Source: European Medicines Agency (EU) Revision Year: 2018 Publisher: Novartis Europharm Limited, Vista Building, Elm Park, Merrion Road, Dublin 4, Ireland
Symptomatic treatment of mild to moderately severe Alzheimer’s dementia.
Treatment should be initiated and supervised by a physician experienced in the diagnosis and treatment of Alzheimer’s dementia. Diagnosis should be made according to current guidelines. 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.
| Transdermal patches | Rivastigmine in vivo release rates per 24 h |
|---|---|
| Exelon 4.6 mg/24 h | 4.6 mg |
| Exelon 9.5 mg/24 h | 9.5 mg |
| Exelon 13.3 mg/24 h | 13.3 mg |
Treatment is started with 4.6 mg/24 h.
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.
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 (e.g. decrease in the MMSE) and/or functional decline (based on physician judgement) while on the recommended daily effective dose of 9.5 mg/24 h (see section 5.1).
The clinical benefit of rivastigmine should be reassessed on a regular basis. Discontinuation should also be considered when evidence of a therapeutic effect at the optimal dose is no longer present.
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.
Based on comparable exposure between oral and transdermal rivastigmine (see section 5.2), patients treated with Exelon capsules or oral solution can be switched to Exelon transdermal patches as follows:
After switching to 4.6 mg/24 h transdermal patches, provided these are well tolerated after a minimum of four weeks of treatment, the dose of 4.6 mg/24 h should be increased to 9.5 mg/24 h, which is the recommended effective dose.
It is recommended to apply the first transdermal patch on the day following the last oral dose.
There is no relevant use of Exelon in the paediatric population in the treatment of Alzheimer’s disease.
Particular caution should be exercised in titrating patients with body weight below 50 kg above the recommended effective dose of 9.5 mg/24 h (see section 4.4). They may experience more adverse reactions and may be more likely to discontinue due to adverse reactions.
Due to increased exposure in mild to moderate hepatic impairment as observed with the oral formulation, 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. Patients with severe hepatic impairment have not been studied. Particular caution should be exercised in titrating these patients (see sections 4.4 and 5.2).
No dose adjustment is necessary for patients with renal impairment (see section 5.2).
Transdermal patches should be applied once a day 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.
Patients and caregivers should be instructed on important administration instructions:
Most cases of accidental overdose of oral rivastigmine have not been associated with any clinical signs or symptoms and almost all of the patients concerned continued rivastigmine treatment 24 hours after the overdose.
Cholinergic toxicity has been reported with muscarinic symptoms that are observed with moderate poisonings such as miosis, flushing, digestive disorders including abdominal pain, nausea, vomiting and diarrhoea, bradycardia, bronchospasm and increased bronchial secretions, hyperhidrosis, involuntary urination and/or defecation, lacrimation, hypotension and salivary hypersecretion.
In more severe cases nicotinic effects might develop such as muscular weakness, fasciculations, seizures and respiratory arrest with possible fatal outcome.
Additionaly there have been post-marketing cases of dizziness, tremor, headache, somnolence, confusional state, hypertension, hallucinations and malaise. Overdose with Exelon transdermal patch resulting from misuse/dosing errors (application of multiple patches at a time) has been reported in the post-marketing setting and rarely in clinical trials.
As rivastigmine has a plasma half-life of about 3.4 hours and a duration of acetylcholinesterase inhibition of about 9 hours, it is recommended that in cases of asymptomatic overdose all Exelon transdermal patches should be removed immediately and no further transdermal patch should be applied for the next 24 hours. In overdose accompanied by severe nausea and vomiting, the use of antiemetics should be considered. Symptomatic treatment for other adverse reactions should be given as necessary.
In massive overdose, atropine can be used. An initial dose of 0.03 mg/kg intravenous atropine sulphate is recommended, with subsequent doses based on clinical response. Use of scopolamine as an antidote is not recommended.
2 years.
Do not store above 25°C.
Keep the transdermal patch in the sachet until use.
Each child-resistant sachet is made of a paper/polyester/aluminium/polyacrylonitrile multilaminated material. One sachet contains one transdermal patch.
Exelon 4.6 mg/24 h transdermal patch: Available in packs containing 7, 30 or 42 sachets and in multipacks containing 60, 84 or 90 sachets.
Exelon 9.5 mg/24 h transdermal patch: Available in packs containing 7, 30 or 42 sachets and in multipacks containing 60, 84 or 90 sachets.
Exelon 13.3 mg/24 h transdermal patch: Available in packs containing 7 or 30 sachets and in multipacks containing 60 or 90 sachets.
Not all pack sizes may be marketed.
Used transdermal patches should be folded in half, with the adhesive side inwards, placed in the original sachet and discarded safely and out of the reach and sight of children. Any used or unused transdermal patches should be disposed of in accordance with local requirements or returned to the pharmacy.
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