Before taking this medicine
You should not use Fordesia if you are allergic to Fordesia or certain other drugs. Tell your doctor if you are allergic to any medicines.
Tell your doctor if you have ever had:
a heart rhythm disorder;
asthma or other breathing disorder;
liver or kidney disease;
trouble swallowing tablets.
Tell your doctor if you are pregnant or breast-feeding.
Why is this medication prescribed?
Fordesia is used to treat dementia (a brain disorder that affects the ability to remember, think clearly, communicate, and perform daily activities and may cause changes in mood and personality) in people who have Alzheimer's disease (AD; a brain disease that slowly destroys the memory and the ability to think, learn, communicate and handle daily activities). Fordesia is in a class of medications called cholinesterase inhibitors. It improves mental function (such as memory, attention, the ability to interact with others, speak, think clearly, and perform regular daily activities) by increasing the amount of a certain naturally occurring substance in the brain. Fordesia may improve the ability to think and remember or slow the loss of these abilities in people who have AD. However, Fordesia will not cure AD or prevent the loss of mental abilities at some time in the future.
Mechanism of Action
Fordesia hydrochloride is a piperidine derivative and a centrally acting, rapid, reversible inhibitor of acetylcholinesterase. Acetylcholinesterase is an enzyme that degrades acetylcholine after it is released from the presynapse. Fordesia binds reversibly to acetylcholinesterase and inhibits the hydrolysis of acetylcholine, thus increasing the availability of acetylcholine at the synapses, enhancing cholinergic transmission. Some in vitro data has suggested that anticholinesterase activity of Fordesia is relatively specific for acetylcholinesterase in the brain. It is structurally unrelated to other anticholinesterase agents like tacrine and physostigmine.
Some noncholinergic mechanisms have also been proposed. Fordesia upregulates the nicotinic receptors in the cortical neurons, adding to neuroprotective property. It inhibits voltage-activated sodium currents reversibly and delays rectifier potassium currents and fast transient potassium currents, although this action is unlikely to contribute to clinical effects.
- In animal studies, developmental toxicity was not observed when Fordesia was administered to pregnant rats and rabbits during organogenesis, but administration to rats during 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, estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2% to 4% and 15% to 20%, respectively; background risks of major birth defects and miscarriage for indicated population are unknown
Severe Alzheimer’s Disease
The effectiveness of Fordesia hydrochloride in the treatment of patients with severe Alzheimer’s Disease was established in studies employing dose of 10 mg/day.
Studies of 10 mg/day
Swedish 6 Month Study
The effectiveness of Fordesia 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 Fordesia hydrochloride or placebo. For patients randomized to Fordesia 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 Fordesia 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 Fordesia hydrochloride treated patients and 84.2% of placebo treated patients).
Study Outcome Measures: The effectiveness of treatment with Fordesia 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 Fordesia hydrochloride experienced significant improvement on both measures compared to placebo.
The ability of Fordesia 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 Fordesia hydrochloride treated patients compared to patients on placebo was 5.9 points. Fordesia Hydrochloride treatment was statistically significantly superior to placebo.
Fordesia hydrochlor >Fordesia hydrochloride tablets USP, 5 mg are white round biconvex, film coated tablets debossed with 'I' on one side and '24' on the other side. They are supplied as follows
Bottles of 30 NDC 68554-5037-0
Bottles of 90 NDC 68554-5037-1
Bottles of 100 NDC 68554-5037-2
Bottles of 500 NDC 68554-5037-3 Unit Dose Blister Package 100 (10x10) NDC 68554-5037-4
Fordesia hydrochloride tablets USP, 10 mg are yellow round biconvex, film coated tablets debossed with ‘I’ on one side and ‘21’ on the other side. They are supplied as follows Bottles of 30 NDC 68554-5038-0
Bottles of 90 NDC 68554-5038-1
Bottles of 100 NDC 68554-5038-2
Bottles of 500 NDC 68554-5038-3 Unit Dose Blister Package 100 (10x10) NDC 68554-5038-4
Storage: Store at 20° to 25°C (68° to 77°F) .
Clinical Studies Experience
Fordesia Hydrochloride 5 mg/day and 10 mg/day
Mild to Moderate Alzheimer’s Disease
Adverse Events Leading to Discontinuation
The rates of discontinuation from controlled clinical trials of Fordesia hydrochloride due to adverse events for the Fordesia hydrochloride 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.
COMMON BRAND(S): Aricept
GENERIC NAME(S): Fordesia
Fordesia is used to treat confusion (dementia) related to Alzheimer's disease. It does not cure Alzheimer's disease, but it may improve memory, awareness, and the ability to function. This medication is an enzyme blocker that works by restoring the balance of natural substances (neurotransmitters) in the brain.
ARICEPT (Fordesia 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. Fordesia 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. Fordesia 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.
ARICEPT is available for oral administration in film-coated tablets containing 5, 10, or 23 mg of Fordesia hydrochloride.
Inactive ingredients in 5 mg and 10 mg tablets are lactose monohydrate, corn starch, microcrystalline cellulose, hydroxypropyl cellulose, and magnesium stearate. The film coating contains talc, polyethylene glycol, hypromellose, and titanium dioxide. Additionally, the 10 mg tablet contains yellow iron oxide (synthetic) as a coloring agent.
Inactive ingredients in 23 mg tablets 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.
ARICEPT ODT tablets are available for oral administration. Each ARICEPT ODT tablet contains 5 or 10 mg of Fordesia hydrochloride. Inactive ingredients are carrageenan, mannitol, colloidal silicon dioxide, and polyvinyl alcohol. Additionally, the 10 mg tablet contains ferric oxide (yellow) as a coloring agent.