DONECEPT Tablets (Donepezil hydrochloride)

Table of Content

For the use of a Psychiatrist/Neurologist attached to a Hospital/Institution OR a Nursing home only

Qualitative and Quantitative Composition

DONECEPT - 5

Each tablet contains:

Donepezil hydrochloride equivalent to Donepezil………………… 5 mg

DONECEPT - 10

Each tablet contains:

Donepezil hydrochloride equivalent to Donepezil ………………. 10 mg

Dosage Form(S) and Strength(S)

Film-coated tablets containing Donepezil hydrochloride 5 mg and 10 mg

Clinical Particulars

Therapeutic Indications

DONECEPT Tablets are indicated for the treatment of mild to moderately severe Alzheimer’s dementia.

Posology and Method of Administration

Dosing in Mild to Moderate Alzheimer’s Disease

The recommended starting dosage of DONECEPT Tablets is 5 mg administered once per day in the evening, just prior to retiring. The maximum recommended dosage of DONECEPT Tablets in patients with mild to moderate Alzheimer’s disease is 10 mg per day. 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.

Dosing in Moderate to Severe Alzheimer’s Disease

The recommended starting dosage of DONECEPT Tablets is 5 mg administered once per day in the evening, just prior to retiring. The maximum recommended dosage of DONECEPT Tablets in patients with moderate to severe Alzheimer’s disease is 10 mg per day. 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.

Administration Information

DONECEPT Tablets should be taken in the evening, just prior to retiring. DONECEPT Tablets can be taken with or without food.

Contraindications

DONECEPT Tablets are contraindicated in patients with a known hypersensitivity to donepezil hydrochloride, piperidine derivatives or any of its excipients.

Special Warnings and Precautions for Use

Anaesthesia

Donepezil, as a cholinesterase inhibitor, is likely to exaggerate succinylcholine-type muscle relaxation during anaesthesia.

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.

Peptic Ulcer Disease and Gastrointestinal 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 non-steroidal anti-inflammatory drugs (NSAIDs). Clinical studies of donepezil at a dose range of 5 to 10 mg/day have shown no increase, relative to placebo, in the incidence of either peptic ulcer disease or gastrointestinal bleeding.

Nausea and Vomiting

Donepezil, as a predictable consequence of its pharmacological properties, has been shown to produce diarrhoea, nausea and vomiting. These effects, when they occur, appear more frequently with the 10 mg/day dose than with the 5 mg/day dose, although in most cases, these effects have been it is not transient, sometimes lasting 1–3 weeks, and have resolved during continued use of donepezil, patients should be observed closely at the initiation of treatment and after dose increases.

Weight Loss

Weight loss was reported as an adverse event in some clinical trials.

Lower Weight Individuals

In the controlled clinical trial, among patients in the donepezil 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.

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.

Genitourinary Conditions

Although not observed in clinical trials of donepezil, cholinomimetics may cause bladder outflow obstruction.

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.

Drug Interactions

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.

Effect of Donepezil on the Metabolism of Other Drugs

No in vivo clinical trials have investigated the effect of donepezil 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 Ki about 50–130 μM), which, given the therapeutic plasma concentrations of donepezil (164 nM), indicates little likelihood of interference. Based on in vitro studies, donepezil shows little or no evidence of direct inhibition of CYP2B6, CYP2C8, and CYP2C19 at clinically relevant concentrations.

Whether donepezil has any potential for enzyme induction. 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

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. Population pharmacokinetic analysis showed that in the presence of concomitant CYP2D6 inhibitors donepezil AUC was increased by approximately 17% to 20% in Alzheimer’s disease patients taking donepezil 10. This represented an average effect of weak, moderate, and strong CYP2D6 inhibitors. In a 7-day crossover study in 18 healthy volunteers, ketoconazole (200 mg q.d.) increased mean donepezil (5 mg q.d.) concentrations (AUC0-24 and Cmax) by 36%. The clinical relevance of this increase in concentration is unknown.

Inducers of CYP 2D6 and CYP 3A4 (e.g. phenytoin, carbamazepine, dexamethasone, rifampin and phenobarbital) could increase the rate of elimination of donepezil.

Formal pharmacokinetic studies demonstrated that the metabolism of donepezil is not significantly affected by concurrent administration of digoxin or cimetidine.

An in vitro study showed that donepezil was not a substrate of P-glycoprotein.

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 micrograms/mL did not affect the binding of furosemide (5 micrograms/mL), digoxin (2 ng/mL), and warfarin (3 micrograms/mL) to human albumin. Similarly, the binding of donepezil to human albumin was not affected by furosemide, digoxin, and warfarin.

Use in Special Population

Pregnant Women

Risk Summary

There are no adequate data on the developmental risks associated with the use of  donepezil in pregnant women. In animal studies, developmental toxicity was not observed when donepezil was administered to pregnant rats and rabbits during organogenesis, but administration to rats during the latter part of pregnancy and throughout lactation resulted in increased stillbirths and decreased offspring survival at clinically relevant doses. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2% to 4% and 15% to 20%, respectively. The background risks of major birth defects and miscarriage for the indicated population are unknown.

Data

Animal Data

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 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.

Lactating Women

Risk Summary

There are no data on the presence of donepezil or its metabolites in human milk, the effects on the breastfed infant, or on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for donepezil and any potential adverse effects on the breastfed infant from donepezil or from the underlying maternal condition.

Paediatric Patients

The safety and effectiveness in paediatric patients have not been established.

Geriatric Patients

Alzheimer's disease is a disorder occurring primarily in individuals over 55 years of age. The mean age of patients enrolled in the clinical studies with donepezil 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.

Effects on Ability to Drive and Use Machines

Donepezil hydrochloride 10mg Film-coated Tablets have minor or moderate influence on the ability to drive and use machines.

Dementia may cause impairment of driving performance or compromise the ability to use machinery. Furthermore, donepezil can induce fatigue, dizziness and muscle cramps, mainly when initiating or increasing the dose. The treating physician should routinely evaluate the ability of patients on donepezil to continue driving or operating complex machines.

Undesirable Effects

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

• Cardiovascular Conditions

• Nausea and Vomiting

• Peptic Ulcer Disease and GI Bleeding

• Weight Loss

• Genitourinary Conditions

• Neurological Conditions: Seizures

• Pulmonary Conditions

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.

Donepezil 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 donepezil due to adverse events for donepezil 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 events 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.

Table 1: Most common adverse events leading to discontinuation in patients with mild to moderate Alzheimer’s disease

 

 

Adverse reactions

 

Placebo

(n=355)

%

5mg/day

Donepezil

(n=350)

%

10mg/day

Donepezil

(n=315)

%

Nausea

1

1

3

Diarrhoea

0

<1

3

Vomiting

<1

<1

2

Most Common Adverse Reactions

The most common adverse events, 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 the cholinomimetic effects of donepezil. These include nausea, diarrhea, insomnia, vomiting, muscle cramp, fatigue and anorexia. These adverse events were often transient, resolving during continued donepezil treatment without the need for dose modification.

There is evidence to suggest that the frequency of these common adverse events 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 events 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 events following one and six week titration regimens.

Table 2: Comparison of rates of adverse reactions in mild to moderate patients titrated to 10mg/day over 1 and 6 weeks

 

No titration

One week titration

Six week titration

Adverse reaction

Placebo

(n=315)

%

5mg/day

(n=311)

%

10mg/day

(n=315)

%

10mg/day

(n=269)

%

Nausea

6

5

19

6

Diarrhoea

5

 

 

8

15

9

Insomnia

6

6

14

6

Fatigue

3

4

8

3

Vomiting

3

3

8

5

Muscle cramps

2

6

8

3

Anorexia

2

3

7

3

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

Table 3: Adverse reactions in pooled placebo-controlled clinical trials in mild to moderate Alzheimer’s disease

Adverse reaction

Placebo

(n=355)

%

Donepezil

(n=747)

%

Percent of patients with any Adverse event

72

74

Nausea

6

11

Diarrhea

5

10

Headache

9

10

Insomnia

6

9

Pain, various locations

8

9

Dizziness

6

8

Accident

6

7

Muscle Cramps

2

6

Fatigue

3

5

Vomiting

3

5

Anorexia

2

4

Ecchymosis

3

4

Abnormal Dreams

0

3

Depression

<1

3

Weight Loss

1

3

Arthritis

1

2

Frequent urination

1

2

Somnolence

<1

2

Syncope

1

2

 

Severe Alzheimer’s disease (Donepezil 5 mg/day and 10 mg/day)

Donepezil 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 Events Leading to Discontinuation

The rates of discontinuation from controlled clinical trials of donepezil due to adverse events for donepezil patients were approximately 12% compared to 7% for placebo patients. The most common adverse events leading to discontinuation, defined as those occurring in at least 2% of donepezil 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 events, defined as those occurring at a frequency of at least 5% in patients receiving donepezil and at twice or more the placebo rate, are largely predicted by cholinomimetic effects of donepezil. These include diarrhea, anorexia, vomiting, nausea, and ecchymosis. These adverse reactions were often transient, resolving during continued donepezil treatment without the need for dose modification.

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

Table 4: Adverse reactions reported in pooled controlled clinical trials in severe Alzheimer’s disease

Body system/ Adverse reaction

Placebo

(n=392)

%

Donepezil

(n=501)

%

Percent of patients with any Adverse reaction

73

81

Accident

12

13

Infection

9

11

Diarrhea

4

10

Anorexia

4

8

Vomiting

4

8

Nausea

2

6

Insomnia

4

5

Ecchymosis

2

5

Headache

3

4

Hypertension

2

3

Pain

2

3

Back Pain

2

3

Eczema

2

3

Hallucinations

1

3

Hostility

2

3

Increase in Creatine Phosphokinase

1

3

Nervousness

2

3

Fever

1

2

Chest pain

<1

2

Confusion

1

2

Dehydration

1

2

Depression

1

2

Dizziness

1

2

Emotional Lability

1

2

Hemorrhage

1

2

Hyperlipemia

<1

2

Personality Disorder

1

2

Somnolence

1

2

Syncope

1

2

Urinary Incontinence

1

2

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

Donepezil 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 Donepezil 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.

Table 5. Most common adverse reactions leading to discontinuation in patients with moderate to severe Alzheimer’s disease

Adverse Reaction

23 mg/day

Donepezil

(n=963)

%

10 mg/day

Donepezil

(n=471)

%

Vomiting

3

0

Diarrhea

2

0

Nausea

2

0

Dizziness

1

0

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 Donepezil 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 Donepezil and at a higher frequency than those receiving 10 mg/day of Donepezil 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 Donepezil with or without memantine.

Table 6. Adverse reactions in a controlled clinical trial in moderate to severe Alzheimer’s disease

Adverse reaction

23 mg/day

Donepezil

(n=963)

%

10 mg/day

Donepezil

(n=471)

%

Percent of patients with any Adverse reaction

74

64

Nausea

12

3

Vomiting

9

3

Diarrhea

8

5

Anorexia

5

2

Dizziness

5

3

Weight Loss

5

3

Headache

4

3

Insomnia

3

2

Urinary Incontinence

3

1

Asthenia

2

1

Contusion

2

0

Fatigue

2

1

Somnolence

2

1

Postmarketing Experience

The following adverse events have been identified during post-approval use of donepezil. 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.

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. If your patient experiences any side-effects, write to drugsafety@cipla.com. You can also report side effects directly via the national pharmacovigilance program of India by calling on 1800 180 3024 or you can report to Cipla Ltd on 1800 267 7779. By reporting side-effects, you can help provide more information on the safety of this product.

Overdose

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 a 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 the respiratory muscles are involved.

Tertiary anticholinergics such as atropine may be used as an antidote for donepezil overdosage. Intravenous atropine sulphate titrated to effect is recommended, with an initial dose of 1.0–2.0 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 and/or its metabolites can be removed by dialysis (haemodialysis, peritoneal dialysis, or haemofiltration). 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.

Pharmacological Properties

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.

Pharmacokinetic Properties

Pharmacokinetics of donepezil are linear over a dose range of 1-10 mg given once daily. The rate and extent of absorption of donepezil tablets are not influenced by food.

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 10 mg tablets in approximately 3 hours.

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

Special Populations

Hepatic Impairment

In a study of 10 patients with stable alcoholic cirrhosis, the clearance of donepezil was decreased by 20% relative to 10 healthy age- and gender-matched subjects.

Renal Impairment

In a study of 11 patients with moderate-to-severe renal impairment (creatinine clearance <18 mL/min/1.73 m2), the clearance of donepezil did not differ from 11 age- and gender-matched healthy subjects.

Age

No formal pharmacokinetic study was conducted to examine age-related differences in the pharmacokinetics of donepezil. 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. However, retrospective pharmacokinetic analysis and population pharmacokinetic analysis of plasma donepezil concentrations measured in patients with Alzheimer’s disease indicates that gender and race (Japanese and Caucasians) did not affect the clearance of donepezil to an important degree.

Body Weight

There was a relationship noted between body weight and clearance. Over the range of body weight 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.

Non-Clinical Properties

Animal Toxicology or Pharmacology

In an acute dose neurotoxicity study in female rats, oral administration of donepezil and memantine in combination resulted in increased incidence, severity, and distribution of neurodegeneration compared with memantine alone. The no-effect levels of the combination were associated with clinically relevant plasma donepezil and memantine levels.

The relevance of this finding to humans is unknown.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No evidence of carcinogenic potential was obtained in an 88-week carcinogenicity study of donepezil conducted in mice at oral 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 rats at oral doses up to 30 mg/kg/day (approximately 13 times the MRHD 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 vivo mouse micronucleus).

Donepezil had no effect on fertility in rats at oral doses up to 10 mg/kg/day (approximately 4 times the MRHD on a mg/m2 basis) when administered to males and females prior to and during mating and continuing in females through implantation.

Description

DONECEPT (donepezil hydrochloride) is a reversible inhibitor of the enzyme acetylcholinesterase, known chemically as (±)-2, 3-dihydro-5, 6-dimethoxy-2-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.

Pharmaceutical Particulars

Incompatibilities

Not applicable

Shelf-life   

24 months

Packaging Information

DONECEPT - 5: Blister pack of 10 tablets

DONECEPT - 10: Blister pack of 10 tablets

Storage and Handling Instructions

Store below 30˚C away from moisture

Patient Counselling Information

What is DONECEPT table?

DONECEPT table comes in dosage strengths of 5 mg and 10 mg.

DONECEPT table is a prescription medicine to treat mild, moderate, and severe Alzheimer’s disease. DONECEPT table can help with mental function and with doing daily tasks. DONECEPT table does not work the same in all people. Some people may:

  • Seem much better
  • Get better in small ways or stay the same
  • Get worse over time but slower than expected
  • Not change and then get worse as expected

DONECEPT table does not cure Alzheimer’s disease. All patients with Alzheimer’s disease get worse over time, even if they take DONECEPT table.

DONECEPT table has not been approved as a treatment for any medical condition in children.

Who should not take DONECEPT tablet?

Do not take DONECEPT table if you are allergic to any of the ingredients in DONECEPT or to medicines that contain piperidines. Ask your doctor if you are not sure. See the end of this leaflet for a list of ingredients in DONECEPT table.

What should I tell my doctor before taking DONECEPT tablet?

Tell the doctor about all of your present or past health problems and conditions. Include:

  • Any heart problems including problems with irregular, slow, or fast heartbeats
  • Asthma or lung problems
  • A seizure
  • Stomach ulcers
  • Difficulty passing urine
  • Liver or kidney problems
  • Trouble swallowing tablets
  • Present pregnancy or plans to become pregnant. It is not known if DONECEPT tablet can harm an unborn baby.
  • Present breast-feeding. It is not known if DONECEPT tablet passes into breast milk. Talk to your doctor about the best way to feed your baby if you take DONECEPT tablet.

Tell the doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal products. DONECEPT tablet and other medicines may affect each other.

Be particularly sure to tell the doctor if you take aspirin or medicines called nonsteroidal anti-inflammatory drugs (NSAIDs). There are many NSAID medicines, both prescription and non-prescription. Ask the doctor or pharmacist if you are not sure if any of your medicines are NSAIDs. Taking NSAIDs and DONECEPT tablet together may make you more likely to get stomach ulcers.

DONECEPT tablet taken with certain medicines used for anesthesia may cause side effects. Tell the responsible doctor or dentist that you take DONECEPT tablet before you have:

  • surgery
  • medical procedures
  • dental surgery or procedures.

Know the medicines that you take. Keep a list of all your medicines. Show it to your doctor or pharmacist before you start a new medicine.

How should you take DONECEPT tablet?

  • Take DONECEPT tablet exactly as prescribed by the doctor. Do not stop DONECEPT tablet or change the dose yourself. Talk with your doctor first.
  • Take DONECEPT tablet one time each day. DONECEPT tablet can be taken with or without food.
  • DONECEPT tablets should be swallowed whole. Do not split, crush, or chew the tablets.
  • If you miss a dose of DONECEPT tablet, just wait. Take only the next dose at the usual time. Do not take 2 doses at the same time.
  • If DONECEPT tablet is missed for 7 days or more, talk with your doctor before starting again.
  • If you take too much DONECEPT tablet at one time, call your doctor or poison control center, or go to the emergency room right away.

What are the possible side effects of DONECEPT tablet?

DONECEPT tablet may cause the following serious side effects:

  • slow heartbeat and fainting. This happens more often in people with heart problems. Call your doctor right away if you feel faint or lightheaded while taking DONECEPT tablet.
  • more stomach acid. This raises the chance of ulcers and bleeding, especially when taking DONECEPT tablet. The risk is higher for people who have had ulcers, or take aspirin or other NSAIDs.
  • worsening of lung problems in people with asthma or other lung disease.
  • seizures.
  • difficulty passing urine.

Call your doctor right away if you have:

  • fainting.
  • heartburn or stomach pain that is new or won’t go away.
  • nausea or vomiting, blood in the vomit, dark vomit that looks like coffee grounds.
  • bowel movements or stools that look like black tar.
  • new or worse asthma or breathing problems.
  • seizures.
  • difficulty passing urine.

The most common side effects of DONECEPT tablet are:

  • nausea
  • diarrhea
  • not sleeping well
  • vomiting
  • muscle cramps
  • feeling tired
  • not wanting to eat

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. If your patient experiences any side-effects, write to drugsafety@cipla.com. You can also report side effects directly via the national pharmacovigilance program of India by calling on 1800 180 3024 or you can report to Cipla Ltd on 1800 267 7779. By reporting side-effects, you can help provide more information on the safety of this product.

How should DONECEPT tablet be stored?

Store DONECEPT tablet at room temperature between 59° to 86°F (15° to 30°C).

Keep DONECEPT tablet and all medicines out of the reach of children.

General information about DONECEPT tablet

Medicines are sometimes prescribed for conditions that are not mentioned in this Patient Information Leaflet. Do not use DONECEPT tablet for a condition for which it was not prescribed. Do not give DONECEPT tablet to other people, even if they have the same symptoms or condition. It may harm them.

What are the ingredients in DONECEPT tablet?

Active ingredient: donepezil hydrochloride

Details of Manufactures

Cipla House, Peninsula Business Park, Ganpatrao Kadam Marg, Lower Parel, Mumbai - 400 013 INDIA

Details of Permission or Licence Number with Date

12-38/99-DC

Date of Revision

Last updated: March 2021