Atrovent

Generic Name: Ipratropium Bromide
Class: Antimuscarinics/Antispasmodics
Molecular Formula: C₂₀H₃₀BrNO₃•H₂O
CAS Number: 66985-17- 9

Introduction

Bronchodilator; a nonselective, competitive antagonist at muscarinic receptors.^{2 224 225 232}

Uses for Atrovent

Bronchospasm in COPD

Long-term treatment of reversible bronchospasm associated with COPD,^{1 2 4 58 76 114 115 118 120 121 122 123 124 127 128 130 228 230 244 245 253 254 255 256 257 258 259 260 261 262 263 267 278 281 285 292 293 294} including chronic bronchitis^{1 2 4 36 55 61 76 90 116 117 119 120 121 124 125 129 131 281} and emphysema.^{1 2 4 90 91 119 120 125 281 343 344 345 347}

Fixed combination with albuterol sulfate is used for the symptomatic management of bronchospasm associated with COPD in patients who continue to have evidence of bronchospasm despite the regular use of an orally inhaled bronchodilator and who require a second bronchodilator.^{320 347}

Bronchospasm in Asthma

Has been used for symptomatic treatment of acute or chronic bronchial asthma†;^{36 55 56 76 91 92 115 124 125 129 153 161 162 164 180 181 211 225 228 268 302 303 331 336 337} β₂-adrenergic agonist bronchodilators generally preferred initially for relief of bronchospasm in asthmatic patients.^{161 164 225 257 268 302 303 331 337}

May be useful as alternative therapy in adults experiencing adverse effects (e.g., tachycardia, arrhythmia, tremor) with a β-adrenergic agonist†.^{331 336 337}

Some clinicians consider ipratropium as adjunctive therapy in patients with moderate or severe exacerbations (peak expiratory flow rate ≤80% of predicted) of asthma† who fail to respond adequately to β-adrenergic agonists and corticosteroids.^{331 337}

May be useful for prevention or reversal of bronchospasm induced by β-adrenergic blocking agents† (e.g., propranolol) in asthmatic patients; β-adrenergic bronchodilators generally ineffective for this indication in such patients.^{31 191 194 225 268}

Atrovent Dosage and Administration

Administration

Administer by oral inhalation using an oral aerosol inhaler^{1 10 320} or via nebulization.^{4 281 329}

Oral Inhalation via Metered-dose Aerosol

Ipratropium Bromide

Aerosol delivers ≥200 metered sprays per canister.¹

Patient should be instructed to clear excessive sputum from chest before inhalation.¹⁰

Shake well immediately prior to use.^{1 10 320} Actuate aerosol inhaler 3 times prior to the initial use or if it has not been used for >24 hours.¹

Do not use mouthpiece for other aerosol drugs.¹

Exhale slowly and completely and place the mouthpiece of the inhaler well into the mouth with the lips closed around it.^{10 348} To avoid contact of the drug with the eyes and subsequent adverse effects, close eyes during inhalation of aerosol.^{1 10 348} Inhale slowly and deeply through the mouth while actuating the inhaler.^{1 10} Hold the breath for 10 seconds, withdraw the mouthpiece, and exhale slowly.^{1 10}

Allow ≥15 seconds to elapse between subsequent inhalations from the aerosol inhaler.^{10 348}

Wash the mouthpiece in hot running water as needed.^{10 348} If soap is used, rinse mouthpiece thoroughly with plain water.^{10 348}

Ipratropium Bromide and Albuterol Sulfate

Aerosol delivers ≥200 metered sprays per canister.³⁴⁶

Shake well immediately prior to use.³⁴⁶ Actuate 3 times prior to the initial use or if it has not been used for >24 hours.³⁴⁶ Do not use actuator provided for other aerosol drugs.³⁴⁶ To avoid contact of the drug with the eyes and subsequent adverse effects, close eyes during inhalation of aerosol.³⁴⁶

Exhale deeply and place mouthpiece of the inhaler into the mouth.³⁴⁶ Inhale slowly and deeply through the mouth while actuating the inhaler.³⁴⁶ Hold the breath for 10 seconds, withdraw the mouthpiece, and exhale slowly.³⁴⁶ Allow approximately 2 minutes to elapse and repeat the procedure.³⁴⁶ Rinse the mouthpiece in hot water as needed.³⁴⁶ If soap is used, rinse the mouthpiece thoroughly with plain water.³⁴⁶ When dry, replace the cap on the mouthpiece when the inhaler is not in use.³⁴⁶

Oral Inhalation via Nebulization

Ipratropium Bromide

Empty entire contents of the single-use vial of solution into the nebulizer reservoir and attach reservoir to the mouthpiece or face mask and to the compressor according to the manufacturer’s instructions.^{4 328 350}

Use care when a face mask is used to avoid leakage since transient blurred vision and other adverse effects may result if the drug enters the eyes.^{2 225 250 275 328 350} (See Ocular Effects under Cautions.) Use of a mouthpiece may avoid inadvertent entry of drug into the eye.⁴

Place the mouthpiece of the nebulizer in the mouth or put on the nebulizer face mask.^{4 15 328} Breathe as calmly, deeply, and evenly as possible until the nebulizer stops producing mist.^{4 328}

Duration of treatment usually is about 5–15 minutes.^{4 328}

Ipratropium Bromide and Albuterol Sulfate

Empty entire contents of the single-use vial of solution into the nebulizer reservoir and attach reservoir to the mouthpiece or face mask and to the compressor according to the manufacturer’s instructions.³²⁸

Place the mouthpiece of the nebulizer in the mouth or put on the nebulizer face mask.³²⁸ Breathe as calmly, deeply, and evenly as possible until the nebulizer stops producing mist.³²⁸

Duration of treatment usually is about 5–15 minutes.³²⁸

Clean the nebulizer after use according to the manufacturer’s instructions.³²⁸

Dosage

Available as ipratropium bromide.

Dosage of oral inhalation aerosol expressed in terms of the monohydrate.^{1 320}

Dosage of inhalation solution for nebulization expressed in terms of anhydrous drug.^{4 329 330}

Using in vitro testing at an average flow rate of 3.6 L per minute for an average of ≤15 minutes, the Pari-LC Plus nebulizer delivered at the mouthpiece approximately 46 or 42% of the original dosage of albuterol or ipratropium bromide, respectively.³²⁷

Pediatric Patients

COPD

Inhalation

Patients ≥12 years of age: 36 mcg (2 inhalations) 4 times daily via a metered-dose aerosol, given alone or in fixed combination with albuterol (90 mcg via the mouthpiece).^{1 2 320} Additional inhalations should not exceed 216 mcg (12 inhalations) of ipratropium bromide in 24 hours.^{1 320}

Patients ≥12 years of age: 500 mcg (contents of 1 unit-dose vial) 3 or 4 times daily (i.e., every 6–8 hours) via a nebulizer.^{4 329}

Adults

COPD

Inhalation

Initially, 36 mcg (2 inhalations) 4 times daily via a metered-dose aerosol, given alone or in fixed combination with albuterol (90 mcg from the mouthpiece).^{1 2 320} Additional inhalations should not exceed 216 mcg (12 inhalations) in 24 hours.^{1 320}

Initially, 500 mcg 3 or 4 times daily (i.e., every 6–8 hours) via a nebulizer.^{4 329} With ipratropium bromide in fixed combination with albuterol sulfate (DuoNeb), 500 mcg 4 times daily.³²⁷ Additional inhalations should not exceed 6 inhalations daily.³²⁷

Prescribing Limits

Pediatric Patients

COPD

Inhalation

Maximum 216 mcg (12 inhalations via a metered-dose inhaler) in 24 hours.^{1 320}

Maximum 12 inhalations via metered-dose inhaler in 24 hours with the fixed combination of ipratropium bromide and albuterol sulfate.³²⁰

500 mcg 3–4 times daily via a nebulizer in patients ≥12 years of age.^{4 329}

Adults

COPD

Inhalation

Maximum 216 mcg (12 inhalations via a metered-dose inhaler) in 24 hours;^{1 320} frequency of administration should not exceed 4 times daily.^{1 267 323}

Maximum 12 inhalations via metered-dose inhaler in 24 hours with the fixed combination of ipratropium bromide and albuterol sulfate.³²⁰

500 mcg 3–4 times daily via a nebulizer.^{4 329}

Special Populations

Geriatric Patients

Dosage adjustments based solely on age are not necessary.^{1 4}

Cautions for Atrovent

Contraindications

• 
  

  Known hypersensitivity to the drug or any other component of the formulation, or to atropine or its derivatives.^{1 4 329}

  
  


• 
  

  Known hypersensitivity to soya lecithin or related food products, including soybeans and peanuts.^{1 277 320}

  
  

Warnings/Precautions

Warnings

Acute Bronchospasm

Delayed onset of action; not indicated for initial treatment.^{1 4} Generally should not be used alone for the management of acute bronchospasm, when a rapid response is required.^{1 4 164 225}

Sensitivity Reactions

Immediate hypersensitivity reactions, including rash, angioedema of the tongue, lips, and face, urticaria, bronchospasm, oropharyngeal edema, and anaphylactic reaction.^{1 4 196 213 277 285 320 329}

Possible paradoxical bronchospasm.^{1 4 190 191 196 270 271 272 273 320}

General Precautions

Worsening COPD

Contact a clinician immediately if a previously effective dosage regimen fails to provide the usual relief (e.g., need to increase the dose or frequency of administration of the drug).¹ Do not increase the dose or frequency of inhalation without consultation with a clinician.¹

Ocular Effects

Possible temporary blurred vision,^{1 2 4 10 328 349} mydriasis,^{1 225 250 275} ocular pain,^{4 328 329 349} conjunctival or corneal congestion associated with visual halos or colored images,¹ or precipitation or worsening of angle-closure glaucoma^{4 173 329 337 349} following inadvertent contact of ipratropium with the eyes.^{4 190 191 328 349}

Minimize ocular exposure by using a mouthpiece rather than a face mask during administration via a nebulizer.^{4 190 191 329} During oral inhalation of aerosol, close eyes.^{1 2} Inhalation aerosol should not be administered using the open-mouth technique in these patients with angle-closure glaucoma.^{173 190 191} Use with caution in patients with angle-closure glaucoma.^{1 4}

Genitourinary Effects

Possible urinary retention/difficulty,^{1 4 251 252 320 329} urinary tract infection,^{4 320 329} or dysuria.^{4 320}

Use with caution in patients with bladder neck obstruction or prostatic hypertrophy.^{1 4 190 191 225 329}

Cardiovascular Effects

Possible adverse cardiovascular effects (e.g., tachycardia, palpitations, aggravated hypotension or hypertension).^{1 4 329}

Use of Fixed Combination

When used in fixed combination with other agents, consider the cautions, precautions, and contraindications associated with the concomitant agents.

Specific Populations

Pregnancy

Category B.¹

Lactation

Use with caution.^{1 2 4 329}

Pediatric Use

Safety and efficacy of oral inhalation not established in children <12 years of age.^{1 4 320 329}

Hepatic Impairment

Use with caution.^{4 329}

Renal Impairment

Use with caution.^{4 329}

Common Adverse Effects

Bronchitis, upper respiratory tract infection,³²⁰ cough,^{1 2 4 87 120 285} and dryness of the mouth,^{1 2 14 16 60 90 120 127} throat,^{1 75 90} or tongue⁸⁷ with ipratropium aerosol. Adverse effects resulting in discontinuance of nebulized ipratropium most frequently include bronchitis, dyspnea, and bronchospasm.^{4 329}

Interactions for Atrovent

Limited systemic absorption following oral inhalation; interactions with systemically administered drugs unlikely.^{2 190 191}

Specific Drugs

Drug	Interaction	Comments
Antimuscarinic agents	Potential pharmacodynamic interaction (additive effects)1 320	Caution advised with concomitant administration1
Methylxanthine derivatives	No adverse drug interactions reported115 120 121 132 157 158 149 187 220 261 305 329
β-Adrenergic agonists	Potential pharmacodynamic interaction (additive effects)4 6 133 147 152 155 225 228 246 248 260 262 278 279 285 287 288 289	If concomitant therapy is required, consider cautious use of cardioselective β-adrenergic blocking agents115 132 139 146 153 154 181 216
Corticosteroids	No adverse drug interactions reported91 115 119 120 121 124 132 153 154 160 329
Cromolyn sodium	No adverse drug interactions reported132 159

Atrovent Pharmacokinetics

Absorption

Bioavailability

Only minimally absorbed into systemic circulation following oral inhalation.^{1 2 4 6 14 106 228 229 230}

Onset

Bronchodilation evident within 15 minutes following oral aerosol inhalation^{1 2 111 120 230} and within 15–30 minutes following oral inhalation via nebulization.^{4 86 281}

Duration

Bronchodilation generally persists for 3–4 hours following oral aerosol inhalation^{1 2 111 120 230} and for 4–5 hours following nebulization.^{4 86 281}

Distribution

Extent

Does not readily penetrate the CNS.^{2 4 12} It is not known whether the drug crosses the placenta or is distributed into milk.^{1 4 6}

Plasma Protein Binding

0–9%.^{1 4}

Elimination

Metabolism

Metabolized partially to at least 8 metabolites.^{4 8 106}

Elimination Route

Excreted principally in feces as unchanged drug.^{2 3 6 7 107 109} Following oral inhalation of radiolabeled ipratropium bromide, about 69 and 3.2% of the dose was excreted in feces and urine, respectively, within 6–7 days.^{6 106 109} Undergoes some biliary elimination.^{6 7}

Half-life

1.6 hours (t_½β with IV administration).^{4 190 229}

Stability

Storage

Oral Inhalation

15–30 °C (metered-dose inhalers or inhalation solution of ipratropium bromide).^{1 3 4 281 320}

2–25°C (oral inhalation solution of ipratropium bromide in fixed combination with albuterol sulfate); protect from light.^{327 328}

ActionsActions

• 
  

  A nonselective competitive antagonist at muscarinic receptors present in airways and other organs.^{2 224 225 232}

  
  


• 
  

  Relaxes smooth muscles of bronchi and bronchioles.^{1 2 4 6}

  
  


• 
  

  Blocks acetylcholine-induced stimulation of guanyl cyclase and reduces formation of cyclic guanosine monophosphate (cGMP), a mediator of bronchoconstriction.^{1 2 4 6}

  
  


• 
  

  Exhibits greater antimuscarinic activity on bronchial smooth muscle than on secretory (e.g., salivary, gastric) glands.^{6 7 12 16 18 34 225}

  
  


• 
  

  Tolerance to bronchodilating effect does not develop with prolonged use.^{4 14 90 91 92 115 116 117 118 119 120 121 168 225 278}

  
  

Advice to Patients

• 
  

  Importance of providing patients with a copy of the manufacturer’s patient information.^{1 4}

  
  


• 
  

  Importance of using proper administration technique.^{1 4}

  
  


• 
  

  Importance of advising patients that oral inhalation is not intended for occasional use.^{1 4} Use consistently throughout the course of therapy for maximum effectiveness.^{1 4}

  
  


• 
  

  Importance of contacting a clinician if symptoms of COPD are not relieved by usually effective doses or if they worsen.¹ Do not increase the dosage or frequency of administration without consultation with a clinician.¹

  
  


• 
  

  Importance of advising patients to close their eyes during oral inhalation of aerosol^{1 2} to avoid inadvertent contact of the drug with the eyes and subsequent adverse effects.^{1 10}

  
  


• 
  

  Importance of contacting a clinician immediately if ocular symptoms develop.¹

  
  


• 
  

  Importance of advising patients that blurring of vision, precipitation or aggravation of narrow angle glaucoma, mydriasis, visual halos, colored images in association with conjunctival or corneal congestion, or eye pain or discomfort may result from contact of the inhalation solution with the eyes.¹

  
  


• 
  

  Importance of informing clinicians if ocular adverse effects develop.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.³²⁰

  
  


• 
  

  Importance of informing patients of other important precautionary information. (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Ipratropium Bromide

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral Inhalation	Aerosol	18 mcg/metered spray	Atrovent (with chlorofluorohydrocarbon propellants and soya lecithin)	Boehringer Ingelheim
	Solution, for nebulization	0.02%*	Atrovent (preservative-free)	Boehringer Ingelheim
			Ipratropium Bromide Inhalation Solution (preservative-free)	Alpharma, Dey, Holopack, Nephron, Novex, Roxane, RxElite, Teva, Warrick

Ipratropium Bromide Combinations

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral Inhalation Only	Aerosol	18 mcg with Albuterol Sulfate 90 mcg (of albuterol) per metered spray	Combivent (with chlorofluorohydrocarbon propellants and soya lecithin)	Boehringer Ingelheim
	Solution, for nebulization	0.5 mg with Albuterol Sulfate 2.5 mg (of albuterol) per 3 mL	DuoNeb	Dey

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Combivent 103-18MCG/ACT Aerosol (BOEHRINGER INGELHEIM): 14/$189.99 or 44/$535.94

DuoNeb 0.5-2.5 (3)MG/3ML Solution (DEY LABS): 180/$134.89 or 540/$386.3

DuoNeb 0.5-2.5 (3)MG/3ML Solution (DEY LABS): 90/$73.58 or 270/$207.64

Ipratropium Bromide 0.02% Solution (WATSON LABS): 62/$13.99 or 125/$18.98

Ipratropium-Albuterol 0.5-2.5 (3)MG/3ML Solution (MYLAN): 90/$39.99 or 270/$99.96

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions July 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Boehringer Ingelheim. Atrovent (ipratropium bromide) inhalation aerosol prescribing information. Ridgefield, CT; 2002 Mar 27.

2. Boehringer Ingelheim. Atrovent product monograph. Ridgefield, CT; 1987 Feb.

3. Boehringer Ingelheim. Atrovent product information form for American Hospital Formulary Service. Ridgefield, CT; 1987 Feb.

4. Boehringer Ingelheim. Atrovent (ipratropium bromide) 0.02% inhalation solution prescribing information. Ridgefield, CT; 1998 Oct.

5. Budavari S, O’Neil MJ, Smith A et al, eds. The Merck index. 11th ed. Rahway, NJ: Merck & Co., Inc; 1989:4956-7.

6. Pakes GE, Brogden RN, Heel RC et al. Ipratropium bromide: a review of its pharmacological properties and therapeutic efficacy in asthma and chronic bronchitis. Drugs. 1980; 20:237-66. [IDIS 124386] [PubMed 6448137]

7. Bauer R, Banholzer R, Grieben C et al. Ipratropium bromide. In: Goldberg ME, ed. Pharmacological and biochemical properties of drug substances. 1979; 2:489-515.

8. Deckers W. The chemistry of new derivatives of tropane alkaloids and the pharmacokinetics of a new quaternary compound. Postgrad Med J. 1975; 51(Suppl 7):76-81. [PubMed 134360]

9. Winthrop-Breon. How to correctly use your Tornalate (bitolterol meyslate) metered dose inhaler. New York; 1985 Jan.

10. Boehringer Ingelheim. Questions and answers about Atrovent (ipratropium bromide) inhalation aerosol 18 mcg per puff. Ridgefield, CT; 1987 Mar.

11. Brown JH. Atropine, scopolamine, and related antimuscarinic drugs. In: Gilman AG, Rall TW, Nies AS et al, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 8th ed. New York: Pergamon Press; 1990:159-60.

12. Englehardt A. Pharmacology and toxicology of Atrovent. Scand J Respir Dis. 1979; 103(Suppl):110-5.

13. Bauer R, Kuhn FJ, Stockhaus K et al. Allgemeine Pharmakologie und seckretionshemmende Wirkung von (8r)-3α-Hydroxy-8-isopropyl- 1αH,5αH-tropaniumbromid-()tropat (Ipratropiumbromid). (German; with English abstract.) Arzneim-Forsch. 1976; 26:974-80.

14. Gross NJ, Skorodin MS. Anticholinergic, antimuscarinic bronchodilators. Am Rev Respir Dis. 1984; 129:856-70. [IDIS 185268] [PubMed 6372560]

15. Genentech, Inc. Patient information booklet: your guide to Pulmozyme (dornase alfa) therapy for cystic fibrosis (CF). South San Francisco, CA; 1994.

16. Bleichert A. Zur Frage der Nebenwirkungen anticholinerger Drogen in Abhängigkeit von der Applikationsart: inhalation versus intravenöse Injektion von Ipratropiumbromid. (German; with English abstract.) Arzneim-Forsch. 1976; 26:1010-3.

17. Otto P. Untersuchungen über die Hemmung der Magensaftsekretion beim Menschen durch den Atropinabkömmling N-Isopropyl-nortropintropasäureester-brommethylat. (German; with English abstract.) Arzneim-Forsch. 1973; 23:1334-6.

18. Bauer R, Püschmann S, Wick H et al. Wirkung von (8r)-3α-Hydroxy-8-isopropyl-1αH,5αH-tropaniumbromid-()- tropat (Ipratropiumbromid) auf Spasmen des Tracheobronchialbaumes und die Bronchialsekretion, die Speichelsekretion, EKG und Herzfrequenz. (German; with English abstract.) Arzneim-Forsch. 1976; 26:981-5.

19. Morris HG. Review of ipratropium bromide in induced bronchospasm in patients with asthma. Am J Med. 1986; 81(Suppl 5A):36-44. [IDIS 228924] [PubMed 2947459]

20. Cockcroft DW, Ruffin RE, Hargreave FE. Effect of Sch1000 in allergen-induced asthma. Clin Allergy. 1978; 8:361-72. [PubMed 152170]

21. Bandouvakis J, Cartier A, Roberts R et al. The effect of ipratropium and fenoterol on methacholine- and histamine-induced bronchoconstriction. Br J Dis Chest. 1981; 75:295-305. [PubMed 6457620]

22. Woenne R, Kattan M, Orange RP et al. Bronchial hyperreactivity to histamine and methacholine in asthmatic children after inhalation of SCH 1000 and chlorpheniramine maleate. J Allergy Clin Immunol. 1978; 62:119-24. [IDIS 115343] [PubMed 149804]

23. Giulekas D, Tsakalos N, Georgopoulos D et al. Effect of ipratropium bromide on repeated methacholine challenges. Ann Allergy. 1985; 55:835-9. [IDIS 209734] [PubMed 2934009]

24. Larsson K. Ipratropium bromide: bronchodilator action and effect on methacholine-induced bronchoconstriction. J Asthma. 1987; 24:29-35. [PubMed 2975285]

25. de Vries K. The protective effect of inhaled Sch 1000 MDI on bronchoconstriction induced by serotonin, histamine, acetylcholine and propranolol. Postgrad Med J. 1975; 51(Suppl 7):106.

26. Nolte D. The action of Sch 1000 MDI on experimental bronchoconstriction induced by various types of nonspecific and pharmacodynamic irritants in young asthmatics. Postgrad Med J. 1975; 51(Suppl 7):103.

27. Beumer HM. The antagonistic effect of several doses of inhaled Sch 1000 administered by metered dose inhaler (MDI) on a Bird respirator on acetylcholine-induced bronchospasm. Postgrad Med J. 1975; 51(Suppl 7):101-2.

28. Harnett J, Spector SL. Blocking effect of SCH 1000, isoproterenol, and the combination on methacholine and histamine inhalations. J Allergy Clin Immunol. 1976; 57:261.

29. Kersten W. The role of Sch 1000 MDI in preventing a rise in total airways resistance (R_t) induced by inhaled allergen in patients with atopic asthma. Postgrad Med J. 1975; 51(Suppl 7):103.

30. Killian D, Mellon A, Hargreave FE. Protective effect of drugs on histamine-induced asthma. J Allergy Clin Immunol. 1976; 57:263.

31. Germouty J. The possible antagonism between Sch 1000 MDI and beta-blocking agents. Postgrad Med. 1975; 51(Suppl 7):103.

32. Chan-Yeung M. The effect of Sch 1000 and disodium cromoglycate on exercise-induced asthma. Chest. 1977; 71:320-3. [PubMed 138577]

33. Tullett WM, Patel KR, Berkin KE et al. Effect of lignocaine, sodium cromoglycate, and ipratropium bromide in exercise-induced asthma. Thorax. 1982; 37:737-40. [PubMed 6218645]

34. Hartley JPR, Davies BH. Cholinergic blockade in the prevention of exercise-induced asthma. Thorax. 1980; 35:680-5. [PubMed 6449753]

35. Borut TC, Tashkin DP, Fischer TJ et al. Comparison of aerosolized atropine sulfate and Sch 1000 on exercise-induced bronchospasm in children. J Allergy Clin Immunol. 1977; 60:127-33. [IDIS 92840] [PubMed 141471]

36. Poppius H, Salorinne Y, Viljanen AA. Inhalation of a new anticholinergic drug, Sch 1000, in asthma and chronic bronchitis: effect on airway resistance, thoracic gas volume, blood gases and exercise-induced asthma. Bull Physiopathol Resp. 1972; 8:643-52.

37. Poppius H, Salorinne Y, Viljanen AA. The role of Sch 1000 MDI in preventing exercise-induced asthma. Postgrad Med J. 1975; 51(Suppl 7):105.

38. Weinberg EG. Experience with Sch 1000 MDI in the treatment of exercise-induced asthma in children. Postgrad Med J. 1975; 51(Suppl 7):128.

39. Thomson NC, Patel KR, Kerr JW. Sodium cromoglycate and ipratropium bromide in exercise-induced asthma. Thorax. 1978; 33:694-9. [PubMed 154747]

40. Sanguinetti CM, De Luca S, Gasparini S et al. Evaluation of Duovent in the prevention of exercise-induced asthma. Respiration. 1986; 50(Suppl 2):181-5. [PubMed 2951802]

41. Dry J, Pradalier A, Leynadier F et al. Recherche d’une prévention de la bronchoconstriction induite par une épreuve d’efforts chez l’asthmatique par un atropinique de synthèse: le Sch 1000. (French; with English abstract.) Thérapie. 1977; 32:181-8.

42. Anderson S, Seale JP, Ferris L et al. An evaluation of pharmacotherapy for exercise-induced asthma. J Allergy Immunol. 1979; 64:612-24.

43. Poppius H, Sovijärvi ARA, Tammilehto L. Controlled study on the preventing effect of inhaled ipratropium powder on asthma induced by breathing cold air during exercise. Respiration. 1984; 46(Suppl):45-6. [PubMed 6436932]

44. Wolkove N, Kreisman H, Frank H et al. The effect of ipratropium on exercise-induced bronchoconstriction. Ann Allergy. 1981; 47:311-5. [IDIS 164243] [PubMed 6459045]

45. Scano G, Stendardi L, Gigliotti G et al. Comparative effects of SCH 1000 and fenoterol after histamine-induced bronchoconstricition in asymptomatic asthmatics. Intl J Clin Pharmacol Ther Toxicol. 1984; 22:81-5.

46. Dorward AJ, Patel KR. A comparison of ketotifen with clemastine, ipratropium bromide and sodium cromoglycate in exercise-induced asthma. Clin Allergy. 1982; 12:355-61. [PubMed 6214337]

47