Rivastigmine is a cholinesterase inhibitor (ChEI). Rivastigmine (oral and transdermal) is approved for the symptomatic management of mild to moderate Alzheimer's disease and mild to moderate Parkinson's disease dementia. Transdermal rivastigmine is approved for severe Alzheimer's disease. Small improvements in cognition and activities of daily living may be observed during treatment with ChEIs; however, the drugs do not prevent or delay the progression of the disease. According to an effectiveness review from the Agency for Healthcare Research and Quality (AHRQ), the evidence suggests that in patients with mild to moderate Alzheimer's disease, oral rivastigmine 12 mg/day and transdermal rivastigmine 9.5 mg/day are associated with small improvements in cognition, function, staging, and clinical impression of change and there is an increase in withdrawals due to adverse events. The evidence also suggests that oral rivastigmine 12 mg/day and transdermal rivastigmine 9.5 mg/day show small improvements in clinical impression of change in moderate to severe Alzheimer's disease, although the evidence is insufficient for cognition. In mild to moderate Alzheimer's disease, low doses of rivastigmine (i.e., 4 mg/day PO, 4.6 mg/day transdermal) show no difference in cognition, a minor improvement in the clinical impression of change, and insufficient evidence for global staging. The evidence is insufficient to evaluate the efficacy and harms of rivastigmine in treating behavioral and psychological symptoms of dementia (BPSD). No drugs have established efficacy for vascular dementia and the benefit of rivastigmine for vascular dementia is not well established. Most treatment guidelines support a trial of a ChEI for improving cognition in dementia with Lewy bodies (DLB). Studies of ChEIs for mild cognitive impairment (MCI) or frontotemporal dementia (FTD) have failed to show benefit in these populations, and ChEIs may cause agitation in patients with FTD. In contrast to donepezil and similar to galantamine, rivastigmine requires multiple daily dosages and a slow dosage titration to limit GI side effects.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
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.
Many dose-limiting side effects of rivastigmine are related to the cholinergic pharmacology of the drug. Such side effects are more likely to be apparent during dosage titration. Although rivastigmine is reported to be well-tolerated at oral dosages of < 6 mg/day, dosages of 6 mg/day PO or greater are associated with a discontinuation rate approaching 15% during dosage titration (vs. 5% for placebo) and 6% during maintenance dosing (vs. 4% with placebo) due to intolerable side effects. To reduce the incidence of intolerable side effects, administration of oral rivastigmine should always occur with food to avoid high peak plasma concentrations. Following the recommended slow titration schedule for both the oral and transdermal formulation should help limit common gastrointestinal (GI) adverse reactions. Adverse effects may respond to holding a few doses or dosage reduction to the previously tolerated dosage level. Patients below 50 kg of body weight may experience more side effects and discontinue treatment, since rivastigmine exposure is higher in those with low body weight. Caution is advised when titrating transdermal doses or exceeding 9.5 mg/24 hours in those with low body weight.
In clinical trials of oral rivastigmine for the treatment of dementia associated with Alzheimer's disease or Parkinson's disease, nausea was reported in 29-47% of patients receiving rivastigmine and 11-12% of those receiving placebo; vomiting occurred in 13-31% of the active treatment group and 2-6% of those in the placebo group. Nausea and vomiting were among the most common side effects leading to discontinuation of the oral formulation. In a placebo-controlled comparison of the 9.5 mg/24 hour rivastigmine transdermal system to oral rivastigmine (up to 6 mg BID), nausea and vomiting were reported as follows in the transdermal rivastigmine group, the oral rivastigmine group, and the placebo group, respectively: nausea (7%, 23%, 5%) and vomiting (6%, 17%, 3%). In the same clinical trial, severe vomiting was only reported in those receiving the oral formulation (1% of subjects). However, when manufacturer recommended transdermal doses are exceeded, a high incidence of nausea/vomiting (21%/19%) has been observed. Female patients were found to be more susceptible to nausea/vomiting. In one clinical trial of transdermal rivastigmine for severe Alzheimer's disease, nausea/vomiting were reported in 3% of patients receiving the 4.6 mg/24 hour dose and 6-7% of patients receiving the 13.3 mg/24 hour dose. If intolerable GI adverse effects occur, treatment with rivastigmine can be withheld and followed by re-initiation of therapy according to manufacturer's dosing instructions (see Dosage). There has been one post-marketing case of severe vomiting with esophageal rupture reported to have occurred after reinitiating treatment at an inappropriate single dose of 4.5 mg following discontinuation for eight weeks.
In clinical trials of oral rivastigmine for the treatment of dementia associated with Alzheimer's disease or Parkinson's disease, diarrhea was reported in 7-19% of patients who received rivastigmine compared to 4-11% of patients who received placebo. In a placebo-controlled comparison of the 9.5 mg/24 hour rivastigmine transdermal system to oral rivastigmine (up to 6 mg BID), diarrhea was reported in the transdermal rivastigmine group (6%), the oral rivastigmine group (5%), and the placebo group (3%). When manufacturer recommended transdermal doses are exceeded, a high incidence of diarrhea (10%) has been observed. In one clinical trial of transdermal rivastigmine for severe Alzheimer's disease, diarrhea was reported in 5% of patients receiving the 4.6 mg/24 hour dose and 7% of patients receiving the 13.3 mg/24 hour dose. If GI adverse effects occur, treatment with rivastigmine can be withheld (the recommendation is for several doses). Those who have interrupted rivastigmine therapy for longer than several days should reinitiate with the lowest daily dose and titrate slowly back to their maintenance dose as prescribed. There has been one post-marketing case of severe vomiting with esophageal rupture reported to have occurred after reinitiating treatment at an inappropriate single dose of 4.5 mg following discontinuation for eight weeks.
In clinical trials of oral rivastigmine in the treatment of dementia associated with Alzheimer's disease or Parkinson's disease, anorexia was reported in 6-17% of patients receiving rivastigmine compared to 3% of patients who received placebo. Anorexia was among the most common side effects leading to discontinuation of the oral formulation. In a placebo-controlled comparison of the 9.5 mg/24 hour rivastigmine transdermal system to oral rivastigmine (up to 6 mg BID), anorexia was reported in the transdermal rivastigmine group (3%), the oral rivastigmine group (9%), and the placebo group (2%). In one clinical trial of transdermal rivastigmine for severe Alzheimer's disease, anorexia was reported in 1% of patients receiving the 4.6 mg/24 hour dose and 5% of patients receiving the 13.3 mg/24 hour dose. When manufacturer recommended transdermal doses are exceeded, a high incidence of anorexia (9%) has been observed. Female patients were found to be more susceptible to loss of appetite (anorexia). If GI adverse effects occur, treatment with rivastigmine can be withheld (the recommendation is for several doses). Those who have interrupted rivastigmine therapy for longer than several days should reinitiate with the lowest daily dose and titrate slowly back to their maintenance dose as prescribed. There has been one post-marketing case of severe vomiting with esophageal rupture reported to have occurred after reinitiating treatment at an inappropriate single dose of 4.5 mg following discontinuation for eight weeks.
In clinical trials of oral rivastigmine in the treatment of dementia associated with Alzheimer's disease or Parkinson's disease, GI adverse reactions were common and were reported more frequently in the rivastigmine group compared to the placebo group. Common GI adverse reactions included abdominal pain (13% vs. 6%), upper abdominal pain (4% vs 1%), dyspepsia (9% vs. 4%), and hypersalivation (1-2% vs 0%). In a placebo-controlled comparison of the 9.5 mg/24 hour rivastigmine transdermal system to oral rivastigmine (up to 6 mg BID), the following GI effects were reported in the transdermal rivastigmine group, the oral rivastigmine group, and the placebo group, respectively: abdominal pain (2%, 1%, 1%) and upper abdominal pain (1%, 2%, 2%). In one clinical trial of transdermal rivastigmine for mild to moderate Parkinson's disease dementia, abdominal pain was reported in 2% of patients. GI effects observed in at least 1% of patients during clinical trial evaluation of oral rivastigmine included constipation, flatulence, and gastritis. Infrequently reported effects (0.1-1%) included dysphagia, fecaloma, peptic ulcer, gastroesophageal reflux, GI bleeding (hemorrhage), hernia, melena, rectal hemorrhage, duodenal ulcer, hematemesis, and pancreatitis. Constipation and gastritis were reported in at least 1% of patients receiving transdermal rivastigmine during clinical trial evaluation; infrequent events (0.1-1%) included gastroesophageal reflux, hematochezia, peptic ulcer, hematemesis, pancreatitis, and hypersalivation. Causality to the drug has not been established for all reported reactions. If GI adverse effects occur, treatment with rivastigmine can be withheld (the recommendation is for several doses). Those who have interrupted rivastigmine therapy for longer than several days should reinitiate with the lowest daily dose and titrate slowly back to their maintenance dose as prescribed. There has been one post-marketing case of severe vomiting with esophageal rupture reported to have occurred after reinitiating treatment at an inappropriate single dose of 4.5 mg following discontinuation for eight weeks.
In controlled clinical trials of oral rivastigmine for the treatment of dementia associated with Alzheimer's disease or Parkinson's disease, weight loss occurred in 3% of patients on rivastigmine versus < 1% on placebo. Decreased appetite was reported in 5-8% of patients in the active treatment groups versus 5% of patients in the placebo groups. Weight loss has also been observed with transdermal rivastigmine. This can be a clinically significant adverse reaction; weight loss of more than 7% of baseline weight occurred in 8% of patients receiving transdermal rivastigmine versus 11% of patients receiving oral rivastigmine. In one clinical trial of transdermal rivastigmine for severe Alzheimer's disease, weight loss of more than 7% of baseline weight was reported in 11% of patients receiving the 4.6 mg/24 hour dose and 14.1% of patients receiving the 13.3 mg/24 hour dose. Weight loss averaged 1.39 kg in those receiving oral rivastigmine at >= 6 mg/day in European trials. Weight loss of >= 7% of baseline body weight occurred in 26% of women and 18% of men who received oral rivastigmine at the higher end of the dosage range (i.e., > 9 mg/day) vs. an average 4-6% weight loss in those receiving placebo. When manufacturer recommended transdermal doses are exceeded, a higher incidence of weight loss (12%) has been observed. Female patients were found to be more susceptible to weight loss.
Cholinomimetics, such as rivastigmine, may exacerbate or cause extrapyramidal symptoms. In clinical trials of oral rivastigmine in the treatment of dementia associated with Parkinson's disease, the following effects were reported more frequently with rivastigmine than placebo: pseudoparkinsonism, including cogwheel rigidity (1-3% vs <= 1%), worsening of Parkinson's disease (3% vs 1%), bradykinesia (3% vs 2%), dyskinesias (1-3% vs 1%), and hypokinesia (1-2% vs 0%). During clinical trials of oral rivastigmine for dementia associated with Alzheimer's disease or Parkinson's disease, tremor was reported more frequently in the active treatment groups than the placebo groups (4-10% vs 1-4%). In one clinical trial of transdermal rivastigmine for mild to moderate Parkinson's disease dementia, the following extrapyramidal effects occurred in at least 2% of patients: tremor (7%), hypokinesia (4%), bradykinesia (4%), cogwheel rigidity (3%), and dyskinesia (3%). Tremor was reported in at least 1% of patients receiving transdermal rivastigmine during clinical trial evaluation and pseudoparkinsonism was reported infrequently (0.1-1%). Worsening of Parkinson's disease has occurred during post-marketing use of rivastigmine.
In clinical trials of oral rivastigmine for the treatment of dementia associated with Alzheimer's disease or Parkinson's disease, the following CNS effects occurred in >= 2% of rivastigmine treated patients and at a higher frequency than placebo-treated patients, respectively: dizziness (6-21% vs. 1-11%); headache (4-17% vs. 3-12%); syncope (3% vs 2%), insomnia (3-9% vs 2-7%), restlessness (1-3% vs 2%), and somnolence/drowsiness (4-5% vs. 3%). Falls were reported in 6-10% of patients receiving active treatment versus 6% of patients receiving placebo. Dizziness resulted in drug discontinuation in roughly 2% of rivastigmine treated patients vs. < 1% receiving placebo. In a placebo-controlled comparison of the 9.5 mg/24 hour rivastigmine transdermal system to oral rivastigmine (up to 6 mg BID), the following CNS effects were reported in the transdermal rivastigmine group, the oral rivastigmine group, and the placebo group, respectively: headache (3%, 6%, 2%), insomnia (1%, 2%, 2%), vertigo (0%, 1%, 1%), and dizziness (2%, 7%, 2%). In one clinical trial of transdermal rivastigmine for severe Alzheimer's disease, insomnia was reported in 4% of patients receiving the 4.6 mg/24 hour dose and 7% of patients receiving the 13.3 mg/24 hour dose. In the same trial, fall occurred more frequently with high-dose versus low-dose transdermal rivastigmine (8% vs 6%). In a separate clinical trial of transdermal rivastigmine for mild to moderate Parkinson's disease dementia, the following CNS effects occurred in at least 2% of patients: insomnia (6%), dizziness (6%), somnolence (4%), fall (12%), and gait disturbance (4%). CNS effects observed in at least 1% of patients during clinical trial evaluation of oral rivastigmine included abnormal gait, ataxia, paresthesias, and seizures. Infrequently reported effects (0.1-1%) included dysphonia, hypoesthesia, migraine, and nystagmus. The following effects were reported in 0.1-1% of patients receiving transdermal rivastigmine during clinical trial evaluation: migraine and epilepsy; causality to the drug has not been established. Seizures were reported during post-marketing use of transdermal rivastigmine.
Behavioral changes may occur with cholinesterase inhibitor therapy but are also evident in patients with dementia as part of the pathologic process. In clinical trials of oral rivastigmine for the treatment of dementia associated with Alzheimer's disease or Parkinson's disease, the following psychiatric effects occurred in 2% or more of rivastigmine-treated patients and at a higher frequency than placebo-treated patients: confusion (8%); depression (6%); anxiety (4% to 5%); hallucinations (4%); and aggressive reaction (3%). In a comparison of the 9.5 mg/24 hour rivastigmine transdermal system to oral rivastigmine (up to 6 mg twice daily), the following psychiatric effects were reported in the transdermal rivastigmine group, the oral rivastigmine group, and the placebo group, respectively: depression (4%, 4%, 1%) and anxiety (3%, 2%, 1%). In a clinical trial of transdermal rivastigmine for severe Alzheimer's disease, the following psychiatric effects were reported in patients receiving the 4.6 mg/24 hour dose versus the 13.3 mg/24 hour dose, respectively: agitation (14% vs. 12%), depression (4% vs. 5%), anxiety (5% vs. 5%), and hallucinations (5% vs. 2%). In a separate clinical trial of transdermal rivastigmine for mild to moderate Parkinson's disease dementia, the following psychiatric effects occurred in at least 2% of patients: depression (6%), anxiety (5%), and agitation (3%). Psychiatric effects observed in at least 1% of patients during clinical trials for oral rivastigmine included agitation, depression, and confusion. Infrequently reported effects (0.1% to 1%) included apathy, suicide attempt, libido increase, and suicidal ideation. Delusions were reported infrequently (0.1% to 1%) in patients receiving transdermal rivastigmine during clinical trial evaluation. Aggression and nightmares have occurred during post-marketing use, although causality to the drug has not been established.
During clinical trials of oral rivastigmine for the treatment of dementia associated with Alzheimer's disease or Parkinson's disease, the following general effects occurred more frequently with rivastigmine than placebo: accidental trauma (10% vs 9%), fatigue (4-9% vs 3-5%), malaise (5% vs 2%), and asthenia (2-6% vs 1-2%). In a comparison of the 9.5 mg/24 hour rivastigmine transdermal system to oral rivastigmine (up to 6 mg twice daily), the following general effects were reported in the transdermal rivastigmine group, the oral rivastigmine group, and the placebo group, respectively: asthenia (2%, 6%, 1%) and fatigue (2%, 1%, 1%). In one clinical trial of transdermal rivastigmine for mild to moderate Parkinson's disease dementia, the following general effects occurred in at least 2% of patients: asthenia (2%) and fatigue (4%). General effects observed in at least 1% of patients during clinical trial evaluation of oral rivastigmine included allergy (unspecified) and hot flashes. Peripheral edema, increased creatine phosphokinase, increased lipase, increased blood amylase, and hip fracture were reported infrequently (0.1-1%). Causality to the drug has not been established.
Genitourinary effects observed in at least 1% of patients during clinical trial evaluation of oral rivastigmine included hematuria. Acute renal failure (unspecified), dysuria, and urinary incontinence were reported in 0.1-1% of patients. Urinary incontinence was reported in at least 1% of patients receiving transdermal rivastigmine during clinical trial evaluation and pollakiuria (increased urinary frequency), hematuria, nocturia, and renal failure were reported infrequently (0.1-1%). Causality to the drug has not been established.
In clinical trials of oral rivastigmine for the treatment of dementia associated with Alzheimer's disease, hypertension occurred more frequently in rivastigmine-treated patients than placebo-treated patients (3% vs 2%). In one clinical trial of transdermal rivastigmine for mild to moderate Parkinson's disease dementia, hypertension was reported in 3% of patients. Cardiovascular effects observed in at least 1% of patients during clinical trial evaluation of oral rivastigmine included chest pain (unspecified), hypotension, orthostatic hypotension, atrial fibrillation, bradycardia, angina, myocardial infarction, and palpitations. Infrequent effects (0.1% to 1%) included AV block, sick sinus syndrome, supraventricular tachycardia (SVT), extrasystoles, and sinus tachycardia. The following cardiac effects were reported in 0.1% to 1% of patients receiving transdermal rivastigmine during clinical trial evaluation: angina pectoris, chest pain (unspecified), heart failure, hypotension, bradycardia, atrial fibrillation, supraventricular systoles, myocardial infarction, sinus tachycardia, arrhythmia, and AV block. Hypertension and tachycardia have occurred during post-marketing use of transdermal rivastigmine; causality to the drug has not been established.
Disseminated hypersensitivity reactions have been reported during use of oral and transdermal rivastigmine; treatment should be discontinued in these cases. Dermatologic effects observed in at least 1% of patients during clinical trial evaluation of oral rivastigmine and for which causality to the drug has not been established include erythematous rash (unspecified), maculopapular rash, atopic dermatitis, bullous rash, exfoliative rash, and psoriaform rash. Urticaria and contact dermatitis occurred infrequently (0.1-1%). Pruritus was reported in at least 1% of patients receiving transdermal rivastigmine during clinical trial evaluation. Erythema, atopic dermatitis, unspecified dermatitis, erythematous rash, skin ulcer, application site dermatitis, application site irritation, and application site eczema occurred infrequently (0.1-1%). In one clinical trial of transdermal rivastigmine for severe Alzheimer's disease, application site erythema was reported in 12% of patients receiving the 4.6 mg/24 hour dose and 13% of patients receiving the 13.3 mg/24 hour dose. In a separate trial of transdermal rivastigmine for mild to moderate Parkinson's disease dementia, the following application site reactions were reported: erythema (11%), pruritus (5%), irritation (3%), and rash (2%). Application site reactions most frequently associated with discontinuation of treatment during clinical trials were pruritus and erythema. Stevens-Johnson syndrome has been reported during post-marketing use of oral rivastigmine. During post-marketing use of transdermal rivastigmine, the following dermatologic effects have been reported: application site hypersensitivity, urticaria, blister, and allergic dermatitis. Skin reactions to transdermal rivastigmine are usually mild to moderate; however, in some cases, allergic contact dermatitis can develop. Treatment with the patch should be discontinued 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), and if symptoms do not significantly improve within 48 hours after patch removal. If rivastigmine therapy is still required, switch to oral administration only after a negative allergy test and with close monitoring. Some patients with sensitivity to the patch may not be able to take rivastigmine in any form.
Elevated hepatic enzymes (e.g., alkaline phosphatase, gamma-glutamyltransferase) have been observed in 0.1-1% of patients receiving oral rivastigmine during clinical trial evaluation. Cholecystitis was reported during clinical trial evaluation of transdermal rivastigmine (0.1-1%). Causality to the drug has not been established. Abnormal liver function tests and hepatitis have been reported during post-marketing use.
In clinical trials of oral rivastigmine for the treatment of dementia associated with Alzheimer's disease or Parkinson's disease, the following effects occurred more frequently in rivastigmine-treated patients than placebo-treated patients: hyperhidrosis (2-4% vs 1%) and dehydration (2% vs 1%). Polydipsia and dehydration were observed in at least 1% of patients during other clinical trial evaluations of oral or transdermal rivastigmine. Causality to the drug has not been established.
In clinical trials of oral rivastigmine for the treatment of dementia associated with Alzheimer's disease, the following respiratory effects, infections, or related symptoms occurred more frequently in rivastigmine-treated patients than placebo-treated patients: urinary tract infection (7% vs 6%). In a comparison of the 9.5 mg/24 hour rivastigmine transdermal system to oral rivastigmine (up to 6 mg twice daily), urinary tract infection was reported in the transdermal rivastigmine group (2%), the oral rivastigmine group (1%), and the placebo group (1%). In one clinical trial of transdermal rivastigmine for severe Alzheimer's disease, urinary tract infection was reported in 10% of patients receiving the 4.6 mg/24 hour dose and 8% of patients receiving the 13.3 mg/24 hour dose. Dyspnea was observed in at least 1% of patients during clinical trial evaluation of oral rivastigmine. Infrequently reported effects (0.1-1%) included bronchospasm, cough, herpes simplex, otitis media, and lymphadenopathy. The following effects were reported in at least 1% of patients receiving transdermal rivastigmine during clinical trial evaluation: nasopharyngitis and pneumonia; infrequent effects (0.1-1%) included dyspnea, bronchospasm, chronic obstructive pulmonary disease, and fever. Causality to the drug has not been established.
Tinnitus was observed in at least 1% of patients during clinical trial evaluation of oral rivastigmine. Tinnitus was also observed in 0.1-1% of patients receiving transdermal rivastigmine during clinical trials. Causality to the drug has not been established.
Hypokalemia (>= 1%) and hyponatremia (0.1-1%) were observed during clinical trial evaluation of oral rivastigmine. Causality to the drug has not been established.
Back pain was reported in at least 1% of patients during clinical trial evaluation of oral rivastigmine. Myasthenia and muscle stiffness were reported in 0.1-1% of patients. Infrequent events (0.1-1%) reported in patients receiving transdermal rivastigmine during clinical trial evaluation included arthralgia, muscle spasms, and myalgia. Causality to the drug has not been established.
Anemia was reported in at least 1% of patients receiving transdermal rivastigmine during clinical trial evaluation. Causality to the drug has not been established.
Reproductive effects observed in 0.1-1% of patients during clinical trial evaluation of oral rivastigmine included breast pain (mastalgia). Prostatic hypertrophy was reported infrequently (0.1-1%) in patients receiving transdermal rivastigmine during clinical trial evaluation; causality to the drug has not been established.
Cataracts were observed in at least 1% of patients during clinical trial evaluation of oral rivastigmine. Other ophthalmic effects reported in 0.1-1% of patients included diplopia, glaucoma or ocular hypertension, and blurred vision. Infrequent events (0.1-1%) reported in patients receiving transdermal rivastigmine during clinical trial evaluation included cataracts, glaucoma, and blurred vision. Causality to the drug has not been established.
Transient ischemic attack was reported in at least 1% of patients during clinical trial evaluation of oral rivastigmine. Vascular effects observed in 0.1-1% of patients included peripheral ischemia and intracranial bleeding (hemorrhage). Causality to the drug has not been established.
Rivastigmine is a carbamate derivative and is contraindicated in patients with carbamate hypersensitivity or a history of hypersensitivity to rivastigmine or any inactive ingredient in the formulation. Rivastigmine patch is contraindicated in patients who have a history of application site reactions with rivastigmine patch suggestive of allergic contact dermatitis. In patients currently receiving transdermal rivastigmine, discontinue treatment if allergic contact dermatitis is suspected. If use of rivastigmine is still required, switch to oral administration only after a negative allergy test and with close monitoring. Some patients with sensitivity to the patch may not be able to take rivastigmine in any form.
Rivastigmine treatment should be initiated and supervised by a prescriber experienced in the diagnosis and treatment of Alzheimer's disease and the elderly. The use of rivastigmine has not been investigated in patients with other types of memory impairment (e.g., age-related cognitive decline). Diagnosis should be made according to current guidelines. Therapy requires the availability of a caregiver that will regularly monitor drug intake by the patient. In general, avoid abrupt discontinuation of therapy where possible to limit sudden decline in cognitive function or increase in behavioral disturbances. However, the presence of intolerable side effects may require temporary or permanent drug discontinuation.
The ability to perform tasks requiring mental alertness, such as driving or operating machinery, may diminish as dementia progresses. Adverse reactions associated with rivastigmine, including dizziness, drowsiness, vertigo, or fatigue, may additionally impair the ability to perform these functions. It is advisable for patients to undergo routine evaluation of cognition while receiving rivastigmine.
Because rivastigmine potentiates the actions of acetylcholine, an increase in gastric acid secretion should be expected. Gastrointestinal disorders such as nausea and vomiting may occur, particularly when initiating treatment and/or increasing the rivastigmine dose. These adverse events occur more commonly in females, and may require dose reduction or temporary discontinuation. There is limited experience related to restarting the drug after an interruption in therapy at doses higher than the recommended initial dose. However, to reduce the possibility of severe vomiting, those who have interrupted rivastigmine therapy for longer than several days should be reinitiated with the lowest daily dose and titrated slowly back to their maintenance dose as described. There has been one post-marketing case of severe vomiting with esophageal rupture reported to have occurred after reinitiating treatment at an inappropriate single dose of 4.5 mg following discontinuation for eight weeks. Although patients with Alzheimer's disease and other dementias commonly lose weight, cholinesterase inhibitors, including rivastigmine, have been associated with anorexia and weight loss in these patients. During rivastigmine therapy, weight must be monitored. Weight loss may respond to dosage reduction (see Dosage).
Because rivastigmine potentiates the actions of acetylcholine, an increase in gastric acid secretion should be expected. Although rivastigmine did not show an increased incidence of GI ulcers relative to placebo, care should be exercised in treating patients with active peptic ulcer disease or patients pre-disposed to these conditions. Patients with a history of peptic ulcer disease or those receiving NSAIDs concurrently should be monitored closely for symptoms of active or occult GI disease. Other GI symptoms, such as diarrhea, may occur. Cholinergic effects may also exacerbate conditions involving GI obstruction or ileus. Discontinue use in cases of active GI bleeding.
Rivastigmine should be used cautiously in hepatic disease. Pharmacokinetic data reveal that rivastigmine maximum concentrations and AUCs are increased in the presence of mild to moderate hepatic disease. Dosage reduction may be necessary if intolerance occurs.
In clinical trials in patients with renal impairment, the Cmax and AUC of rivastigmine were more than twice as high in subjects with moderate renal impairment compared with healthy subjects. However, there were no changes in pharmacokinetic parameters of rivastigmine in subjects with renal failure. Due to the conflicting nature of these results, dosage adjustment may be necessary in some patients.
Rivastigmine should be used with caution in patients with asthma, chronic obstructive pulmonary disease (COPD), or other obstructive-type pulmonary disease. Although rivastigmine is relatively specific for CNS cholinesterase, it does have weak affinity for peripheral cholinesterase, which may increase bronchoconstriction and bronchial secretion. Monitor respiratory status in those with pulmonary disease, as safety has not been demonstrated.
Use rivastigmine with caution in patients with certain types of cardiac disease, such as sick sinus syndrome, severe cardiac arrhythmias, or cardiac conduction disturbances (e.g., sino-atrial block, AV block). An increase in vagal tone induced by the cholinomimetic may produce bradycardia. Hypotension or syncope may also be exacerbated. In clinical trials with rivastigmine, no increased incidence of adverse cardiovascular events, vital signs, or ECG abnormalities was noted. Syncopal events were noted more frequently in those receiving rivastigmine than in placebo-treated patients.
Cholinomimetics, such as rivastigmine, may induce or exacerbate urinary tract obstruction/bladder obstruction. Although this has not been observed with rivastigmine, caution is recommended in treating patients predisposed to these disorders. Although not observed during clinical trials, the relatively weak peripheral cholinergic effects of rivastigmine may cause bladder outflow obstruction.
Cholinomimetics may induce or exacerbate seizures. Although this has not been observed with rivastigmine, caution is recommended in treating patients predisposed to seizure disorder (e.g., head trauma, increased intracranial pressure, or unstable metabolic conditions). However, seizure activity may also be a manifestation of Alzheimer's disease. While used in patient's with Parkinson's disease, cholinomimetics may also increase tremor or extrapyramidal symptoms (EPS) in some of these patients.
Because of their mechanism of action, cholinesterase inhibitors, such as rivastigmine, have the potential to interfere with the activity of anticholinergic medications.
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.
Safe and effective use of rivastigmine in children has not been established.
Rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under anesthesia. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade.
Tobacco smoking has been shown to increase the oral clearance of rivastigmine by 23% versus patients who are non-smokers.
According to the Beers Criteria, acetylcholinesterase inhibitors may cause bradycardia and are considered potentially inappropriate medications (PIMs) in geriatric adults with an underlying history of syncope; avoid use in those whose syncope may be due to bradycardia.
Because some rivastigmine transdermal systems (e.g., Exelon) contain aluminum or other metal components, patients should be instructed to remove the patch before undergoing magnetic resonance imaging (MRI). Metal components contained in the backing of some transdermal systems can overheat during an MRI scan and cause skin burns in the area where the patch is adhered.
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.
Maximum Dosage Limits:
-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.
Patients with Hepatic Impairment Dosing
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.
Patients with Renal Impairment Dosing
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.
*non-FDA-approved indication
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; Ibuprofen: (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.
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.
Acetylcholine Chloride: (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.
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.
Amitriptyline: (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.
Amlodipine; Celecoxib: (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.
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.
Bethanechol: (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.
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. (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.
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.
Celecoxib: (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.
Celecoxib; Tramadol: (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.
Cevimeline: (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.
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; Amitriptyline: (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.
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; 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. (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.
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.
Clomipramine: (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.
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.
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.
Desflurane: (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.
Desipramine: (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.
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.
Diclofenac: (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.
Diclofenac; Misoprostol: (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.
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.
Diflunisal: (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.
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. (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.
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. (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.
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.
Doxepin: (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.
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.
Etodolac: (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.
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.
Fenoprofen: (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.
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.
Flurbiprofen: (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.
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.
Guanidine: (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.
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.
Hydrocodone; Ibuprofen: (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.
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.
Ibuprofen: (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.
Ibuprofen; Famotidine: (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.
Ibuprofen; Oxycodone: (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.
Ibuprofen; Pseudoephedrine: (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.
Imipramine: (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.
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.
Indomethacin: (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.
Isoflurane: (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.
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.
Ketoprofen: (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.
Ketorolac: (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.
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.
Meclofenamate Sodium: (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.
Mefenamic Acid: (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.
Meloxicam: (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.
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.
Nabumetone: (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.
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.
Naproxen: (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.
Naproxen; Esomeprazole: (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.
Naproxen; Pseudoephedrine: (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.
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.
Nortriptyline: (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.
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.
Oxaprozin: (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.
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.
Perphenazine; Amitriptyline: (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.
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.
Pilocarpine: (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.
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.
Piroxicam: (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.
Pralidoxime: (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.
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.
Protriptyline: (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.
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.
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.
Sevoflurane: (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.
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.
Sulindac: (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.
Sumatriptan; Naproxen: (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.
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.
Tolmetin: (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.
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.
Trimipramine: (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.
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.
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.
-Route-Specific Pharmacokinetics
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.
-Special Populations
Hepatic Impairment
In patients with mild to moderate hepatic impairment, the rivastigmine AUC was roughly 2.3-fold higher than in healthy subjects, but the changes may be attributable to changes in plasma protein levels, fluid balance or other non-metabolic conditions that occur in these subjects. No dosage adjustments are specifically recommended. Rivastigmine has not been studied in patients with severe hepatic impairment.
Renal Impairment
The pharmacokinetics of transdermal rivastigmine in patients with renal impairment have not been studied; however, based on population analysis, creatinine clearance did not show any clear effect on steady-state concentrations of rivastigmine or its metabolite. Therefore, no dosage adjustment of the transdermal formulation is necessary in patients with renal impairment. Pharmacokinetic evaluation of oral rivastigmine indicated that clearance in patients with moderate renal impairment (GFR 10-50 ml/min) was decreased by 64% compared to healthy controls while the clearance in patients with severe renal impairment (GFR < 10 ml/min) was increased by 43% compared to healthy controls; however, dosage adjustments may not be required in renal impairment since the dose is individually titrated to tolerability.