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Zeyzelf® twice weekly rivastigmine transdermal patch is the first of its kind in the UK that does not need daily application

Zeyzelf® twice weekly rivastigmine transdermal patch is indicated for the symptomatic treatment of mild to moderately severe Alzheimer’s dementia and it can help reduce symptoms and lessen the care burden for patients and their caregivers. It is the first ever rivastigmine patch available in the UK that does not need daily application.

 

Alzheimer’s disease (AD), which affects multiple brain functions, is the most common form of dementia and it is a progressive condition, with symptoms developing gradually over many years and eventually becoming more severe (NHS 2024).

Zeyzelf® is bioequivalent to the originator Exelon (daily) rivastigmine transdermal patch (Schurad et al 2022), but because it is applied on fixed days, twice a week (for example Monday and Friday), it can be easier to administer and help the patient and caregiver maintain adherence (Luye Pharma Ltd 2024). Zeyzelf® is available in two strengths – 4.6mg/24hr is the starting strength and, if this is well tolerated for at least four weeks, patients can be switched to 9.5mg/24hr.

Below is a schematic representation of patch application. 

Rivastigmine therapy in Alzheimer’s dementia

The active substance of Zeyzelf® is rivastigmine, which belongs to a class of substances called cholinesterase inhibitors. In patients with AD, certain nerve cells die in the brain, resulting in low levels of the neurotransmitter acetylcholine (a substance that allows nerve cells to communicate with each other). Rivastigmine works by blocking the enzymes that break down acetylcholine: acetylcholinesterase and butyrylcholinesterase. By blocking these enzymes, rivastigmine allows levels of acetylcholine to be increased in the brain, helping to reduce the symptoms of Alzheimer’s.

Rivastigmine not only offers improvement in Alzheimer’s symptoms, but may also delay disease progression, allowing patients to remain independent for longer (Farlow 2002). It is also an option for Alzheimer’s patients for whom minimising interaction with other medications is a priority, as rivastigmine has low potential for drug-drug interaction (Luye Pharma Ltd 2024, Grossberg et al 2000). This lack of interaction has been confirmed with commonly prescribed medications in elderly Alzheimer’s patients including, anti-hypertensives, calcium-channel blockers, digoxin, diabetic drugs, nonsteroidal anti-inflammatory drugs, and oestrogens (Grossberg et al 2000).

The advantages of transdermal over oral delivery of rivastigmine

Transdermal patches offer superior tolerability vs orally administered rivastigmine (Winblad et al 2007)*. Fewer patients reported nausea (7.2% vs 23.1%) and vomiting (6.2% vs 17%) on transdermal patches compared with oral rivastigmine (Winblad et al 2007). Transdermal administration also delivers reduction in certain side effects vs oral rivastigmine due to:

• Avoiding the first pass effects (Sozio et al 2012)
• Lowered maximum plasma concentration (Cmax) and prolonged time to reach Cmax (Tmax) for the same exposure (Winblad et al 2007).
• Reduced fluctuations of plasma drug levels and continuous delivery (Sozio et al 2012, Winblad et al 2007).

In addition to lower risk of side effects, the transdermal route of administration can provide greater adherence to the treatment regimen and has less risk of dose dumping compared with the oral route. This is especially important because of the increased need for medication in older patients who may have multiple chronic conditions (Vadivelu and Hines 2008).

National Institute for Health and Care Excellence (NICE) guidance includes transdermal rivastigmine patches as a treatment option for patients with dementia (NICE 2018).

Dysphagia is very common in people with Alzheimer’s dementia

Transdermal delivery is useful when elderly patients are unable to tolerate or unwilling to swallow oral medications (Vadivelu and Hines 2008). Difficulty swallowing – known as dysphagia - occurs in AD patients because the disease affects the cortical areas of the brain that control swallowing, which can make eating and drinking more challenging (Mira et al 2022).

The condition is thought to affect between 84% and 93% of people with moderate to severe AD (Mira et al 2022) and in a recent study, 63.9% and 90% of people with mild and moderate Alzheimer’s respectively experienced dysphagia, compared with 40% of cognitively intact people (Güner et al 2023).

Transdermal patches and the importance of skin adhesion

Skin adhesion is one of the most important functional properties for a transdermal patch and is critical to the safety, efficacy and quality of the patch (Wokovich et al 2006). In a study, Zeyzelf® demonstrated better adhesion properties when compared with the Exelon patch, despite the longer dosing intervals (Schurad et al 2022). Almost 95% of Zeyzelf® assessments showed adhesion ≥90% and there were no cases of complete patch detachments (Schurad et al 2022).

Zeyzelf® also has a unique adhesive cover to apply over the patch, that gives security with peace of mind for the patients and their caregivers. The patch cover can be written on, so carers can record details, such as the date and time of application and/or for the patch change and also acts as an easy-to-see visual indicator of adherence.

Below is a picture of a Zeyzelf® patch and Zeyzelf® adhesive cover.

The care burden of dementia

There are currently almost 1 million people in the UK who have dementia (NHS 2023), and it is estimated that up to 1.7 million people could be living with the condition in England and Wales by 2040 (Chen et al 2023).

The cost of dementia is forecast to be £42 billion in 2024, rising to £90 billion by 2040. These costs are made up of healthcare costs, social care costs, costs to unpaid care and quality of life and economic losses (Alzheimer’s Society 2024b). In hospitals alone, a quarter of beds are occupied by people living with dementia who are over 65 (Alzheimer’s Society 2009). The cost of drug prescriptions represents a very small proportion of these costs and reducing the care burden is essential (Alzheimer’s Society 2024a).

Zeyzelf® can potentially reduce carer time, as the patches only need to be changed twice a week, as opposed to every day. In a comparative study comparing single-day rivastigmine patches to rivastigmine capsules, >70% of caregivers preferred the patches to the capsules with respect to ease of use and ease of following the schedule and indicated greater satisfaction overall and less interference with daily life (Blesa et al 2007)**.

Zeyzelf® is priced at £35.09 for 28 days treatment for both the 4.6mg/24hr (starting dose) and the 9.5mg/24hr dose strengths (NHS Business Service Authority 2024).

Zeyzelf® has been launched by Luye Pharma Ltd, who specialise in diseases of the central nervous system (CNS).
For further information about Zeyzelf® click here

Adverse events should be reported

Reporting forms and information can be found here
Adverse events should also be reported to Luye Pharma Ltd at safety@luyepharma.co.uk

For Zeyzelf® prescribing information click here

_{*Data from a study comparing 9.5 mg/24 h daily patch (n=229) vs 12 mg/day oral rivastigmine (n=266)
**The IDEAL study compared rivastigmine once daily patch with the capsule}

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References

• Alzheimer’s Society (2009) Counting the Cost: Caring for People with Dementia on Hospital Wards (Last accessed: October 2024.)
• Alzheimer’s Society (2024a) How Much Does Dementia Cost? (Last accessed: October 2024.)
• Alzheimer’s Society (2024b) What are the Costs of Dementia Diagnosis and Care in the UK? (Last accessed: October 2024.)
• Blesa R, Ballard C, Orgogorzo JM et al (2007) Caregiver preference for rivastigmine patches versus capsules for the treatment of Alzheimer disease. Neurology. 69, 4, Suppl 1, S23–S28. doi: 10.1212/01.wnl.0000281848.25142.11
• Chen Y, Bandosz P, Stoye G et al (2023) Dementia incidence trend in England and Wales, 2002–19, and projection for dementia burden to 2040: analysis of data from the English Longitudinal Study of Ageing. Lancet Public Health. 8, 11, e859-e867. doi: 10.1016/S2468-2667(23)00214-1
• Farlow MR (2002) Do cholinesterase inhibitors slow progression of Alzheimer's disease? International Journal of Clinical Practice: Supplement. 127, 37–44.
• Farlow MR, Small GW, Quarg P et al (2005) Efficacy of rivastigmine in Alzheimer's disease patients with rapid disease progression: results of a meta-analysis. Dementia and Geriatric Cognitive Disorders. 20, 2-3, 192–197. doi: 10.1159/000087301
• Grossberg GT, Stahelin HB, Messina JC et al (2000) Lack of adverse pharmacodynamic drug interactions with rivastigmine and twenty-two classes of medications. International Journal of Geriatric Psychiatry. 15, 3, 242–247. doi: 10.1002/(sici)1099-1166(200003)15:3<242::aid-gps110>3.0.co;2-7
• Güner M, Bas AO, Ceylan S et al (2023) Dysphagia is closely related to frailty in mild-to-moderate Alzheimer's disease. BMC Geriatrics. 23, 1, 304. doi: 10.1186/s12877-023-04020-y
• Luye Pharma Ltd (2024) Summary of Product Characteristics: Zeyzelf® Twice Weekly Transdermal Patch (Last accessed: October 2024.)
• Mira A, Gonçalves R, Rodrigues IR et al (2022) Dysphagia in Alzheimer’s disease: a systematic review. Dementia and Neuropsychologia. 16, 3, 261–269. doi: 10.1590/1980-5764-DN-2021-0073
• National Institute for Health and Care Excellence (2018) Dementia: Assessment, Management and Support for People Living with Dementia and their Carers. NICE Guideline NG97. (Last accessed: October 2024.)
• NHS (2023) What Is Dementia? (Last accessed: October 2024.)
• NHS (2024) Overview: Alzheimer’s Disease. (Last accessed: October 2024)
• NHS Business Service Authority (2024) Drug Tariff. (Last accessed: October 2024.)
• Schurad B, Koch C, Schug B et al (2022) Comparative bioavailability study of a novel multi-day patch formulation of Rivastigmine (twice weekly) with Exelon® transdermal patch (daily): a randomized clinical trial. Current Alzheimer Research. 19, 7, 541-553. doi: 10.2174/1567205019666220823105059
• Sozio P, Cerasa SL, Marinelli L et al (2012)Transdermal donepezil on the treatment of Alzheimer's diseas.  Neuropsychiatric Disease and Treatment. 8, 361–368. doi: 10.2147/NDT.S16089
• Vadivelu N, Hines RL (2008) Management of chronic pain in the elderly: focus on transdermal buprenorphine. Clinical Interventions in Aging. 3, 3, 421–430. doi: 10.2147/cia.s1880
• Winblad B, Grossberg G, Frölich L et al (2007) A 6-month, double-blind, placebo-controlled study of the first skin patch for Alzheimer disease. International Journal of Geriatric Psychiatry. 69, 4, Suppl 1, 14–22. doi: 10.1212/01.wnl.0000281847.17519.e0
• Wokovich AM, Prodduturi S, Doub WH et al (2006) Transdermal drug delivery system (TDDS) adhesion as a critical safety, efficacy and quality attribute. European Journal of Pharmaceutics and Biopharmaceutics. 64, 1, 1-8. doi: 10.1016/j.ejpb.2006.03.009

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UK-ZEY-85 January 2025