Asthma, moderate to severe, maintenance:
Note: For symptoms not well controlled with a medium- to high-dose inhaled corticosteroid and long-acting beta agonist (LABA), may consider as add-on therapy or substitute tiotropium for the LABA. In patients intolerant to LABAs, may use in combination with an inhaled corticosteroid (GINA 2021; NAEPP 2020).
Soft-mist inhaler (1.25 mcg/actuation): Oral inhalation: 2 inhalations once daily.
Chronic obstructive pulmonary disease, maintenance:
Note: Depending on symptoms and exacerbation risk, may use a single long-acting bronchodilator (LABA or long-acting muscarinic antagonist [LAMA]) or dual-acting bronchodilator (LABA and LAMA), with or without an inhaled corticosteroid. In addition, a short-acting bronchodilator is used for symptom relief (GOLD 2021).
Spiriva HandiHaler: Dry powder inhaler (18 mcg/capsule): Oral inhalation: Contents of 1 capsule inhaled once daily using HandiHaler device. Note: To ensure drug delivery, the contents of each capsule should be inhaled twice.
Spiriva Respimat: Soft mist inhaler (2.5 mcg/actuation): Oral inhalation: 2 inhalations once daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl >60 mL/minute: No dosage adjustment necessary.
CrCl ≤60 mL/minute: No dosage adjustment necessary; use with caution and closely for anticholinergic adverse events.
No dosage adjustment necessary.
(For additional information see "Tiotropium: Pediatric drug information")
Note: Maximum benefits may take up to 4 to 8 weeks of dosing.
Asthma, maintenance treatment: Children ≥6 years of age and Adolescents: Spiriva Respimat (1.25 mcg/actuation): Soft-mist inhaler: Oral inhalation: Two inhalations (2.5 mcg) once daily; maximum daily dose: 2 inhalations/day.
Asthma, severely uncontrolled or acute exacerbation: Children ≥6 years and Adolescents: Inhalation: Spiriva Respimat (2.5 mcg/actuation): Soft-mist inhaler: Oral inhalation: Two inhalations (5 mcg) once daily as add-on therapy to inhaled corticosteroids and other maintenance therapies (GINA 2020; Szefler 2017).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥6 years and Adolescents:
CrCl >60 mL/minute: No dosage adjustment necessary.
CrCl ≤60 mL/minute: No dosage adjustment necessary; use with caution and closely for anticholinergic adverse events.
No dosage adjustment necessary.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Aerosol Solution, Inhalation:
Spiriva Respimat: 1.25 mcg/actuation (4 g); 2.5 mcg/actuation (4 g) [contains benzalkonium chloride, disodium edta]
Capsule, Inhalation:
Spiriva HandiHaler: 18 mcg [contains milk protein]
No
Spiriva Respimat 4 g cartridges contain 60 metered actuations (institutional pack contains 28 metered actuations).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Aerosol Solution, Inhalation:
Spiriva Respimat: 2.5 mcg/actuation (1 ea) [contains benzalkonium chloride, disodium edta]
Capsule, Inhalation:
Spiriva: 18 mcg [contains milk protein]
Inhalation: For oral inhalation only.
Spiriva HandiHaler: Dry powder inhaler: Do not swallow capsule. Administer at the same time each day. Do not remove capsule from blister until immediately before use. Place capsule in the center chamber of the HandiHaler Inhaler. Must only use the HandiHaler Inhaler. Close mouthpiece firmly until a click is heard, leaving dustcap open. The capsule is pierced by pressing and releasing the green piercing button on the side of the HandiHaler device. Exhale fully. Close lips tightly around mouthpiece; do not exhale into inhaler. Tilt head slightly back and inhale (rapidly, steadily, and deeply); the capsule vibration (rattle) may be heard within the device. Hold breath for a few seconds then repeat inhalation procedure using the same tiotropium capsule. Do not pierce the capsule a second time. Throw away empty capsule by tipping into a trash can without touching it; do not leave in inhaler. Keep capsules and inhaler dry. Discard any capsules that are exposed to air and not used immediately.
Spiriva Respimat: Soft-mist inhaler: Prior to first use, insert cartridge into the inhaler and prime the unit by actuating the inhaler toward the ground until an aerosol cloud is visible; repeat three more times and then the unit is primed and ready for use. If not used for more than 3 days, actuate the inhaler once to prepare the inhaler for use. If not used for more than 21 days, actuate the inhaler until an aerosol cloud is visible and then repeat the process three more times to prepare the inhaler for use.
Inhalation: For oral inhalation only.
Spiriva Respimat: Asthma: Soft-mist inhaler: Prior to first use, insert cartridge into the inhaler and prime the unit by actuating the inhaler toward the ground until an aerosol cloud is visible; repeat 3 more times and then the unit is primed and ready for use. If not used for more than 3 days, actuate the inhaler once to prepare the inhaler for use. If not used for more than 21 days, actuate the inhaler until an aerosol cloud is visible and then repeat the process 3 more times to prepare the inhaler for use.
Asthma , moderate to severe, maintenance (Spiriva Respimat only): Maintenance treatment of asthma in patients ≥6 years.
Chronic obstructive pulmonary disease, maintenance: Maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema; reduction of COPD exacerbations.
Limitations of use: Not indicated for the relief of acute bronchospasm.
Spiriva may be confused with Apidra, Inspra, Serevent
Tiotropium may be confused with ipratropium
Spiriva capsules for inhalation are for administration via HandiHaler device and are not for oral use
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Gastrointestinal: Xerostomia (4% to 16%)
Respiratory: Pharyngitis (9% to 16%), sinusitis (3% to 11%), upper respiratory tract infection (41%)
1% to 10%:
Cardiovascular: Angina pectoris (1% to 3%; includes exacerbation of angina pectoris), chest pain (≤7%), edema (dependent: 5%), hypertension (1% to 2%), palpitations (≤3%)
Dermatologic: Pruritus (1% to 3%), skin rash (1% to 4%)
Endocrine & metabolic: Hypercholesterolemia (1% to 3%), hyperglycemia (1% to 3%)
Gastrointestinal: Abdominal pain (5%; upper abdominal pain: <1%), constipation (1% to 5%), diarrhea (1% to 2%), dyspepsia (6%), gastroesophageal reflux disease (≤3%), oropharyngeal candidiasis (1% to 3%), stomatitis (includes ulcerative stomatitis: 1% to 3%), vomiting (4%)
Genitourinary: Urinary tract infection (1% to 7%)
Hypersensitivity: Hypersensitivity reaction (≤3%)
Infection: Candidiasis (4%), herpes zoster (≤3%), infection (4%)
Nervous system: Depression (1% to 4%), dizziness (1% to 3%), headache (4% to 6%), insomnia (≤4%), paresthesia (1% to 3%), voice disorder (≤3%)
Neuromuscular & skeletal: Arthralgia (≤4%), arthritis (≥3%), limb pain (≤3%), myalgia (4%), skeletal pain (1% to 3%)
Ophthalmic: Cataract (1% to 3%)
Respiratory: Allergic rhinitis (1% to 2%), bronchitis (3%), cough (≥1%), epistaxis (≤4%), flu-like symptoms (≥3%), laryngitis (≤3%), rhinitis (≤6%)
Miscellaneous: Fever (1% to 2%)
<1%:
Cardiovascular: Atrial fibrillation, supraventricular tachycardia
Dermatologic: Dermal ulcer, skin infection, xeroderma
Endocrine & metabolic: Dehydration
Gastrointestinal: Dysphagia, gingivitis, intestinal obstruction, paralytic ileus
Genitourinary: Dysuria, urinary retention
Hepatic: Abnormal hepatic function tests, hepatic insufficiency
Hypersensitivity: Angioedema
Neuromuscular & skeletal: Joint swelling, muscle spasm
Respiratory: Oropharyngeal pain, tonsillitis
Postmarketing:
Cardiovascular: Tachycardia
Dermatologic: Urticaria
Gastrointestinal: Glossitis, oral mucosa ulcer
Hypersensitivity: Type I hypersensitivity reaction
Local: Application site irritation
Ophthalmic: Blurred vision, glaucoma, increased intraocular pressure
Respiratory: Bronchospasm, hoarseness, pharyngolaryngeal pain, throat irritation
Hypersensitivity to ipratropium, tiotropium, or any component of the formulation
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to atropine or its derivatives
Concerns related to adverse effects:
• Bronchospasm: Paradoxical bronchospasm may occur with use of inhaled agents; discontinue use and consider other therapy if bronchospasm occurs.
• CNS effects: May cause dizziness and blurred vision; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).
• Hypersensitivity reactions: Immediate hypersensitivity reactions (urticaria, angioedema, rash, bronchospasm, anaphylaxis, itching) have been reported. Discontinue immediately if signs/symptoms occur. Use with caution in patients with a history of hypersensitivity to atropine.
Disease-related concerns:
• Glaucoma: May worsen symptoms of narrow-angle glaucoma; use with caution.
• Prostatic hyperplasia/bladder neck obstruction: May worsen the symptoms of prostatic hyperplasia and/or bladder neck obstruction; use with caution.
• Renal impairment: Use with caution in patients with moderate to severe renal impairment (CrCl ≤60 mL/minute); monitor closely for anticholinergic adverse events.
Dosage form specific issues:
• Lactose: Capsule for oral inhalation may contain lactose; use with caution in patients with severe milk protein allergy.
Other warnings/precautions:
• Appropriate administration: Not indicated for the initial (rescue) treatment of acute episodes of bronchospasm.
• Appropriate use: Spiriva HandiHaler: The contents of Spiriva capsules are for inhalation only via the HandiHaler device. Capsules should not be swallowed; there have been reports of incorrect administration (swallowing of the capsules).
• Appropriate use: Spiriva Respimat: The contents of Spiriva inhalation spray are for inhalation only via the Respimat inhaler.
• Avoid ocular contact: Avoid inadvertent instillation into the eyes; may dilate pupils and/or cause blurred vision.
Substrate of CYP2D6 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy
Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Amantadine: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Anticholinergic Agents: May enhance the anticholinergic effect of Tiotropium. Risk X: Avoid combination
Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Risk C: Monitor therapy
Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Risk X: Avoid combination
Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination
Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy
Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor therapy
Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Risk X: Avoid combination
Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Risk C: Monitor therapy
Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Risk X: Avoid combination
Loxapine: Agents to Treat Airway Disease may enhance the adverse/toxic effect of Loxapine. More specifically, the use of Agents to Treat Airway Disease is likely a marker of patients who are likely at a greater risk for experiencing significant bronchospasm from use of inhaled loxapine. Management: This is specific to the Adasuve brand of loxapine, which is an inhaled formulation. This does not apply to non-inhaled formulations of loxapine. Risk X: Avoid combination
Methacholine: Long-acting muscarinic antagonists (LAMAs) may diminish the therapeutic effect of Methacholine. Management: Hold long-acting muscarinic antagonists (LAMAs) for at least 7 days before methacholine use. Risk D: Consider therapy modification
Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Risk C: Monitor therapy
Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor therapy
Opioid Agonists: Anticholinergic Agents may enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Risk C: Monitor therapy
Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Risk X: Avoid combination
Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Risk X: Avoid combination
Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Risk X: Avoid combination
Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy
Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Risk X: Avoid combination
Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Risk D: Consider therapy modification
Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy
Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Risk C: Monitor therapy
Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Uncontrolled asthma is associated with adverse events in pregnancy (increased risk of perinatal mortality, preeclampsia, preterm birth, low birth weight infants, cesarean delivery, and the development of gestational diabetes). Poorly controlled asthma or asthma exacerbations may have a greater fetal/maternal risk than what is associated with appropriately used asthma medications. Maternal treatment improves pregnancy outcomes by reducing the risk of some adverse events (eg, preterm birth, gestational diabetes) (ERS/TSANZ [Middleton 2020]; GINA 2020).
Although information related to tiotropium use in pregnancy is limited, use is likely acceptable. Maternal asthma symptoms should be monitored monthly during pregnancy (ERS/TSANZ [Middleton 2020]).
Data collection to monitor pregnancy and infant outcomes associated with asthma and the medications used to treat asthma in pregnancy is ongoing. Health care providers are encouraged to enroll exposed pregnant females in the MotherToBaby Pregnancy Studies conducted by the Organization of Teratology Information Specialists (1-877-311-8972 or https://mothertobaby.org). Patients may also enroll themselves.
It is not known if tiotropium is present in breast milk.
According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. However, females with asthma should be encouraged to breastfeed (GINA 2020). Tiotropium oral inhalation is considered compatible with breastfeeding (ERS/TSANZ [Middleton 2020]).
FEV1, peak flow (or other pulmonary function studies); anticholinergic adverse reactions (patients with CrCl ≤50 mL/min); signs and symptoms of narrow angle glaucoma and urinary retention
Competitively and reversibly inhibits the action of acetylcholine at type 3 muscarinic (M3) receptors in bronchial smooth muscle causing bronchodilation
Absorption: Poorly absorbed from GI tract, systemic absorption may occur from lung
Distribution: Vd: 32 L/kg
Protein binding: 72%
Metabolism: Hepatic (minimal), via CYP2D6 and CYP3A4
Bioavailability: Following inhalation, 19.5% (dry powder inhaler) or ~33% (soft-mist inhaler); Oral solution: 2% to 3%
Half-life elimination:
Dry powder inhaler: COPD: ~25 hours
Soft-mist inhaler: Asthma: 44 hours; COPD: 25 hours
Time to peak, plasma:
Dry powder inhaler: 7 minutes (following inhalation)
Soft-mist inhaler: 5 to 7 minutes (following inhalation)
Excretion: Urine (7% of an inhaled dose [dry powder inhaler]; 18.6% of an inhaled dose [COPD] or 12.8% [asthma] [soft-mist inhaler])
Renal function impairment: Reduced clearance and increased plasma concentrations may occur.
Geriatric: Reduced clearance may occur.
Aerosol solution (Spiriva Respimat Inhalation)
1.25 mcg/ACT (per gram): $149.14
2.5 mcg/ACT (per gram): $22.50
Capsules (Spiriva HandiHaler Inhalation)
18 mcg (per each): $19.88
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