hear or feel the SPIRIVA capsule vibrate (rattle). (See Figure M)
  • Hold your breath for a few seconds and, at the same time, take your HandiHaler device out of your mouth.
  • Breathe normally again.

The rattle tells you that you breathed in correctly. If you do not hear or feel a rattle, see the section, “If you do not hear or feel the SPIRIVA capsule rattle as you breathe in your medicine.”

Figure M

Breathe in deeply - Illustration

Figure N

Breathe out completely - Illustration

To get your full daily dose, you must again, breathe out completely (See Figure N) and for a second time, breathe in (See Figure O) from the same SPIRIVA capsule.

Important: Do not press the green piercing button again.

Remember: To get your full medicine dose each day, you must breathe in 2 times from the same SPIRIVA capsule. Make sure you breathe out completely each time before you breathe in from your HandiHaler device.

Figure O

For a second time, breathe in - Illustration

Caring for and storing your SPIRIVA HandiHaler:

  • After taking your daily dose, open the mouthpiece and tip out the used SPIRIVA capsule into your trash can, without touching it.
  • Remove any SPIRIVA capsule pieces or SPIRIVA powder buildup by turning your HandiHaler device upside down and gently, but firmly, tapping it. (See Figure P) Then, close the mouthpiece and dustcap for storage.
  • Do not store your HandiHaler device and SPIRIVA capsules (blisters) in a damp moist place. Always store SPIRIVA capsules in the sealed blisters.

Figure P

Remove any SPIRIVA capsule pieces or SPIRIVA powder - Illustration

If you do not hear or feel the SPIRIVA capsule rattle as you breathe in your medicine:

Do not press the green piercing button again.

Hold your HandiHaler device with the mouthpiece pointed up and tap your HandiHaler device gently on a table. (See Figure Q)

Check to see that the mouthpiece is completely closed. Breathe out completely before deeply breathing in again with the mouthpiece in your mouth. (See Figure O)

If you still do not hear or feel the SPIRIVA capsule rattle after repeating the above steps:

  • Throw away the SPIRIVA capsule.
  • Open the base by lifting the green piercing button and check the center chamber for pieces of the SPIRIVA capsule. SPIRIVA capsule pieces in the center chamber can cause a SPIRIVA capsule not to rattle.
  • Turn your HandiHaler device upside down and gently, but firmly, tap to remove the SPIRIVA capsule pieces. Call your doctor for instructions.

Figure Q

Tap your HandiHaler device gently - Illustration

Cleaning your HandiHaler device:

Clean your HandiHaler device as needed. (See Figure R)

  • It takes 24 hours to air dry your HandiHaler device after you clean it.
  • Do not use cleaning agents or detergents.
  • Do not place your HandiHaler device in the dishwasher for cleaning.

Cleaning Steps:

  • Open the dust cap and mouthpiece
  • Open the base by lifting the green piercing button.
  • Look in the center chamber for SPIRIVA capsule pieces or powder buildup. If seen, tap out.
  • Rinse your HandiHaler device with warm water, pressing the green piercing button a few times so that the center chamber and the piercing needle is under the running water. Check that any powder buildup or SPIRIVA capsule pieces are removed.
  • Dry your HandiHaler device well by tipping the excess water out on a paper towel. Air-dry afterwards, leaving the dust cap, mouthpiece, and base open by fully spreading it out so that it dries completely.
  • Do not use a hair dryer to dry your HandiHaler device.
  • Do not use your HandiHaler device when it is wet. If needed, you may clean the outside of the mouthpiece with a clean damp cloth.

Figure R

Clean your HandiHaler device as needed - Illustration

Helpful Hints to help ensure that you are properly taking your full daily dose of SPIRIVA HandiHaler:

  • Press the green piercing button 1 time; Breathe in 2 times; Breathe out completely before each of the 2 inhalations.
  • Always use the new HandiHaler device provided with your medicine.
  • Keep your HandiHaler device with the mouthpiece pointed up when pressing the green piercing button.
  • Press the green piercing button 1 time to pierce the SPIRIVA capsule.
  • Do not breathe out into your HandiHaler device.
  • Keep your HandiHaler device in a horizontal position and keep your head upright, looking straight ahead, when breathing in.
  • Check the center chamber of your HandiHaler device for SPIRIVA capsule pieces or powder build-up. If pieces or powder are seen, tap out before use.
  • Clean your HandiHaler as needed and dry thoroughly.

For more information, ask your doctor or pharmacist, or go to www.spiriva.com or call 1-800-XXX-XXX.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Last reviewed on RxList: 9/7/2011
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Spiriva Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

TIOTROPIUM POWDER IN CAPSULE - INHALATION

(TYE-oh-TROE-pee-um)

COMMON BRAND NAME(S): Spiriva

USES: Tiotropium is used to control and prevent symptoms (such as wheezing, shortness of breath) caused by ongoing lung disease (chronic obstructive pulmonary disease-COPD which includes bronchitis and emphysema). It works by relaxing the muscles around the airways so that they open up and you can breathe more easily. Tiotropium belongs to a class of drugs known as anticholinergics. Controlling symptoms of breathing problems can decrease time lost from work or school.

This medication must be used regularly to be effective. It does not work immediately and should not be used to relieve sudden breathing problems. If wheezing or sudden shortness of breath occurs, use your quick-relief inhaler (such as albuterol, also called salbutamol in some countries) as prescribed.

HOW TO USE: Read the Patient Information Leaflet and instruction sheet if available from your pharmacist before you start using tiotropium and each time you get a refill. Learn how to use this inhaler properly. If you have any questions, ask your doctor or pharmacist.

Do not swallow these capsules by mouth. Use the special inhaler to inhale the powder in the capsules. Inhale this medication by mouth as directed by your doctor, usually once daily. Inhale 2 times per capsule to make sure you inhale all of the drug. Do not breathe out into the mouthpiece at any time. Avoid getting this medication into your eyes. It may cause eye pain/irritation, temporary blurred vision, and other vision changes.

Use this medication regularly in order to get the most benefit from it. This medication works best if used at evenly spaced intervals. To help you remember, use it at the same time each day. Do not increase your dose, use this medication more frequently, or stop using it without first consulting your doctor.

Rinse your mouth after using the inhaler to prevent dry mouth and throat irritation.

Clean the inhaler at least once a month with water. Allow to air-dry fully before using again.

Learn which of your inhalers you should use every day and which you should use if your breathing suddenly worsens. Ask your doctor ahead of time what to do if you have worsening cough or shortness of breath, wheezing, increased sputum, worsening peak flow meter readings, increased use of your quick-relief inhaler, or if your quick-relief inhaler does not seem to be working well. Learn when you can self-medicate and when you should get medical help right away.

Tell your doctor if your symptoms do not improve or if they worsen.

Disclaimer

Spiriva Consumer (continued)

SIDE EFFECTS: Dry mouth or constipation may occur. If either of these effects persists or worsens, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Infrequently, this medication may cause severe sudden worsening of breathing problems right after use. If you have sudden worsening of breathing, use your quick-relief inhaler and get medical help right away.

Tell your doctor right away if you have any serious side effects, including: vision changes (such as blurred vision, seeing halos), eye pain, difficult/painful urination, fast heartbeat.

A very serious allergic reaction to this product is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Spiriva (tiotropium bromide) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: Before using tiotropium, tell your doctor or pharmacist if you are allergic to it or to ipratropium; or to atropine or other belladonna-type drugs; or if you have any other allergies. This product may contain inactive ingredients (such as milk proteins), which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, glaucoma (narrow-angle), difficulty urinating (for example, due to enlarged prostate).

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Older adults may be more sensitive to the side effects of this drug, especially dry mouth and constipation.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is unknown if this medication passes into breast milk. Consult your doctor before breast-feeding.

Disclaimer

Spiriva Consumer (continued)

DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

Some products that may interact with this drug include: other anticholinergics (such as ipratropium).

OVERDOSE: If the capsule is swallowed, this medication will not work and may be harmful. If swallowing or overdose is suspected, contact a poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store the capsules at room temperature away from light and moisture. Keep the capsules in the blister package until ready to use. Do not store capsules in the inhaler device. Once the blister package for a capsule is opened, that capsule should be used right away. Discard any capsule that has its blister package opened and not used right away. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (US) or 1-800-668-1507 (Canada).

Information last revised September 2011. Copyright(c) 2011 First Databank, Inc.

Spiriva Patient Information Including Side Effects

Brand Names: Spiriva

Generic Name: tiotropium inhalation (Pronunciation: tye oh TROE pee um)

What is tiotropium inhalation (Spiriva)?

Tiotropium inhalation is used to prevent bronchospasm (narrowing of the airways in the lungs) in people with bronchitis, emphysema, or COPD (chronic obstructive pulmonary disease).

Tiotropium inhalation may also be used for other purposes not listed in this medication guide.

What are the possible side effects of tiotropium inhalation (Spiriva)?

Stop using tiotropium inhalation and get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • tongue swelling or redness;
  • sores or white patches of your mouth, lips, or tongue; or
  • urinating less than usual or not at all.

Less serious side effects may include:

  • dry mouth, cough, hoarseness;
  • blurred vision;
  • trouble swallowing;
  • nausea, constipation, upset stomach;
  • stuffy nose, nosebleed;
  • fast heart rate;
  • drowsiness; or
  • white patches in your mouth or throat.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

Read the Spiriva (tiotropium bromide) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about tiotropium inhalation (Spiriva)?

Tiotropium capsules are for use only in the HandiHaler device. Use only one capsule at a time. Do not take the capsules by mouth.

Before using this medication, tell your doctor if you have narrow-angle glaucoma, or an enlarged prostate or bladder obstruction. If you have any of these conditions, you may not be able to use tiotropium inhalation or you may need a dosage adjustment or special tests during treatment.

Tiotropium inhalation is used to prevent bronchospasm attacks. Do not use this medication to treat a bronchospasm attack that has already begun. It will not work fast enough to reverse your symptoms. Use only a fast-acting inhalation medication to treat an attack. Talk with your doctor if any of your medications do not seem to work as well in treating or preventing bronchospasm attacks.

Use this medication exactly as it was prescribed for you. Do not use it in larger doses or for longer than recommended by your doctor.

Call your doctor right away if you feel that this medicine is not working as well as usual, or if it makes your condition worse. If it seems like you need to use more of any of your medications in a 24-hour period, talk with your doctor.

Side Effects Centers

Spiriva Patient Information including How Should I Take

What should I discuss with my healthcare provider before using tiotropium inhalation (Spiriva)?

Do not use this medication if you are allergic to tiotropium, ipratropium (Atrovent) or atropine (Atreza, Sal-Tropine).

Tiotropium inhalation is used to prevent bronchospasm attacks. Do not use this medication to treat a bronchospasm attack that has already begun. It will not work fast enough to reverse your symptoms. Use only a fast-acting inhalation medication to treat an attack. Talk with your doctor if any of your medications do not seem to work as well in treating or preventing bronchospasm attacks.

Before using tiotropium inhalation, tell your doctor if you are allergic to any drugs, or if you have:

  • narrow-angle glaucoma; or
  • an enlarged prostate or a bladder obstruction.

If you have any of these conditions, you may need a dose adjustment or special tests to safely use tiotropium inhalation.

FDA pregnancy category C. It is not known whether tiotropium inhalation is harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known if tiotropium passes into breast milk or if it could harm a nursing baby. Do not use tiotropium inhalation without telling your doctor if you are breast-feeding a baby.

How should I use tiotropium inhalation (Spiriva)?

Use this medication exactly as it was prescribed for you. Do not use it in larger doses or for longer than recommended by your doctor. Follow the directions on your prescription label.

Tiotropium inhalation is used to prevent bronchospasm attacks. Do not use this medication to treat a bronchospasm attack that has already begun. It will not work fast enough to reverse your symptoms. Use only a fast-acting inhalation medication to treat an attack. Talk with your doctor if any of your medications do not seem to work as well in treating or preventing bronchospasm attacks.

Tiotropium inhalation and its inhaler device come with patient instructions for safe and effective use. Follow these directions carefully. Ask your doctor or pharmacist if you have any questions.

Tiotropium capsules are for use only in the HandiHaler device. Use only one capsule at a time. Do not take the capsules by mouth.

It is important to use tiotropium inhalation regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

Call your doctor right away if you feel that this medicine is not working as well as usual, or if it makes your condition worse. If it seems like you need to use more of any of your medications in a 24-hour period, talk with your doctor.

To be sure this medication is helping your condition, your lung function will need to be tested on a regular basis. Do not miss any scheduled appointments.

Keep each tiotropium capsule in its blister pack until you are ready to place the capsule into the HandiHaler and use the device for your dose.

Store tiotropium inhalation at room temperature away from moisture and heat.

Side Effects Centers

Spiriva Patient Information including If I Miss a Dose

What happens if I miss a dose (Spiriva)?

Use the medication as soon as you remember. If it is almost time for the next dose, skip the missed dose and wait until your next regularly scheduled dose. Do not use extra medicine to make up the missed dose.

What happens if I overdose (Spiriva)?

Seek emergency medical attention if you think you have used too much of this medicine.

Overdose symptoms may include dry mouth, eye redness, constipation, stomach pain, and confusion or drowsiness.

What should I avoid while using tiotropium inhalation (Spiriva)?

Avoid getting this medication in your eyes. If this happens, rinse with water.

What other drugs will affect tiotropium inhalation (Spiriva)?

Before using tiotropium inhalation, tell your doctor if you are using any of the following medicines:

  • atropine (Donnatal, and others);
  • belladonna;
  • cimetidine (Tagamet);
  • clidinium (Quarzan);
  • dicyclomine (Bentyl);
  • glycopyrrolate (Robinul);
  • hyoscyamine (Anaspaz, Cystospaz, Levsin, and others);
  • mepenzolate (Cantil);
  • methantheline (Provocholine);
  • methscopolamine (Pamine);
  • propantheline (Pro-Banthine); or
  • scopolamine (Transderm-Scop).

This list is not complete and there may be other drugs that can interact with tiotropium inhalation. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about tiotropium inhalation.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 3.03. Revision date: 12/15/2010.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

Healthwise

Side Effects Centers

توزیع کنندگان این دارو
شرکت های تولید کننده یا وارد کننده دارو

دارونـــما
نوآوری برای سلامت

طراحی و اجرا M.Ramezani
ارتباط با ما Info@darunama.com