Spiriva HandiHaler TIOTROPIUM BROMIDE 18 ug Capsule, 30-count
Past resolved recalls for this product (1)
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Anticholinergic class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Tiotropium is used to prevent wheezing, shortness of breath, coughing, and chest tightness in patients with chronic obstructive pulmonary disease (COPD, a group of diseases that affect the lungs and airways) such as chronic bronchitis (swelling of the air passages that lead to the lungs) and emphysema (damage to air sacs in the lungs). Tiotropium is in a class of medications called bronchodilators. It works by relaxing and opening the air passages to the lungs to make breathing easier.
Read the full MedlinePlus article ↗- No — tiotropium is a maintenance inhaler, which means it works slowly over time to keep your airways open day to day. It won't act fast enough to help during a sudden attack. Make...
- Can I use my tiotropium inhaler when I'm having a sudden asthma or COPD attack?
- You'll likely notice some improvement in your breathing within the first few days of daily use. However, for asthma patients, the full benefit to your lung function may take up to...
- How long does it take for tiotropium to start working?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Tiotropium Bromide — tap one for details:
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
Where does this data come from?
IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $10.618 | $318.53 / 30 capsules |
| Medicaid paysCMS SDUD · 12 mo | $11.06 | $331.82 / 30 capsules |
| Medicare drug plans payPart D · Q2 2026 | $10.66 | $319.89 / 30 capsules |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Spiriva HandiHaler 18 ugthis 00597-0075-41 | Boehringer | 30 capsules | $10.618 | AB | Availability likely | — |
| Tiotropium Bromide 18 ug 68180-0964-12 | Lupin | 30 capsules | $11.712 | AB | Availability likely | +10% |
| Spiriva HandiHaler 18 ug 50090-4248-00 | A-S | 30 capsules | — | AB | FDA listed | — |
| Spiriva HandiHaler 18 ug 50090-7645-00 | A-S | 30 capsules | — | AB | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 8022082 ↗ | Method of use | U-1186 | Jan 19, 2026 |
| US 8022082*PED ↗ | Drug product | — | Jul 19, 2026 |
Is there a generic version of SPIRIVA HANDIHALER 18 MCG CAP?
The FDA approved a generic — why can’t I get it at my pharmacy yet?
Why do different websites show different generic release dates?
What does “FDA listed” mean?
What does a patent or protection date mean here?
What does “current Orange Book estimate” mean?
Can a generic come out before the last patent expires?
Can a generic come out after the listed dates?
What is the difference between patents and exclusivity?
Why are there multiple patent dates?
Where does this data come from?
🗺️ Medicaid utilization & spend
💊 Medicaid utilization by pack size
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Where does this data come from?
📦 Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Status |
|---|---|---|---|---|---|
| 00597-0075-41 You're viewing this | 3 BLISTER PACK in 1 CARTON (0597-0075-41) / 10 CAPSULE in 1 BLISTER PACK | $10.62 / ea | $318.53 | 2005-10-11 | Active |
| 00597-0075-47 | 9 BLISTER PACK in 1 CARTON (0597-0075-47) / 10 CAPSULE in 1 BLISTER PACK | $10.62 / ea | $955.42 | 2005-10-11 | Active |
| 00597-0075-75 | 1 BLISTER PACK in 1 CARTON (0597-0075-75) / 5 CAPSULE in 1 BLISTER PACK | $11.74 / ea | $58.68 | 2005-10-11 | Active |
This pack effectively ties for the lowest per-ea cost of the 3 priced pack sizes ($10.62 NADAC).
In Medicaid, this is the most-dispensed pack of this product — about 98% of fills over the last four reported quarters. See all packs ↓
Pack size FAQ
What quantity is in NDC 00597-0075-41?
What is the difference between NDC 00597-0075-41 and NDC 00597-0075-75?
What NDC number is used to bill for this package of Spiriva HandiHaler TIOTROPIUM BROMIDE 18 ug Capsule?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE 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. SPIRIVA HANDIHALER is an anticholinergic indicated for the long-term, once-daily, maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), and for reducing COPD exacerbations ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION For oral inhalation only. Do not swallow SPIRIVA capsules, as the intended effects on the lungs will not be obtained. The contents of the SPIRIVA capsules should only be used with the HANDIHALER device [see Overdosage (10) ] .
The recommended dosage of SPIRIVA HANDIHALER is two inhalations of the powder contents of one SPIRIVA capsule, once-daily, with the HANDIHALER device [see Patient Counseling Information (17) ] . Do not take more than one dose in 24 hours. 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 Counseling Information (17) ] . 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 (5.6) , Use in Specific Populations (8.5 , 8.6 , 8.7) , and Clinical Pharmacology (12.3) ] . For oral inhalation only. DO NOT swallow SPIRIVA capsules.
Only use SPIRIVA capsules with the HANDIHALER device ( 2 ) Two inhalations of the powder contents of a single SPIRIVA capsule (18 mcg) once daily ( 2 )
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Inhalation Powder: SPIRIVA HANDIHALER consists of SPIRIVA capsules containing tiotropium powder for oral inhalation and a HANDIHALER device. SPIRIVA capsules contain 18 mcg of tiotropium (equivalent to 22.5 mcg tiotropium bromide monohydrate) in a light green, hard gelatin capsule with "TI 01" printed on one side and Boehringer Ingelheim company symbol on the other side. The HANDIHALER device is only intended for use with the SPIRIVA capsules.
Inhalation powder: SPIRIVA capsules contain 18 mcg tiotropium powder (equivalent to 22.5 mcg tiotropium bromide monohydrate) for use with HANDIHALER device ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS SPIRIVA HANDIHALER is contraindicated in patients with a hypersensitivity to tiotropium, ipratropium, or any components of this product [see Warnings and Precautions (5.2) ] . 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 [see Warnings and Precautions (5.2) ]. Hypersensitivity to tiotropium, ipratropium, or any components of SPIRIVA capsules ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Not for acute use: Not a rescue medication ( 5.1 ) Immediate hypersensitivity reactions: Discontinue SPIRIVA HANDIHALER at once and consider alternatives if immediate hypersensitivity reactions, including angioedema, urticaria, rash, bronchospasm, or anaphylaxis, occur. Use with caution in patients with severe hypersensitivity to milk proteins. ( 5.2 ) Paradoxical bronchospasm: Discontinue SPIRIVA HANDIHALER and consider other treatments if paradoxical bronchospasm occurs ( 5.3 ) Worsening of narrow-angle glaucoma may occur.
Use with caution in patients with narrow-angle glaucoma and instruct patients to consult a physician immediately if this occurs. ( 5.4 ) Worsening of urinary retention may occur. Use with caution in patients with prostatic hyperplasia or bladder-neck obstruction and instruct patients to consult a physician immediately if this occurs.
( 5.5 )
5.1Not for Acute Use SPIRIVA HANDIHALER is intended as a once-daily maintenance treatment for COPD and should not be used for relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm.
5.2Immediate Hypersensitivity Reactions Immediate hypersensitivity reactions, including urticaria, angioedema (including swelling of the lips, tongue, or throat), rash, bronchospasm, anaphylaxis, or itching, 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 or its derivatives 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.
5.3Paradoxical Bronchospasm Inhaled medicines, including SPIRIVA HANDIHALER, may cause paradoxical bronchospasm. If this occurs, it should be treated immediately with an inhaled short-acting beta 2 -agonist such as albuterol. Treatment with SPIRIVA HANDIHALER should be stopped and other treatments considered.
5.4Worsening 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.
5.5Worsening 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 urinary retention (e.g., difficulty passing urine, painful urination), especially in patients with prostatic hyperplasia or bladder-neck obstruction. Instruct patients to consult a physician immediately should any of these signs or symptoms develop.
5.6Renal Impairment As a predominantly renally excreted drug, patients with moderate to severe renal impairment (creatinine clearance of <60 mL/min) treated with SPIRIVA HANDIHALER should be monitored closely for anticholinergic side effects [see Clinical Pharmacology (12.3) ] .
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following adverse reactions are described, or described in greater detail, in other sections: Immediate hypersensitivity reactions [see Warnings and Precautions (5.2) ] Paradoxical bronchospasm [see Warnings and Precautions (5.3) ] Worsening of narrow-angle glaucoma [see Warnings and Precautions (5.4) ] Worsening of urinary retention [see Warnings and Precautions (5.5) ] The most common adverse reactions (>5% incidence in the 1-year placebo-controlled trials) were upper respiratory tract infection, dry mouth, sinusitis, pharyngitis, non-specific chest pain, urinary tract infection, dyspepsia, and rhinitis ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Boehringer Ingelheim Pharmaceuticals, Inc. at 1-800-542-6257 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, the incidence of adverse reactions observed in the clinical trials of a drug cannot be directly compared to the incidences in the clinical trials of another drug and may not reflect the incidences observed in practice. 6-Month to 1-Year Trials The data described below reflect exposure to SPIRIVA HANDIHALER in 2,663 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, 1,308 patients were treated with SPIRIVA HANDIHALER at the recommended dosage 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 (FEV 1 ) 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 reacti…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Anticholinergics: May interact additively with concomitantly used anticholinergic medications. Avoid administration of SPIRIVA HANDIHALER with other anticholinergic-containing drugs. ( 7.2 )
7.1Sympathomimetics, 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 reactions.
7.2Anticholinergics 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 (5.4 , 5.5) and Adverse Reactions (6) ] .
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Patients with moderate to severe renal impairment should be monitored closely for potential anticholinergic side effects ( 2 , 8.6 )
8.1Pregnancy Risk Summary The limited human data with SPIRIVA HANDIHALER use during pregnancy are insufficient to inform a drug-associated risk of adverse pregnancy-related outcomes. Based on animal reproduction studies, no structural abnormalities were observed when tiotropium was administered by inhalation to pregnant rats and rabbits during the period of organogenesis at doses 790 and 8 times, respectively, the maximum recommended human daily inhalation dose (MRHDID). Increased post-implantation loss was observed in rats and rabbits administered tiotropium at maternally toxic doses 430 times and 40 times the MRHDID, respectively [see Data ] .
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data Animal Data In 2 separate embryo-fetal development studies, pregnant rats and rabbits received tiotropium during the period of organogenesis at doses up to approximately 790 and 8 times the MRHDID, respectively (on a mcg/m 2 basis at inhalation doses of 1,471 and 7 mcg/kg/day in rats and rabbits, respectively). No evidence of structural abnormalities was observed in rats or rabbits. However, in rats, tiotropium caused fetal resorption, litter loss, decreases in the number of live pups at birth and the mean pup weights, and a delay in pup sexual maturation at tiotropium doses of approximately 40 times the MRHDID (on a mcg/m 2 basis at a maternal inhalation dose of 78 mcg/kg/day).
In rabbits, tiotropium caused an increase in post-implantation loss at a tiotropium dose of approximately 430 times the MRHDID (on a mcg/m 2 basis at a maternal inhalation dose of 400 mcg/kg/day). Such effects were not observed at approximately 5 and 95 times the MRHDID, respectively (on a mcg/m 2 basis at inhalation doses of 9 and 88 mcg/kg/day in rats and rabbits, respectively).
8.2Lactation Risk Summary There are no data on the presence of tiotropium in human milk, the effects on the breastfed infant, or the effects on milk production. Tiotropium is present in milk of lactating rats; however, due to species-specific differences in lactation physiology, the clinical relevance of these data are not clear [see Data ] . The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for SPIRIVA HANDIHALER and any potential adverse effects on the breastfed child from SPIRIVA HANDIHALER or from the underlying maternal condition.
Data The distribution of tiotropium bromide into milk was investigated after a single intravenous administration of 10 mg/kg to lactating rats. Tiotropium and/or its metabolites are present in the milk of lactating rats at concentrations above those in plasma.
8.4Pediatric Use SPIRIVA HANDIHALER is not indicated for use in children. The safety and effectiveness of SPIRIVA HANDIHALER in pediatric patients have not been established.
8.5Geriatric Use Based on available data, no adjustment of SPIRIVA HANDIHALER dosage in geriatric patients is warranted [see Clinical Pharmacology (12.3) ] . 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 con…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary The limited human data with SPIRIVA HANDIHALER use during pregnancy are insufficient to inform a drug-associated risk of adverse pregnancy-related outcomes. Based on animal reproduction studies, no structural abnormalities were observed when tiotropium was administered by inhalation to pregnant rats and rabbits during the period of organogenesis at doses 790 and 8 times, respectively, the maximum recommended human daily inhalation dose (MRHDID). Increased post-implantation loss was observed in rats and rabbits administered tiotropium at maternally toxic doses 430 times and 40 times the MRHDID, respectively [see Data ] .
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data Animal Data In 2 separate embryo-fetal development studies, pregnant rats and rabbits received tiotropium during the period of organogenesis at doses up to approximately 790 and 8 times the MRHDID, respectively (on a mcg/m 2 basis at inhalation doses of 1,471 and 7 mcg/kg/day in rats and rabbits, respectively). No evidence of structural abnormalities was observed in rats or rabbits. However, in rats, tiotropium caused fetal resorption, litter loss, decreases in the number of live pups at birth and the mean pup weights, and a delay in pup sexual maturation at tiotropium doses of approximately 40 times the MRHDID (on a mcg/m 2 basis at a maternal inhalation dose of 78 mcg/kg/day).
In rabbits, tiotropium caused an increase in post-implantation loss at a tiotropium dose of approximately 430 times the MRHDID (on a mcg/m 2 basis at a maternal inhalation dose of 400 mcg/kg/day). Such effects were not observed at approximately 5 and 95 times the MRHDID, respectively (on a mcg/m 2 basis at inhalation doses of 9 and 88 mcg/kg/day in rats and rabbits, respectively).
🧒 Pediatric Use ▾
8.4Pediatric Use SPIRIVA HANDIHALER is not indicated for use in children. The safety and effectiveness of SPIRIVA HANDIHALER in pediatric patients have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use Based on available data, no adjustment of SPIRIVA HANDIHALER dosage in geriatric patients is warranted [see Clinical Pharmacology (12.3) ] . 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.
🆘 Overdosage ▾
10 OVERDOSAGE 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.
Treatment of overdosage consists of discontinuation of SPIRIVA HANDIHALER together with institution of appropriate symptomatic and/or supportive therapy. 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism 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, M 1 to M 5 . In the airways, it exhibits pharmacological effects through inhibition of M 3 -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.
12.2Pharmacodynamics Cardiac Electrophysiology In a multicenter, randomized, double-blind trial using tiotropium dry powder for inhalation 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 tiotropium dry powder for inhalation on QT interval was also evaluated in a randomized, placebo- and positive-controlled crossover study in 53 healthy volunteers. Subjects received tiotropium dry powder for inhalation 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 tiotropium dry powder for inhalation 18 mcg and 54 mcg, respectively. No subject showed a new onset of QTc >500 msec or QTc changes from baseline of ≥60 msec.
12.3Pharmacokinetics Tiotropium is administered by dry powder inhalation. Some of the pharmacokinetic data described below were obtained with higher doses than recommended for therapy. A dedicated pharmacokinetic study in patients with COPD evaluating once-daily tiotropium delivered from the RESPIMAT inhaler (5 mcg) and as inhalation powder (18 mcg) from the HANDIHALER device resulted in a similar systemic exposure between the two products.
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. Oral solutions of tiotropium have an absolute bioavailability of 2-3%. Food is not expected to influence the absorption of tiotropium.
Maximum tiotropium plasma concentrations were observed 7 minutes after inhalation. Distribution Tiotropium is 72% bound to plasma protein and had a volume of distribution of 32 L/kg after intravenous administration to young healthy volunteers. 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. Elimination The terminal half-life of tiotropium in COPD patients following once daily inhalation of 5 mcg tiotropium was approximately 25 hours. Total clearance was 880 mL/min after intravenous administration in young healthy volunteers.
After chronic once-daily dry powder inhalation by COPD patients, pharmacokinetic steady state was reached by day 7 with no accumulation thereafter. Metabolism The extent of metabolism is 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 no…
🧬 Mechanism of Action ▾
12.1Mechanism 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, M 1 to M 5 . In the airways, it exhibits pharmacological effects through inhibition of M 3 -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.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING SPIRIVA HANDIHALER consists of SPIRIVA capsules and the HANDIHALER device. SPIRIVA capsules contain 18 mcg of tiotropium (equivalent to 22.5 mcg tiotropium bromide monohydrate) and are light green, with the Boehringer Ingelheim company symbol 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), and the Boehringer Ingelheim company symbol. 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) (institutional pack) 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) Keep out of reach of children.
Do not get powder into eyes. Storage Store at 20°C to 25°C (68° to 77°F); excursions permitted to 15°C to 30°C (59°F to 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.
📦 Storage and Handling ▾
Storage Store at 20°C to 25°C (68° to 77°F); excursions permitted to 15°C to 30°C (59°F to 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.
📋 Description ▾
11 DESCRIPTION SPIRIVA HANDIHALER consists of SPIRIVA capsules and a HANDIHALER device. Each light green, hard gelatin SPIRIVA capsule contains a dry powder consisting of 18 mcg tiotropium (equivalent to 22.5 mcg tiotropium bromide monohydrate) blended with lactose monohydrate (which may contain milk proteins). The contents of SPIRIVA capsules are intended for oral inhalation only, and are intended for administration only with the HANDIHALER device.
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, 4β, 5α, 7β)-7-[(Hydroxydi-2-thienylacetyl)oxy]-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.0 2,4 ]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: Tiotropium bromide (monohydrate) has a molecular mass of 490.4 and a molecular formula of C 19 H 22 NO 4 S 2 Br ∙ H 2 O. 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 FEV 1
1.02L (range 0.45 to
2.24L); 37.6% of predicted (range 16% to 65%)], the median peak inspiratory flow (PIF) through the HANDIHALER device was
30.0L/min (range 20.4 to
45.6L/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. Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Not for Acute Use: Instruct patients 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). Immediate Hypersensitivity Reactions: Inform patients that anaphylaxis, angioedema (including swelling of the lips, tongue, or throat), urticaria, rash, bronchospasm, or itching, may occur after administration of SPIRIVA HANDIHALER.
Advise patient to immediately discontinue treatment and consult a physician should any of these signs or symptoms develop. Paradoxical Bronchospasm: Inform patients that SPIRIVA HANDIHALER can produce paradoxical bronchospasm. Advise patients that if paradoxical bronchospasm occurs, patients should discontinue SPIRIVA HANDIHALER.
Worsening of Narrow-Angle Glaucoma: Instruct patients to be alert for signs and symptoms of 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 and symptoms develop. Inform patients 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.
Since dizziness and blurred vision may occur with the use of SPIRIVA HANDIHALER, caution patients about engaging in activities such as driving a vehicle or operating appliances or machinery. Worsening of Urinary Retention: Instruct patients to be alert for signs and symptoms of urinary retention (e.g., difficulty passing urine, painful urination). Instruct patients to consult a physician immediately should any of these signs or symptoms develop.
Instructions for Administering SPIRIVA HANDIHALER: Instruct patients on how to correctly administer SPIRIVA capsules using the HANDIHALER device [see Patient Counseling Information (17) ] . Instruct patients that SPIRIVA capsules should only be administered via the HANDIHALER device and the HANDIHALER device should not be used for administering other medications. Remind patients that the contents of SPIRIVA capsules are for oral inhalation only and must not be swallowed .
Instruct patients always to store SPIRIVA capsules in sealed blisters and to remove only one SPIRIVA capsule immediately before use or its effectiveness may be reduced. Instruct patients to discard unused additional SPIRIVA capsules that are exposed to air (i.e., not intended for immediate use).