Rivastigmine

Generic name: Rivastigmine

Trade name: Exelon

Full names: Rivastigmine transdermal patch, Exelon, Rivastigmine, Exelon

Indications:

Symptomatic treatment of mild to moderately severe Alzheimer's disease dementia.

Dosage:

Treatment should be initiated and supervised by a physician experienced in the diagnosis and treatment of Alzheimer's disease dementia. Diagnosis should be made according to current guidelines. Similar to any treatment started in people with dementia, treatment with rivastigmine should only be started if there is a caregiver available to regularly manage and monitor the treatment.

Initial dose

Start treatment at 4.6 mg/24 hours.

Maintenance dose

After at least 4 weeks of treatment, if well tolerated as directed by the attending physician, the dose of 4.6 mg/24 hours should be increased to 9.5 mg/24 hours, the recommended daily effective dose, and should be continued until the patient continues to demonstrate treatment benefit.

Can be upgraded

9.5 mg/24 hours is the recommended daily effective dose and should be continued as long as patients continue to demonstrate therapeutic benefit. If well tolerated and only after at least 6 months of treatment at 9.5 mg/24 hours, the treating physician may consider increasing the dose to 13.3 mg/24 hours in patients who have demonstrated significant cognitive deterioration (e.g., decreased MMSE) and/or functional decline (based on physician judgment), whereas the recommended daily effective dose is 9.5 mg/24 hours.

The clinical benefit of rivastigmine should be periodically reassessed. Discontinuation should also be considered when evidence of therapeutic efficacy at the optimal dose no longer exists.

If gastrointestinal adverse reactions are observed, treatment should be temporarily interrupted until these adverse reactions subside. Transdermal patch therapy can be resumed at the same dose if treatment is not interrupted for more than three days. Otherwise treatment should be restarted at 4.6 mg/24 hours.

Switching from Capsules or Oral Solution to Transdermal Patch

Based on comparable exposure to oral and transdermal rivastigmine, patients receiving Exelon capsules or oral solution may be switched to the Exelon transdermal patch as follows:

Patients taking oral rivastigmine 3 mg/day may be switched to the 4.6 mg/24 hour transdermal patch.

Patients taking rivastigmine 6 mg/day orally can switch to a 4.6 mg/24-hour transdermal patch.

Patients who are stable and well tolerated by oral rivastigmine at 9 mg/day can switch to the 9.5 mg/24-hour transdermal patch. If the 9 mg/day oral dose is unstable and well tolerated, it is recommended to switch to the 4.6 mg/24 hour transdermal patch.

Patients taking oral rivastigmine 12 mg/day can switch to a 9.5 mg/24-hour transdermal patch.

After switching to the 4.6 mg/24 hour transdermal patch, if well tolerated after at least 4 weeks of treatment, the 4.6 mg/24 hour dose should be increased to 9.5 mg/24 hours, which is the recommended effective dose.

It is recommended that the first transdermal patch be used the day after the last oral dose.

Specifications:

Exelon 4.6 mg/24 hours 4.6 mg

Exelon 9.5 mg/24 hours 9.5 mg

Exelon 13.3 mg/24 hours 13.3 mg

Adverse Reactions:

The most common adverse reactions (less than 5% higher than placebo): nausea, vomiting and diarrhea.

Contraindications:

Hypersensitivity to the active substance rivastigmine, other carbamate derivatives, or any of the listed excipients.

Past history of application site reactions is suggestive of rivastigmine patch allergic contact dermatitis.

Note:

Hospitalizations and rarely deaths have been reported due to the simultaneous application of multiple patches. Ensure that patients or caregivers receive instructions on appropriate dosage and administration.

Gastrointestinal Adverse Reactions: May include severe nausea, vomiting, diarrhea, anorexia/loss of appetite, and weight loss and may result in treatment discontinuation. Dehydration can be caused by prolonged vomiting or diarrhea and can be associated with serious consequences.

Application site reactions may occur with esrentigmine patches: If there is evidence of a more intense local reaction (e.g., increased dermatitis, edema, papules, blisters), and if symptoms do not significantly improve within 48 hours after patch removal, the application site reaction spreads beyond the patch, discontinue treatment.

Storage:

Do not store above 25°C.

Keep the transdermal patch in the sachet until use.

Mechanism of Action:

Rivastigmine is a carbamate-type acetylcholinesterase inhibitor thought to promote cholinergic neurotransmission by slowing the degradation of acetylcholine released by functionally intact cholinergic neurons. Therefore, rivastigmine may have ameliorating effects on cholinergic-mediated cognitive deficits in dementia associated with Alzheimer's disease.

Rivastigmine interacts with its target enzyme by forming a covalently bound complex that temporarily inactivates the enzyme. In healthy young men, an oral 3 mg dose reduced acetylcholinesterase (AChE) activity in CSF by approximately 40% within the first 1.5 hours after administration. Approximately 9 hours after maximal inhibition is achieved, enzyme activity returns to baseline levels. In patients with Alzheimer's disease, oral rivastigmine inhibited AChE in cerebrospinal fluid in a dose-dependent manner up to 6 mg twice daily, which was the highest dose tested. Inhibition of butyrylcholinesterase activity in the CSF of 14 Alzheimer's disease patients treated with oral rivastigmine was similar to inhibition of AChE activity.

Safety and efficacy:

Foreign clinical trial studies show that using Exelon® Patch once a day can improve the memory and ability to maintain daily activities of Alzheimer's patients. The therapeutic effect of the low-dose patch administration group is equivalent to that of the oral administration group, but the incidence of nausea and vomiting in the oral administration group is three times that of the patch administration group. The high-dose patch administration group had slightly higher cognitive scores than the oral administration group, and the incidence of adverse reactions was similar. More than 70% of caregivers believe that patches are better than capsules, as patients are more willing to cooperate with doctors' instructions and have less interference with daily life. Transdermal patches could become an effective new treatment for Alzheimer's disease.