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  • CLASSES

    Anti-AlzheimerAgents, Cholinesterase Inhibitors

    DEA CLASS

    Rx

    DESCRIPTION

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

    COMMON BRAND NAMES

    Exelon, Exelon Patch

    HOW SUPPLIED

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

    DOSAGE & INDICATIONS

    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 with food, initially. If this dose is well tolerated after 2 weeks, may increase to 3 mg PO twice daily. Subsequent increases to 4.5 mg and then 6 mg PO twice daily are based on tolerance after 2 weeks at the previous dose. The usual maintenance dosage is 3—6 mg PO twice per day (max: 12 mg/day). If GI adverse effects occur, (e.g., abdominal pain, loss of appetite, vomiting or weight loss), discontinue treatment 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 re-titrate to effective dose to limit the risk of GI ADRs. To achieve maximum therapeutic benefit, maintain the highest well-tolerated dose. Most clinical studies have found that cognitive function most improved with doses of 6—12 mg/day PO, if tolerated. However, only 30% of patients will tolerate a maximum dose of 12 mg/day. Periodic evaluation after initiation and during continuation of therapy may be helpful to the clinician in deciding treatment duration (i.e., continue treatment if improvement or stability in functional, cognitive or behavioral status continues).

    Transdermal dosage
    Adults

    One 4.6 mg/24 hours patch transdermally once daily is the initial dose. If well tolerated, increase to the recommended dose of 9.5 mg/24 hours patch after 4 weeks. Continue the recommended effective dose of 9.5 mg/24 hours for as long as therapeutic benefit persists. If needed, may increase 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 decreasing 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 severe Alzheimer's disease.
    Transdermal dosage
    Adults

    One 4.6 mg/24 hours patch transdermally once daily, initially. If well tolerated, increase to 9.5 mg/24 hours after 4 weeks. Thereafter, increase to the recommended effective dose of 13.3 mg/24 hours. If treatment is interrupted for more than 3 days, begin with initial titration. Patients < 50 kg may experience more adverse effects; titrate with caution and consider reducing the maintenance dose 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 Dementia with Lewy bodies†.
    Oral dosage
    Adults

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

    For the treatment of vascular dementia†.
    Oral dosage
    Adults

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

    †Indicates off-label use

    MAXIMUM DOSAGE

    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.

    DOSING CONSIDERATIONS

    Hepatic Impairment

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

    Renal Impairment

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

    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.

    STORAGE

    Exelon:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Exelon Patch:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Carbamate hypersensitivity

    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.

    Abrupt discontinuation

    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.

    Driving or operating machinery

    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.

    Females, vomiting

    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).

    Diarrhea, GI bleeding, GI disease, GI obstruction, ileus, peptic ulcer disease

    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.

    Hepatic disease

    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.

    Renal failure, renal impairment

    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.

    Asthma, chronic obstructive pulmonary disease (COPD)

    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.

    AV block, bradycardia, cardiac arrhythmias, cardiac disease, hypotension, sick sinus syndrome, syncope

    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.

    Bladder obstruction, urinary tract obstruction

    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.

    Head trauma, increased intracranial pressure, seizure disorder, seizures

    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.

    Anticholinergic medications

    Because of their mechanism of action, cholinesterase inhibitors, such as rivastigmine, have the potential to interfere with the activity of anticholinergic medications.

    Pregnancy

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

    Breast-feeding

    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.

    Children

    Safe and effective use of rivastigmine in children has not been established.

    Surgery

    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

    Tobacco smoking has been shown to increase the oral clearance of rivastigmine by 23% versus patients who are non-smokers.

    Geriatric

    An increase in vagal tone induced by cholinomimetics such as rivastigmine may produce bradycardia in patients with or without known underlying cardiac conduction abnormalities. Orthostatic hypotension and syncope have been reported infrequently. According to the Beers Criteria, acetylcholinesterase inhibitors cause bradycardia and are considered potentially inappropriate medications (PIMs) in geriatric patients with an underlying history of syncope and should be avoided in patients whose syncope may be due to bradycardia. According to the federal Omnibus Budget Reconciliation Act (OBRA) which regulates medication use in residents of long-term care facilities (LTCFs), the continued use of rivastigmine should be re-evaluated as the underlying cognitive disorder progresses into advanced stages. Cholinesterase inhibitors should be used cautiously in patients with severe asthma or obstructive pulmonary disease. Cholinesterase inhibitors may cause insomnia, dizziness, nausea, vomiting, diarrhea, anorexia, weight loss, and cardiac conduction abnormalities.

    Magnetic resonance imaging (MRI)

    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.

    ADVERSE REACTIONS

    Severe

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

    Moderate

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

    Mild

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

    DRUG INTERACTIONS

    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; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (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; Phenyltoloxamine; Salicylamide: (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; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Acetaminophen; Diphenhydramine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Acrivastine; Pseudoephedrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Amantadine: (Moderate) Concurrent use of amantadine and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Amantadine may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Ambenonium Chloride: (Major) Other cholinesterase inhibitors (e.g., rivastigmine) can produce additive pharmacodynamic effects if used concomitantly with ambenonium. Concurrent use is unlikely to be to be tolerated by the patient and should be avoided.
    Amifampridine: (Moderate) Coaministration of amifampridine and rivastigmine may increase the risk for adverse reactions due to additive cholinergic effects. Monitor patients closely for new or worsening side effects such as headache, visual disturbances, watery eyes, excessive sweating, shortness of breath, nausea, vomiting, diarrhea, bradycardia, loss of bladder control, confusion, or tremors.
    Amoxapine: (Moderate) Concurrent use of amoxapine and rivastigmine should be avoided if possible. Amoxapine may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Anticholinergics: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Articaine; Epinephrine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Concurrent use of certain muscle relaxants, such as cyclobenzaprine or orphenadrine, with rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Use of cyclobenzaprine or high doses of orphenadrine may result in significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Atenolol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
    Atenolol; Chlorthalidone: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
    Atracurium: (Moderate) A higher atracurium dose may be required to achieve neuromuscular block with concomitant use of a cholinesterase inhibitor, such as rivastigmine.
    Atropine: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Atropine; 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.
    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.
    Atropine; Edrophonium: (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 Alkaloids; Ergotamine; Phenobarbital: (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.
    Bendroflumethiazide; 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.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Benztropine: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Beta-blockers: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
    Betaxolol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
    Bisoprolol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
    Brimonidine; Timolol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
    Brompheniramine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Brompheniramine; Carbetapentane; 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; Dextromethorphan; Guaifenesin: (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; Guaifenesin; 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.
    Brompheniramine; Hydrocodone; 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; 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; 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.
    Carbetapentane; 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.
    Carbetapentane; 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.
    Carbetapentane; 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.
    Carbetapentane; Phenylephrine; 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.
    Carbetapentane; 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.
    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.
    Carbinoxamine; 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.
    Carbinoxamine; Hydrocodone; 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.
    Carbinoxamine; Hydrocodone; 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.
    Carbinoxamine; 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.
    Carbinoxamine; 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.
    Carteolol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
    Carvedilol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
    Chlophedianol; Dexbrompheniramine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Chlorcyclizine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Chlordiazepoxide; Clidinium: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Chloroprocaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Chlorpheniramine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Chlorpheniramine; Codeine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Chlorpheniramine; Dextromethorphan: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Chlorpheniramine; Dihydrocodeine; 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; Guaifenesin; Hydrocodone; 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; Hydrocodone; Phenylephrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Chlorpheniramine; Hydrocodone; 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; Ibuprofen; Pseudoephedrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Chlorpheniramine; Phenylephrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Chlorpheniramine; Pseudoephedrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Chlorpromazine: (Moderate) Conventional antipsychotics with significant anticholinergic effects, such as chlorpromazine, are more likely than other conventional antipsychotics to diminish the therapeutic action of rivastigmine, and use of an alternative antipsychotic should be considered. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and exerts its therapeutic effect by improving the availability of acetylcholine. Consider the use of an antipsychotic with less prominent anticholinergic effects.
    Cholinergic agonists: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
    Cisatracurium: (Moderate) A higher cisatracurium dose may be required to achieve neuromuscular block with concomitant use of a cholinesterase inhibitor, such as rivastigmine.
    Clemastine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Clozapine: (Moderate) Concurrent use of rivastigmine and clozapine should be avoided if possible. Clozapine exhibits considerable anticholinergic activity, and is more likely than other atypical antipsychotics to diminish the therapeutic action of rivastigmine. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Consider the use of an antipsychotic with less prominent anticholinergic effects.
    Cocaine: (Major) cholinesterase inhibitors reduce the metabolism of cocaine, therefore, prolonging cocaine's effects or increasing the risk of toxicity. It should be taken into consideration that the cholinesterase inhibition caused by echothiophate, demecarium, or isoflurophate may persist for weeks or months after the medication has been discontinued. Additionally, local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Dosage adjustment of the cholinesterase inhibitor may be necessary to control the symptoms of myasthenia gravis.
    Codeine; Phenylephrine; Promethazine: (Moderate) Promethazine exhibits anticholinergic properties that could potentially interfere with the cholinesterase inhibitor activity of rivastigmine. When concurrent use cannot be avoided, monitor the patient for reduced rivastigmine efficacy.
    Codeine; Promethazine: (Moderate) Promethazine exhibits anticholinergic properties that could potentially interfere with the cholinesterase inhibitor activity of rivastigmine. When concurrent use cannot be avoided, monitor the patient for reduced rivastigmine efficacy.
    Cyclizine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Cyclobenzaprine: (Moderate) Concurrent use of certain muscle relaxants, such as cyclobenzaprine or orphenadrine, with rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Use of cyclobenzaprine or high doses of orphenadrine may result in significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Cyproheptadine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Dexbrompheniramine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Dexbrompheniramine; Pseudoephedrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Dexchlorpheniramine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Dicyclomine: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Digoxin: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may be increased when given with other medications known to cause bradycardia such as digoxin. In one study involving multiple doses of galantamine at 24 mg/day with digoxin at a dose of 0.375 mg/day, there was no effect on the pharmacokinetics of digoxin, except one healthy subject was hospitalized due to second and third degree heart block and bradycardia.
    Dimenhydrinate: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Diphenhydramine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Diphenhydramine; Hydrocodone; 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.
    Diphenhydramine; Ibuprofen: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Diphenhydramine; Naproxen: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Diphenhydramine; Phenylephrine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Diphenoxylate; Atropine: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Disopyramide: (Moderate) Concurrent use of disopyramide and rivastigmine should be avoided if possible. When concurrent use cannot be avoided, monitor the patient for reduced rivastigmine efficacy. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Disopyramide may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Dorzolamide; Timolol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
    Doxylamine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Doxylamine; Pyridoxine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Esmolol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
    Etomidate: (Moderate) Muscle relaxation produced by succinylcholine can be prolonged when the drug is administered with a cholinesterase inhibitor. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade. Other neuromuscular blockers may interact with cholinesterase inhibitors in a similar fashion. Cholinesterase inhibitors are therefore also likely to exaggerate muscle relaxation under general anesthetics.
    Flavoxate: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Fospropofol: (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.
    Glycopyrrolate: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Glycopyrrolate; Formoterol: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Halogenated Anesthetics: (Moderate) Muscle relaxation produced by succinylcholine can be prolonged when the drug is administered with a cholinesterase inhibitor. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade. Other neuromuscular blockers may interact with cholinesterase inhibitors in a similar fashion. Cholinesterase inhibitors are therefore also likely to exaggerate muscle relaxation under general anesthetics.
    Homatropine; Hydrocodone: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Hydroxyzine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Hyoscyamine: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Indacaterol; Glycopyrrolate: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Ketamine: (Moderate) Muscle relaxation produced by succinylcholine can be prolonged when the drug is administered with a cholinesterase inhibitor. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade. Other neuromuscular blockers may interact with cholinesterase inhibitors in a similar fashion. Cholinesterase inhibitors are therefore also likely to exaggerate muscle relaxation under general anesthetics.
    Labetalol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
    Levobetaxolol: (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.
    Levobupivacaine: (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.
    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; 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.
    Mepenzolate: (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.
    Meperidine; 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.
    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.
    Mepivacaine; Levonordefrin: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Methocarbamol: (Moderate) Methocarbamol may inhibit the effect of cholinesterase inhibitors. Methocarbamol also has sedative properties that may interfere with cognition. Therefore, methocarbamol should be used with caution in patients receiving cholinesterase inhibitors.
    Methohexital: (Moderate) Muscle relaxation produced by succinylcholine can be prolonged when the drug is administered with a cholinesterase inhibitor. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade. Other neuromuscular blockers may interact with cholinesterase inhibitors in a similar fashion. Cholinesterase inhibitors are therefore also likely to exaggerate muscle relaxation under general anesthetics.
    Methscopolamine: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Metoclopramide: (Major) Metoclopramide is a central dopamine antagonist and may cause extrapyramidal reactions (e.g., acute dystonic reactions, pseudo-parkinsonism, akathisia, or tardive dyskinesia), and rarely, neuroleptic malignant syndrome. Metoclopramide is contraindicated with other drugs that are likely to cause extrapyramidal effects since the risk of these effects may be increased. Cholinomimetics such as rivastigmine may cause or worsen extrapyramidal symptoms such as pseudoparkinsonism, dyskinesia, and dystonia, although the incidences of these effects during clinical trials with rivastigmine were infrequent. The risk of extrapyramidal effects may be increased during concurrent use of metoclopramide and rivastigmine; close monitoring is advisable if combination therapy is necessary.
    Metoprolol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
    Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
    Mivacurium: (Moderate) A higher mivacurium dose may be required to achieve neuromuscular block with concomitant use of a cholinesterase inhibitor, such as rivastigmine.
    Nadolol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
    Nebivolol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
    Nebivolol; Valsartan: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
    Nonsteroidal antiinflammatory drugs: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
    Olanzapine: (Moderate) Olanzapine exhibits moderate anticholinergic activity, and is more likely than most other atypical antipsychotics to diminish the therapeutic action of rivastigmine. Consider the use of an antipsychotic with less prominent anticholinergic effects. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and exerts its therapeutic effect by improving the availability of acetylcholine.
    Olanzapine; Fluoxetine: (Moderate) Olanzapine exhibits moderate anticholinergic activity, and is more likely than most other atypical antipsychotics to diminish the therapeutic action of rivastigmine. Consider the use of an antipsychotic with less prominent anticholinergic effects. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and exerts its therapeutic effect by improving the availability of acetylcholine.
    Olanzapine; Samidorphan: (Moderate) Olanzapine exhibits moderate anticholinergic activity, and is more likely than most other atypical antipsychotics to diminish the therapeutic action of rivastigmine. Consider the use of an antipsychotic with less prominent anticholinergic effects. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and exerts its therapeutic effect by improving the availability of acetylcholine.
    Orphenadrine: (Moderate) Concurrent use of certain muscle relaxants, such as cyclobenzaprine or orphenadrine, with rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Use of cyclobenzaprine or high doses of orphenadrine may result in significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Oxybutynin: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Pancuronium: (Moderate) A higher pancuronium dose may be required to achieve neuromuscular block with concomitant use of a cholinesterase inhibitor, such as rivastigmine.
    Penbutolol: (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.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Pindolol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
    Prilocaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Prilocaine; Epinephrine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Procaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Promethazine: (Moderate) Promethazine exhibits anticholinergic properties that could potentially interfere with the cholinesterase inhibitor activity of rivastigmine. When concurrent use cannot be avoided, monitor the patient for reduced rivastigmine efficacy.
    Promethazine; Dextromethorphan: (Moderate) Promethazine exhibits anticholinergic properties that could potentially interfere with the cholinesterase inhibitor activity of rivastigmine. When concurrent use cannot be avoided, monitor the patient for reduced rivastigmine efficacy.
    Promethazine; Phenylephrine: (Moderate) Promethazine exhibits anticholinergic properties that could potentially interfere with the cholinesterase inhibitor activity of rivastigmine. When concurrent use cannot be avoided, monitor the patient for reduced rivastigmine efficacy.
    Propantheline: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Propofol: (Moderate) Muscle relaxation produced by succinylcholine can be prolonged when the drug is administered with a cholinesterase inhibitor. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade. Other neuromuscular blockers may interact with cholinesterase inhibitors in a similar fashion. Cholinesterase inhibitors are therefore also likely to exaggerate muscle relaxation under general anesthetics.
    Propranolol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
    Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
    Pseudoephedrine; Triprolidine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Pyrilamine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Rocuronium: (Moderate) A higher rocuronium dose may be required to achieve neuromuscular block with concomitant use of a cholinesterase inhibitor, such as rivastigmine.
    Scopolamine: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Sedating H1-blockers: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Solifenacin: (Moderate) The therapeutic benefits of the cholinesterase inhibitors for dementia or other neurologic conditions may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. Some of the common selective antimuscarinic drugs for bladder problems, (such as solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia.
    Sotalol: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
    Succinylcholine: (Moderate) A synergistic effect may be expected when succinylcholine is given concomitantly with a cholinesterase inhibitor, such as rivastigmine.
    Tetracaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Thiopental: (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.
    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: (Moderate) Tobacco smoking (i.e., nicotine) has been shown to increase the oral clearance of rivastigmine by 23% versus patients who are non-smokers. Tobacco smoke contains polycyclic aromatic hydrocarbons that induce hepatic CYP450 microsomal enzymes (e.g., CYP1A1, CYP1A2, CYP2E1); however, rivastigmine is not metabolized by the CYP450 isoenzymes. Thus, the mechanism and clinical significance of this potential interaction are not clear. The sudden cessation of tobacco smoking may result in a reduced clearance of rivastigmine, despite the initiation of a nicotine replacement product.
    Tolterodine: (Moderate) The therapeutic benefits of the cholinesterase inhibitors for dementia or other neurologic conditions may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. Some of the common selective antimuscarinic drugs for bladder problems, (such as tolterodine), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia.
    Tricyclic antidepressants: (Moderate) Concurrent use of tricyclic antidepressants and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Tricyclic antidepressants with significant anticholinergic activity, such as amitriptyline, imipramine, doxepin, and clomipramine, are more likely to interfere with the therapeutic effect of rivastigmine than other tricyclics.
    Trihexyphenidyl: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Triprolidine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Trospium: (Moderate) The therapeutic benefits of the cholinesterase inhibitors for dementia or other neurologic conditions may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. Some of the common selective antimuscarinic drugs for bladder problems, (such as trospium), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia.
    Vecuronium: (Moderate) A higher vecuronium dose may be required to achieve neuromuscular block with concomitant use of a cholinesterase inhibitor, such as rivastigmine.

    PREGNANCY AND LACTATION

    Pregnancy

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

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

    MECHANISM OF ACTION

    Mechanism of Action: Patients with Alzheimer's disease show behavioral consequences (e.g., decline in memory and learning) that are partially related to cholinergic deficits. CNS structural defects noted on biopsy or postmortem exam include cholinergic lesions in the nuclei projecting from the forebrain nucleus up to the cerebral cortex and the hippocampus, which is the specific region involved with the function of memory. The cholinergic system is known to be important in attentional processing and as a modulator of excitatory amino acid (EAA) neurotransmission. 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 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.

    PHARMACOKINETICS

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

    Oral Route

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

    Topical Route

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