Aricept ODT

Drugs with anti-cholinergic properties that can cross into the brain, such as atropine, benztropine (Cogentin), and trihexyphenidyl (Artane) counteract the effects of donepezil and should be avoided during therapy with donepezil.

Donepezil is metabolized (eliminated) by enzymes in the liver. The rate of metabolism of donepezil may be increased by medications that increase the amounts of these enzymes, such as carbamazepine (Tegretol), dexamethasone (Decadron), phenobarbital, phenytoin (Dilantin), and rifampin (Rifadin). By increasing elimination, these drugs may reduce the effects of donepezil.

Ketoconazole (Nizoral) has been shown to block the enzymes in the liver that metabolize donepezil. Therefore, concurrent use of ketoconazole and donepezil may result in increased concentrations of donepezil in the body and possibly lead to donepezil side effects. Quinidine (Quinidex, Quinaglute) also has been shown to inhibit the enzymes that metabolize donepezil and may cause donepezil side effects.

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Aricept ODT there are no specific foods that you must exclude from your diet when receiving Aricept ODT.

Dosage Forms & Strengths

tablet

• 5mg
• 10mg
• 23mg

tablet, oral disintegrating

• 5mg
• 10mg

Alzheimer's Disease

Dementia of the Alzheimer's type

Mild to moderate

• 5 mg PO qHS initially, may increase to 10 mg/day after 4-6 weeks if warranted

Moderate to severe

• 5 mg PO qHS initially, may increase to 10 mg qDay after 4-6 weeks; may further increase to 23 mg/day after 3 months if warranted

Administration

Take at bedtime before retiring

Take with or without food

ODT: Dissolve on tongue and follow with water

Dose Modification

Renal Impairment

• Not studied

Hepatic Impairment

• Not studied

Not recommended

• If you have an allergy to donepezil or any other part of Aricept ODT (donepezil orally disintegrating tablets).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you are breast-feeding or plan to breast-feed.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Very bad dizziness or passing out.
• Slow heartbeat.
• A heartbeat that does not feel normal.
• Trouble passing urine.
• Seizures.
• Heartburn.
• Very bad belly pain.
• Throwing up blood or throw up that looks like coffee grounds.
• Black, tarry, or bloody stools.
• Very upset stomach or throwing up.
• Trouble breathing that is new or worse.
• Dark urine.
• Muscle pain or weakness.
• A very bad and sometimes deadly health problem called neuroleptic malignant syndrome (NMS) may happen. Call your doctor right away if you have any fever, muscle cramps or stiffness, dizziness, very bad headache, confusion, change in thinking, fast heartbeat, heartbeat that does not feel normal, or are sweating a lot.

The following serious adverse reactions are described below and elsewhere in the labeling:

• Cardiovascular Conditions [see Warnings and Precautions (5.2)]
  
• Nausea and Vomiting [see Warnings and Precautions (5.3)]
  
• Peptic Ulcer Disease and GI Bleeding [see Warnings and Precautions (5.4)]
  
• Weight Loss [see Warnings and Precautions (5.5)]
  
• Genitourinary Conditions [see Warnings and Precautions (5.6)]
  
• Neurological Conditions: Seizures [see Warnings and Precautions (5.7)]
  
• Pulmonary Conditions [see Warnings and Precautions (5.8)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

ARICEPT has been administered to over 1,700 individuals during clinical trials worldwide. Approximately 1200 of these patients have been treated for at least 3 months and more than 1,000 patients have been treated for at least 6 months. Controlled and uncontrolled trials in the United States included approximately 900 patients. In regards to the highest dose of 10 mg/day, this population includes 650 patients treated for 3 months, 475 patients treated for 6 months, and 116 patients treated for over 1 year. The range of patient exposure is from 1 to 1,214 days.

Mild to Moderate Alzheimer’s Disease 

Adverse Reactions Leading to Discontinuation
The rates of discontinuation from controlled clinical trials of ARICEPT due to adverse reactions for the ARICEPT 5 mg/day treatment groups were comparable to those of placebo treatment groups at approximately 5%. The rate of discontinuation of patients who received 7-day escalations from 5 mg/day to 10 mg/day was higher at 13%.

The most common adverse reactions leading to discontinuation, defined as those occurring in at least 2% of patients and at twice or more the incidence seen in placebo patients, are shown in Table 1.

Most Common Adverse Reactions

The most common adverse reactions, defined as those occurring at a frequency of at least 5% in patients receiving 10 mg/day and twice the placebo rate, are largely predicted by ARICEPT’s cholinomimetic effects. These include nausea, diarrhea, insomnia, vomiting, muscle cramp, fatigue, and anorexia. These adverse reactions were often transient, resolving during continued ARICEPT treatment without the need for dose modification.

There is evidence to suggest that the frequency of these common adverse reactions may be affected by the rate of titration. An open-label study was conducted with 269 patients who received placebo in the 15- and 30-week studies. These patients were titrated to a dose of 10 mg/day over a 6-week period. The rates of common adverse reactions were lower than those seen in patients titrated to 10 mg/day over one week in the controlled clinical trials and were comparable to those seen in patients on 5 mg/day.

See Table 2 for a comparison of the most common adverse reactions following one and six week titration regimens.

Table 3 lists adverse reactions that occurred in at least 2% of patients in pooled placebo-controlled trials who received either ARICEPT 5 mg or 10 mg and for which the rate of occurrence was greater for patients treated with ARICEPT than with placebo. In general, adverse reactions occurred more frequently in female patients and with advancing age.

Severe Alzheimer’s Disease (ARICEPT 5 mg/day and 10 mg/day)

ARICEPT has been administered to over 600 patients with severe Alzheimer’s disease during clinical trials of at least 6 months duration, including three double-blind, placebo-controlled trials, two of which had an open label extension.

Adverse Reactions Leading to Discontinuation

The rates of discontinuation from controlled clinical trials of ARICEPT due to adverse reactions for the ARICEPT patients were approximately 12% compared to 7% for placebo patients. The most common adverse reactions leading to discontinuation, defined as those occurring in at least 2% of ARICEPT patients and at twice or more the incidence seen in placebo, were anorexia (2% vs. 1% placebo), nausea (2% vs. <1% placebo), diarrhea (2% vs. 0% placebo), and urinary tract infection (2% vs. 1% placebo).

Most Common Adverse Reactions

The most common adverse reactions, defined as those occurring at a frequency of at least 5% in patients receiving ARICEPT and at twice or more the placebo rate, are largely predicted by ARICEPT’s cholinomimetic effects. These include diarrhea, anorexia, vomiting, nausea, and ecchymosis. These adverse reactions were often transient, resolving during continued ARICEPT treatment without the need for dose modification.

Table 4 lists adverse reactions that occurred in at least 2% of patients in pooled placebo-controlled trials who received ARICEPT 5 mg or 10 mg and for which the rate of occurrence was greater for patients treated with ARICEPT than with placebo.

Moderate to Severe Alzheimer’s Disease (ARICEPT 23 mg/day)

ARICEPT 23 mg/day has been administered to over 1300 individuals globally in clinical trials. Approximately 1050 of these patients have been treated for at least three months and more than 950 patients have been treated for at least six months. The range of patient exposure was from 1 to over 500 days.

Adverse Reactions Leading to Discontinuation

The rate of discontinuation from a controlled clinical trial of ARICEPT 23 mg/day due to adverse reactions was higher (19%) than for the 10 mg/day treatment group (8%). The most common adverse reactions leading to discontinuation, defined as those occurring in at least 1% of patients and greater than those occurring with 10 mg/day are shown in Table 5.

The majority of discontinuations due to adverse reactions in the 23 mg group occurred during the first month of treatment.

Most Common Adverse Reactions with ARICEPT 23 mg/day

The most common adverse reactions, defined as those occurring at a frequency of at least 5%, include nausea, diarrhea, vomiting, and anorexia.

Table 6 lists adverse reactions that occurred in at least 2% of patients who received 23 mg/day of ARICEPT and at a higher frequency than those receiving 10 mg/day of ARICEPT in a controlled clinical trial that compared the two doses. In this study, there were no important differences in the type of adverse reactions in patients taking ARICEPT with or without memantine.

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of ARICEPT. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Abdominal pain, agitation, aggression, cholecystitis, confusion, convulsions, hallucinations, heart block (all types), hemolytic anemia, hepatitis, hyponatremia, neuroleptic malignant syndrome, pancreatitis, rash, rhabdomyolysis, QTc prolongation, and torsade de pointes.

7.1 Use with Anticholinergics

Because of their mechanism of action, cholinesterase inhibitors have the potential to interfere with the activity of anticholinergic medications.

7.2 Use with Cholinomimetics and Other Cholinesterase Inhibitors

A synergistic effect may be expected when cholinesterase inhibitors are given concurrently with succinylcholine, similar neuromuscular blocking agents, or cholinergic agonists such as bethanechol.

Because strategies for the management of overdose are continually evolving, it is advisable to contact a Poison Control Center to determine the latest recommendations for the management of an overdose of any drug.

As in any case of overdose, general supportive measures should be utilized. Overdosage with cholinesterase inhibitors can result in cholinergic crisis characterized by severe nausea, vomiting, salivation, sweating, bradycardia, hypotension, respiratory depression, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Tertiary anticholinergics such as atropine may be used as an antidote for ARICEPT overdosage. Intravenous atropine sulfate titrated to effect is recommended: an initial dose of 1.0 to 2.0 mg IV with subsequent doses based upon clinical response. Atypical responses in blood pressure and heart rate have been reported with other cholinomimetics when co-administered with quaternary anticholinergics such as glycopyrrolate. It is not known whether ARICEPT and/or its metabolites can be removed by dialysis (hemodialysis, peritoneal dialysis, or hemofiltration).

Dose-related signs of toxicity in animals included reduced spontaneous movement, prone position, staggering gait, lacrimation, clonic convulsions, depressed respiration, salivation, miosis, tremors, fasciculation, and lower body surface temperature.

Applies to donepezil: oral tablet, oral tablet disintegrating

Along with its needed effects, donepezil (the active ingredient contained in Aricept ODT) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor as soon as possible if any of the following side effects occur while taking donepezil:

• Diarrhea
• loss of appetite
• muscle cramps
• nausea
• trouble in sleeping
• unusual tiredness or weakness
• vomiting

• Abnormal dreams
• constipation
• dizziness
• drowsiness
• fainting
• frequent urination
• headache
• joint pain, stiffness, or swelling
• mental depression
• pain
• unusual bleeding or bruising
• weight loss

• Black, tarry stools
• bloating
• bloody or cloudy urine
• blurred vision
• burning, prickling, or tingling sensations
• cataract
• chills
• clumsiness or unsteadiness
• confusion
• cough
• decreased urination
• difficult or painful urination
• dryness of mouth
• eye irritation
• fever
• flushing of skin
• frequent urge to urinate
• high or low blood pressure
• hives
• hot flashes
• increase in sexual desire or performance
• increased heart rate and breathing
• increased sweating
• increased urge to urinate during the night
• irregular heartbeat
• itching
• loss of bladder control
• loss of bowel control
• mood or mental changes, including abnormal crying, aggression, agitation, delusions, irritability, nervousness, or restlessness
• nasal congestion
• pain in chest, upper stomach, or throat
• problems with speech
• runny nose
• severe thirst
• shortness of breath
• sneezing
• sore throat
• sunken eyes
• tightness in chest
• tremor
• troubled breathing
• wheezing
• wrinkled skin

• Back, leg, or stomach pains
• bleeding gums
• chest pain or discomfort
• coma
• convulsions
• dark urine
• difficulty breathing
• fast or irregular heartbeat
• fatigue
• general body swelling
• general tiredness and weakness
• high fever
• increased thirst
• indigestion
• light-colored stools
• muscle pain or cramps
• nausea and vomiting
• nosebleeds
• pains in stomach, side, or abdomen, possibly radiating to the back
• pale skin
• rash
• seeing, hearing, or feeling things that are not there
• seizures
• severe muscle stiffness
• severe nausea
• slow or irregular heartbeat
• stomach pain
• sweating
• swelling of face, ankles, or hands
• tiredness
• unusually pale skin
• upper right abdominal or stomach pain
• yellow eyes and skin

• Convulsions (seizures)
• increased sweating
• increased watering of mouth
• increasing muscle weakness
• low blood pressure
• severe nausea
• severe vomiting
• slow heartbeat
• troubled breathing

Applies to donepezil: oral tablet, oral tablet disintegrating

General

The most common adverse events were diarrhea, muscle cramps, fatigue, nausea, vomiting, anorexia and insomnia. Most adverse events are mild in severity and transient in nature.[Ref]

Frequency of common adverse effects may be influenced by the rate of titration.[Ref]

Gastrointestinal

Very common (10% or more): Diarrhea, nausea
Common (1% to 10%): Vomiting, abdominal disturbance, tooth ache, fecal incontinence, gastrointestinal bleeding, bloating, epigastric pain
Uncommon (0.1% to 1%): Gastrointestinal hemorrhage, gastric and duodenal ulcers, eructation, gingivitis, flatulence, periodontal abscess, cholelithiasis, drooling, dry mouth, fever sore, gastritis, irritable colon, tongue edema, epigastric distress, gastroenteritis, increased transaminases, hemorrhoids, ileus, increased thirst, jaundice, melena, polydipsia, duodenal ulcer, stomach ulcer, hernia hiatal[Ref]

Nervous system

Very common (10% or more): Headache
Common (1% to 10%): Dizziness, insomnia, somnolence, tremor, paresthesia, ataxia, nervousness, aphasia
Uncommon (0.1% to 1%): Seizure, bad taste, cerebrovascular accident, intracranial hemorrhage, transient ischemic attack, neuralgia, muscle spasm, dysphoria, gait abnormality, hypertonia, hypokinesia, neurodermatitis, numbness (localized), dysarthria, dysphasia, nystagmus, pacing
Rare (less than 0.1%): Extrapyramidal symptoms
Very rare (less than 0.01%): Neuroleptic malignant syndrome[Ref]

Cardiovascular

Common (1% to 10%): Hypertension, hemorrhage, syncope, vasodilation, atrial fibrillation, hot flashes, hypotension
Uncommon (0.1% to 1%): Bradycardia, angina pectoris, postural hypotension, myocardial infarction, AV block (first degree), congestive heart failure, arteritis, peripheral vascular disease, supraventricular tachycardia, deep vein thrombosis.
Rare (less than 0.1%): SA block, AV block[Ref]

Dermatologic

Common (1% to 10%): Eczema rash, pruritus, ecchymosis, diaphoresis, urticaria
Uncommon (0.1% to 1%): Dermatitis, erythema, skin discoloration, hyperkeratosis, alopecia, fungal dermatitis, hirsutism, skin striae, night sweats, skin ulcer[Ref]

Genitourinary

Common (1% to 10%): Urinary incontinence, nocturia
Uncommon (0.1% to 1%): Dysuria, hematuria, urinary urgency, metrorrhagia, cystitis, enuresis, prostate hypertrophy, pyelonephritis, inability to empty bladder, breast fibroadenosis, fibrocystic breast, mastitis, pyuria, renal failure, vaginitis[Ref]

Metabolic

Common (1% to 10%): Anorexia, decreased weight, dehydration
Uncommon (0.1% to 1%): Increased appetite, gout, hypokalemia, hyperglycemia, increased lactate dehydrogenase[Ref]

Musculoskeletal

Common (1% to 10%): Muscle cramps, arthritis, bone fracture
Uncommon (0.1% to 1%): Muscle weakness, muscle fasciculation[Ref]

Ocular

Common (1% to 10%): Cataract, eye irritation, vision blurred
Uncommon (0.1% to 1%): Dry eyes, glaucoma, blepharitis, retinal hemorrhage, conjunctival hemorrhage, spots before eyes, periorbital edema[Ref]

Other

Common (1% to 10%): Fatigue, pain, accidental overdose, vertigo, abnormal crying
Uncommon (0.1% to 1%): Minor increase in serum concentration of muscle creatine kinase, diverticulitis, earache, tinnitus, decreased hearing, otitis externa, otitis media, ear buzzing, motion sickness, herpes zoster, coldness (localized), fever, edema face, abscess, cellulitis, chills, generalized coldness, head fullness[Ref]

Psychiatric

Common (1% to 10%): Hallucinations, agitation, aggressive behavior, abnormal dreams, nightmares, delusions, irritability, aggression, increased libido, restlessness
Uncommon (0.1% to 1%): Emotional lability, paranoia, hostility, decreased libido, melancholia, emotional withdrawal, listlessness[Ref]

Respiratory

Common (1% to 10%): Common cold, influenza, chest pain, dyspnea, sore throat, bronchitis
Uncommon (0.1% to 1%): Epistaxis, post nasal drip, pneumonia, hyperventilation, pulmonary congestion, wheezing, hypoxia, pharyngitis, pleurisy, pulmonary collapse, sleep apnea, snoring[Ref]

Endocrine

Uncommon (0.1% to 1%): Diabetes mellitus, goiter[Ref]

Hematologic

Uncommon (0.1% to 1%): Anemia, thrombocythemia, thrombocytopenia, eosinophilia, erythrocytopenia[Ref]

Hepatic

Rare (less than 0.1%): Liver dysfunction (including hepatitis)[Ref]

Some side effects of Aricept ODT may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

This medicine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.