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Drug Interactions between Aricept and clozapine

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

cloZAPine donepezil

Applies to: clozapine and Aricept (donepezil)

GENERALLY AVOID: Due to opposing effects, agents that possess anticholinergic activity (e.g., sedating antihistamines; antispasmodics; neuroleptics; phenothiazines; skeletal muscle relaxants; tricyclic antidepressants; class IA antiarrhythmics especially disopyramide; carbamazepine; cimetidine; ranitidine) may negate the already small pharmacologic benefits of acetylcholinesterase inhibitors in the treatment of dementia. These agents may also adversely affect elderly patients in general. Clinically significant mental status changes associated with anticholinergic agents can range from mild cognitive impairment to delirium, and patients with Alzheimer's disease and other dementia are especially sensitive.

MANAGEMENT: Drugs that possess anticholinergic activity should generally be avoided in patients with Alzheimer's disease or other cognitive impairment, regardless of whether they are receiving an acetylcholinesterase inhibitor. For patients requiring treatment to counteract adverse effects of acetylcholinesterase inhibitor therapy (e.g., gastrointestinal intolerance, urinary problems), an agent without anticholinergic properties should be used whenever possible. Otherwise, a dosage reduction, slower titration, or even discontinuation of the acetylcholinesterase inhibitor should be considered. For patients who are already receiving an acetylcholinesterase inhibitor with anticholinergic agents, every attempt should be made to discontinue the latter or substitute them with less anticholinergic alternatives. Caution is required, however, since anticholinergic withdrawal may occur. Seizures have been reported following abrupt discontinuation of anticholinergics during acetylcholinesterase inhibitor therapy.

References (6)
  1. Beers MH, Ouslander JG, Rollingher I, Reuben DB, Brooks J, Beck JC (1991) "Explicit criteria for determining inappropriate medication use in nursing home residents." Arch Intern Med, 151, p. 1825-32
  2. Katz IR, Sands LP, Bilker W, DiFilippo S, Boyce A, D'Angelo K (1998) "Identification of medications that cause cognitive impairment in older people: the case of oxybutynin chloride." J Am Geriatr Soc, 46, p. 8-13
  3. Roe CM, Anderson MJ, Spivack B (2002) "Use of anticholinergic medications by older adults with dementia." J Am Geriatr Soc, 50, p. 836-42
  4. Edwards KR, O'Connor JT (2002) "Risk of delirium with concomitant use of tolterodine and acetylcholinesterase inhibitors." J Am Geriatr Soc, 50, p. 1165-6
  5. Fick DM, Cooper JW, Wade WE, Waller JL, Maclean JR, Beers MH (2003) "Updating the Beers criteria for potentially inappropriate medication use in older adults: results of a US consensus panel of experts." Arch Intern Med, 163, p. 2716-2724
  6. Carnahan RM, Lund BC, Perry PJ, Chrischilles EA (2004) "The concurrent use of anticholinergics and cholinesterase inhibitors: rare event or common practice?" J Am Geriatr Soc, 52, p. 2082-7

Drug and food interactions

Moderate

cloZAPine food

Applies to: clozapine

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References (4)
  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
Moderate

cloZAPine food

Applies to: clozapine

MONITOR: Smoking cessation may lead to elevated plasma concentrations and enhanced pharmacologic effects of drugs that are substrates of CYP450 1A2 (and possibly CYP450 1A1) and/or certain drugs with a narrow therapeutic index (e.g., flecainide, pentazocine). One proposed mechanism is related to the loss of CYP450 1A2 and 1A1 induction by polycyclic aromatic hydrocarbons in tobacco smoke; when smoking cessation agents are initiated and smoking stops, the metabolism of certain drugs may decrease leading to increased plasma concentrations. The mechanism by which smoking cessation affects narrow therapeutic index drugs that are not known substrates of CYP450 1A2 or 1A1 is unknown. The clinical significance of this interaction is unknown as clinical data are lacking.

MANAGEMENT: Until more information is available, caution is advisable if smoking cessation agents are used concomitantly with drugs that are substrates of CYP450 1A2 or 1A1 and/or those with a narrow therapeutic range. Patients receiving smoking cessation agents may require periodic dose adjustments and closer clinical and laboratory monitoring of medications that are substrates of CYP450 1A2 or 1A1.

References (4)
  1. (2024) "Product Information. Cytisine (cytisinicline)." Consilient Health Ltd
  2. jeong sh, Newcombe D, sheridan j, Tingle M (2015) "Pharmacokinetics of cytisine, an a4 b2 nicotinic receptor partial agonist, in healthy smokers following a single dose." Drug Test Anal, 7, p. 475-82
  3. Vaughan DP, Beckett AH, Robbie DS (1976) "The influence of smoking on the intersubject variation in pentazocine elimination." Br J Clin Pharmacol, 3, p. 279-83
  4. Zevin S, Benowitz NL (1999) "Drug interactions with tobacco smoking: an update" Clin Pharmacokinet, 36, p. 425-38
Minor

cloZAPine food

Applies to: clozapine

Caffeine may increase clozapine serum concentrations and exacerbate psychotic symptoms. The mechanism is unknown but may be related to competition for the same metabolic pathway. No specific intervention is necessary; however, if an interaction is suspected it is recommended that caffeine intake be avoided.

References (4)
  1. Carrillo JA, Jerling M, Bertilsson L (1995) "Interaction between caffeine and clozapine - comment." J Clin Psychopharmacol, 15, p. 376-7
  2. Odom-White A, de Leon J (1996) "Clozapine levels and caffeine." J Clin Psychiatry, 57, p. 175-6
  3. Vainer JL, Chouinard G (1994) "Interaction between caffeine and clozapine." J Clin Psychopharmacol, 14, p. 284
  4. Hagg S, Spiset O, Mjorndal T, Dalqvist R (2000) "Effect of caffeine on clozapine pharmacokinetics in healthy volunteers." Br J Clin Pharmacol, 49, p. 59-63

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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