Prescribing Information
Please refer to the Zeyzelf Summary of Product Characteristics (SmPC) for full details.
Presentations: Transdermal patches each releasing either 4.6 mg or 9.5mg of rivastigmine per 24 hours. Indication: Symptomatic treatment of mild to moderately severe Alzheimer’s dementia. Dosage and administration: Zeyzelf twice weekly transdermal patches should be applied twice weekly on fixed days (after four and three days, respectively). Treatment should be initiated and supervised by a physician experienced in the diagnosis and treatment of Alzheimer’s dementia. Similar to any treatment initiated in patients with dementia, therapy with rivastigmine should only be started if a caregiver is available to regularly administer and monitor the treatment. Dosage: Initial dose: Treatment is started with 4.6 mg/24 h. Maintenance dose: After a minimum of four weeks of treatment and if well tolerated according to the treating physician, the dose of 4.6 mg/24 h should be increased to 9.5 mg/24 h, the daily recommended effective dose, which should be continued for as long as the patient continues to demonstrate therapeutic benefit. Dose escalation: 9.5 mg/24 h is the recommended daily effective dose which should be continued for as long as the patient continues to demonstrate therapeutic benefit. If well tolerated and only after a minimum of six months of treatment at 9.5 mg/24 h, the treating physician may consider increasing the dose to 13.3 mg/24 h in patients who have demonstrated a meaningful cognitive deterioration while on the recommended daily effective dose of 9.5 mg/24 h. The 13.3 mg/24 h dose strength cannot be achieved with Zeyzelf twice weekly. Treatment should be temporarily interrupted if gastrointestinal adverse reactions are observed until these adverse reactions resolve. Transdermal patch treatment can be resumed at the same dose if treatment is not interrupted for more than three days. Otherwise treatment should be re-initiated with 4.6 mg/24 h. Switching from capsules or oral solution to transdermal patches: Refer to SmPC. Special populations: Patients with body weight below 50 kg: Particular caution should be exercised in titrating patients with body weight below 50 kg above the recommended effective dose of 9.5mg/24 h. Hepatic impairment: In mild to moderate hepatic impairment dosing recommendations to titrate according to individual tolerability should be closely followed. Patients with clinically significant hepatic impairment may experience more dose-dependent adverse reactions. have not been studied. Particular caution should be exercised in titrating patients with severe hepatic impairment. Renal impairment: No dose adjustment is necessary for patients with renal impairment. Method of administration: Zeyzelf twice weekly is for transdermal use. Transdermal patches should be applied twice weekly on fixed days (after four and three days, respectively) to clean, dry, hairless, intact healthy skin on the upper or lower back, upper arm or chest, in a place which will not be rubbed by tight clothing. It is not recommended to apply the transdermal patch to the thigh or to the abdomen due to decreased bioavailability of rivastigmine observed when the transdermal patch is applied to these areas of the body. The transdermal patch should not be applied to skin that is red, irritated or cut. Reapplication to the exact same skin location within 14 days should be avoided to minimise the potential risk of skin irritation. To prevent interference with the adhesive properties of the transdermal patch, no cream, lotion or powder should be applied to the skin area where the medicinal product is to be applied. Patients and caregivers should be instructed on important administration instructions: Refer to SmPC. Common Adverse Reactions: Application site skin reactions (usually mild to moderate application site erythema) are the most frequent adverse reactions observed with the use of rivastigmine transdermal patch. The next most common adverse reactions are gastrointestinal in nature including nausea and vomiting. List of common adverse reactions reported in 1,670 patients with Alzheimer’s dementia treated in randomised, double-blind, placebo and active-controlled clinical studies with rivastigmine transdermal patches for a duration of 24-48 weeks and from post-marketing data: Urinary tract infection. Anorexia, decreased appetite Anxiety, depression, delirium, agitation. Headache, syncope, dizziness. Nausea, vomiting, diarrhoea, dyspepsia, abdominal pain. Rash. Urinary incontinence. Application site skin reactions (application site erythema, pruritus, oedema, dermatitis, irritation), asthenic conditions (e.g. fatigue, asthenia), pyrexia, weight decreased. Please consult the full SmPC for other adverse reactions. Contraindications: Hypersensitivity to the active substance rivastigmine, to other carbamate derivatives or to any other excipients. Previous history of application site reactions suggestive of allergic contact dermatitis with rivastigmine patch. Warnings and Precautions: Zeyzelf twice weekly transdermal patches are multiday patches. Care should be exercised and application of more than one patch at the same time should be avoided. The incidence and severity of adverse reactions generally increase with increasing doses, particularly at dose changes. If treatment is interrupted for more than three days, it should be re-initiated with 4.6 mg/24 h. Misuse of the medicinal product and dosing errors resulting in overdose: Misuse of the medicinal product and dosing errors with rivastigmine transdermal patch have resulted in serious adverse reactions; some cases have required hospitalisation, and rarely led to death. Patients and their caregivers must be instructed on important administration instructions for rivastigmine transdermal patch. Gastrointestinal disorders: Gastrointestinal disorders such as nausea, vomiting and diarrhoea are dose related, and may occur when initiating treatment and/or increasing the dose. These adverse reactions occur more commonly in women. Weight loss: Patients with Alzheimer’s disease may lose weight whilst taking cholinesterase inhibitors, including rivastigmine. The patient’s weight should be monitored during therapy. Bradycardia: Rivastigmine may cause bradycardia which constitutes a risk factor in the occurrence of torsade de pointes, predominantly in patients with risk factors. Care must be taken when prescribing Zeyzelf twice weekly transdermal patches to patients with sick sinus syndrome or conduction defects (sino-atrial block, atrio-ventricular block); patients with active gastric or duodenal ulcers or patients predisposed to these conditions because rivastigmine may cause increased gastric secretions; patients predisposed to urinary obstruction and seizures because cholinomimetics may induce or exacerbate these diseases; patients with a history of asthma or obstructive pulmonary disease. Skin application site reactions: Skin application site reactions may occur with rivastigmine patch and are usually mild or moderate in intensity. Patients and caregivers should be instructed accordingly. These reactions are not in themselves an indication of sensitisation. However, use of rivastigmine patch may lead to allergic contact dermatitis. In these cases, treatment should be discontinued. It is possible that some patients sensitised to rivastigmine by exposure to rivastigmine patch may not be able to take rivastigmine in any form. There have been rare post-marketing reports of patients experiencing allergic dermatitis (disseminated) when administered rivastigmine irrespective of the route of administration (oral, transdermal). In these cases, treatment should be discontinued. Other warnings and precautions: Rivastigmine may exacerbate or induce extrapyramidal symptoms. Contact with the eyes should be avoided after handling Zeyzelf twice weekly transdermal patches. Hands should be washed with soap and water after removing the patch. In case of contact with eyes or if the eyes become red after handling the patch, rinse immediately with plenty of water and seek medical advice if symptoms do not resolve. Interactions: Refer to the SmPC for full details. Rivastigmine may exaggerate the effects of succinylcholine-type muscle relaxants during anaesthesia. Caution is recommended when selecting anaesthetic agents. Possible dose adjustments or temporarily stopping treatment can be considered if needed. Rivastigmine should not be given concomitantly with other cholinomimetic substances. Rivastigmine might interfere with the activity of anticholinergic medicinal products (e.g. oxybutynin, tolterodine). Caution should be exercised when rivastigmine is combined with beta-blockers and other bradycardia medicinal products (e.g.class III antiarrhythmic medicinal products, calcium channel antagonists, digitalis glycoside, pilocarpin). The combination of rivastigmine with torsades de pointes-inducing medicinal products should be observed with caution and clinical monitoring (ECG) may also be required. Effects on ability to drive and use machines: Alzheimer’s disease may cause gradual impairment of driving performance or compromise the ability to use machines. Marketing Authorisation Number and Basic NHS Price: Zeyzelf twice weekly 4.6 mg/24 h transdermal patch PLGB 50827/0023 (8 patches: £35.09); Zeyzelf twice weekly 9.5 mg/24 h transdermal patch PLGB 50827/0024 (8 patches: £35.09). Marketing Authorisation Holder: Luye Pharma Ltd 40 Occam Road, Guildford, GU2 7YG, United Kingdom. Legal Category: POM. Further information: Luye Pharma Ltd., 40 Occam Road, Guildford, GU2 7YG. info@luyepharma.co.uk. Date of preparation: February 2024. Item number: UK-ZEY-26
Adverse events should be reported
Reporting forms and information can be found at https://yellowcard.mhra.gov.uk/.
Adverse events should also be reported to Luye Pharma Ltd at safety@luyepharma.co.uk.