cholinergics (cholinesterase inhibitors)
Treatment of moderate to severe Alzheimer's type dementia in patients currently being managed by donepezil 10 mg plus memantine (5–10 mg twice daily or 14–28 mg extended-release once daily).
- 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.
- Decreased symptoms of dementia/cognitive decline. Does not slow progression.
- Temporary cognitive enhancement.
Absorption: Well absorbed after oral administration.
Protein Binding: 96%.
Metabolism and Excretion: Partially metabolized by the liver (CYP2D6 and CYP3A4 enyzmes) and partially excreted by kidneys (17% unchanged). Two metabolites are pharmacologically active.
Half-life: 70 hr.
Absorption: Well absorbed after oral administration.
Metabolism and 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.
|Donepezil PO†||unknown||several wk||6 wk|
|Memantine PO-ER‡||unknown||9–12 hr||24 hr|
- 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: Lactation: Pedi: Safety not established; donepezil is assumed to be secreted in breast milk. Discontinue drug or discontinue breastfeeding..
Adverse Reactions/Side Effects
CNS: headache, abnormal dreams, depression, dizziness, drowsiness, fatigue, insomnia, syncope, sedation (unusual)
CV: atrial fibrillation, hypertension, hypotension, vasodilation
GI: anorexia, diarrhea, nausea, vomiting, weight gain (unusual)
GU: frequent urination
Metabolic: hot flashes, weight loss
MS: arthritis, muscle cramps
CNS: dizziness, headache, fatigue, sedation
GI: diarrhea, weight gain
GU: urinary frequency
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- Exaggerates muscle relaxation from succinylcholine .
- Interferes with the action of anticholinergics .
- ↑ cholinergic effects of bethanechol .
- May ↑ risk of GI bleeding from NSAIDs .
- Quinidine and ketoconazole ↓ metabolism of donepezil.
- Rifampin, carbamazepine, dexamethasone, phenobarbital, and phenytoin induce the enzymes that metabolize donepezil and may ↓ its effects.
Jimson weed and scopolia may antagonize cholinergic effects.
Medications that ↑ urine pH (e.g. carbonic anhydrase inhibitors, sodium bicarbonate ) may ↓ excretion and ↑ blood levels.
PO (Adults) If previous dose was memantine 10 mg twice daily or 28 mg once daily as extended-release plus donepezil 10 mg once daily– Menantine 28 mg (extended-release)/donepezil 10 mg once daily.
(Adults) with severe renal impairment) If previous dose was memantine 5 mg twice daily or 14 mg once daily as extended-release plus donepezil 10 mg once daily– Menantine 14 mg (extended-release)/donepezil 10 mg once daily.
Capsules: memantine extended-release 14 mg/donepezil 10 mg, memantine extended-release 28 mg/donepezil 10 mg
- Assess cognitive function (memory, attention, reasoning, language, ability to perform simple tasks) periodically during therapy.
- Monitor heart rate periodically during therapy. May cause bradycardia.
Lab Test Considerations:
May cause anemia.
- PO May be administered without regard to food. Swallow capsules whole; do not open, crush, or chew. Capsules may be opened, sprinkled on applesauce, and swallowed; do not chew. Entire contents of each capsule should be consumed; do not divide dose.
- 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 female patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
- Emphasize the importance of follow-up exams to monitor progress.
Temporary improvement in cognitive function (memory, attention, reasoning, language, ability to perform simple tasks) in patients with Alzheimer's disease.
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