donepezil/memantine

Contraindicated in:

Known hypersensitivity to donepezil, memantine, piperidine derivatives or other components of the formulation.

Use Cautiously in:

Underlying cardiac disease, especially sick sinus syndrome or supraventricular conduction defects;
History of ulcer disease or currently taking NSAIDs;
History of seizures;
History of asthma or obstructive pulmonary disease;
Severe renal impairment (↓ dose);
Concurrent use of other NMDA antagonists (amantadine, rimantadine, ketamine, dextromethorphan);
Concurrent use of drugs or diets that cause alkaline urine;
Conditions that ↑ urine pH including severe urinary tract infections or renal tubular acidosis (lead to ↓ excretion and ↑ levels);
OB: Safety not established in pregnancy or lactation;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

Donepezil

CV: atrial fibrillation, hypertension, hypotension, vasodilation

Derm: ecchymoses

GI: anorexia, diarrhea, nausea, vomiting, weight gain (unusual)

GU: frequent urination

Metab: ↓weight, hot flashes

MS: arthritis, muscle cramps

Neuro: dizziness, headache, headache, abnormal dreams, depression, dizziness, drowsiness, fatigue, fatigue, insomnia, sedation, sedation (unusual), syncope

Memantine

CV: hypertension

Derm: rash

GI: diarrhea, weight gain

GU: urinary frequency

Hemat: anemia

Interactions ⬆ ⬇

Drug-drug:

Donepezil exaggerates muscle relaxation from succinylcholine.
Donepezil interferes with the action of anticholinergics.
↑cholinergic effects of donepezil with bethanechol.
Donepezil may ↑ risk of GI bleeding from NSAIDs.
Quinidine and ketoconazole may ↑ levels and risk of toxicity of donepezil.
Rifampin, carbamazepine, dexamethasone, phenobarbital, and phenytoinmay ↓ levels and effectiveness of donepezil.
Medications that urine pH (e.g. carbonic anhydrase inhibitors, sodium bicarbonate) may ↓ excretion and ↑ levels of memantine.

Drug-Natural Products:

Jimson weed and scopolia may antagonize cholinergic effects of donepezil.

Availability ⬆ ⬇

Capsules: extended-release memantine 7 mg/donepezil 10 mg; extended-release memantine 14 mg/donepezil 10 mg; extended-release memantine 21 mg/donepezil 10 mg; extended-release memantine 28 mg/donepezil 10 mg

Route/Dosage ⬆ ⬇

PO (Adults ): Stabilized on donepezil and not currently receiving memantine: Extended-release memantine 7 mg/donepezil 10 mg once daily in the evening; if well tolerated, ↑ dose of memantine in 7–mg increments on weekly basis (max daily dose = extended-release memantine 28 mg/donepezil 10 mg); Stabilized on memantine 10 mg twice daily or 28 mg once daily as extended-release plus donepezil 10 mg once daily: Extended-release memantine 28 mg/donepezil 10 mg once daily in the evening.

Renal Impairment

(Adults CCr 5–29 mL/min): Stabilized on donepezil and not currently receiving memantine: Extended-release memantine 7 mg/donepezil 10 mg once daily in the evening; may ↑ to extended-release memantine 14 mg/donepezil 10 mg once daily in 1 wk (not to exceed daily dose of extended-release memantine 14 mg/donepezil 10 mg); Stabilized on memantine 5 mg twice daily or 14 mg once daily as extended-release plus donepezil 10 mg once daily: Extended-release memantine 14 mg/donepezil 10 mg once daily.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Donepezil: Inhibits acetylcholinesterase thus improving cholinergic function by making more acetylcholine available.
Memantine: Binds to CNS N-methyl-D-aspartate (NMDA) receptor sites, preventing binding of glutamate, an excitatory neurotransmitter.

Therapeutic effects:

Decreased symptoms of dementia/cognitive decline. Does not slow progression.
Temporary cognitive enhancement.

Classifications ⬆ ⬇

Therapeutic Classification: anti-Alzheimers's agents, none assigned

Pharmacologic Classification: cholinergics (cholinesterase inhibitors), n methyl d aspartate antagonist

Pharmacokinetics ⬆ ⬇

Donepezil

Absorption: Well absorbed after oral administration.

Distribution: Unknown.

Protein Binding: 96%.

Metabolism/Excretion: Partially metabolized by the liver (CYP2D6 and CYP3A4 isoenyzmes) and partially excreted by kidneys (17% unchanged). Two metabolites are pharmacologically active. The CYP2D6 enzyme system exhibits genetic polymorphism (∼7% of population may be poor metabolizers and may have significantly ↑ donepezil concentrations and an ↑ risk of adverse effects).

Half-Life: 70 hr.

Memantine

Absorption: Well absorbed after oral administration.

Distribution: Unknown.

Metabolism/Excretion: 57–82% excreted unchanged in urine by active tubular secretion moderated by pH dependent tubular reabsorption. Remainder metabolized; metabolites are not pharmacologically active.

Half-Life: 60–80 hr.

Time/Action Profile ⬆ ⬇

ROUTE	ONSET	PEAK	DURATION
Donepezil PO‡	unknown	several wk	6 wk
Memantine PO-ER‡	unknown	9–12 hr	24 hr

‡Improvement in symptoms. .

‡Blood levels.

Patient/Family Teaching ⬆ ⬇

Emphasize the importance of taking donepezil daily, as directed. Missed doses should be skipped and regular schedule returned to the following day. Do not take more than prescribed; higher doses do not increase effects but may increase side effects.
Inform patient/family that it may take wk before improvement in baseline behavior is observed.
Caution patient and caregiver that donepezil/memantine may cause drowsiness and dizziness. Caution patient to avoid activities requiring alertness.
Advise patient and caregiver to notify health care professional if nausea, vomiting, diarrhea, or changes in color of stool occur or if new symptoms occur or previously noted symptoms increase in severity.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other Rx, OTC, or herbal products.
Advise patient and caregiver to notify health care professional of medication regimen before treatment or surgery.
Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
Emphasize the importance of follow-up exams to monitor progress.

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Indications ⬇

Contraind./Precautions ⬆ ⬇