Exelon

Anti-AlzheimerAgents, Cholinesterase Inhibitors

Oral Administration

All dosage forms: Administered twice daily with food (AM meal and PM meal). Administration with food increases drug tolerability.

Oral Liquid Formulations

Oral solution: Dosing of the oral solution is equivalent to the capsules; measure dose with the supplied oral syringe. May be administered undiluted, or it may be diluted in a small glass of water, cold fruit juice, or soda. Stir diluted solution well, then have patient drink entire glass to ensure proper dose. The solution is stable for up to 4 hours once mixed with these beverages.

Topical Administration Transdermal Patch Formulations

Apply once daily to clean, dry, hairless, intact healthy skin in an area not rubbed by tight clothing or elastic. Application to the upper or lower back may be preferable to avoid removal by the patient; however, the chest or upper arm may be used. Do not apply to red, irritated, or damaged skin. Do not use on areas with recent application of lotions, creams, or powder.
Rotate application sites daily. Do not apply to the same site more than once every 14 days.
Remove protective liner prior to application to the skin. Press firmly in place until the edges stick well.
May be used while bathing, swimming, showering, or in hot weather. Avoid excessive sunlight or other sources of external heat such as saunas.
Apply patch at approximately the same time every day.
Always remove the old patch before applying a new patch. NOTE: Medication errors resulting in overdose, and rarely leading to death, have involved use of multiple patches at one time and failure to remove the old patch when applying a new one.
Patients and/or caregivers should be given instruction on the proper administration of rivastigmine transdermal patches.
Discontinue treatment if there is evidence suggesting allergic contact dermatitis such as application site reactions spreading beyond the patch size, intense local reaction (e.g., increasing erythema, edema, papules, vesicles), or symptoms that do not significantly improve within 48 hours after patch removal.

Severe

GI bleeding / Delayed / 0.1-1.0
hematemesis / Delayed / 0.1-1.0
peptic ulcer / Delayed / 0.1-1.0
pancreatitis / Delayed / 0.1-1.0
suicidal ideation / Delayed / 0.1-1.0
renal failure (unspecified) / Delayed / 0.1-1.0
AV block / Early / 0.1-1.0
heart failure / Delayed / 0.1-1.0
cholecystitis / Delayed / 0.1-1.0
bronchospasm / Rapid / 0.1-1.0
prostatic hypertrophy / Delayed / 0.1-1.0
ocular hypertension / Delayed / 0.1-1.0
intracranial bleeding / Delayed / 0.1-1.0
seizures / Delayed / 1.0
bradycardia / Rapid / 0.1
myocardial infarction / Delayed / 1.0
atrial fibrillation / Early / 1.0
Stevens-Johnson syndrome / Delayed / Incidence not known

Moderate

confusion / Early / 8.0-8.0
depression / Delayed / 4.0-6.0
hallucinations / Early / 2.0-5.0
dyskinesia / Delayed / 1.0-3.0
pseudoparkinsonism / Delayed / 1.0-3.0
hypertension / Early / 3.0-3.0
melena / Delayed / 0.1-1.0
dysphagia / Delayed / 0.1-1.0
migraine / Early / 0.1-1.0
dysphonia / Delayed / 0.1-1.0
nystagmus / Delayed / 0.1-1.0
peripheral edema / Delayed / 0.1-1.0
hematuria / Delayed / 0.1-1.0
dysuria / Early / 0.1-1.0
sinus tachycardia / Rapid / 0.1-1.0
supraventricular tachycardia (SVT) / Early / 0.1-1.0
contact dermatitis / Delayed / 0.1-1.0
erythema / Early / 0.1-1.0
elevated hepatic enzymes / Delayed / 0.1-1.0
lymphadenopathy / Delayed / 0.1-1.0
hyponatremia / Delayed / 0.1-1.0
myasthenia / Delayed / 0.1-1.0
blurred vision / Early / 0.1-1.0
constipation / Delayed / 1.0
gastritis / Delayed / 1.0
ataxia / Delayed / 1.0
hot flashes / Early / 1.0
urinary incontinence / Early / 1.0
angina / Early / 1.0
hypotension / Rapid / 1.0
palpitations / Early / 1.0
chest pain (unspecified) / Early / 1.0
orthostatic hypotension / Delayed / 1.0
bullous rash / Early / 1.0
psoriaform rash / Delayed / 1.0
atopic dermatitis / Delayed / 1.0
dehydration / Delayed / 1.0
dyspnea / Early / 1.0
hypokalemia / Delayed / 1.0
anemia / Delayed / 1.0
cataracts / Delayed / 0.1
hepatitis / Delayed / Incidence not known

Mild

nausea / Early / 7.0-47.0
vomiting / Early / 6.0-31.0
weight loss / Delayed / 3.0-26.0
dizziness / Early / 2.0-21.0
diarrhea / Early / 5.0-19.0
anorexia / Delayed / 3.0-17.0
headache / Early / 3.0-17.0
abdominal pain / Early / 1.0-13.0
dyspepsia / Early / 9.0-9.0
insomnia / Early / 1.0-9.0
fatigue / Early / 2.0-9.0
asthenia / Delayed / 2.0-6.0
drowsiness / Early / 4.0-5.0
anxiety / Delayed / 2.0-5.0
malaise / Early / 5.0-5.0
hyperhidrosis / Delayed / 2.0-4.0
restlessness / Early / 1.0-3.0
syncope / Early / 3.0-3.0
hypersalivation / Early / 1.0-2.0
gastroesophageal reflux / Delayed / 0.1-1.0
hypoesthesia / Delayed / 0.1-1.0
libido increase / Delayed / 0.1-1.0
nocturia / Early / 0.1-1.0
increased urinary frequency / Early / 0.1-1.0
urticaria / Rapid / 0.1-1.0
cough / Delayed / 0.1-1.0
fever / Early / 0.1-1.0
arthralgia / Delayed / 0.1-1.0
mastalgia / Delayed / 0.1-1.0
diplopia / Early / 0.1-1.0
flatulence / Early / 1.0
tremor / Early / 1.0
vertigo / Early / 1.0
paresthesias / Delayed / 1.0
agitation / Early / 1.0
maculopapular rash / Early / 1.0
rash / Early / 1.0
pruritus / Rapid / 1.0
polydipsia / Early / 1.0
infection / Delayed / 1.0
tinnitus / Delayed / 0.1
myalgia / Early / 0.1
back pain / Delayed / 1.0
nightmares / Early / Incidence not known

Exelon, Exelon Patch

Rx

Oral and transdermal cholinesterase inhibitor
Oral and transdermal formulations approved for mild to moderate dementia due to Alzheimer's or Parkinson's disease; transdermal patch also approved for severe Alzheimer's disease; may provide cognitive benefit in dementia with Lewy bodies
Requires slow dosage titration to limit GI side effects

For the treatment of mild to moderate Parkinson's disease dementia (PDD). Oral dosage Adults

Initially, 1.5 mg PO twice daily with food. If this dose is well tolerated after 4 weeks, may increase to 3 mg PO twice daily. Subsequently, increase dose by 1.5 mg PO twice daily at intervals of 4 weeks or more to the highest tolerated dose (doses in clinical trials ranged from 3—12 mg/day). If GI adverse effects occur, discontinue for several doses, then restart at less than or equal to the same dose. If treatment is interrupted for several days, reinitiate with the lowest daily dose (1.5 mg PO twice daily) and slowly retitrate to the effective dose to limit the risk of ADRs. Significant results have been demonstrated in the 24-week Exelon in Parkinson's disease dementia (EXPRESS) study. In this study, 541 patients with Parkinson's-related dementia (mean age, 73 years; 65%, men; 410 completed the study) were randomized to receive rivastigmine or placebo. Significant but moderate changes compared to placebo were seen in the primary outcome variables, the Alzheimer Disease Assessment Scale-cognition (ADAS-cog; +2.1 points vs -0.7) and Alzheimer Disease Cooperative Study-Clinician's Global Impression of Change scale (ADCS-CGIC; mean score at 24 weeks 3.8 vs 4.3). Nausea (29 vs. 11%), vomiting (17 vs. 2%), and tremor (10 vs. 4%) were significant rivastigmine-related adverse events in this study.

Transdermal dosage Adults

Initially, apply one 4.6 mg/24 hours patch transdermally once daily. After a minimum of 4 weeks, may increase to the 9.5 mg/24 hours patch if tolerated. Continue the recommended effective dose of 9.5 mg/24 hours for as long as therapeutic benefit persists. Patients can then be increased to the maximum effective dose of 13.3 mg/24 hours. If treatment is interrupted for more than 3 days, begin with initial titration. Patients below 50 kg may experience more adverse effects; titrate with caution and consider reducing the maintenance dose to 4.6 mg/24 hours if intolerability develops. For patients receiving less than 6 mg/day of oral rivastigmine and switching to the rivastigmine patch, apply one 4.6 mg/24 hours patch transdermally once daily. For patients receiving 6—12 mg/day of oral rivastigmine and switching to the rivastigmine patch, apply one 9.5 mg/24 hours patch transdermally once daily. Apply the first patch on the day following the last oral dose. If dermal sensitivity reactions occur, consider switch to oral dosing, only after sensitivity testing is negative.

For the treatment of Alzheimer's disease. For the treatment of mild to moderate Alzheimer's disease. Oral dosage Adults

1.5 mg PO twice daily, initially. Increase the dose to 3 mg PO twice daily after 2 weeks if tolerated, then by 1.5 mg/dose after a minimum of 2 weeks at the previous dose if well tolerated. Usual dose: 6 to 12 mg/day. Max: 12 mg/day. There is evidence from clinical trials that doses at the higher end of the range may be more beneficial. Discontinue treatment for several days if adverse effects occur and restart at the same or next lower dose level; if dosing is interrupted for more than 3 days, restart at 1.5 mg PO twice daily and titrate again.

Transdermal dosage (rivastigmine-naive) Adults weighing 50 kg or more

4.6 mg/24 hours transdermally once daily, initially. Increase the dose to 9.5 mg/24 hours transdermally once daily after 4 weeks if tolerated and continue for as long as therapeutic benefit persists. May increase the dose to 13.3 mg/24 hours transdermally once daily if needed. If treatment is interrupted for 3 days or less, restart with the same or lower strength; if treatment is interrupted for more than 3 days, restart 4.6 mg/24 hours transdermally once daily and titrate again.

Adults weighing less than 50 kg

4.6 mg/24 hours transdermally once daily, initially. Increase the dose to 9.5 mg/24 hours transdermally once daily after 4 weeks if tolerated and continue for as long as therapeutic benefit persists. May increase the dose to 13.3 mg/24 hours transdermally once daily if needed. If treatment is interrupted for 3 days or less, restart with the same or lower strength; if treatment is interrupted for more than 3 days, restart 4.6 mg/24 hours transdermally once daily and titrate again. Carefully titrate and monitor persons with low body weight for toxicities and consider reducing the dose to 4.6 mg/24 hours transdermally if adverse events occur.

Transdermal dosage (converting from oral rivastigmine) Adults

4.6 mg/24 hours transdermally once daily for less than 6 mg/day PO and 9.5 mg/24 hours transdermally once daily for 6 to 12 mg/day PO.

For the treatment of severe Alzheimer's disease. Transdermal dosage Adults weighing 50 kg or more

4.6 mg/24 hours transdermally once daily, initially. Increase the dose to 9.5 mg/24 hours transdermally once daily after 4 weeks if tolerated and continue for as long as therapeutic benefit persists. May increase the dose to 13.3 mg/24 hours transdermally once daily if needed. If treatment is interrupted for 3 days or less, restart with the same or lower strength; if treatment is interrupted for more than 3 days, restart 4.6 mg/24 hours transdermally once daily and titrate again.

Adults weighing less than 50 kg

4.6 mg/24 hours transdermally once daily, initially. Increase the dose to 9.5 mg/24 hours transdermally once daily after 4 weeks if tolerated and continue for as long as therapeutic benefit persists. May increase the dose to 13.3 mg/24 hours transdermally once daily if needed. If treatment is interrupted for 3 days or less, restart with the same or lower strength; if treatment is interrupted for more than 3 days, restart 4.6 mg/24 hours transdermally once daily and titrate again. Carefully titrate and monitor persons with low body weight for toxicities and consider reducing the dose to 4.6 mg/24 hours transdermally if adverse events occur.

Transdermal dosage (converting from oral rivastigmine) Adults

4.6 mg/24 hours transdermally once daily for less than 6 mg/day PO and 9.5 mg/24 hours transdermally once daily for 6 to 12 mg/day PO.

For the treatment of Dementia with Lewy bodies†. Oral dosage Adults

Results from one placebo-controlled study (n = 120) of patients with a clinical diagnosis of probable Dementia with Lewy bodies (DLB) indicate that rivastigmine may be beneficial in reducing neuropsychiatric symptoms of DLB such as apathy, anxiety, delusions, and hallucinations. Almost twice as many patients in the rivastigmine group showed at least a 30% improvement from baseline than those receiving placebo. Ninety-two patients completed the 20-week treatment. Patients received placebo or titrated doses of rivastigmine beginning with 1.5 mg PO twice daily followed by dose escalations of 1.5 mg twice daily for a maximum of 2 weeks at each dose until 6 mg twice daily or a maximum well-tolerated dose was reached. At the end of the titration period at week 8, the mean daily dose was 9.4 mg. Adverse effects occurring significantly more frequently in the rivastigmine group than the placebo group included nausea (37%), vomiting (25%), anorexia (19%), and somnolence (9%).

For the treatment of vascular dementia†. Oral dosage Adults

In one study, patients with subcortical vascular dementia (sVaD) (n = 100) or multi-infarct dementia (MID) (n = 100) received rivastigmine beginning at 3 mg/day PO, with titration to 6 mg/day over 8 weeks according to response, or the comparator drug nimodipine at 30 mg/day with titration up to 60 mg/day over 8 weeks. After 14 months of treatment, there was significant improvement in behavioral symptoms (e.g., hallucinations, activity disturbances, sleep disturbances, anxieties) in the rivastigmine group with MID as assessed by the Behavioral Pathology in Alzheimer's Disease scale (BEHAVE-AD) whereas patients in the nimodipine group showed significant deterioration, except for the symptoms of aggressiveness, affective disturbances, and delusions. Affective disturbances in the rivastigmine group with MID remained unchanged whereas some deterioration was observed in the nimodipine group. Delusions improved slightly with both drugs in patients with MID. Statistically significant improvements in the BEHAVE-AD scores occurred in sVaD patients at month 14 in the rivastigmine group compared to the nimodipine group for all behavioral symptoms except delusions, which remained unchanged in both groups.

†Indicates off-label use

Hepatic Impairment

The mean clearance of rivastigmine is approximately 65% lower in patients with mild to moderate hepatic impairment. However, dosage adjustments are not necessary as the dose is individually titrated to tolerability.

Renal Impairment

Transdermal rivastigmine: No dosage adjustment is necessary in patients with renal impairment.
Oral rivastigmine: Clearance may be decreased in moderate renal impairment but increased in severe renal impairment. Dose adjustments should be individualized and based upon tolerability.
 
Intermittent hemodialysis
Adjust regular dose based on patient tolerance and response. Based on the short plasma half-life of rivastigmine, hemodialysis does not appear to influence drug clearance.

Acebutolol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Acetaminophen; Chlorpheniramine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Acetaminophen; Diphenhydramine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Acrivastine; Pseudoephedrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Amantadine: (Moderate) Concurrent use of amantadine and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Amantadine may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Amifampridine: (Moderate) Coaministration of amifampridine and rivastigmine may increase the risk for adverse reactions due to additive cholinergic effects. Monitor patients closely for new or worsening side effects such as headache, visual disturbances, watery eyes, excessive sweating, shortness of breath, nausea, vomiting, diarrhea, bradycardia, loss of bladder control, confusion, or tremors.
Amoxapine: (Moderate) Concurrent use of amoxapine and rivastigmine should be avoided if possible. Amoxapine may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Anticholinergics: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Articaine; Epinephrine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Concurrent use of certain muscle relaxants, such as cyclobenzaprine or orphenadrine, with rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Use of cyclobenzaprine or high doses of orphenadrine may result in significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Atenolol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
Atenolol; Chlorthalidone: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
Atracurium: (Moderate) A higher atracurium dose may be required to achieve neuromuscular block with concomitant use of a cholinesterase inhibitor, such as rivastigmine.
Atropine: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Atropine; Difenoxin: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Belladonna; Opium: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Benztropine: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Beta-blockers: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
Betaxolol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
Bisoprolol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
Brimonidine; Timolol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
Brompheniramine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Brompheniramine; Phenylephrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Brompheniramine; Pseudoephedrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Bupivacaine Liposomal: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Bupivacaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Bupivacaine; Epinephrine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Bupivacaine; Lidocaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary. (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
Bupivacaine; Meloxicam: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Carbinoxamine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Carteolol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
Carvedilol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
Chlophedianol; Dexbrompheniramine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Chlorcyclizine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Chlordiazepoxide; Clidinium: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Chloroprocaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Chlorpheniramine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Chlorpheniramine; Codeine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Chlorpheniramine; Dextromethorphan: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Chlorpheniramine; Hydrocodone: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Chlorpheniramine; Phenylephrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Chlorpheniramine; Pseudoephedrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Chlorpromazine: (Moderate) Conventional antipsychotics with significant anticholinergic effects, such as chlorpromazine, are more likely than other conventional antipsychotics to diminish the therapeutic action of rivastigmine, and use of an alternative antipsychotic should be considered. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and exerts its therapeutic effect by improving the availability of acetylcholine. Consider the use of an antipsychotic with less prominent anticholinergic effects.
Cholinergic agonists: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
Cisatracurium: (Moderate) A higher cisatracurium dose may be required to achieve neuromuscular block with concomitant use of a cholinesterase inhibitor, such as rivastigmine.
Clemastine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Clozapine: (Moderate) Concurrent use of rivastigmine and clozapine should be avoided if possible. Clozapine exhibits considerable anticholinergic activity, and is more likely than other atypical antipsychotics to diminish the therapeutic action of rivastigmine. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Consider the use of an antipsychotic with less prominent anticholinergic effects.
Cocaine: (Major) cholinesterase inhibitors reduce the metabolism of cocaine, therefore, prolonging cocaine's effects or increasing the risk of toxicity. It should be taken into consideration that the cholinesterase inhibition caused by echothiophate, demecarium, or isoflurophate may persist for weeks or months after the medication has been discontinued. Additionally, local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Dosage adjustment of the cholinesterase inhibitor may be necessary to control the symptoms of myasthenia gravis.
Codeine; Phenylephrine; Promethazine: (Moderate) Promethazine exhibits anticholinergic properties that could potentially interfere with the cholinesterase inhibitor activity of rivastigmine. When concurrent use cannot be avoided, monitor the patient for reduced rivastigmine efficacy.
Codeine; Promethazine: (Moderate) Promethazine exhibits anticholinergic properties that could potentially interfere with the cholinesterase inhibitor activity of rivastigmine. When concurrent use cannot be avoided, monitor the patient for reduced rivastigmine efficacy.
Cyclizine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Cyclobenzaprine: (Moderate) Concurrent use of certain muscle relaxants, such as cyclobenzaprine or orphenadrine, with rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Use of cyclobenzaprine or high doses of orphenadrine may result in significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Cyproheptadine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Dexbrompheniramine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Dexchlorpheniramine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Dicyclomine: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Digoxin: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may be increased when given with other medications known to cause bradycardia such as digoxin. In one study involving multiple doses of galantamine at 24 mg/day with digoxin at a dose of 0.375 mg/day, there was no effect on the pharmacokinetics of digoxin, except one healthy subject was hospitalized due to second and third degree heart block and bradycardia.
Dimenhydrinate: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Diphenhydramine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Diphenhydramine; Ibuprofen: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Diphenhydramine; Naproxen: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Diphenhydramine; Phenylephrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Diphenoxylate; Atropine: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Disopyramide: (Moderate) Concurrent use of disopyramide and rivastigmine should be avoided if possible. When concurrent use cannot be avoided, monitor the patient for reduced rivastigmine efficacy. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Disopyramide may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Dorzolamide; Timolol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
Doxylamine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Doxylamine; Pyridoxine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Esmolol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
Etomidate: (Moderate) Muscle relaxation produced by succinylcholine can be prolonged when the drug is administered with a cholinesterase inhibitor. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade. Other neuromuscular blockers may interact with cholinesterase inhibitors in a similar fashion. Cholinesterase inhibitors are therefore also likely to exaggerate muscle relaxation under general anesthetics.
Flavoxate: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Glycopyrrolate: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Glycopyrrolate; Formoterol: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Halogenated Anesthetics: (Moderate) Muscle relaxation produced by succinylcholine can be prolonged when the drug is administered with a cholinesterase inhibitor. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade. Other neuromuscular blockers may interact with cholinesterase inhibitors in a similar fashion. Cholinesterase inhibitors are therefore also likely to exaggerate muscle relaxation under general anesthetics.
Homatropine; Hydrocodone: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Hydroxyzine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Hyoscyamine: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Indacaterol; Glycopyrrolate: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Ketamine: (Moderate) Muscle relaxation produced by succinylcholine can be prolonged when the drug is administered with a cholinesterase inhibitor. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade. Other neuromuscular blockers may interact with cholinesterase inhibitors in a similar fashion. Cholinesterase inhibitors are therefore also likely to exaggerate muscle relaxation under general anesthetics.
Labetalol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
Levobunolol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
Lidocaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
Lidocaine; Epinephrine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
Lidocaine; Prilocaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary. (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
Maprotiline: (Moderate) Concurrent use of maprotiline and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Maprotiline may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Meclizine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Mepivacaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Methocarbamol: (Moderate) Methocarbamol may inhibit the effect of cholinesterase inhibitors. Methocarbamol also has sedative properties that may interfere with cognition. Therefore, methocarbamol should be used with caution in patients receiving cholinesterase inhibitors.
Methohexital: (Moderate) Muscle relaxation produced by succinylcholine can be prolonged when the drug is administered with a cholinesterase inhibitor. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade. Other neuromuscular blockers may interact with cholinesterase inhibitors in a similar fashion. Cholinesterase inhibitors are therefore also likely to exaggerate muscle relaxation under general anesthetics.
Methscopolamine: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Metoclopramide: (Major) Metoclopramide is a central dopamine antagonist and may cause extrapyramidal reactions (e.g., acute dystonic reactions, pseudo-parkinsonism, akathisia, or tardive dyskinesia), and rarely, neuroleptic malignant syndrome. Metoclopramide is contraindicated with other drugs that are likely to cause extrapyramidal effects since the risk of these effects may be increased. Cholinomimetics such as rivastigmine may cause or worsen extrapyramidal symptoms such as pseudoparkinsonism, dyskinesia, and dystonia, although the incidences of these effects during clinical trials with rivastigmine were infrequent. The risk of extrapyramidal effects may be increased during concurrent use of metoclopramide and rivastigmine; close monitoring is advisable if combination therapy is necessary.
Metoprolol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
Mivacurium: (Moderate) A higher mivacurium dose may be required to achieve neuromuscular block with concomitant use of a cholinesterase inhibitor, such as rivastigmine.
Nadolol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
Nebivolol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
Nebivolol; Valsartan: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
Neostigmine; Glycopyrrolate: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Nonsteroidal antiinflammatory drugs: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Olanzapine: (Moderate) Olanzapine exhibits moderate anticholinergic activity, and is more likely than most other atypical antipsychotics to diminish the therapeutic action of rivastigmine. Consider the use of an antipsychotic with less prominent anticholinergic effects. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and exerts its therapeutic effect by improving the availability of acetylcholine.
Olanzapine; Fluoxetine: (Moderate) Olanzapine exhibits moderate anticholinergic activity, and is more likely than most other atypical antipsychotics to diminish the therapeutic action of rivastigmine. Consider the use of an antipsychotic with less prominent anticholinergic effects. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and exerts its therapeutic effect by improving the availability of acetylcholine.
Olanzapine; Samidorphan: (Moderate) Olanzapine exhibits moderate anticholinergic activity, and is more likely than most other atypical antipsychotics to diminish the therapeutic action of rivastigmine. Consider the use of an antipsychotic with less prominent anticholinergic effects. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and exerts its therapeutic effect by improving the availability of acetylcholine.
Orphenadrine: (Moderate) Concurrent use of certain muscle relaxants, such as cyclobenzaprine or orphenadrine, with rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Use of cyclobenzaprine or high doses of orphenadrine may result in significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Oxybutynin: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Pancuronium: (Moderate) A higher pancuronium dose may be required to achieve neuromuscular block with concomitant use of a cholinesterase inhibitor, such as rivastigmine.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Pindolol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
Prilocaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase

inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Prilocaine; Epinephrine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Promethazine: (Moderate) Promethazine exhibits anticholinergic properties that could potentially interfere with the cholinesterase inhibitor activity of rivastigmine. When concurrent use cannot be avoided, monitor the patient for reduced rivastigmine efficacy.
Promethazine; Dextromethorphan: (Moderate) Promethazine exhibits anticholinergic properties that could potentially interfere with the cholinesterase inhibitor activity of rivastigmine. When concurrent use cannot be avoided, monitor the patient for reduced rivastigmine efficacy.
Promethazine; Phenylephrine: (Moderate) Promethazine exhibits anticholinergic properties that could potentially interfere with the cholinesterase inhibitor activity of rivastigmine. When concurrent use cannot be avoided, monitor the patient for reduced rivastigmine efficacy.
Propantheline: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Propofol: (Moderate) Muscle relaxation produced by succinylcholine can be prolonged when the drug is administered with a cholinesterase inhibitor. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade. Other neuromuscular blockers may interact with cholinesterase inhibitors in a similar fashion. Cholinesterase inhibitors are therefore also likely to exaggerate muscle relaxation under general anesthetics.
Propranolol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
Pseudoephedrine; Triprolidine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Pyrilamine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Rocuronium: (Moderate) A higher rocuronium dose may be required to achieve neuromuscular block with concomitant use of a cholinesterase inhibitor, such as rivastigmine.
Scopolamine: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Sedating H1-blockers: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Solifenacin: (Moderate) The therapeutic benefits of the cholinesterase inhibitors for dementia or other neurologic conditions may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. Some of the common selective antimuscarinic drugs for bladder problems, (such as solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia.
Sotalol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
Succinylcholine: (Moderate) A synergistic effect may be expected when succinylcholine is given concomitantly with a cholinesterase inhibitor, such as rivastigmine.
Tetracaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Thioridazine: (Moderate) Conventional antipsychotics with significant anticholinergic effects, such as chlorpromazine and thioridazine, are more likely than other conventional antipsychotics to diminish the therapeutic action of rivastigmine, and use of an alternative antipsychotic should be considered. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and exerts its therapeutic effect by improving the availability of acetylcholine. Consider the use of an antipsychotic with less prominent anticholinergic effects.
Timolol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
Tobacco: (Major) Advise patients to avoid smoking tobacco while taking rivastigmine. Tobacco smoking has been shown to increase the oral clearance of rivastigmine by 23% versus patients who are non-smokers.
Tolterodine: (Moderate) The therapeutic benefits of the cholinesterase inhibitors for dementia or other neurologic conditions may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. Some of the common selective antimuscarinic drugs for bladder problems, (such as tolterodine), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia.
Tricyclic antidepressants: (Moderate) Concurrent use of tricyclic antidepressants and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Tricyclic antidepressants with significant anticholinergic activity, such as amitriptyline, imipramine, doxepin, and clomipramine, are more likely to interfere with the therapeutic effect of rivastigmine than other tricyclics.
Trihexyphenidyl: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Triprolidine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Trospium: (Moderate) The therapeutic benefits of the cholinesterase inhibitors for dementia or other neurologic conditions may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. Some of the common selective antimuscarinic drugs for bladder problems, (such as trospium), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia.
Vecuronium: (Moderate) A higher vecuronium dose may be required to achieve neuromuscular block with concomitant use of a cholinesterase inhibitor, such as rivastigmine.

Exelon Patch/Rivastigmine Topical Film ER: 4.6mg, 9.5mg, 13.3mg, 24h
Exelon Patch/Rivastigmine Transdermal Film ER: 4.6mg, 9.5mg, 13.3mg, 24h
Exelon/Rivastigmine/Rivastigmine Tartrate Oral Cap: 1.5mg, 3mg, 4.5mg, 6mg

Adults

12 mg/day PO; 13.3 mg/24 hours transdermally.

Geriatric

12 mg/day PO; 13.3 mg/24 hours transdermally.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Rivastigmine is a potent, selective inhibitor of brain acetylcholinesterase (AChE) and butylcholinesterase (BChE). In animal studies, rivastigmine produced a 10-fold greater inhibition of AChE in the hippocampus and cortex than its effects on BChE and AChE in the heart, skeletal muscle, and other peripheral tissues, which may explain its relatively low incidence of peripheral cholinergic side effects with appropriate dose titration. The selective effect in the cortex and hippocampus may be due to its preferential inhibition of the G1 form of the acetylcholinesterase enzyme, which is present in relatively higher concentrations in these brain areas. Unlike tacrine, donepezil, galantamine and physostigmine, which are reversible inhibitors of cholinesterase, and metrifonate, which is considered to be an irreversible inhibitor, rivastigmine is considered a pseudo-irreversible inhibitor of AChE. Rivastigmine binds to the esteratic site of the acetylcholinesterase enzyme but dissociates much more slowly than acetylcholine. This 'pseudo-irreversible' action explains why the cholinesterase inhibition of rivastigmine in the brain lasts much longer (average 10 hours) than the short plasma half-life of the drug would predict. There is no evidence to suggest that the underlying disease process is affected by administration of rivastigmine. Patients with Alzheimer's disease show behavioral consequences (e.g., decline in memory and learning) that are partially related to cholinergic deficits. Although not a cure, therapy with cholinesterase inhibitors is designed to offset the loss of presynaptic cholinergic function and slow the decline of memory and the ability to perform functions of daily living. This mechanism requires that intact cholinergic neurons be present. As dementia progresses, fewer intact cholinergic neurons remain, and cholinesterase inhibitors become less effective. There is considerable evidence indicating that, as in Alzheimer's disease, the central cholinergic system is also impaired in vascular dementia (VaD) and in patients with Alzheimer's disease with cerebrovascular disease ('mixed' dementia), as well as other conditions.

Rivastigmine is administered orally or transdermally. Intersubject variability in rivastigmine exposure is lower for the transdermal system (43%—49%) than the oral formulation (73—103%). Rivastigmine is weakly bound to plasma proteins (approximately 40%). It readily crosses the blood brain barrier and is widely distributed. Approximately 50% of the drug load is released from the transdermal system over 24 hours.
 
Hepatic cytochrome P450 isoenzymes (CYP450) are minimally involved in rivastigmine metabolism. Rivastigmine is rapidly and extensively metabolized primarily at CNS receptor sites via cholinesterase, which mediates hydrolysis to the decarbamylated phenolic metabolite (i.e., ZNS 114—666). This metabolite is detected within 2 hours of rivastigmine administration. In vitro, the decarbamylated metabolite shows minimal inhibition of acetylcholinesterase (< 10%). The ZNN—666 metabolite is N-demethylated or sulfated in the liver, but is of no therapeutic consequence. Consistent with these observations is the finding that no drug interactions relating to CYP450 have been observed in humans. The plasma half-lives of rivastigmine and the ZNN—666 metabolite are roughly 1 hour and 2 hours, respectively; however, the cholinesterase inhibition in the CNS lasts much longer (average 10 hours) than the short plasma half-life would predict. This is due to the fact that when rivastigmine's phenolic ZNN—666 metabolite is formed, it leaves behind a carbamate moiety that stays attached to the AChE receptor for up to 10 hours, which prevents the hydrolysis of ACh. Renal excretion of the ZNN—666 metabolite is the major route of elimination; unchanged rivastigmine is not found in the urine. Renal elimination is essentially complete (> 90%) within 24 hours. Less than 1% of the administered dose is excreted in the feces. Although patients with Alzheimer's disease demonstrate 30—50% higher plasma concentrations of rivastigmine and its decarbamylated metabolite than do healthy elderly patients, there is no evidence of drug accumulation, which is consistent with the short plasma half-life.

Oral Route

Following oral administration, it is rapidly and completely absorbed and peak plasma concentrations are reached in approximately 1 hour. Absolute bioavailability after a 3-mg oral dose is 36%, indicating a significant first-pass effect. Oral administration with food delays absorption and lowers Cmax by roughly 30%, but increases the AUC by approximately 30%. Thus, oral rivastigmine should be taken with food to enhance bioavailability and to increase tolerability of the medication.

Topical Route

Following transdermal application, absorption begins within 30 minutes to 1 hour and peak plasma concentrations are typically reached in 8 hours (range: 8—16 hours). With transdermal application, trough levels are about 60—80% of peak levels at steady state. Body weight affects rivastigmine exposure; steady state concentrations are approximately doubled in a patient weighing 35 kg compared to 65 kg. Following a transdermal dose of 9.5 mg/24 hours, drug exposure is similar to an oral dose of 6 mg twice daily. Approximately 50% of the drug load is released from the transdermal system over 24 hours.

Pregnancy

There are no adequate data on the developmental risks associated with rivastigmine use in human pregnancy. In animals, doses of 2 to 4 times the maximum human recommended dose (MHRD) did not produce evidence of teratogenicity. The effects of rivastigmine in labor and delivery are unknown.

Use rivastigmine during lactation with caution; the developmental and health benefits of breast-feeding should be considered along with the need of the mother for rivastigmine and any potential adverse effects to the breastfed infant or from the underlying maternal condition. There are no data on the presence of rivastigmine in human milk, the effects on the breastfed infant, or the effects of rivastigmine on milk production. Rivastigmine and its metabolites are found in rat milk at approximately 2 times the levels of maternal plasma; however, animal data may not reliably predict drug concentrations in human milk due to species-specific differences in lactation physiology.