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Criteria for Outpatient Use Guidelines

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Aerosolized Agents -
Metered-Dose Inhalers (MDIs): Anticholinergic Drugs

[Developed, January 1995; Revised, August 1995; February 1997; February 1998; February 1999; January 2000; March 2000; January 2001; January 2002; January 2003; January 2008; October 2010]

Information on indications for use or diagnosis is assumed to be unavailable. All criteria may be applied retrospectively; prospective application is indicated with [*].

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1.* Dosage

Adults
Ipratropium (Atrovent®), a short-acting, inhalational anticholinergic agent, is FDA-approved to manage bronchospasm associated with chronic bronchitis and emphysema, collectively known as chronic obstructive pulmonary disease (COPD).  Ipratropium is considered a second-line agent in the treatment of asthma as the bronchodilatory effects seen with ipratropium are less than those seen with beta-adrenergic drugs.  While not FDA approved, the Expert Panel 3 guidelines from the National Heart Lung and Blood Institute document benefit when multiple ipratropium doses are administered adjunctively with beta2-agonists in the emergency department to manage more severe acute asthma exacerbations, and the Global Initiative for Asthma (GINA) guidelines state that ipratropium may be considered an alternative bronchodilator in patients who experience adverse effects to short-acting beta2-agonists (e.g., tachycardia, arrhythmia, tremor).  Ipratropium is available as a metered-dose, inhalation aerosol solution. Ipratropium is also available in combination with albuterol sulfate (Combivent®) as a metered-dose, inhalation aerosol solution, and is FDA-approved for use in adult COPD patients receiving an aerosol bronchodilator who continue to have bronchospasm and require a second bronchodilator.  

Tiotropium (Spiriva®) is a long-acting, inhalational anticholinergic agent FDA-approved for use in managing bronchospasm associated with COPD, and reducing COPD exacerbations.  Tiotropium is available as a dry inhalation powder in capsule form for oral inhalation through an inhalation device.  Due to the compound’s extended duration of action, tiotropium is approved for only once daily administration.

Recommended doses for anticholinergic MDI monotherapy and combination products are summarized in Table 1. Dosages exceeding the approved recommendations will be reviewed.

 

TABLE 1
Maximum Recommended Adult Daily Dose for Anticholinergic Metered-Dose Inhalers
DRUG MAXIMUM DAILY DOSE
Monotherapy : ipratropium bromide HFA (Atrovent® HFA)
aerosol (17 mcg/actuation) 		12 actuations/day (total dose = 204 mcg)
Monotherapy: tiotropium (Spiriva® HandiHaler®) aerosol (18 mcg/actuation) 2 inhalations of powder contents of one capsule daily (total dose = 18 mcg)
Combination Therapy : Ipratropium/albuterol (Combivent®) aerosol [18 mcg ipratropium/90 mcg albuterol base per actuation]: 12 actuations/day [total dose = 216 mcg ipratropium/1080 mcg albuterol base)]

Pediatrics

Safety and efficacy of inhaled ipratropium and tiotropium in children have not been established, as COPD does not usually develop in the pediatric population.

2. Duration of Therapy

Inhalational anticholinergic agents are suitable for chronic administration as side effects are minimal and drug effectiveness is maintained over years of regular, continuous use.  Since inhalation anticholinergics are indicated in the management of chronic, lifelong diseases, there is no basis for limiting the duration of therapy.  However, days supply for each MDI anticholinergic canister is limited based on the number of inhalations per canister as well as the maximum recommended dose per day. Days supply for inhalational anticholinergic therapy is summarized in Table 2, based on the maximum recommended dose listed in Table 1 and the number of actuations per canister or number of capsules per blister card listed in Table 2. Excessive use may be identified based on refill frequency.  Inappropriate supply of inhaled anticholinergic agents will be monitored by reviewing excessive refills.

TABLE 2
Days Supply for Anticholinergic MDI Products
DRUG # OF ACTUATIONS PER CANISTER DAYS SUPPLY
Monotherapy: Ipratropium bromide HFA (12.9 g inhaler) 200 actuations ~16-17 days
Monotherapy: Tiotropium (5 capsules, 30 capsules, 90 capsules) 5 to 90 actuations (based on number of capsules prescribed) 5 to 90 days (based on number of capsules prescribed)
Combination Therapy: Ipratropium/albuterol (14.7 g inhaler) 200 actuations ~16-17 days

3.* Duplicative Therapy

Concurrent administration of ipratropium and tiotropium has not been evaluated in controlled studies and may not offer additional clinical benefit.  Combined administration of ipratropium and tiotropium is not recommended and will be reviewed.

References

  1. Drug Facts and Comparisons.  Clin-eguide [database online].  St. Louis, MO:  Wolters Kluwer Health, Inc; 2010.  Available at:  http://clineguide.com.  Accessed October 8th, 2010.
  2. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc; 2010. Available at: http://www.clinicalpharmacology.com. Accessed October 8th, 2010.
  3. DRUGDEX® System (electronic version). Thomson Reuters (Healthcare) Inc., Greenwood Village, Colorado, USA. Available at: http://www.thomsonhc.com.libproxy.uthscsa.edu.   Accessed October 8th, 2010.
  4. Ipratropium bromide HFA inhalation aerosol (Atrovent® HFA) package insert.  Boehringer Ingelheim Pharmaceuticals, Inc., July 2010.
  5. Tiotropium inhalation powder (Spiriva® HandiHaler®) package insert.  Boehringer Ingelheim Pharmaceuticals, Inc., June 2010.
  6. Ipratropium/albuterol inhalation aerosol (Combivent®) package insert.  Boehringer Ingelheim Pharmaceuticals, Inc., September 2010.
  7. Self TH, Chrisman CR, Finch CK.  Asthma.  In:  Koda-Kimble MA, Young LY, Alldredge BK, et al, eds.  Applied therapeutics: the clinical use of drugs.  9th ed.  Philadelphia:  Lippincott Williams & Wilkins; 2009:22-1-40.
  8. U.S. Department of Health and Human Services.  National Institutes of Health.  National Heart, Lung and Blood Institute. National Asthma Education and Prevention Program.  Expert Panel 3: guidelines for the diagnosis and management of asthma.  Full report 2007.  NIH Publication No. 08-4051.  Available at:  http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.  Accessed October 7th, 2010. 
  9. Global Initiative for Chronic Obstructive Lung Disease.  Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease.  Updated 2009.    Available at: http://www.goldcopd.com/Guidelineitem.asp?l1=2&l2=1&intId=2003.  Accessed October 8th, 2010.
  10. Barnes PJ.  The role of anticholinergics in chronic obstructive pulmonary disease.  Am J Med. 2004;117(Suppl12A):24S-32S.
  11. Appleton S, Jones T, Poole P, et al.  Ipratropium bromide versus short acting beta-2 agonists for stable chronic obstructive pulmonary disease.  Cochrane Database Syst Rev. 2006;(2):CD001387.
  12. Barr RG, Bourbeau J, Camargo CA, Ram FS.  Tiotropium for stable chronic obstructive pulmonary disease: a meta-analysis.  Thorax.  2006;61:854-62.
  13. Currie GP, Rossiter C, Miles SA, Lee DK, Dempsey OJ.  Effects of tiotropium and other long acting bronchodilators in chronic obstructive pulmonary disease.  Pulm Pharmacol Ther. 2006;19:112-9.
  14. Somand H, Remington TL.  Tiotropium: a bronchodilator for chronic obstructive pulmonary disease.  Ann Pharmacother. 2005;39:1467-75.
  15. Wilt TJ. Niewoehner D. MacDonald R. Kane RL. Management of stable chronic obstructive pulmonary disease: a systematic review for a clinical practice guideline.  Ann Intern Med. 2007;147:639-53.
  16. American Thoracic Society/European Respiratory Society.  Standards for the diagnosis and management of patients with COPD (2004).  Available at:  http://www.thoracic.org/clinical/copd-guidelines/index.php.  Accessed October 8th, 2010.
  17. Barr RG, Bourbeau J, Camargo CA.  Tiotropium for stable chronic obstructive pulmonary disease.  Cochrane Database Syst Rev. 2005;(2):CD002876.

Prepared by: Drug Information Service, the University of Texas Health Science Center at San Antonio, and the College of Pharmacy, The University of Texas at Austin.