Exelon Patch

/ Novartis

Initial dose and dose titration to the effective dose: Treatment is started with Exelon Patch 5 once a day. After a minimum of four weeks of treatment and if well tolerated, this dose should be increased to Exelon Patch 10, the recommended effective dose, which can be continued for as long as a therapeutic benefit for the patient exists. Individual responses to rivastigmine may vary and some patients may derive additional benefit from higher doses. Subsequent increases to Exelon Patch 15 should always be based on good tolerability of the current dose and may be considered only after a minimum of four weeks of treatment at each dose level.
Severe dementia of the Alzheimer’s type
Initial dose and dose titration to the effective dose: Treatment is started with Exelon Patch 5 once a day. Subsequently the dose should be increased to Exelon Patch 10 and then to Exelon Patch 15 which is the demonstrated effective dose. These dose increases should always be based on good tolerability of the current dose and may be considered only after a minimum of four weeks of treatment at each dose level.
Interruption of treatment: Treatment should be temporarily interrupted if gastrointestinal adverse effects and/or worsening of existing extrapyramidal symptoms (e.g. tremor) are observed until these adverse effects resolve. 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 Exelon Patch 5. If adverse effects persist on re-initiation of therapy, the dose should be temporarily reduced to the previous well-tolerated dose.
Switching from capsules or oral solution: Patients treated with Exelon capsules or oral solution may be switched to Exelon patches as follows: A patient who is on a dose of < = 6 mg per day oral rivastigmine can be switched to Exelon Patch 5. A patient who is on a dose of 9 or 12 mg per day oral rivastigmine may be directly switched to Exelon Patch 10. It is recommended to apply the first patch on the day following the last oral dose.
Special population
Patients with body weight below 50 kg: Caution should be exercised in titrating these patients as they may experience more adverse reactions. Carefully titrate and monitor these patients for adverse reactions (e.g. excessive nausea or vomiting) and consider reducing the dose if such adverse reactions develop.
Renal impairment: No dose adjustment is necessary for patients with renal impairment.
Paediatric patients: Children and adolescents (age below 18 years): Rivastigmine is not recommended for use in children.
Method of administration: Exelon 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. The patch should be replaced by a new one after 24 hours.
Important administration instructions (patients and caregivers should be instructed): The previous day’s patch must be removed before applying a new one. The patch should be replaced by a new one after 24 hours. Only one patch should be worn at a time. The patch should not be applied to skin that is red, irritated or cut. It is recommended to change the application site daily to avoid potential irritation, although consecutive patches can be applied to the same general anatomic site (e.g., another spot on the upper back). The patch should be pressed down firmly for at least 30 seconds using the palm of the hand until the edges stick well. If the patch falls off, a new one should be applied for the rest of the day, then it should be replaced at the same time as usual the next day. The patch can be used in everyday situations, including bathing and during hot weather. The patch should not be exposed to any external heat sources (e.g. excessive sunlight, saunas, solarium) for long periods of time. The patch should not be cut into pieces.
For full details see prescribing information.

Exelon patch 5, Exelon patch 10: Treatment of mild to moderate dementia of the Alzheimer’s type.
Exelon patch 15: For the treatment of dementia of the Alzheimer’s type (AD). Efficacy has been demonstrated in patients with mild, moderate and severe Alzheimer’s disease.

The use of Exelon is contraindicated in patients with: Known hypersensitivity to rivastigmine, to other carbamate derivatives or to the excipients of the formulation. Previous history of application site reactions suggestive of allergic contact dermatitis with rivastigmine transdermal patch.

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 Wxelon patch 5.
Misuse of the medicinal product and dosing errors resulting in overdose:
Misuse of the medicinal product and dosing errors with Exelon transdermal patch have resulted in serious adverse reactions; some cases have required hospitalisation, and rarely led to death. Most cases of misuse of the medicinal product and dosing errors have involved not removing the old patch when putting on a new one and the use of multiple patches at the same time. Patients and their caregivers must be instructed on important administration instructions for Exelon 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. Patients who show signs or symptoms of dehydration resulting from prolonged vomiting or diarrhoea can be managed with intravenous fluids and dose reduction or discontinuation if recognised and treated promptly. Dehydration can be associated with serious outcomes.
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 with Exelon transdermal patches.
Bradycardia: Rivastigmine may cause bradycardia which constitutes a risk factor in the occurrence of torsade de pointes, predominantly in patients with risk factors. Caution is advised in patients at higher risk of developing torsade de pointes; for example, those with uncompensated heart failure, recent myocardial infarction, bradyarrhythmias, a predisposition to hypokalaemia or hypomagnesaemia, or concomitant use with medicinal products known to induce QT prolongation and/or torsade de pointes.
Other adverse reactions:
Care must be taken when prescribing Exelon transdermal patches:
– to patients with sick sinus syndrome or conduction defects (sino-atrial block, atrio-ventricular block);
– to patients with active gastric or duodenal ulcers or patients predisposed to these conditions because rivastigmine may cause increased gastric secretions;
– to patients predisposed to urinary obstruction and seizures because cholinomimetics may induce or exacerbate these diseases;
– to 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.
Allergic contact dermatitis should be suspected if application site reactions spread beyond the patch size, if there is evidence of a more intense local reaction (e.g. increasing erythema, oedema, papules, vesicles) and if symptoms do not significantly improve within 48 hours after patch removal. In these cases, treatment should be discontinued.
Patients who develop application site reactions suggestive of allergic contact dermatitis to rivastigmine patch and who still require rivastigmine treatment should only be switched to oral rivastigmine after negative allergy testing and under close medical supervision. 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 Exelon 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.
Special populations:
– Patients with body weight below 50 kg may experience more adverse reactions and may be more likely to discontinue due to adverse reactions. Carefully titrate and monitor these patients for adverse reactions (e.g. excessive nausea or vomiting) and consider reducing the maintenance dose to the 4.6 mg/24 h Exelon patch 5, if such adverse reactions develop.
– Hepatic impairment: Patients with clinically significant hepatic impairment may experience more adverse reactions. Dosing recommendations to titrate according to individual tolerability must be closely followed. Patients with severe hepatic impairment have not been studied. Particular caution must be exercised in titrating these patients.

Application site skin reactions (usually mild to moderate application site erythema), are the most frequent adverse reactions observed with the use of Exelon transdermal patch. The next most common adverse reactions are gastrointestinal in nature including nausea and vomiting.
See prescribing information for full details.

No specific interaction studies have been performed with Exelon transdermal patches.
As a cholinesterase inhibitor, 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.
In view of its pharmacodynamic effects and possible additive effects, rivastigmine should not be given concomitantly with other cholinomimetic substances. Rivastigmine might interfere with the activity of anticholinergic medicinal products (e.g. oxybutynin, tolterodine).
Additive effects leading to bradycardia (which may result in syncope) have been reported with the combined use of various beta-blockers (including atenolol) and rivastigmine. Cardiovascular beta-blockers are expected to be associated with the greatest risk, but reports have also been received in patients using other beta-blockers. Therefore, caution should be exercised when rivastigmine is combined with beta-blockers and also other bradycardia agents (e.g.class III antiarrhythmic agents, calcium channel antagonists, digitalis glycoside, pilocarpin).
Since bradycardia constitutes a risk factor in the occurrence of torsades de pointes, the combination of rivastigmine with torsades de pointes-inducing medicinal products such as antipsychotics i.e. some phenothiazines (chlorpromazine, levomepromazine), benzamides (sulpiride, sultopride, amisulpride, tiapride, veralipride), pimozide, haloperidol, droperidol, cisapride, citalopram, diphemanil, erythromycin IV, halofantrin, mizolastin, methadone, pentamidine and moxifloxacine should be observed with caution and clinical monitoring (ECG) may also be required.
No pharmacokinetic interaction was observed between oral rivastigmine and digoxin, warfarin, diazepam or fluoxetine in studies in healthy volunteers. The increase in prothrombin time induced by warfarin is not affected by administration of oral rivastigmine. No untoward effects on cardiac conduction were observed following concomitant administration of digoxin and oral rivastigmine.
Concomitant administration of rivastigmine with commonly prescribed medicinal products, such as antacids, antiemetics, antidiabetics, centrally acting antihypertensives, calcium channel blockers, inotropic agents, antianginals, non-steroidal anti-inflammatory agents, oestrogens, analgesics, benzodiazepines and antihistamines, was not associated with an alteration in the kinetics of rivastigmine or an increased risk of clinically relevant untoward effects.
According to its metabolism, metabolic interactions with other medicinal products appear unlikely, although rivastigmine may inhibit the butyrylcholinesterase mediated metabolism of other substances.

Pregnancy: In pregnant animals, rivastigmine and /or metabolites crossed the placenta. It is not known if this occurs in humans. No clinical data on exposed pregnancies are available. In peri/postnatal studies in rats, an increased gestation time was observed. Rivastigmine should not be used during pregnancy unless clearly necessary.
Lactation: In animals, rivastigmine is excreted in milk. It is not known if rivastigmine is excreted into human milk. Therefore, women on rivastigmine should not breast-feed.

Symptoms: 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.
Management: 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.

Incompatibilities: To prevent interference with the adhesive properties of the patch, no cream, lotion or powder should be applied to the skin area where the Exelon transdermal patch is to be applied.
Storage: Store below 25°C. Keep the patch in the sachet until use.