Donepezil drug interactions

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Contents 1 Drug-drug interactions 2 Drug-food/drug-herb interactions 3 References

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Drug-drug interactions

Severity level	Drug and description of interaction
4	None known
3	galantamine, rivastigmine, tacrine: This drug is a cholinesterase inhibitor. The additive adverse effects will not be tolerated by patients.[1] bethanechol: This is a parasympathomimetic drug which will likely have additive side effects with donepezil.[2] succinylcholine: There have been case reports of patients going into phase II block and suffering from a long duration of neuromuscular blockade because of this interaction. Caution should be used when administering donepezil and succinylcholine.[2][3] antimuscarinic agents, atropine: These drugs are anticholinergic agents which have the opposite effects of donepezil and will likely decrease the effects of donepezil. The effects of both drugs could be negated.[1][4] It also has the possibility of inciting seizure activity, even in patients without history of seizure activity.[3] It has been found in several studies that patients receiving cholinesterase inhibitors were more likely to receive anticholinergics.[4][5][6]
2	amantadine, amoxapine, clozapine, cyclobenzaprine, disopyramide, first generation antihistamines, maprotiline, olanzapine, orphenadrine, tricyclic antidepressants: These drugs have anticholinergic properties which will likely decrease the effect of donepezil.[4] amiodarone, fluoxetine, paroxetine, sertraline: CYP 2D6 inhibitors may lead to higher concentrations of donepezil and thus, increased side effects.[7] bosentan, carbamazepine, fosphenytoin, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine: CYP 3A4 inducers may decrease the plasma concentrations of donepezil.[1][7][8][9] desipramine: This drug inhibits CYP 2D6, and thus may inhibit the metabolism of donepezil. This drug is also a tricyclic antidepressant which can negate the effect of donepezil.[7] digoxin: Though there is a risk for bradycardia when digoxin and donepezil are coadministered,[10] PK studies have not found any difference in metabolism of donepezil with digoxin. A study in 12 healthy subjects found that when digoxin and donepezil are coadministered, there was found to be no difference in heart rate, QRS duration, and PR interval. Caution must be exhibited when applying this study to elderly patients because this study was conducted in healthy males.[3] imatinib, ranolazine: These drugs inhibit both CYP 2D6 and 3A4, thus leading to higher concentrations of donepezil.[11][12][13] ketoconazole, nefazodone, telithromycin: CYP 3A4 inhibitors may lead to higher concentrations of donepezil and thus, increased side effects.[1][7][14] NSAIDs: May increase the risk of GI bleed when used with donepezil.[1]
1	clarithromycin, dalfopristin/quinupristin, delavirdine, diltiazem, erythromycin, itraconazole, verapamil, voriconazole: CYP 3A4 inhibitors may lead to higher concentrations of donepezil and thus, increased side effects.[7][15] conivaptan, modafinil, nevirapine: CYP 3A4 inducers may decrease the plasma concentrations of donepezil.[7][16] dexamethasone: Use of this drug and donepezil may increase the risk of developing myasthenia gravis.[7] efavirenz: May induce or inhibit CYP 3A4 leading to higher or lower concentrations of donepezil.[17] gefitnib, propafenone, quinidine: CYP 2D6 inhibitors may lead to higher concentrations of donepezil and thus, increased side effects.[7][18]

Drug-food/drug-herb interactions

Severity level	Drug and description of interaction
4	None known
3	None known
2	St. John's Wort: This herb induces CYP3A4 thus leading to lower concentrations of donepezil in the body.[7]
1	None known

References

1. ↑ ^{1.0 1.1 1.2 1.3 1.4} Aricept (Donepezil hydrochloride) package insert, New York, NY; Pfizer:2006 October http:/ www.pfizer.com/pfizer/download/uspi_aricept.pdf.
2. ↑ ^2.0 2.1 Alzheimer's disease: beware of interactions with cholinesterase inhibitors. Prescrire Int. 2006 Jun;15(83):103-6.
3. ↑ ^{3.0 3.1 3.2} Bentue-Ferrer D, Tribut O, Polard E, Allain H, Bentue-Ferrer D, Tribut O, et al. Clinically significant drug interactions with cholinesterase inhibitors: a guide for neurologists. CNS Drugs. 2003;17(13):947-63.
4. ↑ ^{4.0 4.1 4.2} Lu CJ, Tune LE. Chronic exposure to anticholinergic medications adversely affects the course of Alzheimer disease. Am J Geriatr Psychiatry. 2003 Jul-Aug;11(4):458-61.
5. ↑ Gill SS, Mamdani M, Naglie G, Streiner DL, Bronskill SE, Kopp A, et al. A prescribing cascade involving cholinesterase inhibitors and anticholinergic drugs. Archives of internal medicine. 2005 Apr 11;165(7):808-13.
6. ↑ Brown JH, Taylor P. Muscarinic receptor agonists and antagonists. Gilman AG, Hardman JG, Limbird LE, (eds.) In: Goodman and Gilman's Pharmacological Basis of Therapeutics. 10th ed., New York, Mc Graw Hill. 2001. 155—175.
7. ↑ ^{7.0 7.1 7.2 7.3 7.4 7.5 7.6 7.7 7.8} Hansten PD, Horn JR. The Top 100 Drug Interactions - A guide to Patient Management. 2007 Edition. Freeland, WA: H&H Publications; 2007:159—175.
8. ↑ Tracleer® (Bosentan) package insert. South San Francisco, CA: Actelion Pharmaceuticals US, Inc.; 2005 Nov.
9. ↑ Cerebyx® (fosphenytoin sodium) package insert. New York, NY: Parke-Davis; 2002 Jun.
10. ↑ Donepezil Monograph.Clinical Pharmacology (database on the internet) Available at www.clinicalpharmacolgy.com.
11. ↑ Gardner ER, Burger H, van Schaik RH, van Oosterom AT, de Bruijn EA, Guetens G, et al. Association of enzyme and transporter genotypes with the pharmacokinetics of imatinib. Clinical pharmacology and therapeutics. 2006 Aug;80(2):192-201.
12. ↑ Peng B, Lloyd P, Schran H. Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94.
13. ↑ Ranexa™ (ranolazine extended-release tablets) package insert. Palo Alto, CA: CV Therapeutics, Inc.; 2006 Jan.
14. ↑ Ketek™ (telithromycin) package insert. Kansas City, MO: Aventis Pharmaceuticals; 2005 Feb.
15. ↑ Synercid® (dalfopristin; quinupristin) package insert. Bristol, TN: Monarch Pharmaceuticals, Inc.; 2003 Jul.
16. ↑ Kupperman BD, Thomas EL, De Smet MD, et al. Pooled efficacy results from two multinational randomized controlled clinical trials of a single intravitreous injection of highly purified ovine hyaluronidase (Vitrase®) for the management of vitreous hemorrhage. Am J Ophthamol. 2005;140:573—97.
17. ↑ Sustiva® (efavirenz) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2007 Jan.
18. ↑ Iressa® (gefitinib) package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2003 May.