Budesonide + Glycopyrronium Bromide + Formoterol Fumarate interactions

Food & lifestyle

• alcohol

  Moderate

  Synergy

  Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system.

  What to do: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.

  1 source

  1. Linnoila M "Drug effects on psychomotor skills related to driving: interaction of atropine, glycopyrrhonium and alcohol." Eur J Clin Pharmacol 6 (1973): 107-12

• grapefruit juice

  Moderate

  Metabolism

  Grapefruit juice may increase the plasma concentrations and systemic effects of orally administered budesonide. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. According to the manufacturer, the systemic exposure of oral budesonide approximately doubles after extensive intake of grapefruit juice.

  What to do: Patients receiving budesonide should avoid the regular consumption of grapefruits and grapefruit juice to prevent undue increases in plasma budesonide levels and systemic effects.

  1 source

  1. "Product Information. Entocort (budesonide)." AstraZeneca Pharma Inc (2001):

Conditions

Conditions in which Budesonide + Glycopyrronium Bromide + Formoterol Fumarate needs care, as documented in this source.

• Arrhythmias, Cardiac

  Major

  Patients with tachycardia should be supervised closely during treatment with anticholinergic agents. Tachycardia is produced by blocking normal vagal inhibition of the SA node. Paradoxically, bradycardia may occur due to central vagal stimulation which may occur prior to peripheral cholinergic blockade.

  3 sources

  1. Blumensohn R, Razoni G, Shalev A, Munitz H "Bradycardia due to trihexyphenidyl hydrochloride." Drug Intell Clin Pharm 20 (1986): 786-7
  2. Voinov H, Elefante V, Mujica R "Sinus bradycardia related to the use of benztropine mesylate." Am J Psychiatry 149 (1992): 711
  3. "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories (2001):

• Diabetic Neuropathies

  Major

  Agents with anticholinergic activity can exacerbate many of the manifestations of autonomic neuropathy, including tachycardia, anhidrosis, bladder atony, obstipation, dry mouth and eyes, cycloplegia and blurring of vision, and sexual impotence in males. Therapy with antimuscarinic agents and higher dosages of antispasmodic agents (e.g., dicyclomine or oxybutynin) should be administered cautiously in patients with autonomic neuropathy.

  1 source

  1. "Product Information. Atropine Sulfate (atropine)." ESI Lederle Generics (2022):

• Dysentery

  Major

  The use of drugs with antiperistaltic activity (primarily antidiarrheal and antimuscarinic agents, but also antispasmodic agents such as dicyclomine or oxybutynin at high dosages) is contraindicated in patients with diarrhea due to pseudomembranous enterocolitis or enterotoxin-producing bacteria. These drugs may prolong and/or worsen diarrhea associated with organisms that invade the intestinal mucosa, such as toxigenic E. coli, Salmonella and Shigella, and pseudomembranous colitis due to broad-spectrum antibiotics. Other symptoms and complications such as fever, shedding of organisms and extraintestinal illness may also be increased or prolonged. In general, because antiperistaltic agents decrease gastrointestinal motility, they may delay the excretion of infective gastroenteric organisms or toxins and should be used cautiously in patients with any infectious diarrhea, particularly if accompanied by high fever or pus or blood in the stool. Some cough and cold and other combination products may occasionally include antimuscarinic agents for their drying effects and may, therefore, require careful selection when necessary.

  6 sources

  1. Brown JW "Toxic megacolon associated with loperamide therapy." JAMA 241 (1979): 501-2
  2. Walley T, Milson D "Loperamide related toxic megacolon in Clostridium difficile colitis." Postgrad Med J 66 (1990): 582
  3. "Product Information. Imodium (loperamide)." Janssen Pharmaceuticals (2001):
  4. Marshall WF Jr, Rosenthal P, Merritt RJ "Atropine therapy and paralytic ileus in an infant." J Pediatr Gastroenterol Nutr 9 (1989): 532-4
  5. "Lomotil for diarrhea in children." Med Lett Drugs Ther 17 (1975): 104
  6. "Product Information. Atropine Sulfate (atropine)." ESI Lederle Generics (2022):

• Glaucoma

  Major

  Anticholinergic agents are contraindicated in patients with primary glaucoma, a tendency toward glaucoma (narrow anterior chamber angle), or adhesions (synechiae) between the iris and lens, as well as for the elderly and others in whom undiagnosed glaucoma or excessive pressure in the eye may be present. Because anticholinergics cause mydriasis, they may exacerbate these conditions.

  23 sources

  1. Schuller DE, Turkewitz D "Adverse effects of antihistamines." Postgrad Med 79 (1986): 75-86
  2. "Product Information. Dimetane (brompheniramine)." Wyeth-Ayerst Laboratories (2002):
  3. "Product Information. Chlor-Trimeton (chlorpheniramine)." Schering-Plough
  4. "Product Information. Thorazine (chlorpromazine)." SmithKline Beecham (2002):
  5. "Product Information. Periactin (cyproheptadine)." Merck & Co., Inc (2002):
  6. "Product Information. Benadryl (diphenhydramine)." Parke-Davis (2002):
  7. "Product Information. Phenergan (promethazine)." Wyeth-Ayerst Laboratories (2001):
  8. "Product Information. Tavist (clemastine)." Sandoz Pharmaceuticals Corporation (2001):

  Show all 23 sourcesShow fewer sources

  9. "Product Information. Optimine (azatadine)." Schering Corporation (2001):
  10. O'Connor PS, Mumma JV "Atropine toxicity." Am J Ophthalmol 99 (1985): 613-4
  11. Clearkin LG "Angle closure glaucoma precipitated by atropine." Arch Intern Med 152 (1992): 880
  12. Berdy GJ, Berdy SS, Odin LS, Hirst LW "Angle closure glaucoma precipitated by aerosolized atropine." Arch Intern Med 151 (1991): 1658-60
  13. Pecora JL "Malignant glaucoma worsened by miotics in a postoperative angle- closure glaucoma patient." Ann Ophthalmol 11 (1979): 1412-4
  14. Holland MG "Autonomic drugs in ophthalmology: some problems and promises. Section II: Anticholinergic drugs." Ann Ophthalmol 6 (1974): 661-4
  15. Kanto J "New aspects in the use of atropine." Int J Clin Pharmacol Ther Toxicol 21 (1983): 92-4
  16. "Product Information. Atropine Sulfate (atropine)." ESI Lederle Generics (2022):
  17. "Product Information. Compazine (prochlorperazine)." SmithKline Beecham (2001):
  18. Goldstein JH "Effects of drugs on cornea, conjunctiva, and lids." Int Ophthalmol Clin 11 (1971): 13-34
  19. "Product Information. Cogentin (benztropine)." Merck & Co., Inc (2001):
  20. "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories (2001):
  21. "Product Information. Moban (molindone)." Gate Pharmaceuticals (2001):
  22. "Product Information. Orap (pimozide)." Gate Pharmaceuticals
  23. "Product Information. Poly-Histine-D (pyrilamine)." Bock Pharmacal Company (2001):

• Intestinal Obstruction

  Major

  Anticholinergics are contraindicated in patients with obstructive diseases such as achalasia, esophageal stricture or stenosis, pyloroduodenal stenosis, stenosing peptic ulcer, pyloric obstruction, and paralytic ileus. Anticholinergics may further suppress intestinal motility with resultant precipitation or aggravation of toxic megacolon.

  16 sources

  1. Bantz EW, Dolen WK, Chadwick EW, Nelson HS "Chronic chlorpheniramine therapy: subsensitivity, drug metabolism, and compliance." Ann Allergy 59 (1987): 341-6
  2. Simons FE, Frith EM, Simons KJ "The pharmacokinetics and antihistaminic effects of brompheniramine." J Allergy Clin Immunol 70 (1982): 458-64
  3. Blamoutier J "Comparative trial of two antihistamines, mequitazine and brompheniramine." Curr Med Res Opin 5 (1978): 366-70
  4. "Azatadine (optimine)--a new antihistamine." Med Lett Drugs Ther 19 (1977): 77-9
  5. "Product Information. Dimetane (brompheniramine)." Wyeth-Ayerst Laboratories (2002):
  6. "Product Information. Chlor-Trimeton (chlorpheniramine)." Schering-Plough
  7. "Product Information. Periactin (cyproheptadine)." Merck & Co., Inc (2002):
  8. "Product Information. Benadryl (diphenhydramine)." Parke-Davis (2002):

  Show all 16 sourcesShow fewer sources

  9. "Product Information. Phenergan (promethazine)." Wyeth-Ayerst Laboratories (2001):
  10. "Product Information. Tavist (clemastine)." Sandoz Pharmaceuticals Corporation (2001):
  11. "Product Information. Antivert (meclizine)." Roerig Division (2001):
  12. "Product Information. Optimine (azatadine)." Schering Corporation (2001):
  13. Mevorach D "Adverse effects of atropine sulfate autoinjection." Ann Pharmacother 26 (1992): 564
  14. "Product Information. Atropine Sulfate (atropine)." ESI Lederle Generics (2022):
  15. "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories (2001):
  16. "Product Information. Poly-Histine-D (pyrilamine)." Bock Pharmacal Company (2001):

• Myasthenia Gravis

  Major

  The use of glycopyrrolate is contraindicated in patients with myasthenia gravis.

  1 source

  1. "Product Information. Cuvposa (glycopyrrolate)." Shionogi USA Inc (2010):

• Tardive Dyskinesia

  Major

  Anticholinergic agents and agents with secondary anticholinergic activity may aggravate tardive dyskinesia or induce previously suppressed symptoms. Therapy with these agents should be avoided, if possible, or administered cautiously in patients with preexisting tardive dyskinesia, particularly in the elderly. If tardive dyskinesia symptoms develop or worsen during treatment with an anticholinergic agent, prompt withdrawal of therapy will provide better chances of improving the condition.

  7 sources

  1. Brait KA, Zagerman AJ "Dyskinesias after antihistamine use ." N Engl J Med 296 (1977): 111
  2. Jones B, Lal S "Tardive dyskinesia uncovered after ingestion of Sominex, an over-the- counter drug." Can J Psychiatry 30 (1985): 370-1
  3. "Product Information. Benadryl (diphenhydramine)." Parke-Davis (2002):
  4. Yassa R "Antiparkinsonian medication withdrawal in the treatment of tardive dyskinesia: a report of three cases." Can J Psychiatry 30 (1985): 440-2
  5. Burnett GB, Prange AJ Jr, Wilson IC, Jolliff LA, Creese IC, Synder SH "Adverse effects of anticholinergic antiparkinsonian drugs in tardive dyskinesia. An investigation of mechanism." Neuropsychobiology 6 (1980): 109-20
  6. Kiloh LG, Smith JS, Williams SE "Antiparkinson drugs as causal agents in tardive dykinesia." Med J Aust 2 (1973): 591-3
  7. "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories (2001):

• Urinary Bladder Neck Obstruction

  Major

  In general, the use of anticholinergic agents is contraindicated in patients with urinary retention and bladder neck obstruction caused by prostatic hypertrophy. Dysuria may occur and may require catheterization. Also, anticholinergic drugs may aggravate partial obstructive uropathy. Caution is advised even when using agents with mild to moderate anticholinergic activity, particularly in elderly patients.

  20 sources

  1. Bantz EW, Dolen WK, Chadwick EW, Nelson HS "Chronic chlorpheniramine therapy: subsensitivity, drug metabolism, and compliance." Ann Allergy 59 (1987): 341-6
  2. Schuller DE, Turkewitz D "Adverse effects of antihistamines." Postgrad Med 79 (1986): 75-86
  3. "Product Information. Dimetane (brompheniramine)." Wyeth-Ayerst Laboratories (2002):
  4. "Product Information. Chlor-Trimeton (chlorpheniramine)." Schering-Plough
  5. "Product Information. Thorazine (chlorpromazine)." SmithKline Beecham (2002):
  6. "Product Information. Periactin (cyproheptadine)." Merck & Co., Inc (2002):
  7. "Product Information. Benadryl (diphenhydramine)." Parke-Davis (2002):
  8. "Product Information. Phenergan (promethazine)." Wyeth-Ayerst Laboratories (2001):

  Show all 20 sourcesShow fewer sources

  9. "Product Information. Tavist (clemastine)." Sandoz Pharmaceuticals Corporation (2001):
  10. "Product Information. Antivert (meclizine)." Roerig Division (2001):
  11. "Product Information. Optimine (azatadine)." Schering Corporation (2001):
  12. Shutt LE, Bowes JB "Atropine and hyoscine." Anaesthesia 34 (1979): 476-90
  13. O'Kelly SW, Spargo PM "Postoperative urinary retention in men." BMJ 302 (1991): 1403-4
  14. "Product Information. Atropine Sulfate (atropine)." ESI Lederle Generics (2022):
  15. "Product Information. Compazine (prochlorperazine)." SmithKline Beecham (2001):
  16. "Product Information. Zyrtec (cetirizine)." Pfizer U.S. Pharmaceuticals (2001):
  17. "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories (2001):
  18. "Product Information. Moban (molindone)." Gate Pharmaceuticals (2001):
  19. "Product Information. Orap (pimozide)." Gate Pharmaceuticals
  20. "Product Information. Poly-Histine-D (pyrilamine)." Bock Pharmacal Company (2001):

• Cardiovascular Diseases

  Moderate

  Adrenergic bronchodilators can stimulate cardiovascular beta- 1 and beta- 2 receptors, resulting in adverse effects such as tachycardia, palpitation, peripheral vasodilation, blood pressure changes, and ECG changes (e.g., flattening of the T wave; prolongation of the QT interval; ST segment depression). Direct stimulation of cardiac tissues is mediated by beta- 1 receptors and thus less likely to occur with beta-2-selective agents such as albuterol. However, beta-2-selectivity is not absolute and can be lost with larger doses. High dosages of these agents have been associated with precipitation or aggravation of angina, myocardial ischemia, and cardiac arrhythmias. Therapy with adrenergic bronchodilators should be administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism, and/or underlying cardiovascular disorders such as coronary insufficiency, cardiac arrhythmias, or hypertension. The recommended dosages should not be exceeded.

  51 sources

  1. Chazan R, Droszcz W, Maruchin JE "Pharmacodynamics of salbutamol in humans." Int J Clin Pharmacol Ther Toxicol 26 (1988): 385-7
  2. Larsson S "Long-term treatment with beta2-adrenostimulants in asthma. Side effects, selectivity, tolerance, and routes of administration." Acta Med Scand Suppl 608 (1977): 1-40
  3. Mettauer B, Rouleau JL, Burgess JH "Detrimental arrhythmogenic and sustained beneficial hemodynamic effects of oral salbutamol in patients with chronic congestive heart failure." Am Heart J 109 (1985): 840-7
  4. Larsson S, Svedmyr N "Bronchodilating effect and side effects of beta2- adrenoceptor stimulants by different modes of administration (tablets, metered aerosol, and combinations thereof). A study with salbutamol inasthmatics." Am Rev Respir Dis 116 (1977): 861-9
  5. Vathenen AS, Britton JR, Ebden P, Cookson JB, Wharrad HJ, Tattersfield AE "High-dose inhaled albuterol in severe chronic airflow limitation." Am Rev Respir Dis 138 (1988): 850-5
  6. Godfrey S "Worldwide experience with albuterol (salbutamol)." Ann Allergy 47 (1981): 423-6
  7. Finch JS "Cardiovascular toxicity: clinical evaluation of albuterol, isoproterenol and placebo in rising dose tolerance trial." Ann Allergy 47 (1981): 402-4
  8. Neville E, Corris PA, Vivian J, Nariman S, Gibson GJ "Nebulised salbutamol and angina." Br Med J (Clin Res Ed) 285 (1982): 796-7

  Show all 51 sourcesShow fewer sources

  9. Breeden CC, Safirstein BH "Albuterol and spacer-induced atrial fibrillation." Chest 98 (1990): 762-3
  10. Wolfe JD, Yamate M, Biedermann AA, Chu TJ "Comparison of the acute cardiopulmonary effects of oral albuterol, metaproterenol, and terbutaline in asthmatics." JAMA 253 (1985): 2068-72
  11. Wong CS, Pavord ID, Williams J, Britton JR, Tattersfield AE "Bronchodilator, cardiovascular, and hypokalaemic effects of fenoterol, salbutamol, and terbutaline in asthma." Lancet 336 (1990): 1396-9
  12. Shovlin CL, Tam FW "Salbutamol nebuliser and precipitation of critical cardiac ischaemia." Lancet 336 (1990): 1258
  13. Spitzer WO, Suissa S, Ernst P, Horwitz RI, Habbick B, Cockcroft D, Boivin JF, McNutt M, Buist AS, Rebuck AS "The use of beta-agonists and the risk of death and near death from asthma." N Engl J Med 326 (1992): 501-6
  14. Price AH, Clissold SP "Salbutamol in the 1980s. A reappraisal of its clinical efficacy." Drugs 38 (1989): 77-122
  15. Richards DM, Brogden RN "Pirbuterol. A preliminary review of its pharmacological properties and therapeutic efficacy in reversible bronchospastic disease." Drugs 30 (1985): 6-21
  16. Lampert MB, Hibbard J, Weinert L, Briller J, Lindheimer M, Lang RM "Peripartum heart failure associated with prolonged tocolytic therapy." Am J Obstet Gynecol 168 (1993): 493-5
  17. Al-Hillawi AH, Hayward R, Johnson NM "Incidence of cardiac arrhythmias in patients taking slow release salbutamol and slow release terbutaline for asthma." Br Med J (Clin Res Ed) 288 (1984): 367
  18. Bengtsson B, Fagerstrom PO "Extrapulmonary effects of terbutaline during prolonged administration." Clin Pharmacol Ther 31 (1982): 726-32
  19. "Adverse effects and complications of treatment with beta-adrenergic agonist drugs. Committee on drugs, the American Academy of Allergy and Immunology." J Allergy Clin Immunol 75 (1985): 443-9
  20. Wagner JM, Morton MJ, Johnson KA, O'Grady JP, Speroff L "Terbutaline and maternal cardiac function." JAMA 246 (1981): 2697-701
  21. Kinney EL, Trautlein JJ, Harbaugh CV, Lambert D, Zelis RF "Ventricular tachycardia after terbutaline." JAMA 240 (1978): 2247
  22. Whitsett TL, Manion CV, Wilson MF "Cardiac, pulmonary and neuromuscular effects of clenbuterol and terbutaline compared with placebo." Br J Clin Pharmacol 12 (1981): 195-200
  23. Brogden RN, Speight TM, Avery GS "Terbutaline: a preliminary report of its pharmacological properties and therapeutic efficacy in asthma." Drugs 6 (1973): 324-32
  24. Trautlein J, Allegra J, Gillin M "Aerosolized terbutaline sulfate--an evalution of efficacy and side effects in patients with reversible airway disease." J Clin Pharmacol 17 (1977): 76-80
  25. Maguire GP, Emirgil C "Bronchodilator and side effects of different modes of administration of metaproterenol: inhaled, oral, and in combination." Am J Med Sci 291 (1986): 168-74
  26. Ence TJ, Tashkin DP, Ho D, Child JS "Acute bronchial and cardiovascular effects of oral pirbuterol and metaproterenol." Ann Allergy 43 (1979): 229-36
  27. Sanders JP, Potter DE, Ellis S, Bee DE, Grant JA "Metabolic and cardiovascular effects of carbuterol and metaproterenol." J Allergy Clin Immunol 60 (1977): 174-9
  28. "Product Information. Proventil (albuterol)." Schering Corporation (2002):
  29. "Product Information. Ventolin (albuterol)." Glaxo Wellcome (2002):
  30. "Product Information. Brethaire (terbutaline)." Novartis Pharmaceuticals (2001):
  31. Meyer JM, Wenzel CL, Kradjan WA "Salmeterol: a novel, long-acting beta 2-agonist." Ann Pharmacother 27 (1993): 1478-87
  32. Maconochie JG, Forster JK "Dose-response study with high-dose inhaled salmeterol in healthy subjects." Br J Clin Pharmacol 33 (1992): 342-5
  33. Brogden RN, Faulds D "Salmeterol xinafoate. A review of its pharmacological properties and therapeutic potential in reversible obstructive airways disease." Drugs 42 (1991): 895-912
  34. Littner MR, Tashkin DP, Calvarese B, Bautista M "Acute bronchial and cardiovascular effects of increasing doses of pirbuterol acetate aerosol in asthma." Ann Allergy 48 (1982): 14-20
  35. Chodosh S, Crooks LA, Tuck J "Comparative effects of pirbuterol acetate, metaproterenol, and placebo aerosols on pulmonary function and incidence of cardiac ectopy." J Asthma 26 (1989): 309-15
  36. "Product Information. Serevent (salmeterol)." Glaxo Wellcome
  37. "Product Information. Maxair (pirbuterol)." 3M Pharmaceuticals (2001):
  38. "Product Information. Alupent (metaproterenol)." Boehringer-Ingelheim (2001):
  39. Hibbard JU "Chronic terbutaline therapy and peripartum cardiomyopathy: a case-control study." Hypertens Pregnancy 15 (1996): 183-91
  40. Katz M, Robertson PA, Creasy RK "Cardiovascular complications associated with terbutaline treatment for preterm labor." Am J Obstet Gynecol 139 (1981): 605-8
  41. Suissa S, Hemmelgarn B, Blais L, Ernst P "Bronchodilators and acute cardiac death." Am J Respir Crit Care Med 154 (1996): 1598-602
  42. Tranfa CME, Pelaia G, Grembiale RD, Naty S, Durante S, Borrello G "Short-term cardiovascular effects of salmeterol." Chest 113 (1998): 1272-6
  43. Braden GL, Germain MJ, Mulhern JG, Hafer JG, Bria WF "Hemodynamic, cardiac, and electrolyte effects of low-dose aerosolized terbutaline sulfate in asthmatic patients." Chest 114 (1998): 380-7
  44. Jenne JW "Can oral beta(2) agonists cause heart failure?" Lancet 352 (1998): 1081-2
  45. "Product Information. Tornalate (bitolterol)." Apothecon Inc (2022):
  46. Nathan RA, Bronsky EA, Dockhorn RJ, Kemp JP "Multicenter dose-ranging study of bitolterol mesylate solution for nebulization in children with asthma." Ann Allergy 72 (1994): 209-16
  47. Bierman CW, Kemp JP, Nathan RA "Efficacy and safety of inhaled bitolterol mesylate via metered-dose inhaler in children with asthma." Ann Allergy Asthma Immunol 76 (1996): 27-35
  48. Pinnas JL, Bhatt BD, Campbell SC, Kemp JP, Tinkelman DG "Dose-response study of nebulized bitolterol mesylate solution in asthmatic patients." Chest 91 (1987): 533-9
  49. "Product Information. Xopenex (levalbuterol)." Sepracor Inc (2001):
  50. Gawchik SM, Saccar CL, Noonan M, Reasner DS, DeGraw SS "The safety and efficacy of nebulized levalbuterol compared with racemic albuterol and placebo in the treatment of asthma in pediatric patients." J Allerg Clin Immunol 103 (1999): 615-21
  51. "Product Information. Striverdi Respimat (olodaterol)." Boehringer Ingelheim (2014):

• Diabetes Mellitus

  Moderate

  Adrenergic bronchodilators may cause increases in blood glucose concentrations. These effects are usually transient and slight, but may be significant with dosages higher than those normally recommended. Large doses of IV albuterol (not commercially available in the U.S.) and terbutaline sulfate have been reported to cause exacerbation of preexisting diabetes mellitus and ketoacidosis. Therapy with adrenergic bronchodilators should be administered cautiously in patients with diabetes mellitus. Closer monitoring of blood glucose concentrations may be appropriate. Systemic adverse effects are minimized, but not abolished, by administration of these agents via oral inhalation.

  17 sources

  1. Chazan R, Droszcz W, Maruchin JE "Pharmacodynamics of salbutamol in humans." Int J Clin Pharmacol Ther Toxicol 26 (1988): 385-7
  2. Hastwell G, Lambert BE "The effect of oral salbutamol on serum potassium and blood sugar." Br J Obstet Gynaecol 85 (1978): 767-9
  3. Price AH, Clissold SP "Salbutamol in the 1980s. A reappraisal of its clinical efficacy." Drugs 38 (1989): 77-122
  4. Bengtsson B, Fagerstrom PO "Extrapulmonary effects of terbutaline during prolonged administration." Clin Pharmacol Ther 31 (1982): 726-32
  5. "Product Information. Proventil (albuterol)." Schering Corporation (2002):
  6. "Product Information. Ventolin (albuterol)." Glaxo Wellcome (2002):
  7. "Product Information. Brethaire (terbutaline)." Novartis Pharmaceuticals (2001):
  8. Meyer JM, Wenzel CL, Kradjan WA "Salmeterol: a novel, long-acting beta 2-agonist." Ann Pharmacother 27 (1993): 1478-87

  Show all 17 sourcesShow fewer sources

  9. Maconochie JG, Forster JK "Dose-response study with high-dose inhaled salmeterol in healthy subjects." Br J Clin Pharmacol 33 (1992): 342-5
  10. "Product Information. Serevent (salmeterol)." Glaxo Wellcome
  11. "Product Information. Maxair (pirbuterol)." 3M Pharmaceuticals (2001):
  12. "Product Information. Alupent (metaproterenol)." Boehringer-Ingelheim (2001):
  13. "Product Information. Tornalate (bitolterol)." Apothecon Inc (2022):
  14. "Product Information. Xopenex (levalbuterol)." Sepracor Inc (2001):
  15. Gawchik SM, Saccar CL, Noonan M, Reasner DS, DeGraw SS "The safety and efficacy of nebulized levalbuterol compared with racemic albuterol and placebo in the treatment of asthma in pediatric patients." J Allerg Clin Immunol 103 (1999): 615-21
  16. "Product Information. Foradil (formoterol)." Novartis Pharmaceuticals (2001):
  17. "Product Information. Striverdi Respimat (olodaterol)." Boehringer Ingelheim (2014):

• Hypokalemia

  Moderate

  Adrenergic bronchodilators may cause decreases in serum potassium concentrations, primarily when given by nebulization or intravenous administration. Although this effect is usually transient and does not require supplementation, clinically significant hypokalemia may occur in some patients, with the potential to induce cardiovascular adverse effects. The relevance of these observations to oral or oral aerosol/powder for inhalation therapy is unknown. Therapy with adrenergic bronchodilators should be administered cautiously in patients with or predisposed to hypokalemia.

  30 sources

  1. Whyte KF, Addis GJ, Whitesmith R, Reid JL "The mechanism of salbutamol-induced hypokalaemia." Br J Clin Pharmacol 23 (1987): 65-71
  2. Larsson S, Svedmyr N "Bronchodilating effect and side effects of beta2- adrenoceptor stimulants by different modes of administration (tablets, metered aerosol, and combinations thereof). A study with salbutamol inasthmatics." Am Rev Respir Dis 116 (1977): 861-9
  3. Allon M, Dunlay R, Copkney C "Nebulized albuterol for acute hyperkalemia in patients on hemodialysis." Ann Intern Med 110 (1989): 426-9
  4. Hastwell G, Lambert BE "The effect of oral salbutamol on serum potassium and blood sugar." Br J Obstet Gynaecol 85 (1978): 767-9
  5. "Hypokalaemia due to salbutamol overdosage." Br Med J (Clin Res Ed) 283 (1981): 500-1
  6. Kantola I, Tarssanen L "Hypokalemia from usual salbutamol dosage ." Chest 89 (1986): 619-20
  7. Montoliu J, Almirall J, Ponz E, Campistol JM, Revert L "Treatment of hyperkalaemia in renal failure with salbutamol inhalation." J Intern Med 228 (1990): 35-7
  8. Wong CS, Pavord ID, Williams J, Britton JR, Tattersfield AE "Bronchodilator, cardiovascular, and hypokalaemic effects of fenoterol, salbutamol, and terbutaline in asthma." Lancet 336 (1990): 1396-9

  Show all 30 sourcesShow fewer sources

  9. Price AH, Clissold SP "Salbutamol in the 1980s. A reappraisal of its clinical efficacy." Drugs 38 (1989): 77-122
  10. Gross TL, Sokol RJ "Severe hypokalemia and acidosis: a potential complication of beta- adrenergic treatment." Am J Obstet Gynecol 138 (1980): 1225-6
  11. Hurlbert BJ, Edelman JD, David K "Serum potassium levels during and after terbutaline." Anesth Analg 60 (1981): 723-5
  12. Bengtsson B, Fagerstrom PO "Extrapulmonary effects of terbutaline during prolonged administration." Clin Pharmacol Ther 31 (1982): 726-32
  13. Gelmont DM, Balmes JR, Yee A "Hypokalemia induced by inhaled bronchodilators." Chest 94 (1988): 763-6
  14. Sanders JP, Potter DE, Ellis S, Bee DE, Grant JA "Metabolic and cardiovascular effects of carbuterol and metaproterenol." J Allergy Clin Immunol 60 (1977): 174-9
  15. "Product Information. Proventil (albuterol)." Schering Corporation (2002):
  16. "Product Information. Ventolin (albuterol)." Glaxo Wellcome (2002):
  17. "Product Information. Brethaire (terbutaline)." Novartis Pharmaceuticals (2001):
  18. Meyer JM, Wenzel CL, Kradjan WA "Salmeterol: a novel, long-acting beta 2-agonist." Ann Pharmacother 27 (1993): 1478-87
  19. Maconochie JG, Forster JK "Dose-response study with high-dose inhaled salmeterol in healthy subjects." Br J Clin Pharmacol 33 (1992): 342-5
  20. Windom H, Grainger J, Burgess C, Crane J, Pearce N, Beasley R "A comparison of the haemodynamic and hypokalaemic effects of inhaled pirbuterol and salbutamol." N Z Med J 103 (1990): 259-61
  21. "Product Information. Serevent (salmeterol)." Glaxo Wellcome
  22. "Product Information. Maxair (pirbuterol)." 3M Pharmaceuticals (2001):
  23. Tveskov C, Djurhuus MS, Klitgaard NAH, Egstrup K "Potassium and magnesium distribution, ECG changes, and ventricular ectopic beats during beta(2)-adrenergic stimulation with terbutaline in healthy subjects." Chest 106 (1994): 1654-9
  24. "Product Information. Alupent (metaproterenol)." Boehringer-Ingelheim (2001):
  25. Braden GL, vonOeyen PT, Germain MJ, Watson DJ, Haag BL "Ritodrine- and terbutaline-induced hypokalemia in preterm labor: Mechanisms and consequences." Kidney Int 51 (1997): 1867-75
  26. Rakhmanina NY, Kearns GL, Farrar HC "Hypokalemia in an asthmatic child from abuse of albuterol metered dose inhaler." Pediatr Emerg Care 14 (1998): 145-7
  27. "Product Information. Tornalate (bitolterol)." Apothecon Inc (2022):
  28. "Product Information. Xopenex (levalbuterol)." Sepracor Inc (2001):
  29. Gawchik SM, Saccar CL, Noonan M, Reasner DS, DeGraw SS "The safety and efficacy of nebulized levalbuterol compared with racemic albuterol and placebo in the treatment of asthma in pediatric patients." J Allerg Clin Immunol 103 (1999): 615-21
  30. "Product Information. Striverdi Respimat (olodaterol)." Boehringer Ingelheim (2014):

• Psychotic Disorders

  Moderate

  Toxic psychosis manifested as confusion, disorientation, agitation, excitation, memory impairment, delusions and hallucinations may develop at toxic and therapeutic dosages of antimuscarinic agents. Therapy with these agents should be administered cautiously in patients with mental disorders receiving antimuscarinic agents for control of drug-induced extrapyramidal effects, especially at the beginning of therapy or during dosage adjustment. Psychiatric deterioration and psychotic flare-ups have also been reported following withdrawal of therapy. Symptoms include delusions, hallucinations, aggression or violent behavior, and suicidal tendencies. In high dosages, antimuscarinic agents may sometimes produce euphorigenic effects. For this reason, it can be a drug of abuse.

  22 sources

  1. Jellinek T, Gardos G, Cole JO "Adverse effects of antiparkinson drug withdrawal." Am J Psychiatry 138 (1981): 1567-71
  2. Goggin DA, Solomon GF "Trihexyphenidyl abuse for euphorigenic effect." Am J Psychiatry 136 (1979): 459-60
  3. Macvicar K "Abuse of antiparkinsonian drugs by psychiatric patients." Am J Psychiatry 134 (1977): 809-11
  4. Craig DH, Rosen P "Abuse of antiparkinsonian drugs." Ann Emerg Med 10 (1981): 98-100
  5. Pullen GP, Best NR, Maguire J "Anticholinergic drug abuse: a common problem?" Br Med J (Clin Res Ed) 289 (1984): 612-3
  6. Rubinstein JS "Abuse of antiparkinsonism drugs. Feigning of extrapyramidal symptoms to obtain trihexyphenidyl." JAMA 239 (1978): 2365-6
  7. McInnis M, Petursson H "Trihexyphenidyl dependence." Acta Psychiatr Scand 69 (1984): 538-42
  8. Mohan D, Mohandas E, Dube S "Trihexyphenidyl abuse." Br J Addict 76 (1981): 195-7

  Show all 22 sourcesShow fewer sources

  9. Kaminer Y, Munitz H, Wijsenbeek H "Trihexyphenidyl (Artane) abuse: euphoriant and anxiolytic." Br J Psychiatry 140 (1982): 473-4
  10. Warnes H "Toxic psychosis due to antiparkinsonian drugs." Can Psychiatr Assoc J 12 (1967): 323-6
  11. Hidalgo HA, Mowers RM "Anticholinergic drug abuse." DICP 24 (1990): 40-1
  12. Wilcox JA "Psychoactive properties of benztropine and trihexyphenidyl." J Psychoactive Drugs 15 (1983): 319-21
  13. Laski E, Taleporos E "Anticholinergic psychosis in a bilingual: a case study." Am J Psychiatry 134 (1977): 1038-40
  14. Brower KJ "Smoking of prescription anticholinergic drugs." Am J Psychiatry 144 (1987): 383
  15. Baker LA, Cheng LY, Amara IB "The withdrawal of benztropine mesylate in chronic schizophrenic patients." Br J Psychiatry 143 (1983): 584-90
  16. Moreau A, Jones BD, Banno V "Chronic central anticholinergic toxicity in manic depressive illness mimicking dementia." Can J Psychiatry 31 (1986): 339-41
  17. Yassa R "Antiparkinsonian medication withdrawal in the treatment of tardive dyskinesia: a report of three cases." Can J Psychiatry 30 (1985): 440-2
  18. Ananth JV, Jain RC "Benztropine psychosis." Can Psychiatr Assoc J 18 (1973): 409-14
  19. Woody GE, O'Brien CP "Anticholinergic toxic psychosis in drug abusers treated with benztropine." Compr Psychiatry 15 (1974): 439-42
  20. "Product Information. Cogentin (benztropine)." Merck & Co., Inc (2001):
  21. Kulik AV, Wilbur R "Delirium and stereotypy from anticholinergic antiparkinson drugs." Prog Neuropsychopharmacol Biol Psychiatry 6 (1982): 75-82
  22. "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories (2001):

• Seizures

  Moderate

  Adrenergic bronchodilators may cause CNS stimulation. Therapy with adrenergic bronchodilators should be administered cautiously in patients with seizure disorders. Systemic adverse effects are minimized, but not abolished, by administration of these agents via oral inhalation.

  12 sources

  1. Larsson S, Svedmyr N "Bronchodilating effect and side effects of beta2- adrenoceptor stimulants by different modes of administration (tablets, metered aerosol, and combinations thereof). A study with salbutamol inasthmatics." Am Rev Respir Dis 116 (1977): 861-9
  2. Price AH, Clissold SP "Salbutamol in the 1980s. A reappraisal of its clinical efficacy." Drugs 38 (1989): 77-122
  3. "Product Information. Proventil (albuterol)." Schering Corporation (2002):
  4. "Product Information. Ventolin (albuterol)." Glaxo Wellcome (2002):
  5. "Product Information. Brethaire (terbutaline)." Novartis Pharmaceuticals (2001):
  6. "Product Information. Serevent (salmeterol)." Glaxo Wellcome
  7. "Product Information. Maxair (pirbuterol)." 3M Pharmaceuticals (2001):
  8. "Product Information. Alupent (metaproterenol)." Boehringer-Ingelheim (2001):

  Show all 12 sourcesShow fewer sources

  9. "Product Information. Tornalate (bitolterol)." Apothecon Inc (2022):
  10. "Product Information. Xopenex (levalbuterol)." Sepracor Inc (2001):
  11. "Product Information. Foradil (formoterol)." Novartis Pharmaceuticals (2001):
  12. "Product Information. Striverdi Respimat (olodaterol)." Boehringer Ingelheim (2014):

• Fever

  Minor

  Atropine-like agents may increase the risk of hyperthermia in patients with fever by producing anhidrosis. Therapy with atropine-like agents should be administered cautiously in febrile patients.

  6 sources

  1. Stadnyk AN, Glezos JD "Drug-induced heat stroke." Can Med Assoc J 128 (1983): 957-9
  2. Sarnquist F, Larson CP Jr "Drug-induced heat stroke." Anesthesiology 39 (1973): 348-50
  3. Lee BS "Possibility of hyperpyrexia with antipsychotic and anticholinergic drugs." J Clin Psychiatry 47 (1986): 571
  4. Forester D "Fatal drug-induced heat stroke." JACEP 7 (1978): 243-4
  5. "Product Information. Atropine Sulfate (atropine)." ESI Lederle Generics (2022):
  6. "Product Information. Cogentin (benztropine)." Merck & Co., Inc (2001):

• Hypertension

  Minor

  Cardiovascular effects of anticholinergics may exacerbate hypertension. Therapy with anticholinergic agents should be administered cautiously in patients with hypertension.

  7 sources

  1. "Product Information. Benadryl (diphenhydramine)." Parke-Davis (2002):
  2. "Product Information. Antivert (meclizine)." Roerig Division (2001):
  3. "Product Information. Marezine (cyclizine)." Glaxo Wellcome (2001):
  4. Valentin N, Staffeldt H, Kyst A "Effect of i.v. atropine on cardiac rhythm, heart rate, blood pressure and airway secretion during isoflurane anaesthesia." Acta Anaesthesiol Scand 28 (1984): 621-4
  5. "Product Information. Atropine Sulfate (atropine)." ESI Lederle Generics (2022):
  6. "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories (2001):
  7. "Product Information. Atropisol (atropine ophthalmic)." Ciba Vision Ophthalmics (2002):

Therapeutic duplication

Drug classes that overlap with Budesonide + Glycopyrronium Bromide + Formoterol Fumarate, so taking both doubles up the same effect. This source publishes no per-row citations for duplication.

• anticholinergics/antispasmodics

  The recommended maximum number of medicines in the 'anticholinergics/antispasmodics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'anticholinergics/antispasmodics' category.

  Example product in the source data (US market): Olodaterol/tiotropium

• anticholinergics/antispasmodics

  The recommended maximum number of medicines in the 'anticholinergics/antispasmodics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'anticholinergics/antispasmodics' category.

  Example product in the source data (US market): Chlorpheniramine/methscopolamine/phenylephrine

• anticholinergics/antispasmodics

  The recommended maximum number of medicines in the 'anticholinergics/antispasmodics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'anticholinergics/antispasmodics' category.

  Example product in the source data (US market): Urolet mb

• anticholinergics/antispasmodics

  The recommended maximum number of medicines in the 'anticholinergics/antispasmodics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'anticholinergics/antispasmodics' category.

  Example product in the source data (US market): Phosphasal

• anticholinergics/antispasmodics

  The recommended maximum number of medicines in the 'anticholinergics/antispasmodics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'anticholinergics/antispasmodics' category.

  Example product in the source data (US market): Sympak ii

• anticholinergics/antispasmodics

  The recommended maximum number of medicines in the 'anticholinergics/antispasmodics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'anticholinergics/antispasmodics' category.

  Example product in the source data (US market): Motofen

• anticholinergics/antispasmodics

  The recommended maximum number of medicines in the 'anticholinergics/antispasmodics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'anticholinergics/antispasmodics' category.

  Example product in the source data (US market): Librax

• anticholinergics/antispasmodics

  The recommended maximum number of medicines in the 'anticholinergics/antispasmodics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'anticholinergics/antispasmodics' category.

  Example product in the source data (US market): Trelegy ellipta

• anticholinergics/antispasmodics

  The recommended maximum number of medicines in the 'anticholinergics/antispasmodics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'anticholinergics/antispasmodics' category.

  Example product in the source data (US market): Butabarbital/hyoscyamine/phenazopyridine

• anticholinergics/antispasmodics

  The recommended maximum number of medicines in the 'anticholinergics/antispasmodics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'anticholinergics/antispasmodics' category.

  Example product in the source data (US market): B & o supprettes

• anticholinergics/antispasmodics

  The recommended maximum number of medicines in the 'anticholinergics/antispasmodics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'anticholinergics/antispasmodics' category.

  Example product in the source data (US market): Hyoscyamine/phenyltoloxamine

• anticholinergics/antispasmodics

  The recommended maximum number of medicines in the 'anticholinergics/antispasmodics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'anticholinergics/antispasmodics' category.

  Example product in the source data (US market): Duaklir pressair

• anticholinergics/antispasmodics

  The recommended maximum number of medicines in the 'anticholinergics/antispasmodics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'anticholinergics/antispasmodics' category.

  Example product in the source data (US market): Duodote

• anticholinergics/antispasmodics

  The recommended maximum number of medicines in the 'anticholinergics/antispasmodics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'anticholinergics/antispasmodics' category.

  Example product in the source data (US market): Tussigon

• anticholinergics/antispasmodics

  The recommended maximum number of medicines in the 'anticholinergics/antispasmodics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'anticholinergics/antispasmodics' category.

  Example product in the source data (US market): Albuterol/ipratropium

• anticholinergics/antispasmodics

  The recommended maximum number of medicines in the 'anticholinergics/antispasmodics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'anticholinergics/antispasmodics' category.

  Example product in the source data (US market): Vi-atro

• anticholinergics/antispasmodics

  The recommended maximum number of medicines in the 'anticholinergics/antispasmodics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'anticholinergics/antispasmodics' category.

  Example product in the source data (US market): Anoro ellipta

• anticholinergics/antispasmodics

  The recommended maximum number of medicines in the 'anticholinergics/antispasmodics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'anticholinergics/antispasmodics' category.

  Example product in the source data (US market): Prosed ds

• anticholinergics/antispasmodics

  The recommended maximum number of medicines in the 'anticholinergics/antispasmodics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'anticholinergics/antispasmodics' category.

  Example product in the source data (US market): Phenohytro

• cortisones

  The recommended maximum number of medicines in the 'cortisones' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'cortisones' category.

  Example product in the source data (US market): Wixela inhub

• cortisones

  The recommended maximum number of medicines in the 'cortisones' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'cortisones' category.

  Example product in the source data (US market): Formoterol/mometasone

• cortisones

  The recommended maximum number of medicines in the 'cortisones' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'cortisones' category.

  Example product in the source data (US market): Trelegy ellipta

• cortisones

  The recommended maximum number of medicines in the 'cortisones' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'cortisones' category.

  Example product in the source data (US market): Fluticasone/vilanterol

• inhaled smooth muscle relaxants

  The recommended maximum number of medicines in the 'inhaled smooth muscle relaxants' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'inhaled smooth muscle relaxants' category.

  Example product in the source data (US market): Olodaterol/tiotropium

• inhaled smooth muscle relaxants

  The recommended maximum number of medicines in the 'inhaled smooth muscle relaxants' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'inhaled smooth muscle relaxants' category.

  Example product in the source data (US market): Wixela inhub

• inhaled smooth muscle relaxants

  The recommended maximum number of medicines in the 'inhaled smooth muscle relaxants' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'inhaled smooth muscle relaxants' category.

  Example product in the source data (US market): Glycopyrrolate/indacaterol

• inhaled smooth muscle relaxants

  The recommended maximum number of medicines in the 'inhaled smooth muscle relaxants' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'inhaled smooth muscle relaxants' category.

  Example product in the source data (US market): Epinephrine/prilocaine

• inhaled smooth muscle relaxants

  The recommended maximum number of medicines in the 'inhaled smooth muscle relaxants' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'inhaled smooth muscle relaxants' category.

  Example product in the source data (US market): Trelegy ellipta

• inhaled smooth muscle relaxants

  The recommended maximum number of medicines in the 'inhaled smooth muscle relaxants' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'inhaled smooth muscle relaxants' category.

  Example product in the source data (US market): Orabloc

• inhaled smooth muscle relaxants

  The recommended maximum number of medicines in the 'inhaled smooth muscle relaxants' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'inhaled smooth muscle relaxants' category.

  Example product in the source data (US market): Fluticasone/vilanterol

• inhaled smooth muscle relaxants

  The recommended maximum number of medicines in the 'inhaled smooth muscle relaxants' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'inhaled smooth muscle relaxants' category.

  Example product in the source data (US market): Vivacaine

• inhaled smooth muscle relaxants

  The recommended maximum number of medicines in the 'inhaled smooth muscle relaxants' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'inhaled smooth muscle relaxants' category.

  Example product in the source data (US market): Albuterol/ipratropium

• inhaled smooth muscle relaxants

  The recommended maximum number of medicines in the 'inhaled smooth muscle relaxants' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'inhaled smooth muscle relaxants' category.

  Example product in the source data (US market): Anoro ellipta

• inhaled smooth muscle relaxants

  The recommended maximum number of medicines in the 'inhaled smooth muscle relaxants' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'inhaled smooth muscle relaxants' category.

  Example product in the source data (US market): Albuterol/budesonide

• inhaled smooth muscle relaxants

  The recommended maximum number of medicines in the 'inhaled smooth muscle relaxants' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'inhaled smooth muscle relaxants' category.

  Example product in the source data (US market): Epinephrine/lidocaine