Donepezil Hydrochloride (Page 4 of 5)

14.2 Severe Alzheimer’s disease

Swedish 6 Month Study

The effectiveness of donepezil hydrochloride as a treatment for severe Alzheimer’s disease is demonstrated by the results of a randomized, double-blind, placebo-controlled clinical study conducted in Sweden (6 month study) in patients with probable or possible Alzheimer’s disease diagnosed by NINCDS-ADRDA and DSM-IV criteria, MMSE: range of 1 to 10. Two hundred and forty eight (248) patients with severe Alzheimer’s disease were randomized to donepezil hydrochloride or placebo. For patients randomized to donepezil hydrochloride, treatment was initiated at 5 mg once daily for 28 days and then increased to 10 mg once daily. At the end of the 6 month treatment period, 90.5% of the donepezil hydrochloride treated patients were receiving the 10 mg/day dose. The mean age of patients was 84.9 years, with a range of 59 to 99. Approximately 77 % of patients were women, and 23 % were men. Almost all patients were Caucasian. Probable AD was diagnosed in the majority of the patients (83.6% of donepezil hydrochloride treated patients and 84.2% of placebo treated patients).

Study Outcome Measures: The effectiveness of treatment with donepezil hydrochloride 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. This study showed that patients on donepezil hydrochloride experienced significant improvement on both measures compared to placebo.

The ability of donepezil hydrochloride 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.

Daily function was assessed using the Modified Alzheimer’s Disease Cooperative Study Activities of Daily Living Inventory for Severe Alzheimer’s Disease (ADCS-ADL-severe). The ADCS-ADL-severe is derived from the Alzheimer’s Disease Cooperative Study Activities of Daily Living Inventory, which is a comprehensive battery of ADL questions used to measure the functional capabilities of patients. Each ADL item is rated from the highest level of independent performance to complete loss. The ADCS-ADL-severe is a subset of 19 items, including ratings of the patient’s ability to eat, dress, bathe, use the telephone, get around (or travel), and perform other activities of daily living; it has been validated for the assessment of patients with moderate to severe dementia. The ADCS-ADL-severe has a scoring range of 0 to 54, with the lower scores indicating greater functional impairment. The investigator performs the inventory by interviewing a caregiver, in this study a nurse staff member, familiar with the functioning of the patient.

Effects on the SIB:

Figure 7 shows the time course for the change from baseline in SIB score for the two treatment groups over the 6 months of the study. At 6 months of treatment, the mean difference in the SIB change scores for donepezil hydrochloride treated patients compared to patients on placebo was 5.9 points. Donepezil hydrochloride treatment was statistically significantly superior to placebo.

Figure 7
(click image for full-size original)

Figure 8 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 and to placebo have a wide range of responses, the curves show that the donepezil hydrochloride group is more likely to show a greater improvement in cognitive performance.

Figure 8
(click image for full-size original)
Figure 9
(click image for full-size original)

Effects on the ADCS-ADL-severe: Figure 9 illustrates the time course for the change from baseline in ADCS-ADL-severe scores for patients in the two treatment groups over the 6 months of the study. After 6 months of treatment, the mean difference in the ADCS-ADL-severe change scores for donepezil hydrochloride treated patients compared to patients on placebo was 1.8 points. Donepezil hydrochloride treatment was statistically significantly superior to placebo.

Figure 10 shows the cumulative percentages of patients from each treatment group with specified changes from baseline ADCS-ADL-severe scores. While both patients assigned to donepezil hydrochloride and placebo have a wide range of responses, the curves demonstrate that the donepezil hydrochloride group is more likely to show a smaller decline or an improvement.

Figure 10
(click image for full-size original)

Japanese 24-Week Study

In a study of 24 weeks duration conducted in Japan, 325 patients with severe Alzheimer’s disease were randomized to doses of 5 mg/day or 10 mg/day of donepezil, administered once daily, or placebo. Patients randomized to treatment with donepezil were to achieve their assigned doses by titration, beginning at 3 mg/day, and extending over a maximum of 6 weeks. Two hundred and forty eight (248) patients completed the study, with similar proportions of patients completing the study in each treatment group. The primary efficacy measures for this study were the SIB and CIBIC-plus.

At 24 weeks of treatment, statistically significant treatment differences were observed between the 10 mg/day dose of donepezil and placebo on both the SIB and CIBIC-plus. The 5 mg/day dose of donepezil showed a statistically significant superiority to placebo on the SIB, but not on the CIBIC-plus.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 Donepezil hydrochloride tablets

Donepezil hydrochloride tablets are supplied as round, film-coated tablets containing either 5 mg or 10 mg of donepezil hydrochloride.

The 5 mg tablets are white and debossed with SZ 135 on one side.

Boxes of 10x 10 UD 100 NDC 63739-646-10

The 10 mg tablets are yellow and debossed with SZ 136 on one side.

Boxes of 10 x 10 UD 100 NDC 63739-678-10

Storage: Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

17 PATIENT COUNSELING INFORMATION

See FDA-approved Patient Package Insert attached to this label.

To assure safe and effective use of donepezil hydrochloride tablets, the information and instructions provided in the attached Patient Package Insert should be discussed with patients and caregivers.

Patients and caregivers should be instructed to take donepezil hydrochloride tablets only once per day, as prescribed.

Patients and caregivers should be instructed that donepezil hydrochloride tablets can be taken with or without food.

Patients and caregivers should be advised that the product may cause nausea, diarrhea, insomnia, vomiting, muscle cramps, fatigue and decreased appetite.

PATIENT PACKAGE INSERT

DonepezilHydrochlorideTablets

Read the Patient Information that comes with donepezil hydrochloride tablets before the patient starts taking it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with the doctor about Alzheimer’s disease or treatment for it. If you have questions, ask the doctor or pharmacist.

What is donepezil hydrochloride tablet?

Donepezil hydrochloride tablet comes as film-coated tablet in dosage strengths of 5 mg and 10 mg.

Donepezil hydrochloride tablet is a prescription medicine to treat mild, moderate, and severe Alzheimer’s disease. Donepezil hydrochloride tablet can help with mental function and with doing daily tasks. Donepezil hydrochloride tablet 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

Donepezil hydrochloride tablet does not cure Alzheimer’s disease. All patients with Alzheimer’s disease get worse over time, even if they take donepezil hydrochloride tablet.

Donepezil hydrochloride has not been approved as a treatment for any medical condition in children.

Who should not take donepezil hydrochloride tablet?

The patient should not take donepezil hydrochloride tablet if allergic to any of the ingredients in donepezil hydrochloride tablet or to medicines that contain piperidines. Ask the patient’s doctor if you are not sure. See the end of this leaflet for a list of ingredients in donepezil hydrochloride tablet.

What should I tell the doctor before the patient takes donepezil hydrochloride tablet?

Tell the doctor about all the patient’s present or past health problems.

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 donepezil hydrochloride tablet can harm an unborn baby.
Present breast-feeding. It is not known if donepezil hydrochloride passes into breast milk. Donepezil hydrochloride tablet is not for women who are breast-feeding.

Tell the doctor about all the medicines the patient takes, including prescription and non-prescription medicines, vitamins, and herbal products. Donepezil hydrochloride tablets and other medicines may affect each other.

Be particularly sure to tell the doctor if the patient takes 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 the patient’s medicines are NSAIDs. Taking NSAIDs and donepezil hydrochloride tablets together may make the patient more likely to get stomach ulcers.

Donepezil hydrochloride tablets taken with certain medicines used for anesthesia may cause side effects. Tell the responsible doctor or dentist that the patient takes donepezil hydrochloride tablets before the patient has:

surgery
medical procedures
dental surgery or procedures.

Know the medicines that the patient takes. Keep a list of all the patient’s medicines. Show it to the doctor or pharmacist before the patient starts a new medicine.

How should the patient take donepezil hydrochloride tablets?

Give donepezil hydrochloride tablets exactly as prescribed by the doctor. Do not stop donepezil hydrochloride tablets or change the dose yourself. Talk with the doctor first.
Give donepezil hydrochloride tablets one time each day. Donepezil hydrochloride tablets can be taken with or without food.
If you miss giving the patient a dose of donepezil hydrochloride tablet, just wait. Give only the next dose at the usual time. Do not give 2 doses at the same time.
If donepezil hydrochloride tablet is missed for 7 days or more, talk with the doctor before starting again.
If the patient takes too much donepezil hydrochloride tablets at one time, call the doctor or poison control center, or go to the emergency room right away.

What are the possible side effects of donepezil hydrochloride tablets?

Donepezil hydrochloride tablets may cause the following serious side effects:

slow heartbeat and fainting. This happens more often in people with heart problems. Call the doctor right away if the patient faints while taking donepezil hydrochloride tablets.
more stomach acid. This raises the chance of ulcers and bleeding. The risk is higher for patients who 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 the doctor right away if the patient has:

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 donepezil hydrochloride tablets are:

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

These side effects may get better after the patient takes donepezil hydrochloride tablets for a while. This is not a complete list of side effects with donepezil hydrochloride tablets. For more information, ask the doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should donepezil hydrochloride tablets be stored ?

Store donepezil hydrochloride tablets at room temperature between 68° to 77°F (20° to 25°C).

Keep donepezil hydrochloride tablets and all medicines out of the reach of children.

General information about donepezil hydrochloride tablets

Medicines are sometimes prescribed for conditions that are not mentioned in this Patient Information Leaflet. Do not use donepezil hydrochloride tablets for a condition for which it was not prescribed. Do not give donepezil hydrochloride tablets to people other than the patient, even if they have the same symptoms as the patient, as it may harm them.

This leaflet summarizes the most important information about donepezil hydrochloride tablets. If you would like more information talk with the patient’s doctor. You can ask your pharmacist or doctor for information about donepezil hydrochloride tablets that is written for health professionals. For more information about donepezil hydrochloride tablets, call Sandoz Inc., at 1-800-525-8747.

What are the ingredients in donepezil hydrochloride tablets?

Active ingredient: donepezil hydrochloride

Inactive ingredients: lactose monohydrate, cornstarch, microcrystalline cellulose, and magnesium stearate. The film coating contains talc, polyvinyl alcohol, polyethylene glycol, titanium dioxide and lecithin. Additionally, the 10 mg tablet contains yellow iron oxide (synthetic) as a coloring agent.

Manufactured By:
Sandoz, Inc.
506 Carnegie Center, Suite 400
Princeton, NJ 08805

Distributed by:
McKesson Packaging Services
a business unit of McKesson Corporation
7101 Weddington Rd., Concord, NC 28027

IS-4014621

September 2014

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