Donepezil Hydrochloride Tablets USP 5mg Taj Pharma

1. NAME OF THE MEDICINAL PRODUCT

Donepezil Hydrochloride Tablets USP 5mg Taj Pharma
Donepezil Hydrochloride Tablets USP 10mg Taj Pharma

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

a) Each film-coated tablet contains:
Donepezil Hydrochloride USP    5mg
Excipients                                    q.s

b) Each film-coated tablet contains:
Donepezil Hydrochloride USP   10mg
Excipients                                     q.s

For full list of excipients, see section 6.1

3. PHARMACEUTICAL FORM

Film-coated tablets.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Donepezil tablets are indicated for the symptomatic treatment of mild to moderately severe Alzheimer’s dementia.

4.2 Posology and method of administration

Posology

Adults/Elderly:

Treatment is initiated at 5 mg/day (once-a-day dosing).The 5 mg/day dose should be maintained for at least one month in order to allow the earliest clinical responses to treatment to be assessed and to allow steady-state concentrations of donepezil hydrochloride to be achieved. Following a one-month clinical assessment of treatment at 5 mg/day, the dose of donepezil can be increased to 10 mg/day (once-a-day dosing). The maximum recommended daily dose is 10 mg. Doses greater than 10 mg/day have not been studied in clinical trials.

Treatment should be initiated and supervised by a physician experienced in the diagnosis and treatment of Alzheimer’s dementia. Diagnosis should be made according to accepted guidelines (e.g. DSM IV, ICD 10). Therapy with donepezil should only be started if a caregiver is available who will regularly monitor drug intake for the patient. Maintenance treatment can be continued for as long as a therapeutic benefit for the patient exists. Therefore, the clinical benefit of donepezil should be reassessed on a regular basis. Discontinuation should be considered when evidence of a therapeutic effect is no longer present. Individual response to donepezil cannot be predicted.

Upon discontinuation of treatment, a gradual abatement of the beneficial effects of Donepezil is seen.

Renal impairment:

A similar dose schedule can be followed for patients with renal impairment, as clearance of donepezil hydrochloride is not affected by this condition.

Hepatic impairment:

Due to possible increased exposure in mild to moderate hepatic impairment (see section 5.2), dose escalation should be performed according to individual tolerability. There are no data for patients with severe hepatic impairment.

Paediatric population:

Donepezil is not recommended for use in children and adolescents below 18 years of age.

Method of administration

Donepezil tablets should be taken orally, in the evening, just prior to retiring

.

4.3 Contraindications

Donepezil Hydrochloride is contraindicated in patients with hypersensitivity to the active substance, piperidine derivatives, or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

The use of Donepezil in patients with severe Alzheimer’s dementia, other types of dementia or other types of memory impairment (e.g., age-related cognitive decline), has not been investigated.

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 heart rate (e.g., bradycardia). The potential for this action may be particularly important to patients with “sick sinus syndrome” or other supraventricular cardiac conduction conditions, such as sinoatrial or atrioventricular block.

There have been reports of syncope and seizures. In investigating such patients the possibility of heart block or long sinusal pauses should be considered.

Gastrointestinal Conditions: Patients at increased risk for developing ulcers, e.g., those with a history of ulcer disease or those receiving concurrent nonsteroidal anti-inflammatory drugs (NSAIDs), should be monitored for symptoms. However, the clinical studies with Donepezil showed no increase, relative to placebo, in the incidence of either peptic ulcer disease or gastrointestinal bleeding.

Genitourinary: Although not observed in clinical trials of Donepezil, cholinomimetics may cause bladder outflow obstruction.

Neurological Conditions: Seizures: Cholinomimetics are believed to have some potential to cause generalised convulsions. However, seizure activity may also be a manifestation of Alzheimer’s Disease.

Cholinomimetics may have the potential to exacerbate or induce extrapyramidal symptoms

Neuroleptic Malignant Syndrome (NMS): NMS, a potentially life-threatening condition and characterised by hyperthermia, muscle rigidity, autonomic instability, altered consciousness and elevated serum creatine phosphokinase levels, has been reported to occur very rarely in association with donepezil, particularly in patients also receiving concomitant antipsychotics. additional signs may include myoglobinuria (rhabdomyolysis) and acute renal failure. If a patient develops signs and symptoms indicative of NMS, or presents with unexplained high fever without additional clinical manifestations of NMS, treatment should be discontinued.

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.

The administration of Donepezil concomitantly with other inhibitors of acetylcholinesterase, agonists or antagonists of the cholinergic system should be avoided.

Severe Hepatic Impairment: There are no data for patients with severe hepatic impairment.

Excipients: This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

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 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 5 mg, 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 patients 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 nonfatal 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.

4.5 Interaction with other medicinal products and other forms of interaction

Donepezil hydrochloride and/or any of its metabolites do not inhibit the metabolism of theophylline, warfarin, cimetidine or digoxin in humans. The metabolism of donepezil hydrochloride is not affected by concurrent administration of digoxin or cimetidine. In vitro studies have shown that the cytochrome P450 isoenzymes 3A4 and to a minor extent 2D6 are involved in the metabolism of donepezil. Drug interaction studies performed in vitro show that ketoconazole and quinidine, inhibitors of CYP3A4 and 2D6 respectively, inhibit donepezil metabolism. Therefore these and other CYP3A4 inhibitors, such as itraconazole and erythromycin, and CYP2D6 inhibitors, such as fluoxetine could inhibit the metabolism of donepezil. In a study in healthy volunteers, ketoconazole increased mean donepezil concentrations by about 30%. Enzyme inducers, such as rifampicin, phenytoin, carbamazepine and alcohol may reduce the levels of donepezil. Since the magnitude of an inhibiting or inducing effect is unknown, such drug combinations should be used with care. Donepezil hydrochloride has the potential to interfere with medications having anticholinergic activity. There is also the potential for synergistic activity with concomitant treatment involving medications such as succinylcholine, other neuro-muscular blocking agents or cholinergic agonists or beta blocking agents which have effects on cardiac conduction.

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no adequate data from the use of donepezil in pregnant women.

Studies in animals have not shown teratogenic effect but have shown peri- and post-natal toxicity (see section 5.3). The potential risk for humans is unknown.

Donepezil should not be used during pregnancy unless clearly necessary.

Breast-feeding

Donepezil is excreted in the milk of rats. It is not known whether donepezil hydrochloride is excreted in human breast milk and there are no studies in lactating women. Therefore, women on donepezil should not breast feed.

4.7 Effects on ability to drive and use machines

Donepezil has 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.

4.8 Undesirable effects

The most common adverse events are diarrhoea, muscle cramps, fatigue, nausea, vomiting and insomnia.

Adverse reactions reported as more than an isolated case are listed below, by system organ class and by frequency. Frequencies are defined as: very common ≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥1/10,000 to <1/1,000) and very rare (<1/10000) and not known (cannot be estimated from available data).

*In investigating patients for syncope or seizure the possibility of heart block or long sinusal pauses should be considered (see section 4.4)

**Reports of hallucinations, abnormal dreams, nightmares, agitation and aggressive behaviour have resolved on dose-reduction or discontinuation of treatment.

***In cases of unexplained liver dysfunction, withdrawal of donepezil should be considered.

**** Rhabdomyolysis has been reported to occur independently of neuroleptic malignant syndrome and in close temporal association with donepezil initiation or dose increase.

Reporting of suspected adverse reactions

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.

4.9 Overdose

The estimated median lethal dose of donepezil hydrochloride following administration of a single oral dose in mice and rats is 45 and 32 mg/kg, respectively, or approximately 225 and 160 times the maximum recommended human dose of 10 mg per day. Dose-related signs of cholinergic stimulation were observed in animals and included reduced spontaneous movement, prone position, staggering gait, lacrimation, clonic convulsions, depressed respiration, salivation, miosis, fasciculation and lower body surface temperature.

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.

As in any case of overdose, general supportive measures should be utilised. Tertiary anticholinergics such as atropine may be used as an antidote for donepezil overdosage. Intravenous atropine sulphate titrated to effect is recommended: an initial dose of 1.0 to 2.0 mg intravenously 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 and/or its metabolites can be removed by dialysis (hemodialysis, peritoneal dialysis, or hemofiltration).

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Anti-dementia drugs, Anticholinesterase.

Mechanism of action

Donepezil hydrochloride is a specific and reversible inhibitor of acetylcholinesterase, the predominant cholinesterase in the brain. Donepezil hydrochloride is in vitro over 1000 times more potent an inhibitor of this enzyme than of butyrylcholinesterase, an enzyme which is present mainly outside the central nervous system.

Alzheimer’s Dementia

In patients with Alzheimer’s Dementia participating in clinical trials, administration of single daily doses of 5 mg or 10 mg of donepezil produced steady-state inhibition of acetylcholinesterase activity (measured in erythrocyte membranes) of 63.6% and 77.3%, respectively when measured post dose.

The inhibition of acetylcholinesterase (AChE) in red blood cells by donepezil hydrochloride has been shown to correlate to changes in ADAS-cog, a sensitive scale which examines selected aspects of cognition. The potential for donepezil hydrochloride to alter the course of the underlying neuropathology has not been studied. Thus donepezil cannot be considered to have any effect on the progress of the disease.

Efficacy of treatment of Alzheimer’s dementia with donepezil has been investigated in four placebo-controlled trials, 2 trials of 6-month duration and 2 trials of 1-year duration. In the 6 months clinical trial, an analysis was done at the conclusion of donepezil treatment using a combination of three efficacy criteria: the ADAS-Cog (a measure of cognitive performance), the Clinician Interview Based Impression of Change with Caregiver Input (a measure of global function) and the Activities of Daily Living Subscale of the Clinical Dementia Rating Scale (a measure of capabilities in community affairs, home and hobbies and personal care).

Patients who fulfilled the criteria listed below were considered treatment responders.

* p<0.05

** p<0.01

Donepezil produced a dose-dependent statistically significant increase in the percentage of patients who were judged treatment responders.

5.2 Pharmacokinetic properties

General characteristics

Absorption: Maximum plasma levels are reached approximately 3 to 4 hours after oral administration.

Plasma concentrations and area under the curve rise in proportion to the dose. The terminal disposition half-life is approximately 70 hours, thus, administration of multiple single-daily doses results in gradual approach to steady-state. Approximate steady-state is achieved within 3 weeks after initiation of therapy. Once at steady-state, plasma donepezil hydrochloride concentrations and the related pharmacodynamic activity show little variability over the course of the day.

Food did not affect the absorption of donepezil hydrochloride.

Distribution: Donepezil hydrochloride is approximately 95% bound to human plasma proteins. The plasma protein binding of the active metabolite 6-O-desmethyldonepezil in not known. The distribution of donepezil hydrochloride in various body tissues has not been definitively studied.

However, in a mass balance study conducted in healthy male volunteers, 240 hours after the administration of a single 5 mg dose of ¹⁴C-labelled donepezil hydrochloride, approximately 28% of the label remained unrecovered. This suggests that donepezil hydrochloride and/or its metabolites may persist in the body for more than 10 days.

Metabolism/Excretion: Donepezil hydrochloride is both excreted in the urine intact and metabolized by the cytochrome P450 system to multiple metabolites, not all of which have been identified.

Following administration of a single 5 mg dose of ¹⁴C-labeled donepezil hydrochloride, plasma radioactivity, expressed as a percent of the administered dose, was present primarily as intact donepezil hydrochloride (30%), 6-O-desmethyl donepezil (11% – only metabolite that exhibits activity similar to donepezil hydrochloride), donepezil-cis-N-oxide (9%), 5-O-desmethyl donepezil (7%) and the glucuronide conjugate of 5-O-desmethyl donepezil (3%). Approximately 57% of the total administered radioactivity was recovered from the urine (17% as unchanged donepezil), and 14.5% was recovered from the faeces, suggesting biotransformation and urinary excretion as the primary routes of elimination. There is no evidence to suggest enterohepatic recirculation of donepezil hydrochloride and/or any of its metabolites.

Plasma donepezil concentrations decline with a half-life of approximately 70 hours.

Sex, race and smoking history have no clinically significant influence on plasma concentrations of donepezil hydrochloride. The pharmacokinetics of donepezil has not been formally studied in healthy elderly subjects or in Alzheimer’s patients or vascular dementia patients. However mean plasma levels in patients closely agreed with those of young healthy volunteers.

Patients with mild to moderate hepatic impairment had increased donepezil steady state concentrations; mean AUC by 48% and mean C_max by 39% (see section 4.2).

5.3 Preclinical safety data

Extensive testing in experimental animals has demonstrated that this compound causes few effects other than the intended pharmacological effects consistent with its action as a cholinergic stimulator (see Section 4.9). Donepezil is not mutagenic in bacterial and mammalian cell mutation assays. Some clastogenic effects were observed in vitro at concentrations overtly toxic to the cells and more than 3000 times the steady -state plasma concentrations. No clastogenic or other genotoxic effects were observed in the mouse micronucleus model in vivo. There was no evidence of oncogenic potential in long term carcinogenicity studies in either rats or mice.

Donepezil hydrochloride had no effect on fertility in rats, and was not teratogenic in rats or rabbits, but had a slight effect on still births and early pup survival when administered to pregnant rats at 50 times the human dose (see Section 4.6).

6. Pharmaceutical particulars

6.1 List of excipients

Core: Lactose monohydrate, Maize starch, Hydroxypropyl cellulose, Microcrystalline cellulose, Sodium starch glycolate-type A & Magnesium stearate.

Coating: Hypromellose, Titanium dioxide, Macrogol, Talc & Iron oxide yellow.

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

Blister pack of PVC/Aluminum foil.

Pack sizes:7, 14, 28, 30, 50, 60, 90, 100, 200 & 250 film-coated tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements

7.Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

Donepezil Hydrochloride Tablets USP 5mg/10mg Taj Pharma
(Donepezil)

Package leaflet: Information for the patient

The medicine will be referred to as Donepezil tablets throughout the remainder of the leaflet

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Donepezil tablets are and what they are used for
   2. What you need to know before you take Donepezil tablets
   3. How to take Donepezil tablets
   4. Possible side effects
   5. How to store Donepezil tablets
   6. Contents of the pack and other information
2. WHAT DONEPEZIL TABLETS ARE AND WHAT THEY ARE USED FOR

Donepezil tablets contain the active substance donepezil hydrochloride and belong to a group of medicines called acetylcholinesterase inhibitors.

Donepezil increases the levels of a substance (acetylcholine) in the brain involved in memory function by slowing down the breakdown of acetylcholine.

It is used to treat the symptoms of dementia in people diagnosed as having mild and moderately severe Alzheimer’s disease. The symptoms include increasing memory loss, confusion and behavioural changes. As a result, sufferers of Alzheimer’s disease find it more and more difficult to carry out their normal daily activities.

Donepezil tablets are for use in adult patients only.

2. WHAT YOU NEED TO KNOW BEFORE YOU TAKE DONEPEZIL TABLETS

Do not take Donepezil tablets

• if you are allergic to donepezil hydrochloride, or to piperidine derivatives, or any of the other ingredients of this medicine (listed in section 6). An allergic reaction may include rash, itching, swelling of face, lips, or hands/feet, or breathing difficulties.

Warnings and precautions

Talk to your doctor or pharmacist before taking Donepezil tablets if you have or have had:

• stomach or duodenal ulcers
• seizures (fits) or convulsions
• a heart condition (irregular or very slow heart beat)
• asthma or other long term lung disease
• liver problems or hepatitis. Donepezil tablets can be used in patients with mild to moderate liver disease. Patients with severe liver disease should not take Donepezil tablets.
• difficulty passing urine or kidney disease. However, Donepezil tablets can be used in patients with kidney disease.
• any involuntary or abnormal movements of the tongue, face or body (extrapyramidal symptoms). Donepezil may induce or exacerbate extrapyramidal symptoms.

Children and adolescents

Donepezil tablets are not recommended for use in children and adolescents

Other medicines and Donepezil tablets

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This includes medicines that your doctor has not prescribed for you but which you have bought yourself from a chemist/pharmacist. It also applies to medicines you may take some time in the future if you continue to take Donepezil tablets. This is because these medicines may weaken or strengthen the effects of Donepezil tablets.

In particular it is important to tell your doctor if you are taking any of the following types of medicines:

• other Alzheimer’s disease medicines, e.g. galantamine
• pain killers or treatment for arthritis e.g. acetylsalicylic acid, non-steroidal anti-inflammatory drugs (NSAID’s) such as ibuprofen, or diclofenac sodium
• anticholinergics medicines, e.g. tolterodine
• antibiotics e.g. erythromycin, rifampicin
• anti-fungal medicine e.g. ketoconazole, itraconazole
• anti-depressants e.g. fluoxetine
• anticonvulsants e.g. phenytoin, carbamazepine
• medication for a heart condition e.g. quinidine, beta-blockers (propanolol and atenolol)
• muscle relaxants e.g. diazepam, succinylcholine
• general anaesthetic
• medicines obtained without a prescription e.g. herbal remedies

If you are going to have an operation that requires you to have a general anaesthetic, you should tell your doctor and the anaesthetist that you are taking Donepezil tablets. This is because your medicine may affect the amount of anaesthetic needed.

Tell your doctor or pharmacist the name of your caregiver. Your caregiver will help you to take your medicine as prescribed.

Donepezil tablets with food, drink and alcohol

Food will not influence the effect of Donepezil tablets.

Donepezil tablets should not be taken with alcohol because alcohol may reduce its effect.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Donepezil tablets should not be used while breast-feeding.

Driving and using machines

Alzheimer’s disease may impair your ability to drive or operate machinery and you must not perform these activities unless your doctor tells you that it is safe to do so. Also, your medicine can cause tiredness, dizziness and muscle cramp. If you experience any of these effects you must not drive or operate machinery.

Donepezil tablets contain lactose

Donepezil tablets contain lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

3. HOW TO TAKE DONEPEZIL TABLETS

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

How much Donepezil tablets should you take?

Initially the recommended dose is 5 mg of donepezil hydrochloride every night. After one month, your doctor may tell you to take 10 mg of donepezil hydrochloride every night.

The tablet strength you will take may change depending on the length of time you have been taking the medicine and on what your doctor recommends. The maximum recommended dose is 10 mg each night.

Always follow your doctor’s or pharmacist’s advice about how and when to take your medicine.

Do not alter the dose yourself without your doctor’s advice.

Use in children and adolescents

This medicine is not recommended for use in children and adolescents younger than 18 years of age.

Taking your medicine

Oral use.

Swallow your Donepezil tablet with a drink of water before you go to bed at night.

If you take more Donepezil tablets than you should

Contact your doctor or the nearest hospital emergency department immediately if you take more of the medicine than you should. Take this leaflet and any remaining tablets with you.

Overdose symptoms may include feeling and being sick, drooling, sweating, slow heart rate, low blood pressure (light-headedness or dizziness when standing), breathing problems, losing consciousness and seizures (fits) or convulsions.

If you forget to take Donepezil tablets

If you forget to take your medicine, take the next dose at the usual time. Do not take a double dose to make up for a forgotten tablet.

If you forget to take your medicine for more than one week, call your doctor before taking any more medicine.

If you stop taking Donepezil tablets

Do not stop taking the tablets unless told to do so by your doctor. If you stop taking Donepezil tablets, the benefits of your treatment will gradually fade away.

For how long should you take Donepezil tablets?

Your doctor or pharmacist will advise you on how long you should continue to take your tablets. You will need to see your doctor from time to time to review your treatment and assess your symptoms.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The following side effects have been reported by people taking Donepezil tablets.

Tell your doctor if you have any of these effects while you are taking Donepezil tablets

Serious side effects

You must tell your doctor immediately if you notice these serious side effects mentioned. You may need urgent medical treatment.

Uncommon (may affect up to 1 in 100 people):

• Seizures (fits) or convulsions
• Stomach or duodenal ulcers. The symptoms of ulcers are stomach pain and discomfort (indigestion) felt between the navel and the breast bone
• Bleeding in the stomach or intestines. This may cause you to pass black tar like stools or visible blood from the rectum

Rare (may affect up to 1 in 1000 people):

• Slow heart rate associated with dizziness, weakness, confusion
• Liver damage e.g. hepatitis. The symptoms of hepatitis are feeling or being sick, loss of appetite, feeling generally unwell, fever, itching, yellowing of the skin and eyes, and dark coloured urine

Very rare (may affect up to 1 in 10,000 people):

• Fever with muscle stiffness, sweating or a lowered level of consciousness (a disorder called “Neuroleptic Malignant Syndrome”)
• Muscle weakness, tenderness or pain and particularly, if at the same time, you feel unwell, have a high temperature or have dark urine. This may be caused by an abnormal muscle breakdown which can be life threatening and lead to kidney problems (a condition called rhabdomyolysis)

Other side effects

Very common side effects (may affect more than 1 in 10 people):

• diarrhoea
• feeling sick
• headaches

Common side effects (may affect up to 1 in 10 people):

• muscle cramp
• tiredness
• difficulty in sleeping (insomnia)
• the common cold
• loss of appetite (anorexia)
• hallucinations (seeing or hearing things that are not really there)
• unusual dreams including nightmares
• agitation
• aggressive behaviour
• fainting
• dizziness
• stomach feeling uncomfortable, being sick (vomiting)
• rash
• itching
• passing urine uncontrollably
• pain
• accidents (patients may be more prone to falls and accidental injury)

Uncommon side effects (may affect up to 1 in 100 people):

• slow heart beat
• minor increase in serum concentration of muscle creatine kinase
• salivary hypersecretion

Rare side effects (may affect up to 1 in 1,000 people):

• stiffness, shaking or uncontrollable movement especially of the face and tongue but also of the limbs

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

5. HOW TO STORE DONEPEZIL TABLETS

Keep this medicine out of the sight and reach of children.

This medicine does not require any special storage conditions.

Do not use this medicine after the expiry date which is stated on the blister and carton after EXP. The expiry date refers to the last day of that month.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. CONTENTS OF THE PACK AND OTHER INFORMATION

What Donepezil tablets contains

The active substance is donepezil hydrochloride:

a) Each film-coated tablet contains:
Donepezil Hydrochloride USP    5mg
Excipients                                    q.s

b) Each film-coated tablet contains:
Donepezil Hydrochloride USP   10mg
Excipients                                     q.s

The other ingredients are:

Core: Lactose monohydrate, Maize starch, Hydroxypropyl cellulose, Microcrystalline cellulose, Sodium starch glycolate-type A & Magnesium stearate.

Coating: Hypromellose, Titanium dioxide, Macrogol, Talc & Iron oxide yellow.

What Donepezil tablets look like and contents of the pack

Blister pack of PVC/Aluminum foil.

Pack sizes:7, 14, 28, 30, 50, 60, 90, 100, 200 & 250 film-coated tablets.

Not all pack sizes may be marketed.

7.Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com