donepezil
donepezil Uses, Dosage, Side Effects, Food Interaction and all others data.
donepezil reversibly and noncompetitively inhibits centrally-active acetylcholinesterase. donepezil Hydrochloride is a centrally acting anticholinesterase agent. It binds reversibly with acetylcholinesterase and inactivates it, thus inhibiting hydrolysis of acetylcholine. As a result the concentration of acetylcholine increases at cholinergic synapses in the brain.
By inhibiting the acetylcholinesterase enzyme, donepezil improves the cognitive and behavioral signs and symptoms of Alzheimer's Disease, which may include apathy, aggression, confusion, and psychosis.
| Trade Name | donepezil |
| Availability | Prescription only |
| Generic | Donepezil |
| Donepezil Other Names | Domepezil, Donepezil, Donepezilo, Donepezilum |
| Related Drugs | memantine, Aricept, Namenda, rivastigmine, vitamin e, Exelon |
| Weight | 10mg, 23mg, 5mg |
| Type | Oral Tablet, Disintegrating, Tablet |
| Formula | C24H29NO3 |
| Weight | Average: 379.492 Monoisotopic: 379.214743799 |
| Protein binding | Donepezil is 96% protein-bound, with approximately 75% binding to albumin and approximately 21% binding to alpha-1-glycoprotein. |
| Groups | Approved |
| Therapeutic Class | Drugs for Dementia |
| Manufacturer | Guardian Pharmatama, Etercon Pharma, Pratapa Nirmala, Nulab Pharmaceutical Indonesia |
| Available Country | United States, Indonesia |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
donepezil hydrochloride is used for the treatment of mild to moderate dementia of the Alzheimer’s type.
donepezil is also used to associated treatment for these conditions: Alzheimer's Disease (AD), Dementia due to Parkinson's disease, Dementia of the Alzheimer's Type, Dementia, Vascular, Diffuse Lewy Body Disease, Mild Dementia of the Alzheimer's Type, Moderate Alzheimer's Type Dementia, Severe Alzheimer's Type Dementia
How donepezil works
The commonly accepted cholinergic hypothesis proposes that a portion of the cognitive and behavioral decline associated with Alzheimer's are the result of decreased cholinergic transmission in the central nervous system. donepezil selectively and reversibly inhibits the acetylcholinesterase enzyme, which normally breaks down acetylcholine. The main pharmacological actions of this drug are believed to occur as the result of this enzyme inhibition, enhancing cholinergic transmission, which relieves the symptoms of Alzheimer's dementia. In addition to the above, other mechanisms of action of donepezil are possible, including the opposition of glutamate-induced excitatory transmission via downregulation of NMDA receptors and the regulation of amyloid proteins, which have demonstrated significant effects on the disease process of Alzheimer's. Other possible targets for donepezil may also include the inhibition various inflammatory signaling pathways, exerting neuroprotective effects.
Dosage
donepezil dosage
Adult: Initially, 5 mg daily at bedtime, increase if necessary up to 10 mg once daily at bedtime after 4-6 wk.
Elderly: Initially, 5 mg daily at bedtime, increase if necessary up to 10 mg once daily at bedtime after 4-6 wk.
Since food does not affect the rate or extent of absorption of donepezil, it can be administered with or without food.
Side Effects
Generally well tolerated but some patients may experience nausea, vomiting & diarrhoea. These adverse events are of mild intensity and transient, resolving during continued treatment without the need for dose modification. Less frequent side effects are insomnia, fatigue, anorexia, muscle cramps, generalized seizure etc.
Toxicity
LD50
The rat oral LD50 of donepezil is 32.6 mg/kg.
Overdose information
Signs and symptoms of overdose with cholinesterase inhibitors such as donepezil can include severe nausea and vomiting, bradycardia, hypotension, perspiration, seizures, muscle weakness respiratory depression, and collapse. Significant muscle weakness may result in death if the respiratory muscles are affected by donepezil overdose. To manage an overdose, anticholinergics can be employed as antidotes. Atropine at intravenous doses of 1.0 - 2.0 mg can be administered and titrated according to the clinical response. Consult the local poison control center for the most updated guidelines on the management of a donepezil overdose. Whether donepezil can be removed from the body with dialysis is unknown at this time.
Precaution
Caution should be taken in sick sinus syndrome or other supraventricular conduction abnormalities, patients at risk of developing peptic ulcers, asthma, obstructive airway disease and during anaesthetic procedure.
Interaction
May increase the neurotoxic effect of antipsychotics. Concurrent use with systemic corticosteroids may increase the adverse effects of donepezil. May increase the neuromuscular-blocking effect of succinylcholine. May increase the adverse effects of cholinergic agonists. May increase the bradycardic effect of β-blockers.
Food Interaction
- Avoid alcohol.
- Take with or without food. The absorption is unaffected by food.
donepezil Drug Interaction
Moderate: metoprolol, metoprolol, metoprolol, metoprololMinor: aspirin, aspirin, aspirin, aspirinUnknown: apixaban, apixaban, omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, memantine, memantine, acetaminophen, acetaminophen, cyanocobalamin, cyanocobalamin, cholecalciferol, cholecalciferol
donepezil Disease Interaction
Major: bradycardia, bronchospasm, coronary artery disease, parkinsonism, PUD, seizuresModerate: hyperthyroidism, hepatic dysfunction
Volume of Distribution
The volume of distribution of donepezil is 11.8 ± 1.7 L/kg for a 5-mg dose and 11.6 ± 1.91 L/kg for a 10-mg dose. It is largely distributed in the extravascular compartments. donepezil crosses the blood-brain barrier and cerebrospinal fluid concentrations at the above doses have been measured at 15.7%. The volume of distribution at steady-state according to the FDA label for donepezil ranges from 12 - 16 L/kg.
Elimination Route
donepezil is slowly absorbed via the gastrointestinal tract after oral administration. Tmax is 3 to 4 hours with a bioavailability of 100% and steady-state concentrations are attained within 15 to 21 days of administration. The Tmax in one pharmacokinetic study determined a Tmax of 4.1 ± 1.5 hours. The Cmax of 5 mg donepezil tablets is estimated to be 8.34 ng/mL, according to the Canadian monograph. The AUC of 5 mg donepezil tablets has been determined to be 221.90-225.36 ng.hr/mL.
Half Life
The average elimination half-life of donepezil is about 70 hours according to the results of various studies and the FDA label for donepezil.. One pharmacokinetic study determined the average terminal half-life to be 81.5±22.0 h
Clearance
According to the FDA label, the average apparent plasma clearance of this drug is 0.13 – 0.19 L/hr/kg. A 5 mg dose of donepezil in healthy patients was shown to have a plasma clearance of 0.110±0.02 L/h/kg. In 10 patients diagnosed with alcoholic cirrhosis, showed a mean decrease in clearance by 20% when compared to the clearance in 10 healthy subjects. In 4 patients with severe renal impairment compared to 4 healthy subjects, no significant change in clearance was noted.
Elimination Route
In a study of radiolabeled administration donepezil in healthy adults, 57% of measured radioactivity was identified in the urine, and 5% was identified in the feces.
Pregnancy & Breastfeeding use
Pregnancy: There are no adequate and well controlled studies in pregnant woman. donepezil should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing Mother: It is not known whether donepezil Hydrochloride is secreted in human breast milk or not. donepezil is not indicated in nursing mother.
Contraindication
donepezil is contraindicated in patients with known hypersensitivity to donepezil hydrochloride or to piperidine derivatives.
Special Warning
In case of renal & hepatic impairment: A similar dose schedule can be followed for patients with renal or mild to moderate hepatic impairment as clearance of donepezil hydrochloride is not affected by these conditions.
In case of children: There are no adequate and well controlled trials in document to safety and efficacy of donepezil hydrochloride in any illness occurring in children. donepezil is not recommended for use in children.
Acute Overdose
Overdose may result in cholinergic crisis; symptoms include severe nausea, vomiting, salivation, hypotension, bradycardia, resp depression, collapse and seizures. Muscle weakness may increase and death may occur if resp muscles are involved. Treatment includes supportive measures and use of tertiary anticholinergics (such as atropine).
Storage Condition
Store below 30°C
Innovators Monograph
You find simplified version here donepezil
donepezil contains Donepezil see full prescribing information from innovator donepezil Monograph, donepezil MSDS, donepezil FDA label
FAQ
What is donepezil used for?
donepezil is used to treat confusion (dementia) related to Alzheimer's disease. It does not cure Alzheimer's disease, but it may improve memory, awareness, and the ability to function.
What is donepezil used for?
donepezil may cause a slow heart rate and fainting. Call your doctor right away if this happens. Your risk of this issue may be higher if you have heart problems. The long-term administration of donepezil at 5 mg/day was safe in patients with DLB, and is expected to exhibit lasting effects on improving impaired cognitive function and psychiatric symptoms.
How does donepezil work?
donepezil is an enzyme blocker that works by restoring the balance of natural substances (neurotransmitters) in the brain.
What are the common side effects of donepezil?
The most common side effects of donepezil are diarrhoea, headache and feeling sick (nausea). You can take it with or without food.
Is donepezil safe during pregnancy?
It is not known whether donepezil is harmful to the fetus. Safe use during pregnancy has not been established. Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
Is donepezil safe during breastfeeding?
donepezil tablets should not be used while breast-feeding.
Can I drink alcohol with donepezil?
It's usually best to avoid alcohol, or to cut back on your drinking, when taking donepezil. It can stop your medicine from working as well as it should. It can also make you more likely to have side effects. Drinking alcohol can also make the symptoms of dementia worse.
Can I drive after taking donepezil?
The medicine can cause fatigue, dizziness and muscle cramp especially in the beginning of treatment, and if affected you must not drive or operate machinery.
What is the best time to take donepezil?
donepezil should be taken at bedtime unless otherwise directed by your doctor. It may be taken with or without food, on a full or empty stomach.
How many time can I take donepezil daily?
The usual starting dose of donepezil is 5mg, taken once a day. After a month, the doctor may increase your dose to 10mg (one 10mg tablet or two 5ml spoonfuls of liquid), taken once a day.
How long does donepezil take to work?
It takes at least 2 weeks for donepezil to start working. It may take a few weeks or months before you notice any improvement in cognitive function (ability to think and remember).
How long does donepezil stay in my system?
donepezil half-life is approximately 70 hours and a therapeutic level is usually reached within 3 weeks after initiation of therapy. From the available research data it is thought that the drug may persist in the body for more than 10 days.
Who should not take donepezil?
You should not use donepezil if you are allergic to donepezil or donepezil other drugs. Tell your doctor if you are allergic to any medicines.
What happens if I miss a dose?
Skip the missed dose and use your next dose at the regular time. Do not use two doses at one time.
If you miss your doses for more than 7 days in a row, call your doctor before taking the medicine again.
What happens if I overdose?
Seek emergency medical attention. Overdose symptoms may include severe nausea, vomiting, drooling, sweating, blurred vision, feeling light-headed, slow heartbeat, shallow breathing, muscle weakness, fainting, or seizure (convulsions).
Can I just stop taking donepezil?
Do not stop taking donepezil without talking to your doctor. Your doctor may start you on a low dose of donepezil and increase your dose after 4 to 6 weeks.
Can donepezil affects my heart ?
donepezil alone can therefore cause bradycardia, heart block and syncope and this is a possibility in all three case reports.
Can donepezil affect my kidneys?
Pharmacokinetic analysis has shown that donepezil is primarily eliminated by renal excretion rather than biliary excretion in humans. Therefore, patients with impaired renal function are at high risk of toxicity caused by accumulation of this donepezil.
Can donepezil affects my liver?
donepezil has only rarely been implicated as a cause of clinically apparent liver injury.
Why should donepezil be taken at night?
donepezil is taken at night because it can cause irregular or slow heartbeat for some patients, which can cause fainting. When it is taken at bedtime, patients are able to sleep through those side effects.
