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Drug Interactions between Aricept and lumateperone

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

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Interactions between your drugs

Moderate

donepezil lumateperone

Applies to: Aricept (donepezil) and lumateperone

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

lumateperone food

Applies to: lumateperone

GENERALLY AVOID: Grapefruit and grapefruit juice may increase the plasma concentrations of lumateperone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit but has been reported for other CYP450 3A4 inhibitors. In a drug interaction study, the strong CYP450 3A4 inhibitor itraconazole increased lumateperone peak plasma concentration (Cmax) and systemic exposure (AUC) approximately 3.5- and 4-fold, respectively, while diltiazem (a moderate CYP450 3A4 inhibitor) increased lumateperone Cmax and AUC approximately 2- and 2.5-fold, respectively. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

When administered with a high-fat meal, lumateperone Cmax decreased by 33% while its AUC increased by 9% and its median time to peak plasma concentration (Tmax) was delayed by about 1 hour.

MANAGEMENT: Lumateperone should be administered with food. Coadministration of grapefruit or grapefruit juice with lumateperone should be avoided.

References (1)
  1. (2020) "Product Information. Caplyta (lumateperone)." Intra-Cellular Therapies, Inc.

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.