Alzheimer disease, mild to moderate:
Oral: Initial: 1.5 mg twice daily; may increase by 3 mg daily (1.5 mg/dose) every 2 weeks based on tolerability (maximum recommended dose: 6 mg twice daily).
Low body weight: Careful titration and monitoring should be performed in patients with low body weight. In patients <50 kg, monitor closely for toxicities (eg, excessive nausea, vomiting), and consider reducing the dose if such toxicities develop.
Note: If GI adverse events occur, discontinue treatment for several doses then restart at the same or next lower dosage level; antiemetics have been used to control GI symptoms. If dosing is interrupted for ≤3 days, restart the treatment at the same or lower dose and titrate as previously described. If interrupted for >3 days, reinitiate at 1.5 mg twice daily and titrate as previously described.
Transdermal patch: Initial: 4.6 mg per 24 hours patch applied once daily; after a minimum of 4 weeks, increase as tolerated to 9.5 mg per 24 hours; continue as long as therapeutically beneficial. After a minimum of 4 weeks, may increase as tolerated to a maximum dose of 13.3 mg per 24 hours. Doses >13.3 mg per 24 hours have not been shown to be more effective and are associated with significant increases in adverse events. Recommended effective dose: 9.5 mg per 24 hours or 13.3 mg per 24 hours patch applied once daily; remove old patch and replace with a new patch every 24 hours.
Low body weight: Careful titration and monitoring should be performed in patients with low body weight. In patients <50 kg, monitor closely for toxicities (eg, excessive nausea, vomiting) and consider reducing the maintenance dose to 4.6 mg/24 hour if such toxicities develop.
Note: If dosing is interrupted for ≤3 days, restart treatment with the same or a lower strength patch. If interrupted for >3 days, reinitiate at 4.6 mg/24 hours and titrate (no sooner than every 4 weeks) to lowest effective maintenance dose.
Conversion from oral therapy: If oral daily dose <6 mg, switch to 4.6 mg/24 hours patch; if oral daily dose 6 to 12 mg, switch to 9.5 mg/24 hours patch. Apply patch on the day following last oral dose.
Alzheimer disease, severe: Transdermal patch: Initial: Apply 4.6 mg per 24 hours patch once daily. Increase as tolerated every 4 weeks to a maximum of 13.3 mg per 24 hours. Recommended effective dose: 13.3 mg per 24 hours patch applied once daily; remove old patch and replace with a new patch every 24 hours.
Low body weight: Careful titration and monitoring should be performed in patients with low body weight. In patients <50 kg, monitor closely for toxicities (eg, excessive nausea, vomiting) and consider reducing the maintenance dose to 4.6 mg/24 hours if such toxicities develop.
Note: If dosing is interrupted for ≤3 days, restart treatment with the same or a lower strength patch. If interrupted for >3 days, reinitiate at 4.6 mg/24 hour and titrate (no sooner than every 4 weeks) to lowest effective maintenance dose.
Dementia with Lewy bodies (off-label use): Oral: Initial: 1.5 mg twice daily; may increase by 3 mg daily (1.5 mg per dose) every 2 weeks based on tolerability up to a maximum of 6 mg twice daily (Ref).
Parkinson disease dementia, mild to moderate:
Oral: Initial: 1.5 mg twice daily; may increase by 3 mg daily (1.5 mg per dose) every 4 weeks based on tolerability (maximum recommended dose: 6 mg twice daily).
Low body weight: Careful titration and monitoring should be performed in patients with low body weight. In patients <50 kg, monitor closely for toxicities (eg, excessive nausea, vomiting) and consider reducing the dose if such toxicities develop.
Note: If GI adverse events occur, discontinue treatment for several doses then restart at the same or next lower dosage level; antiemetics have been used to control GI symptoms. If dosing is interrupted for ≤3 days, restart the treatment at the same or lower dose and titrate as previously described. If interrupted for >3 days, reinitiate at 1.5 mg twice daily and titrate as previously described.
Transdermal patch: Initial: 4.6 mg per 24 hours patch applied once daily; after a minimum of 4 weeks, increase as tolerated to 9.5 mg per 24 hours; continue as long as therapeutically beneficial. After a minimum of 4 weeks, may increase as tolerated to a maximum dose of 13.3 mg per 24 hours. Doses >13.3 mg per 24 hours have not been shown to be more effective and are associated with significant increases in adverse events. Recommended effective dose: 9.5 mg per 24 hours or 13.3 mg per 24 hours patch applied once daily; remove old patch and replace with a new patch every 24 hours.
Low body weight: Careful titration and monitoring should be performed in patients with low body weight. In patients <50 kg, monitor closely for toxicities (eg, excessive nausea, vomiting) and consider reducing the maintenance dose to 4.6 mg/24 hour if such toxicities develop.
Note: If dosing is interrupted for ≤3 days, restart treatment with the same or a lower strength patch. If interrupted for >3 days, reinitiate at 4.6 mg/24 hours and titrate (no sooner than every 4 weeks) to lowest effective maintenance dose.
Vascular dementia, comorbid (off-label use): Note: For use in patients with suspected comorbid Alzheimer disease, Parkinson disease dementia, or dementia with Lewy bodies (Ref).
Oral: Initial: 1.5 mg twice daily for 4 weeks; may increase dose based on response and tolerability in increments of 3 mg/day (1.5 mg/dose) every 4 weeks up to a maximum of 6 mg twice daily (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Oral: Moderate to severe impairment (CrCl ≤50 mL/minute): There are no dosage adjustments provided in the manufacturer's labeling; patients may only be able to tolerate lower doses. Alternatively, an initial dose of 1.5 mg once daily with slow and cautious titration has been recommended (Ref).
Transdermal: No dosage adjustment necessary.
Oral:
Mild to moderate impairment (Child-Pugh class A and B): There are no dosage adjustments provided in the manufacturer's labeling; clearance is reduced and patients may require lower doses. Alternatively, an initial dose of 1.5 mg once daily with slow and cautious titration has been recommended (Ref).
Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Transdermal:
Mild to moderate impairment (Child-Pugh class A and B): Initial and maximum dose: 4.6 mg/24 hours
Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing. Following oral administration, clearance is reduced in patients >60 years of age, but dosage adjustments are not required. Age was not associated with increased exposure in patients treated transdermally.
Acetylcholinesterase inhibitors, including rivastigmine, have been associated with cardiac effects, such as conduction abnormalities (eg, bradycardia, atrioventricular block, arrhythmias) and hypertension. Syncope has also been reported (Ref).
Mechanism: Related to the mechanism of action; increased cholinergic activity results in vagotonic effects (Ref).
Onset: Delayed; reported months to years after initiation (Ref).
Risk factors:
• Older adults (Ref)
• History of cardiovascular disease (eg, ischemic heart disease, heart failure) (Ref)
• History of cardiac conduction abnormalities or sick sinus syndrome (Ref)
• History of stroke or transient ischemic attack, diabetes, or syncope (Ref)
• Concurrent antihypertensives (especially beta-blockers), antiarrhythmics, antidepressants, and antipsychotics (Ref)
Application-site irritation is the most common cutaneous reaction associated with transdermal rivastigmine (Ref). In addition, allergic contact dermatitis may occur following oral and transdermal administration (Ref). Other cutaneous reactions that have been described include angioedema (Ref), skin rash (symmetric drug-related intertriginous and flexural exanthema [SDRIFE]) (Ref) and erythematous maculopapular rash (Ref).
Mechanism: Non–dose-related; immunologic. Delayed hypersensitivity reactions, including rashes (eg, maculopapular) and allergic contact dermatitis are T-cell-mediated (Ref); may be triggered by rivastigmine and/or excipients within the patch (Ref). Sensitization may occur from repeated application in the same area. Transdermal rivastigmine contains polyisobutylene, which is a known contact sensitizer and has been associated with allergic contact dermatitis from stoma bags (Ref). Application-site irritation is caused by direct toxic effect on epidermal keratinocytes, which trigger the innate immune system (Ref). A positive patch test, positive rechallenge with oral drug, and response to desensitization also suggest a possible immunological mechanism (Ref).
Onset: Delayed hypersensitivity reactions: Varied; most reactions occurred within 5 to 15 days (Ref). Application-site irritation may occur within 12 hours of application (Ref).
Risk factors:
• Cross-reactivity between acetylcholinesterase inhibitors is unknown. A potential cross-reaction between transdermal rivastigmine and oral galantamine has been described (Ref).
• Older adults are at an increased risk of irritant contact dermatitis, but not allergic contact dermatitis, due to thinner and more fragile skin (Ref)
• History of eczema may increase risk of irritant contact dermatitis (Ref)
Dose-related GI effects are the most common adverse reactions associated with rivastigmine. Symptoms may include nausea, vomiting, diarrhea, and abdominal pain (Ref). A systematic review of studies reported more GI effects with oral rivastigmine compared to donepezil (Ref). In another study, oral rivastigmine had the highest rate of GI effects compared to both donepezil and galantamine (Ref). GI effects typically occur with dose titration and are transient and self-limiting; however, dehydration, weight loss, decreased appetite, and/or anorexia may also occur (Ref).
Mechanism: Dose-related; related to mechanism of action. Increased cholinergic activity increases smooth muscle contraction, peristalsis, and sphincter relaxation in the GI tract, leading to GI effects (Ref).
Onset: GI effects: Rapid during dose titration; one study reported GI effects within the first 1 or 2 doses following dose titration (Ref). Weight loss/anorexia: Varied; may occur from the beginning of treatment to any time within the first year of therapy. More research is needed in this area, especially beyond 1 year (Ref).
Risk factors:
• Higher doses
• Rapid dose titration
• Oral versus transdermal formulation (Ref)
• Lack of retitration following prolonged (>3 days) treatment interruption
• Females
• Patients weighing <50 kg
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Gastrointestinal: Abdominal pain (1% to 13%; transdermal: 2%) (table 1) , anorexia (≤17%) (table 2) , diarrhea (oral: 5% to 19%; transdermal: ≤7%) (table 3) , nausea (oral: 23% to 47%; transdermal: 2% to 10%) (table 4) , vomiting (oral: 17% to 31%; transdermal: 2% to 9%) (table 5)
Drug (Rivastigmine) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Rivastigmine) |
Number of Patients (Placebo) |
---|---|---|---|---|---|---|
13% |
6% |
6 to 12 mg/day |
Oral capsules |
Mild-to-moderate Alzheimer disease |
1,189 |
868 |
2% |
1% |
9.5 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
291 |
302 |
1% |
1% |
6 mg twice daily |
Oral capsules |
Mild-to-moderate Alzheimer disease |
294 |
302 |
Drug (Rivastigmine) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Rivastigmine) |
Number of Patients (Placebo) |
Comments |
---|---|---|---|---|---|---|---|
17% |
3% |
6 to 12 mg/day |
Oral capsules |
Mild-to-moderate Alzheimer disease |
1,189 |
868 |
N/A |
9% |
2% |
6 mg twice daily |
Oral capsules |
Mild-to-moderate Alzheimer disease |
294 |
302 |
Described as "anorexia/decreased appetite" |
6% |
3% |
3 to 12 mg/day |
Oral capsules |
Mild-to-moderate Alzheimer disease |
362 |
179 |
N/A |
3% |
2% |
9.5 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
291 |
302 |
Described as "anorexia/decreased appetite" |
Drug (Rivastigmine) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Rivastigmine) |
Number of Patients (Placebo) |
---|---|---|---|---|---|---|
19% |
11% |
6 to 12 mg/day |
Oral capsules |
Mild-to-moderate Alzheimer disease |
1,189 |
868 |
7% |
4% |
3 to 12 mg/day |
Oral capsules |
Mild-to-moderate Alzheimer disease |
362 |
179 |
6% |
3% |
9.5 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
291 |
302 |
5% |
3% |
6 mg twice daily |
Oral capsules |
Mild-to-moderate Alzheimer disease |
294 |
302 |
5% |
N/A |
13.3 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
280 |
N/A |
4% |
N/A |
9.5 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
283 |
N/A |
2% |
N/A |
13.3 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
241 |
N/A |
<1% |
N/A |
9.5 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
246 |
N/A |
7% |
N/A |
13.3 mg per 24 hours |
Transdermal patch |
Severe Alzheimer disease |
355 |
N/A |
5% |
N/A |
4.6 mg per 24 hours |
Transdermal patch |
Severe Alzheimer disease |
359 |
N/A |
Drug (Rivastigmine) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Rivastigmine) |
Number of Patients (Placebo) |
---|---|---|---|---|---|---|
47% |
12% |
6 to 12 mg/day |
Oral capsules |
Mild-to-moderate Alzheimer disease |
1,189 |
868 |
29% |
11% |
3 to 12 mg/day |
Oral capsules |
Mild-to-moderate Alzheimer disease |
362 |
179 |
23% |
5% |
6 mg twice daily |
Oral capsules |
Mild-to-moderate Alzheimer disease |
294 |
302 |
10% |
N/A |
13.3 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
280 |
N/A |
7% |
5% |
9.5 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
291 |
302 |
4% |
N/A |
9.5 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
283 |
N/A |
4% |
N/A |
13.3 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
241 |
N/A |
2% |
N/A |
9.5 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
246 |
N/A |
6% |
N/A |
13.3 mg per 24 hours |
Transdermal patch |
Severe Alzheimer disease |
355 |
N/A |
3% |
N/A |
4.6 mg per 24 hours |
Transdermal patch |
Severe Alzheimer disease |
359 |
N/A |
Drug (Rivastigmine) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Rivastigmine) |
Number of Patients (Placebo) |
---|---|---|---|---|---|---|
31% |
6% |
6 to 12 mg/day |
Oral capsules |
Mild-to-moderate Alzheimer disease |
1,189 |
868 |
17% |
3% |
6 mg twice daily |
Oral capsules |
Mild-to-moderate Alzheimer disease |
294 |
302 |
17% |
2% |
3 to 12 mg/day |
Oral capsules |
Mild-to-moderate Alzheimer disease |
362 |
179 |
9% |
N/A |
13.3 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
280 |
N/A |
6% |
3% |
9.5 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
291 |
302 |
3% |
N/A |
9.5 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
283 |
N/A |
3% |
N/A |
13.3 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
241 |
N/A |
2% |
N/A |
9.5 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
246 |
N/A |
7% |
N/A |
13.3 mg per 24 hours |
Transdermal patch |
Severe Alzheimer disease |
355 |
N/A |
3% |
N/A |
4.6 mg per 24 hours |
Transdermal patch |
Severe Alzheimer disease |
359 |
N/A |
Local: Application-site erythema (transdermal: 1% to 13%)
Nervous system: Agitation (transdermal: 1% to 14%), dizziness (oral: 6% to 21%; transdermal: ≤3%), headache (oral: 4% to 17%; transdermal: ≤4%)
1% to 10%:
Cardiovascular: Bradycardia (oral: ≥1%), hypertension (1% to 3%) (table 6) , syncope (oral: 3%) (table 7)
Drug (Rivastigmine) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Rivastigmine) |
Number of Patients (Placebo) |
---|---|---|---|---|---|---|
3% |
2% |
6 to 12 mg/day |
Oral capsules |
Mild-to-moderate Alzheimer disease |
1,189 |
868 |
3% |
N/A |
13.3 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
280 |
N/A |
2% |
N/A |
9.5 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
283 |
N/A |
1% |
N/A |
13.3 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
241 |
N/A |
1% |
N/A |
9.5 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
246 |
N/A |
Drug (Rivastigmine) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Rivastigmine) |
Number of Patients (Placebo) |
---|---|---|---|---|---|---|
3% |
2% |
6 to 12 mg/day |
Oral capsules |
Mild-to-moderate Alzheimer disease |
1,189 |
868 |
Dermatologic: Diaphoresis (oral: 2% to 4%)
Endocrine & metabolic: Dehydration (2%) (table 8) , weight loss (1% to 7%) (table 9)
Drug (Rivastigmine) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Rivastigmine) |
Number of Patients (Placebo) |
---|---|---|---|---|---|---|
2% |
1% |
3 to 12 mg/day |
Oral capsules |
Mild-to-moderate Alzheimer disease |
362 |
179 |
Drug (Rivastigmine) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Rivastigmine) |
Number of Patients (Placebo) |
---|---|---|---|---|---|---|
5% |
1% |
6 mg twice daily |
Oral capsules |
Mild-to-moderate Alzheimer disease |
294 |
302 |
5% |
N/A |
13.3 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
241 |
N/A |
3% |
<1% |
6 to 12 mg/day |
Oral capsules |
Mild-to-moderate Alzheimer disease |
1,189 |
868 |
3% |
1% |
9.5 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
291 |
302 |
3% |
N/A |
13.3 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
280 |
N/A |
2% |
N/A |
9.5 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
246 |
N/A |
1% |
N/A |
9.5 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
283 |
N/A |
7% |
N/A |
13.3 mg per 24 hours |
Transdermal patch |
Severe Alzheimer disease |
355 |
N/A |
3% |
N/A |
4.6 mg per 24 hours |
Transdermal patch |
Severe Alzheimer disease |
359 |
N/A |
Gastrointestinal: Decreased appetite (≤9%) (table 10) , dyspepsia (oral: 9%), sialorrhea (oral: 1%), upper abdominal pain (≤4%)
Drug (Rivastigmine) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Rivastigmine) |
Number of Patients (Placebo) |
Comments |
---|---|---|---|---|---|---|---|
9% |
2% |
6 mg twice daily |
Oral capsules |
Mild-to-moderate Alzheimer disease |
294 |
302 |
Described as "anorexia/decreased appetite" |
8% |
5% |
3 to 12 mg/day |
Oral capsules |
Mild-to-moderate Alzheimer disease |
362 |
179 |
N/A |
5% |
N/A |
13.3 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
280 |
N/A |
N/A |
3% |
2% |
9.5 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
291 |
302 |
Described as "anorexia/decreased appetite" |
2% |
N/A |
9.5 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
283 |
N/A |
N/A |
2% |
N/A |
13.3 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
241 |
N/A |
N/A |
<1% |
N/A |
9.5 mg per 24 hours |
Transdermal patch |
Mild-to-moderate Alzheimer disease |
246 |
N/A |
N/A |
5% |
N/A |
13.3 mg per 24 hours |
Transdermal patch |
Severe Alzheimer disease |
355 |
N/A |
N/A |
1% |
N/A |
4.6 mg per 24 hours |
Transdermal patch |
Severe Alzheimer disease |
359 |
N/A |
N/A |
Genitourinary: Urinary incontinence (transdermal: ≤2%), urinary tract infection (2% to 10%)
Local: Application-site irritation (severe; transdermal: ≤2%), application-site pruritus (transdermal: ≤4%)
Nervous system: Aggressive behavior (1% to 3%), anxiety (1% to 5%), asthenia (2% to 6%), cogwheel rigidity (oral: 1%), confusion (oral: 8%), depression (2% to 6%), drowsiness (oral: 4% to 5%), falling (3% to 8%), fatigue (2% to 9%), hallucination (2% to 5%), insomnia (1% to 9%), malaise (oral: 5%), parkinsonism (oral: 2%), psychomotor agitation (transdermal: 1% to 3%), restlessness (oral: 3%), tremor (oral: 4% to 10%)
Neuromuscular & skeletal: Bradykinesia (oral: 3%), hypokinesia (oral: 1%)
<1%:
Cardiovascular: Atrial fibrillation, atrioventricular block
Nervous system: Dystonia (Diaz 2015)
Postmarketing:
Cardiovascular: Tachycardia
Dermatologic: Allergic dermatitis (including disseminated allergic dermatitis) (Grieco 2011), erythematous maculopapular rash (Makris 2010), skin blister, skin rash (symmetric drug-related intertriginous and flexural exanthema [SDRIFE]) (Allain-Veyrac 2011), Stevens-Johnson syndrome, urticaria
Gastrointestinal: Severe vomiting (with esophageal rupture; following inappropriate reinitiation of dose)
Hepatic: Hepatitis (Mumoli 2009)
Hypersensitivity: Angioedema (Naharci 2018)
Local: Application-site reaction (hypersensitivity reaction)
Nervous system: Nightmares, seizure (Kumlien 2010)
Hypersensitivity to rivastigmine, other carbamate derivatives, or any component of the formulation; history of application-site reactions with rivastigmine patch
Canadian labeling: Additional contraindications (not in US labeling): Severe hepatic impairment; history of severe skin reactions (eg, allergic dermatitis [disseminated], Stevens-Johnson syndrome) with oral or transdermal rivastigmine; history of QT prolongation and/or torsades de pointes, including congenital long QT syndromes; history of cardiac arrhythmias.
Concerns related to adverse effects:
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).
• Extrapyramidal effects: May exacerbate or induce extrapyramidal symptoms; worsening of symptoms (eg, tremor) in patients with Parkinson disease has been observed.
Disease-related concerns:
• Peptic ulcer disease: Use with caution in patients at risk of ulcer disease (eg, previous history or NSAID use); may increase gastric acid secretion. Monitor for symptoms of active or occult bleeding.
• Respiratory disease: Use with caution in patients with COPD and/or asthma.
• Seizure disorder: Use with caution in patients with a history of seizure disorder.
• Urinary tract obstruction: Use with caution in patients with bladder outlet obstruction; cholinomimetics may cause or worsen outflow obstructions.
Dosage form specific issues:
• Transdermal patch: May contain conducting metal (eg, aluminum); remove patch prior to MRI.
Other warnings/precautions:
• Appropriate use: Postmarketing cases of overdose (including rare fatalities) have been reported in association with medication errors/improper use of rivastigmine transdermal patches. No more than 1 patch should be applied daily and existing patch must be removed prior to applying new patch.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Generic: 1.5 mg, 3 mg, 4.5 mg, 6 mg
Patch 24 Hour, Transdermal:
Exelon: 4.6 mg/24 hr (1 ea, 30 ea); 9.5 mg/24 hr (1 ea, 30 ea); 13.3 mg/24 hr (1 ea, 30 ea)
Generic: 4.6 mg/24 hr (1 ea, 30 ea); 9.5 mg/24 hr (1 ea, 30 ea); 13.3 mg/24 hr (1 ea, 30 ea)
Yes
Capsules (Rivastigmine Tartrate Oral)
1.5 mg (per each): $0.70 - $4.66
3 mg (per each): $0.70 - $4.66
4.5 mg (per each): $0.70 - $4.66
6 mg (per each): $0.70 - $4.66
Patch, 24-hour (Exelon Transdermal)
4.6 mg/24 hrs (per each): $27.43
9.5 mg/24 hrs (per each): $27.43
13.3 mg/24 hrs (per each): $27.43
Patch, 24-hour (Rivastigmine Transdermal)
4.6 mg/24 hrs (per each): $16.20 - $16.90
9.5 mg/24 hrs (per each): $16.20 - $16.90
13.3 mg/24 hrs (per each): $16.20 - $16.90
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Exelon: 1.5 mg, 3 mg, 4.5 mg, 6 mg
Generic: 1.5 mg, 3 mg, 4.5 mg, 6 mg
Patch 24 Hour, Transdermal:
Exelon: 4.6 mg/24 hr (30 ea); 9.5 mg/24 hr (30 ea); 13.3 mg/24 hr (30 ea)
Rivastigmine Patch 5: 4.6 mg/24 hr (30 ea)
Rivastigmine Patch 10: 9.5 mg/24 hr (30 ea)
Rivastigmine Patch 15: 13.3 mg/24 hr (30 ea)
Generic: 4.6 mg/24 hr (30 ea); 9.5 mg/24 hr (30 ea)
Solution, Oral:
Exelon: 2 mg/mL (120 mL) [contains sodium benzoate]
Oral: Administer with meals (breakfast and dinner). Oral solution [Canadian product], which is available for patients who cannot swallow capsules, can be swallowed directly from syringe or mixed with water, soda, or cold fruit juice. Stir well and drink immediately.
Topical: Apply transdermal patch to upper or lower back (alternatively, may apply to upper arm or chest). Do not use patch if the pouch seal is broken or if the patch is cut, altered, or damaged. Avoid reapplication to same spot of skin for 14 days (eg, may rotate sections of back). Apply to clean, dry, and hairless skin. Patch should be pressed down firmly by applying pressure with the hand over the entire patch for at least 30 seconds, making sure edges stick well. Do not apply to red, irritated, or broken skin. Avoid areas of recent application of lotion or powder. After removal, fold patch to press adhesive surfaces together, place in previously saved pouch, and discard. Avoid eye contact; wash hands after handling patch. Remove old patch and replace with a new patch every 24 hours (at the same time each day). If a dose is missed or if the patch falls off, apply a new patch immediately and replace the following day at the usual application time. Do not use overlays, bandages, or tape to secure a patch that has become loose. Avoid exposing the patch to external sources of heat (eg, sauna, excessive light) for prolonged periods of time. No more than 1 patch should be applied daily and existing patch must be removed prior to applying new patch. Discard any used or unused patches by folding adhesive sides together and dispose of in trash away from children and pets.
Alzheimer disease:
Oral: Treatment of mild to moderate dementia of the Alzheimer type.
Transdermal: Treatment of mild, moderate, and severe dementia of the Alzheimer type.
Parkinson disease dementia: Treatment of mild to moderate dementia associated with Parkinson disease.
Dementia with Lewy bodies; Vascular dementia, comorbid
Exelon may be confused with Exelan (manufacturer)
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Amifampridine: Acetylcholinesterase Inhibitors may enhance the therapeutic effect of Amifampridine. Amifampridine side effects may also be increased. Amifampridine may enhance the therapeutic effect of Acetylcholinesterase Inhibitors. Acetylcholinesterase inhibitor side effects may also be increased. Risk C: Monitor therapy
Anticholinergic Agents: May diminish the therapeutic effect of Rivastigmine. Rivastigmine may diminish the therapeutic effect of Anticholinergic Agents. Management: Use of rivastigmine with an anticholinergic agent is not recommended unless clinically necessary. If the combination is necessary, monitor for reduced anticholinergic effects. Risk D: Consider therapy modification
Antipsychotic Agents: Rivastigmine may enhance the neurotoxic (central) effect of Antipsychotic Agents. Risk C: Monitor therapy
Benoxinate: Acetylcholinesterase Inhibitors may enhance the therapeutic effect of Benoxinate. Specifically, the effects of benoxinate may be prolonged. Risk C: Monitor therapy
Beta-Blockers: Rivastigmine may enhance the bradycardic effect of Beta-Blockers. Risk X: Avoid combination
Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Risk C: Monitor therapy
Bromopride: Rivastigmine may enhance the adverse/toxic effect of Bromopride. Specifically, the risk of extrapyramidal adverse reactions may be increased with this combination. Risk X: Avoid combination
Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Risk D: Consider therapy modification
Cholinergic Agonists: May enhance the adverse/toxic effect of Rivastigmine. Specifically, cholinergic effects may be enhanced or increased. Rivastigmine may enhance the adverse/toxic effect of Cholinergic Agonists. Management: Use of rivastigmine with a cholinergic agonist is not recommended unless clinically necessary. If the combination is necessary, monitor for increased cholinergic effects. Risk D: Consider therapy modification
Corticosteroids (Systemic): May enhance the adverse/toxic effect of Acetylcholinesterase Inhibitors. Increased muscular weakness may occur. Risk C: Monitor therapy
Dipyridamole: May diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy
Etrasimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Fexinidazole: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole. Risk X: Avoid combination
Fingolimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Fingolimod. Management: Consult with the prescriber of any bradycardia-causing agent to see if the agent could be switched to an agent that does not cause bradycardia prior to initiating fingolimod. If combined, perform continuous ECG monitoring after the first fingolimod dose. Risk D: Consider therapy modification
Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Risk C: Monitor therapy
Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Risk C: Monitor therapy
Metoclopramide: Rivastigmine may enhance the adverse/toxic effect of Metoclopramide. Specifically, the risk of extrapyramidal adverse reactions may be increased with this combination. Risk X: Avoid combination
Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Neuromuscular-Blocking Agents (Nondepolarizing): Acetylcholinesterase Inhibitors may diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Ozanimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Ponesimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Ponesimod. Management: Avoid coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm. Risk D: Consider therapy modification
Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring. Risk D: Consider therapy modification
Succinylcholine: Acetylcholinesterase Inhibitors may enhance the neuromuscular-blocking effect of Succinylcholine. Risk C: Monitor therapy
Tobacco (Smoked): May decrease the serum concentration of Rivastigmine. Risk C: Monitor therapy
Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Food delays absorption by 90 minutes, lowers Cmax by 30% and increases AUC by 30%. Management: Administer with meals.
Adverse events have not been observed in animal reproduction studies.
It is not known if rivastigmine is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Cognitive function at periodic intervals, symptoms of GI intolerance, decreased weight, signs of cutaneous reactions.
A deficiency of cortical acetylcholine is thought to account for some of the symptoms of Alzheimer disease and Parkinson disease dementia; rivastigmine increases acetylcholine in the central nervous system through reversible inhibition of its hydrolysis by cholinesterase
Duration: Anticholinesterase activity (CSF): ~10 hours (6 mg oral dose)
Absorption: Oral: Fasting: Rapid and complete within 1 hour; Transdermal patch: Within 30 to 60 minutes
Distribution: Vd: 1.8 to 2.7 L/kg; penetrates blood-brain barrier (CSF levels are ~40% of plasma levels following oral administration)
Protein binding: 40%
Metabolism: Extensively via cholinesterase-mediated hydrolysis in the brain; metabolite undergoes N-demethylation and/or sulfate conjugation hepatically; CYP minimally involved; linear kinetics at 3 mg twice daily, but nonlinear at higher doses
Bioavailability: Oral: 36%
Half-life elimination: Oral: 1.5 hours; Transdermal patch: ~3 hours (after removal)
Time to peak: Oral: 1 hour; Transdermal patch: 8 to 16 hours following first dose
Excretion: Urine (97% as metabolites); feces (0.4%)
Altered kidney function:
Moderate impairment: Mean oral clearance is 64% lower.
Severe impairment: Mean oral clearance is 43% higher for unexplained reasons.
Hepatic function impairment: Mean oral clearance is 60% lower.
Older adult: Mean oral clearance was 30% lower.
Cigarette smoking: Oral clearance increases 23%.
Body weight: Exposure is higher in patients with low body weight (<50 kg) and lower in patients with an increased body weight (>100 kg).
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