Donepezilo

Donepezilo Uses, Dosage, Side Effects, Food Interaction and all others data.

Donepezilo reversibly and noncompetitively inhibits centrally-active acetylcholinesterase. Donepezilo 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 Donepezilo
Availability Prescription only
Generic Donepezil
Donepezil Other Names Domepezil, Donepezil, Donepezilo, Donepezilum
Related Drugs memantine, Aricept, Namenda, rivastigmine, vitamin e, Exelon
Type
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
Available Country
Last Updated: September 19, 2023 at 7:00 am
Donepezilo
Donepezilo

Uses

Donepezilo hydrochloride is used for the treatment of mild to moderate dementia of the Alzheimer’s type.

Donepezilo 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 Donepezilo 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. Donepezilo 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

Donepezilo 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.

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. Donepezilo 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

Donepezilo 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. Donepezilo should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mother: It is not known whether Donepezilo Hydrochloride is secreted in human breast milk or not. Donepezilo is not indicated in nursing mother.

Contraindication

Donepezilo 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. Donepezilo 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 Donepezilo

Donepezilo contains Donepezil see full prescribing information from innovator Donepezilo Monograph, Donepezilo MSDS, Donepezilo FDA label

FAQ

What is Donepezilo used for?

Donepezilo 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 Donepezilo used for?

Donepezilo 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 Donepezilo 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 Donepezilo work?

Donepezilo is an enzyme blocker that works by restoring the balance of natural substances (neurotransmitters) in the brain.

What are the common side effects of Donepezilo?

The most common side effects of Donepezilo are diarrhoea, headache and feeling sick (nausea). You can take it with or without food.

Is Donepezilo safe during pregnancy?

It is not known whether Donepezilo 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 Donepezilo safe during breastfeeding?

Donepezilo tablets should not be used while breast-feeding.

Can I drink alcohol with Donepezilo?

It's usually best to avoid alcohol, or to cut back on your drinking, when taking Donepezilo. 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 Donepezilo?

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 Donepezilo?

Donepezilo 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 Donepezilo daily?

The usual starting dose of Donepezilo 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 Donepezilo take to work?

It takes at least 2 weeks for Donepezilo 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 Donepezilo stay in my system?

Donepezilo 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 Donepezilo?

You should not use Donepezilo if you are allergic to donepezil or Donepezilo 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 Donepezilo?

Do not stop taking Donepezilo 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 Donepezilo affects my heart ?

Donepezilo alone can therefore cause bradycardia, heart block and syncope and this is a possibility in all three case reports.

Can Donepezilo affect my kidneys?

Pharmacokinetic analysis has shown that Donepezilo 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 Donepezilo.

Can Donepezilo affects my liver?

Donepezilo has only rarely been implicated as a cause of clinically apparent liver injury.

Why should Donepezilo be taken at night?

Donepezilo 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.

*** Taking medicines without doctor's advice can cause long-term problems.
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