Aricept 23 mg

Donepezil hydrochloride.

Donepezil hydrochloride is a reversible inhibitor of the enzyme acetylcholinesterase, known chemically as (±)-2, 3-dihydro-5, 6-dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-inden-1-one hydrochloride. Donepezil hydrochloride is commonly referred to in the pharmacological literature as E2020. It has an empirical formula of C₂₄H₂₉NO₃HCl and a molecular weight of 415.96. Donepezil hydrochloride is a white crystalline powder and is freely soluble in chloroform, soluble in water and in glacial acetic acid, slightly soluble in ethanol and in acetonitrile and practically insoluble in ethyl acetate and in n-hexane.
Donepezil hydrochloride (ARICEPT) 23 mg tablets is available for oral administration in reddish film-coated tablets containing 23 mg of donepezil hydrochloride.
Excipients/Inactive Ingredients: Inactive ingredients include ethylcellulose, hydroxypropyl cellulose, lactose monohydrate, magnesium stearate and methacrylic acid copolymer, Type C. The film coating includes ferric oxide, hypromellose 2910, polyethylene glycol 8000, talc and titanium dioxide.

Pharmacology: Pharmacodynamics: Mechanism of Action: Current theories on the pathogenesis of the cognitive signs and symptoms of Alzheimer's disease attribute some of them to a deficiency of cholinergic neurotransmission.
Donepezil hydrochloride is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine through reversible inhibition of its hydrolysis by acetylcholinesterase. There is no evidence that donepezil alters the course of the underlying dementing process.
Clinical Studies: The effectiveness of Donepezil hydrochloride (ARICEPT) 23 mg tablets as a treatment for moderate to severe Alzheimer's disease compared to donepezil hydrochloride 10 mg has been demonstrated by the results of a randomized, double-blind, controlled clinical investigation in patients with moderate to severe Alzheimer's disease. The controlled clinical study was conducted globally in patients with probable Alzheimer's disease diagnosed by NINCDS-ADRDA and DSM-IV criteria, MMSE: range of 0-20. Patients were required to have been on a stable dose of Donepezil hydrochloride (ARICEPT) 10 mg/day for at least 3 months prior to screening. One thousand four hundred and thirty four (1434) patients with moderate to severe Alzheimer's disease were randomized to 23 mg/day or 10 mg/day. The mean age of patients was 73.8 years, with a range of 47 to 90. Approximately 63% of patients were women, and 37% were men. Approximately 36% of the patients were taking memantine throughout the study.
Study Outcome Measures: The effectiveness of treatment with Donepezil hydrochloride (ARICEPT) 23 mg tablets was determined using a dual outcome assessment strategy that evaluated cognitive function using an instrument designed for more impaired patients and overall function through caregiver-rated assessment.
The ability of Donepezil hydrochloride (ARICEPT) 23 mg tablets to improve cognitive performance was assessed with the Severe Impairment Battery (SIB). The SIB, a multi-item instrument, has been validated for the evaluation of cognitive function in patients with moderate to severe dementia. The SIB evaluates selective aspects of cognitive performance, including elements of memory, language, orientation, attention, praxis, visuospatial ability, construction, and social interaction. The SIB scoring range is from 0 to 100, with lower scores indicating greater cognitive impairment.
The ability of Donepezil hydrochloride (ARICEPT) 23 mg tablets to produce an overall clinical effect was assessed using a Clinician's Interview-Based Impression of Change that incorporated the use of caregiver information, the CIBIC-plus. The CIBIC-plus used in this trial was a semi-structured instrument that examines four major areas of patient function: General, Cognitive, Behavioral and Activities of Daily Living. It represents the assessment of a skilled clinician based upon his/her observations at an interview with the patient, in combination with information supplied by a caregiver familiar with the behavior of the patient over the interval rated. The CIBIC-plus is scored as a seven point categorical rating, ranging from a score of 1, indicating "markedly improved," to a score of 4, indicating "no change" to a score of 7, indicating "markedly worse".
Effects on the SIB: Figure 1 shows the time course for the change from baseline in SIB score for the two treatment groups over the 24 weeks of the study. At 24 weeks of treatment, the LS mean difference in the SIB change scores for Donepezil hydrochloride (ARICEPT) 23 mg tablets treated patients compared to patients treated with 10 mg donepezil was 2.2 units (p=0.0001). Donepezil hydrochloride (ARICEPT) 23 mg tablets/day was statistically significantly superior to 10 mg/day donepezil. (See Figure 1.)

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Figure 2 illustrates the cumulative percentages of patients from each of the two treatment groups who attained the measure of improvement in SIB score shown on the X-axis. While patients assigned both to Donepezil hydrochloride (ARICEPT) 23 mg tablets and to donepezil hydrochloride 10 mg tablets have a wide range of responses, the curves show that the Donepezil hydrochloride (ARICEPT) 23 mg tablets group is more likely to show a greater improvement in cognitive performance. When such curves are shifted to the left, this indicates a greater percentage of patients responding to treatment on the SIB. (See Figure 2.)

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Effects on the CIBIC-plus: Figure 3 is a histogram of the frequency distribution of CIBIC-plus scores attained by patients at the end of 24 weeks of treatment. The mean difference between Donepezil hydrochloride (ARICEPT) 23 mg tablets mg and donepezil hydrochloride 10 mg tablets was 0.06 units. This difference was not statistically significant. (See Figure 3.)

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Pharmacokinetics: Based on population pharmacokinetic analysis of plasma donepezil concentrations measured in patients with Alzheimer's disease, following oral dosing, peak plasma concentration is achieved for Donepezil hydrochloride (ARICEPT) 23 mg tablets in approximately 8 hours, compared with 3 hours for Donepezil hydrochloride (ARICEPT) 10 mg tablets. Peak plasma concentrations were almost 2-fold higher for ARICEPT 23 mg tablets than Donepezil hydrochloride (ARICEPT) 10 mg tablets.
The elimination half-life of donepezil is about 70 hours, and the mean apparent plasma clearance (Cl/F) is 0.13-0.19 L/hr/kg. Following multiple dose administration, donepezil accumulates in plasma by 4-7 fold, and steady state is reached within 15 days. The steady state volume of distribution is 12-16 L/kg. Donepezil is approximately 96% bound to human plasma proteins, mainly to albumins (about 75%) and alpha₁-acid glycoprotein (about 21%) over the concentration range of 2-1000 ng/mL.
Donepezil is both excreted in the urine intact and extensively metabolized to four major metabolites, two of which are known to be active, and a number of minor metabolites, not all of which have been identified. Donepezil is metabolized by CYP 450 isoenzymes 2D6 and 3A4 and undergoes glucuronidation. Following administration of ¹⁴C-labeled donepezil, plasma radioactivity, expressed as a percent of the administered dose, was present primarily as intact donepezil (53%) and as 6-O-desmethyl donepezil (11%), which has been reported to inhibit AChE to the same extent as donepezil in vitro and was found in plasma at concentrations equal to about 20% of donepezil. Approximately 57% and 15% of the total radioactivity was recovered in urine and feces, respectively, over a period of 10 days, while 28% remained unrecovered, with about 17% of the donepezil dose recovered in the urine as unchanged drug. Examination of the effect of CYP2D6 genotype in Alzheimer's patients showed differences in clearance values among CYP2D6 genotype subgroups. When compared to the extensive metabolizers, poor metabolizers had a 31.5% slower clearance and ultra-rapid metabolizers had a 24% faster clearance. These results suggest CYP2D6 has a minor role in the metabolism of donepezil.
Hepatic Disease: In a study of 10 patients with stable alcoholic cirrhosis, the clearance of donepezil was decreased by 20% relative to 10 healthy age- and sex-matched subjects.
Renal Disease: In a study of 11 patients with moderate to severe renal impairment (Cl_C < 18 mL/min/1.73 m2) the clearance of donepezil did not differ from 11 age- and sex-matched healthy subjects.
Age: No formal pharmacokinetic study was conducted to examine age-related differences in the pharmacokinetics of Donepezil hydrochloride (ARICEPT) 23 mg tablets. Population pharmacokinetic analysis suggested that the clearance of donepezil in patients decreases with increasing age. When compared with 65-year old subjects, 90-year old subjects have a 17% decrease in clearance, while 40-year old subjects have a 33% increase in clearance. The effect of age on donepezil clearance may not be clinically significant.
Gender and Race: No specific pharmacokinetic study was conducted to investigate the effects of gender and race on the disposition of Donepezil hydrochloride (ARICEPT). However, retrospective pharmacokinetic analysis and population pharmacokinetic analysis of plasma donepezil concentrations measured in patients with Alzheimer's disease indicate that gender and race (Japanese and Caucasians) did not affect the clearance of Donepezil hydrochloride (ARICEPT) to an important degree.
Body weight: There was a relationship noted between body weight and clearance. Over the range of weights from 50 kg to 110 kg, clearance increased from 7.77 L/h to 14.04 L/h, with a value of 10 L/hr for 70 kg individuals.
Drugs Highly Bound to Plasma Proteins: Drug displacement studies have been performed in vitro between this highly bound drug (96%) and other drugs such as furosemide, digoxin, and warfarin. Donepezil at concentrations of 0.3-10 μg/mL did not affect the binding of furosemide (5 μg/mL), digoxin (2 ng/mL), and warfarin (3 μg/mL) to human albumin. Similarly, the binding of donepezil to human albumin was not affected by furosemide, digoxin and warfarin.
Toxicology: Carcinogenesis, Mutagenesis, Impairment of Fertility: No evidence of a carcinogenic potential was obtained in an 88-week carcinogenicity study of donepezil hydrochloride conducted in CD-1 mice at doses up to 180 mg/kg/day (approximately 40 times the maximum recommended human dose of 23 mg/day on a mg/m² basis), or in a 104-week carcinogenicity study in Sprague-Dawley rats at doses up to 30 mg/kg/day (approximately 13 times the maximum recommended human dose on a mg/m² basis).
Donepezil was negative in a battery of genotoxicity assays (in vitro bacterial reverse mutation, in vitro mouse lymphoma tk, in vitro chromosomal aberration, and in vitro mouse micronucleus). Donepezil had no effect on fertility in rats at doses up to 10 mg/kg/day (approximately 4 times the maximum recommended human dose on a mg/m² basis) when administered to males and females prior to and during mating and continuing in females through implantation.
Animal Toxicology: In a published study, female rats were given single doses of donepezil and memantine by intraperitoneal injection, each alone or in combination. When given in combination with memantine, donepezil increased the incidence and severity of memantine-induced neurodegeneration. The relevance of this finding to humans is unknown.

Donepezil hydrochloride (ARICEPT) 23 mg tablet is a cholinesterase inhibitor indicated for the symptomatic treatment of moderate to severe Alzheimer's disease.

Donepezil hydrochloride (ARICEPT) 23 mg tablets can be taken once daily in the evening just prior to retiring and can be taken with or without food or as prescribed by the physician. Donepezil hydrochloride (ARICEPT) 23 mg tablets mg should not be split or crushed and should be swallowed whole with water.
The recommended starting dose of donepezil hydrochloride is 5 mg once daily. A dose of 10 mg should not be administered until patients have been on a daily dose of 5 mg for 4 to 6 weeks. Patients who have been established on 10 mg of donepezil hydrochloride daily for at least 3 months can be administered one Donepezil hydrochloride (ARICEPT) 23 mg tablets once daily.

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 Donepezil hydrochloride (ARICEPT) 23 mg tablets 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 Donepezil hydrochloride (ARICEPT) 23 mg tablets 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.

Donepezil hydrochloride (ARICEPT) is contraindicated in patients with known hypersensitivity to donepezil hydrochloride, piperidine derivatives or to any excipients used in the formulation.

Anesthesia: Donepezil hydrochloride (ARICEPT) 23 mg tablets, as a cholinesterase inhibitor, is likely to exaggerate succinylcholine-type muscle relaxation during anesthesia.
Cardiovascular Conditions: Because of their pharmacological action, cholinesterase inhibitors may have vagotonic effects on the sinoatrial and atrioventricular nodes. This effect may manifest as bradycardia or heart block in patients both with and without known underlying cardiac conduction abnormalities. Syncopal episodes have been reported in association with the use of Donepezil hydrochloride (ARICEPT) 23 mg tablets.
Nausea and Vomiting: Donepezil hydrochloride (ARICEPT), as a predictable consequence of its pharmacological properties, has been shown to produce diarrhea, nausea, and vomiting. These effects, when they occur, appear more frequently with the 10 mg/day dose than with the 5 mg/day dose, and more frequently with the 23 mg dose than with the 10 mg dose. Specifically, in a controlled trial that compared a dose of 23 mg/day to 10 mg/day in patients who had been treated with donepezil 10 mg/day for at least three months, the incidence of nausea in the 23 mg group was markedly greater than in the patients who continued on 10 mg/day (11.8% vs 3.4%, respectively), and the incidence of vomiting in the 23 mg group was markedly greater than in the 10 mg group (9.2% vs 2.5%, respectively). The percent of patients who discontinued treatment due to vomiting in the 23 mg group was markedly higher than in the 10 mg group (2.9% vs 0.4%, respectively).
Although in most cases, these effects have been mild and transient, sometimes lasting one to three weeks, and have resolved during continued use of ARICEPT, patients should be observed closely at the initiation of treatment and after dose increases.
Peptic Ulcer Disease and GI Bleeding: Through their primary action, cholinesterase inhibitors may be expected to increase gastric acid secretion due to increased cholinergic activity. Therefore, patients should be monitored closely for symptoms of active or occult gastrointestinal bleeding, especially those at increased risk for developing ulcers, e.g., those with a history of ulcer disease or those receiving concurrent nonsteroidal anti-inflammatory drugs (NSAIDS). Results of a controlled clinical study of Donepezil hydrochloride (ARICEPT) 23 mg tablets showed an increase relative to donepezil hydrochloride 10 mg/day, in the incidence of peptic ulcer disease (0.4% vs. 0.2%) and gastrointestinal bleeding from any site (1.1% vs. 0.6%).
Weight Loss: Weight loss was reported as an adverse event in 4.7% of patients assigned to Donepezil hydrochloride (ARICEPT) 23 mg tablets compared to 2.5% of patients assigned to 10 mg donepezil hydrochloride. Compared to their baseline weights, 8.4% of patients in the Donepezil hydrochloride (ARICEPT) 23 mg tablets group were found to have a weight decrease of ≥ 7% by the end of the study, while 4.9% of the group taking 10 mg donepezil hydrochloride were found to have weight loss of ≥ 7% at the end of the study.
Genitourinary Conditions: Although not observed in clinical trials of Donepezil hydrochloride (ARICEPT), cholinomimetics may cause bladder outflow obstruction.
Neurological Conditions: Seizures: Cholinomimetics are believed to have some potential to cause generalized convulsions. However, seizure activity also may be a manifestation of Alzheimer's disease.
Pulmonary Conditions: Because of their cholinomimetic actions, cholinesterase inhibitors should be prescribed with care to patients with a history of asthma or obstructive pulmonary disease.
Mortality in Vascular Dementia Clinical Trials: Three clinical trials of 6 months duration were conducted studying individuals meeting the NINDS-AIREN criteria for probable or possible vascular dementia (VaD). The NINDS-AIREN criteria are designed to identify patients whose dementia appears to be due solely to vascular causes and to exclude patients with Alzheimer's disease. In the first study, the Donepezil mortality rates were 2/198 (1.0%) on donepezil hydrochloride 5 mg, 5/206 (2.4%) on donepezil hydrochloride 10 mg and 7/199 (3.5%) on placebo. In the second study, the mortality rates were 4/208 (1.9%) on donepezil hydrochloride 5mg, 3/215 (1.4%) on donepezil hydrochloride 10 mg and 1/193 (0.5%) on placebo. In the third study, the mortality rates were 11/648 (1.7%) on donepezil hydrochloride 5 mg and 0/326 (0%) on placebo. The mortality rate for the three VaD studies combined in the donepezil hydrochloride group (1.7%) was numerically higher than in the placebo group (1.1%). However, this difference was not statistically significant.
The majority of deaths in patents taking either donepezil hydrochloride or placebo appear to result from various vascular related causes, which could be expected in this elderly population with underlying vascular disease. An analysis of all serious non-fatal and fatal vascular events showed no difference in the rate of occurrence in the donepezil hydrochloride group relative to placebo.
In pooled Alzheimer's disease studies (n=4146), and when these Alzheimer's disease studies were pooled with other dementia studies including the vascular dementia studies (total n=6888), the mortality rate in the placebo groups numerically exceeded that in the donepezil hydrochloride groups.
Lower Weight Individuals: In the controlled clinical trial, among patients in the Donepezil hydrochloride (ARICEPT) 23 mg tablets treatment group, those patients weighing < 55 kg reported more nausea, vomiting, and decreased weight than patients weighing 55 kg or more. There were more withdrawals due to adverse events as well. This finding may be related to higher plasma exposure associated with lower weight.
Use in Children: The safety and effectiveness of Donepezil hydrochloride (ARICEPT) 23 mg tablets in children have not been established.
Use in Elderly: Alzheimer's disease is a disorder occurring primarily in individuals over 55 years of age. The mean age of patients enrolled in the clinical study with Donepezil hydrochloride (ARICEPT) was 73 years; 80% of these patients were between 65 and 84 years old, and 49% of patients were at or above the age of 75. The efficacy and safety data presented in the clinical trials section were obtained from these patients. There were no clinically significant differences in most adverse events reported by patient groups ≥ 65 years old and < 65 years old.

Use in Pregnancy: Category C: There are no adequate or well-controlled studies in pregnant women. Donepezil hydrochloride (ARICEPT) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Oral administration of donepezil to pregnant rats and rabbits during the period of organogenesis did not produce any teratogenic effects at doses up to 16 mg/kg/day (approximately 6 times the maximum recommended human dose [MRHD] of 23 mg/day on a mg/m² basis) and 10 mg/kg/day (approximately 7 times the MRHD on a mg/m2 basis), respectively. Oral administration of donepezil (1, 3, 10 mg/kg/day) to rats during late gestation and throughout lactation to weaning produced an increase in stillbirths and reduced offspring survival through postpartum day 4 at the highest dose. The no-effect dose of 3 mg/kg/day is approximately equal to the MRHD on a mg/m2 basis.
Use in Lactation: It is not known whether donepezil is excreted in human milk. Caution should be exercised when Donepezil hydrochloride (ARICEPT) is administered to a nursing woman.

Undesirable effects: The most common adverse events are diarrhea, muscle cramps, fatigue, nausea, vomiting and insomnia. The incidence profile for adverse events for severe Alzheimer's disease is similar to that of mild to moderately severe Alzheimer's disease. The table below reflects the incidence of adverse events in patients receiving treatment with Donepezil hydrochloride (ARICEPT) for all stages of Alzheimer's disease.
Adverse reactions reported as more than an isolated case are listed as follows, by system organ class and by frequency. Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1,000, < 1/100), rare (≥ 1/10,000, < 1/1,100), very rare (< 1/10,000) and not known (cannot be estimated from available data). (See Table 1.)

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Clinical Studies Experience: Donepezil hydrochloride (ARICEPT) 23 mg tablets 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 Events Leading to Discontinuation: The rate of discontinuation from a controlled clinical trial of Donepezil hydrochloride (ARICEPT) 23 mg tablets due to adverse events was higher (18.6%) than for the donepezil 10 mg/day treatment group (7.9%).
The most common adverse events leading to discontinuation, defined as those occurring in at least 1% of patients and greater than those occurring with donepezil 10 mg/day doses, are shown in Table 2. (See Table 2.)

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The majority of discontinuations due to adverse events in the Donepezil hydrochloride (ARICEPT) 23 mg tablets group occurred during the first month of treatment.
Most Frequent Adverse Clinical Events Seen in Association with the Use of Donepezil hydrochloride (ARICEPT) 23 mg tablets: The most common adverse events, defined as those occurring at a frequency of at least 5%, include nausea, diarrhea, vomiting, and anorexia. These adverse events were often of mild to moderate intensity.
Adverse Events Reported in Controlled Trials: The events cited reflect experience gained under closely monitored conditions of a controlled clinical trial in a highly selected patient population. In actual clinical practice or in other clinical trials, these frequency estimates may not apply, as the conditions of use, reporting behavior, and the kinds of patients treated may differ. Table 3 lists adverse events that were reported in at least 2% of patients who received 23 mg/day of Donepezil hydrochloride (ARICEPT) and at a higher frequency than those receiving 10 mg/day of Donepezil hydrochloride (ARICEPT) in a controlled clinical trial that compared the two doses. In this study, there were no important differences in the type of adverse events in patients taking Donepezil hydrochloride (ARICEPT) with or without memantine. (See Table 3.)

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Post-marketing Experience with 5 mg and 10 mg Donepezil Hydrochloride (ARICEPT) Tablets: 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. These adverse reactions include the following: abdominal pain, agitation, cholecystitis, confusion, convulsions, hallucinations, heart block (all types), hemolytic anemia, hepatitis, hyponatremia, neuroleptic malignant syndrome, pancreatitis, and rash.

Effect of Donepezil hydrochloride (ARICEPT) 23 mg tablets on the Metabolism of Other Drugs: No in vivo clinical trials have investigated the effect of donepezil hydrochloride on the clearance of drugs metabolized by CYP 3A4 (e.g. cisapride, terfenadine) or by CYP 2D6 (e.g. imipramine). However, in vitro studies show a low rate of binding to these enzymes (mean K_i about 50-130 μM), that, given the therapeutic plasma concentrations of donepezil (164 nM), indicates little likelihood of interference.
Whether Donepezil hydrochloride (ARICEPT) 23 mg tablets has any potential for enzyme induction is not known. Formal pharmacokinetic studies evaluated the potential of donepezil for interaction with theophylline, cimetidine, warfarin, digoxin and ketoconazole. No effects of donepezil on the pharmacokinetics of these drugs were observed.
Effect of Other Drugs on the Metabolism of Donepezil hydrochloride (ARICEPT) 23 mg tablets: Ketoconazole and quinidine, inhibitors of CYP450, 3A4 and 2D6, respectively, inhibit donepezil metabolism in vitro. Whether there is a clinical effect of quinidine is not known. In a 7-day crossover study in 18 healthy volunteers, ketoconazole (200 mg q.d.) increased mean donepezil (5 mg q.d.) concentrations (AUC_0-24 and C_max) by 36%. The clinical relevance of this increase in concentration is unknown.
A small effect of CYP2D6 inhibitors was identified in a population pharmacokinetic analysis of plasma donepezil concentrations measured in patients with Alzheimer's disease. Donepezil clearance was reduced by approximately 17% in patients taking 10 or 23 mg in combination with a known CYP2D6 inhibitor. This result is consistent with the conclusion that CYP2D6 is a minor metabolic pathway of donepezil.
Inducers of CYP 2D6 and CYP 3A4 (e.g., phenytoin, carbamazepine, dexamethasone, rifampin, and phenobarbital) could increase the rate of elimination of Donepezil hydrochloride (ARICEPT) 23 mg tablets.
Formal pharmacokinetic studies demonstrated that the metabolism of donepezil is not significantly affected by concurrent administration of digoxin or cimetidine.
Use with Anticholinergics: Because of their mechanism of action, cholinesterase inhibitors have the potential to interfere with the activity of anticholinergic medications.
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.

Store at temperatures not exceeding 30°C.

Neurodegenerative Disease Drugs

N06DA02 - donepezil ; Belongs to the class of anticholinesterases. Used in the management of dementia.

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