PL Detail-Document #271206 This PL Detail-Document gives subscribers additional insight related to the Recommendations published in PHARMACIST S LETTER / PRESCRIBER S LETTER December 2011 Drugs with Anticholinergic Activity Use of drugs with anticholinergic activity can increase the risk of adverse effects (e.g., cognitive dysfunction, delirium) in the elderly. 1 Anticholinergics also interact with other drugs to reduce their effectiveness (e.g., cholinesterase inhibitors like donepezil [Aricept], etc) or increase the risk of adverse effects (e.g., increased GI irritation with oral potassium tabs or caps). 2 Drugs with low anticholinergic activity may be good alternatives to drugs with more anticholinergic activity. For example, SSRIs with lower anticholinergic activity are preferred over tricyclics for treatment of depression in the elderly. However, it s not just the use of single drugs with significant anticholinergic activity that can cause trouble. Individuals who take multiple meds with low anticholinergic activity may also have increased risk of adverse effects. In fact, even small increases in so-called anticholinergic burden or load increase the risk of morbidity and mortality in older individuals. 1,3,4 The chart below lists anticholinergic drugs,* grouping them by degree of anticholinergic activity. To help you optimize drug use in the elderly, and for therapeutic alternatives for problematic drugs, see our PL Charts, STARTing and STOPPing Medications in the Elderly, Potentially Harmful Drugs in the Elderly: Beers List and More, and Drugs to Avoid in Patients with Dementia. Antibiotics None Ampicillin Cefoxitin Clindamycin Cycloserine (Seromycin)-U.S. only Gentamicin Piperacillin Vancomycin Antidepressants Amitriptyline Amoxapine-U.S. only Clomipramine (Anafranil) Desipramine (Norpramin) Doxepin (Silenor) Imipramine (Tofranil-U.S., Impril-Canada) Nortriptyline (Pamelor-U.S., Aventyl-Canada) Paroxetine (Paxil) Protriptyline (Vivactil)-U.S. only Trimipramine (Surmontil) Bupropion (Wellbutrin, etc) Fluoxetine Fluvoxamine (Luvox) Mirtazapine (Remeron) Sertraline Trazodone
(PL Detail-Document #271206: Page 2 of 6) Antihistamines Brompheniramine Carbinoxamine-U.S. only Chlorpheniramine Clemastine Cyproheptadine Dimenhydrinate Diphenhydramine Hydroxyzine Meclizine-U.S. only Pyrilamine Triprolidine None Antimuscarinics (Overactive Bladder Agents) Anti-Parkinson Agents Darifenacin (Enablex) Flavoxate Oxybutynin (Ditropan) Tolterodine (Detrol) Amantadine Benztropine (Cogentin) Trihexyphenidyl None (Even though other agents not listed on the anticholinergic risk scales used to prepare this chart, all overactive bladder agents have some degree of anticholinergic side effects. These side effects may be reduced with use of long-acting or topical formulations. See our PL Charts, Antimuscarinic Medications for Overactive Bladder (U.S. subscribers) (Canadian subscribers), for a comparison of side effects and incidence.) Bromocriptine (Parlodel) Carbidopa/Levodopa Entacapone (Comtan) Pramipexole (Mirapex) Phenelzine (Nardil) Selegiline (Eldepryl)
(PL Detail-Document #271206: Page 3 of 6) Antipsychotics Clomipramine (Anafranil) Chlorpromazine Haloperidol Risperidone (Risperdal) Clozapine (Clozaril) Ziprasidone (Geodon-U.S., Zeldox-Canada) Fluphenazine Loxapine Olanzapine (Zyprexa) Perphenazine Pimozide (Orap) Quetiapine (Seroquel) Thioridazine-U.S. only Thiothixene (Navane) Trifluoperazine Antiseizure Drugs Carbamazepine (Tegretol) Oxcarbazepine (Trileptal) Valproic Acid Benzodiazepines None Alprazolam (Xanax) Chlordiazepoxide (Librium) Clonazepam (Klonopin-U.S., Clonapam-Canada) Clorazepate (Tranxene) Diazepam (Valium) Estazolam-U.S. only Flurazepam (Dalmane) Lorazepam Midazolam (Versed) Oxazepam Temazepam (Restoril) Triazolam (Halcion)
(PL Detail-Document #271206: Page 4 of 6) Cardiovascular Agents Disopyramide (Norpace-U.S., Rythmodan- Canada) Atenolol Captopril Chlorthalidone Digoxin Diltiazem Furosemide Hydralazine Isosorbide Metoprolol Nifedipine Quinidine Triamterene Gastrointestinal Agents Atropine Belladonna Cimetidine Dicyclomine Hyoscyamine-U.S. only Loperamide Prochlorperazine Promethazine Propantheline-U.S. only Ranitidine Famotidine Metoclopramide Nizatidine Immunosuppressants None Azathioprine (Imuran) Cyclosporine
(PL Detail-Document #271206: Page 5 of 6) Muscle Relaxants Baclofen None Carisoprodol (Soma)-U.S. only Cyclobenzaprine (Flexeril) Methocarbamol (Robaxin) Orphenadrine (Norflex) Tizanidine (Zanaflex) Opioids Meperidine Codeine Fentanyl Morphine Oxycodone Tramadol (Ultram) Respiratory Meds None Fluticasone/Salmeterol (Advair) Theophylline Other None Colchicine (Colcrys-U.S.) Dipyridamole (Persantine) Ketotifen Ophthalmic (Zaditor) Pancuronium Scopolamine Warfarin * This chart may not include all drugs with anticholinergic activity. A number of lists have been created to express the degree of anticholinergic activity of different drugs. The Anticholinergic Cognitive Burden List ranks drugs as a 1 (possible), 2 (definite), or 3 (definite) and is based on expert opinion and literature review. Drugs ranked as at least a 2 on this scale increase the risk of cognitive impairment by almost 50% over a period of six years. 4 The Anticholinergic Risk Scale ranks drugs on a scale of 0 (no or low risk), 1 (moderate), 2 (strong), or 3 (very strong) based on expert opinion and literature review of central and peripheral effects of drugs. 1 The Anticholinergic Drug Scale ranks drugs on a scale of 0 (no anticholinergic activity), 1 (potentially anticholinergic), 2 (anticholinergic adverse events sometimes noted) or 3 (marked anticholinergic activity) based on serum anticholinergic activity. 3 a. Drugs in this column are considered at least a 2 in one or more of the following: the Anticholinergic Cognitive Burden List, the Anticholinergic Risk Scale, or the Anticholinergic Drug Scale. b. Drugs in this column are considered a 1 in at least one of the following: the Anticholinergic Cognitive Burden List, the Anticholinergic Risk Scale, or the Anticholinergic Drug Scale.
(PL Detail-Document #271206: Page 6 of 6) Users of this PL Detail-Document are cautioned to use their own professional judgment and consult any other necessary or appropriate sources prior to making clinical judgments based on the content of this document. Our editors have researched the information with input from experts, government agencies, and national organizations. Information and internet links in this article were current as of the date of publication. Project Leader in preparation of this PL Detail- Document: Stacy A. Hester, R.Ph., BCPS, Assistant Editor 2. Zarowitz BJ. Oral solid potassium chloride and anticholinergic medications: a new drug interaction for an old drug? Geriatr Nurs 2006;27:329-33. 3. Carnahan RM, Lund BC, Perry PJ, et al. The Anticholinergic Drug Scale as a measure of drugrelated anticholinergic burden: associations with serum anticholinergic activity. J Clin Pharmacol 2006;46:1481-6. 4. Indianapolis Discovery Network for Dementia. Anticholinergic Burden List (ACB). http://www.indydiscoverynetwork.org/resources/acb %20Scoring%20List_2011%20NC.pdf. (Accessed November 8, 2011). References 1. Rudolph JL, Salow MJ, Angelini MC, McGlinchey RE. The anticholinergic risk scale and anticholinergic adverse effects in older persons. Arch Intern Med 2008;168:508-13. Cite this document as follows: PL Detail-Document, Drugs with Anticholinergic Activity. Pharmacist s Letter/Prescriber s Letter. December 2011. Evidence and Recommendations You Can Trust 3120 West March Lane, P.O. Box 8190, Stockton, CA 95208 ~ TEL (209) 472-2240 ~ FAX (209) 472-2249 Subscribers to the Letter can get PL Detail-Documents, like this one, on any topic covered in any issue by going to www.pharmacistsletter.com, www.prescribersletter.com, or www.pharmacytechniciansletter.com