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  • CLASSES

    Anti-AlzheimerAgents, Cholinesterase Inhibitors

    DEA CLASS

    Rx

    DESCRIPTION

    Oral cholinesterase inhibitor
    Used for the symptomatic treatment of mild to moderate Alzheimer's disease; may provide cognitive benefit in mixed vascular dementia and Alzheimer's disease
    A slow dosage titration is required to limit GI side effects

    COMMON BRAND NAMES

    Razadyne, Razadyne ER, Reminyl, Reminyl ER

    HOW SUPPLIED

    Galantamine/Galantamine Hydrobromide/Razadyne/Razadyne ER/Reminyl/Reminyl ER Oral Cap ER: 8mg, 16mg, 24mg
    Galantamine/Galantamine Hydrobromide/Razadyne/Reminyl Oral Sol: 1mL, 4mg
    Galantamine/Galantamine Hydrobromide/Razadyne/Reminyl Oral Tab: 4mg, 8mg, 12mg

    DOSAGE & INDICATIONS

    For the treatment of mild to moderate Alzheimer's disease.
    Oral dosage (immediate-release tablets or oral solution)
    Adults

    4 mg PO twice daily, initially. Increase the dose to 8 mg PO twice daily after a minimum of 4 weeks if tolerated, and then 12 mg PO twice daily after a minimum of 4 weeks at 16 mg/day. Usual dose: 16 to 24 mg/day. Max: 24 mg/day. If treatment is interrupted for more than 3 days, restart with 4 mg PO twice daily and titrate again.

    Oral dosage (extended-release capsules)
    Adults

    8 mg PO once daily, initially. Increase the dose to 16 mg PO once daily after a minimum of 4 weeks if tolerated, and then 24 mg PO once daily after a minimum of 4 weeks at 16 mg/day. Max: 24 mg/day. If treatment is interrupted for more than 3 days, restart with 8 mg PO once daily and titrate again.

    For the treatment of mild to moderate vascular dementia†.
    Oral dosage (immediate-release tablets or oral solution)
    Adults

    Safety and efficacy have not been established but has been studied. 4 mg PO twice daily, initially. After 4 weeks, if tolerated, dosage may be increased to 8 mg PO twice daily. May increase at 12 weeks of treatment to 12 mg PO twice daily based on efficacy and tolerability. Max: 24 mg/day. One multi-national trial evaluated the safety and efficacy of this regimen in 788 patients with probable vascular dementia vs. placebo. Significant improvement in the galantamine group was noted at 26 weeks for one of the 2 primary measures of efficacy, the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-cog/11), while changes in the co-primary outcome, the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL), were similar between the groups.

    For the treatment of mild to moderately severe Dementia with Lewy bodies†.
    Oral dosage (immediate-release tablets or oral solution)
    Adults

    Safety and efficacy have not been established; more study is needed. 4 mg PO twice daily, initially. After 4 weeks, if tolerated, may increase to 8 mg PO twice daily. May further increase at 12 weeks of treatment to 12 mg PO twice daily based on efficacy and tolerability. Max: 24 mg/day. An open-label study (n = 50) suggested possible efficacy for treating mild to moderately severe Dementia with Lewy bodies (DLB). Two of the primary endpoints, the Neuropsychiatric Inventory (NPI-12) and the Clinician's Global Impression of Change (CIBIC), showed statistically significant improvements from baseline. The third primary endpoint, the Cognitive Drug Research Computerized Cognitive Assessment System (COGDRAS), did not.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    24 mg/day PO.

    Elderly

    24 mg/day PO.

    Adolescents

    Not indicated.

    Children

    Not indicated.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Moderate hepatic impairment (Child-Pugh score of 7 to 9): After titration, the dosage should generally not exceed 16 mg/day PO.
    Severe hepatic impairment (Child-Pugh score of 10 to 15): Use not recommended.

    Renal Impairment

    Moderate renal impairment (CrCl 9 to 59 mL/minute): The dosage should generally not exceed 16 mg/day PO.
    Severe renal impairment (CrCl less than 9 mL/minute): Use not recommended.
     
    Intermittent hemodialysis
    It is not known whether galantamine and/or its metabolites can be removed by hemodialysis or hemofiltration. Dosage recommendations are not available.
     
    Peritoneal dialysis
    It is not known whether galantamine and/or its metabolites can be removed by CAPD. Dosage recommendations are not available.

    ADMINISTRATION

    Oral Administration

    Advise patients and caregivers to ensure adequate fluid intake during treatment.
    Administration with food may be helpful to lessen some gastrointestinal side effects.
    If therapy has been interrupted for more than 3 days, restart at the lowest dosage and titrate as directed to the patient's current dosage.

    Oral Solid Formulations

    Immediate-release tablets:
    Administer twice per day, preferably with food (e.g., morning and evening meals).
     
    Extended-release capsules (e.g., Razadyne ER):
    Administer once daily in the morning, preferably with food.

    Oral Liquid Formulations

    Galantamine oral solution
    Preparation of dose
    To remove the childproof cap, push the plastic cap on the bottle down while turning the cap counter-clockwise.
    Place the manufacturer-provided pipette fully into the bottle.
    While holding the bottom ring of the pipette (located near the top of the pipette), pull the pipette plunger up to the marking level on the bottle that equals the prescribed dose.
    Remove the pipette from the bottle by holding the bottom ring on the pipette.
    Empty the medication from the pipette into 3 to 4 ounces of any non-alcoholic drink by fully pushing the plunger. Stir the mixture well before administering to the patient.
    Replace bottle cap by turning it clockwise.
    Administration
    Preferably administer the doses with morning and evening meals.
    The patient should swallow all of the prepared liquid to get the full dose. Do not store for later use.
    Rinse the pipette after each use by inserting the open end into a glass of water, pulling the plunger out, and then emptying the pipette contents.

    STORAGE

    Razadyne:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Razadyne ER :
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Reminyl:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Reminyl ER :
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Serious rash

    Galantamine is contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients. Serious rash (e.g., Stevens-Johnson syndrome and acute generalized exanthematous pustulosis) have been reported in patients receiving galantamine. Inform patients and caregivers that the use of galantamine should be discontinued at the first appearance of a skin rash, unless the rash is clearly not drug-related. If signs or symptoms suggest a serious skin reaction, use of this drug should not be resumed and alternative therapy should be considered.

    Hepatic disease

    Use galantamine with caution and with careful dose titration in patients with moderate hepatic disease, due to reduced clearance and increased exposure to the drug. The use of galantamine is not recommended in patients with severe hepatic disease due to further increased exposure to the drug.

    Renal failure, renal impairment

    Galantamine is not recommended for use in patients with renal failure (i.e., creatinine clearance less than 9 mL/minute). Galantamine should be used cautiously and with careful dosage titration in patients with renal impairment and a creatinine clearance of 9 to 59 mL/minute, and the dosage should generally not exceed 16 mg/day in this population.

    Dehydration, diarrhea, GI bleeding, peptic ulcer disease, vomiting

    Galantamine potentiates the actions of acetylcholine, therefore, an increase in gastric secretions should be anticipated. Clinical studies of galantamine have shown no increase, relative to placebo, in the incidence of either peptic ulcer disease or gastrointestinal bleeding. However, care should be exercised in treating patients with active peptic ulcer disease or patients with a history of peptic ulcer disease or those receiving NSAIDs concurrently. Monitor these patients closely for symptoms of active or occult GI bleeding. Discontinue use in cases of active GI bleeding. Due to the pharmacological properties of galantamine, nausea, vomiting, diarrhea, anorexia, and weight loss can occur, and some of these symptoms may lead to dehydration. Therefore, weight should be monitored during treatment. Because effects such as nausea and vomiting are dose-related, the manufacturer's dose titration schedule should be followed. Galantamine should preferably be taken with food. In addition, patients and caregivers should be instructed about the importance of maintaining adequate fluid intake during treatment with galantamine; dehydration was reported during clinical trial evaluation.

    Asthma, chronic obstructive pulmonary disease (COPD)

    Galantamine should be used with caution in patients with asthma, chronic obstructive pulmonary disease (COPD), or other obstructive-type pulmonary disease. Potentiation of the effects of acetylcholine by cholinomimetics, such as galantamine, may result in increased bronchoconstriction and bronchial secretion. Respiratory signs and symptoms should be monitored in patients with pulmonary disease as safety has not been demonstrated.

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

    Use galantamine with caution in patients with cardiac disease, such as sick sinus syndrome, severe cardiac arrhythmias, or cardiac conduction disturbances (e.g., sino-atrial block, AV block). However, postmarketing surveillance suggests that all patients should be considered at risk for adverse cardiac effects due to cholinesterase inhibitors since bradycardia and heart block have occurred in patients without previously diagnosed cardiac conduction abnormalities. Because of their pharmacological action, cholinesterase inhibitors have vagotonic effects on the sino-atrial and atrioventricular nodes, leading to bradycardia and AV block which may exacerbate hypotension or syncope.[32342]

    Bladder obstruction, urinary tract obstruction

    Cholinomimetics may induce or exacerbate urinary tract obstruction and/or bladder obstruction, although, this was not observed during clinical trial evaluation of galantamine. Caution is recommended when administering galantamine to patients predisposed to these disorders.

    Dyskinesia, Parkinson's disease, seizure disorder, seizures

    Caution is recommended when administering galantamine to patients with a seizure disorder or history of seizures. Cholinesterase inhibitors, including galantamine, are believed to have some potential to cause generalized seizures. Seizure activity may also be a manifestation of Alzheimer's disease. Patients with Alzheimer's disease should be closely monitored for seizures while taking galantamine. Additionally, healthcare providers are advised that an increase in cholinergic tone caused by galantamine may worsen symptoms related to extrapyramidal disorder, such as Parkinson's disease or dyskinesia.

    Driving or operating machinery

    Dizziness and somnolence may occur during treatment with galantamine. Therefore, patients should be cautioned about engaging in tasks requiring mental alertness such as driving or operating machinery until they know how the drug will affect their cognition. 

    Surgery

    Galantamine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate the neuromuscular blocking effects of succinylcholine-type and similar neuromuscular blocking agents used during anesthesia. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade.

    Pregnancy

    There are no adequate data on the developmental risk associated with the use of galantamine during human pregnancy. In animal studies, developmental toxicity (increased incidence of morphological abnormalities and decreased offspring growth) and maternal toxicity were observed during the use of doses similar to or greater than the maximum recommended human dose. The effects of galantamine in labor and delivery are unknown.

    Breast-feeding

    The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for galantamine and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition. It is not known whether galantamine is excreted in human breast milk. There are no data regarding the effects of galantamine on the breastfed infant or the effects of the drug on milk production.

    Geriatric, mortality

    During two randomized controlled trials evaluating galantamine in mild cognitive impairment (MCI), there was a statistically higher mortality rate in those receiving galantamine than placebo. The deaths were due to various causes which could be expected in an elderly population; about half of the galantamine deaths appeared to result from various vascular causes (myocardial infarction, stroke, and sudden death). Although the difference in mortality between galantamine- and placebo-treated groups in these two MCI studies was significant, the results are highly discrepant with other studies of galantamine. Pooled studies evaluating Alzheimer's and other dementia patients have noted higher death rates in placebo versus galantamine groups. 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 galantamine 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.

    Children, infants

    The safety and efficacy of galantamine in pediatric patients have not been established. There is no known indication for the use of this drug in adolescents, children, or infants.

    ADVERSE REACTIONS

    Severe

    bradycardia / Rapid / 1.0-1.0
    seizures / Delayed / Incidence not known
    AV block / Early / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known

    Moderate

    depression / Delayed / 3.6-3.6
    hallucinations / Early / Incidence not known
    dyskinesia / Delayed / Incidence not known
    hypotension / Rapid / Incidence not known
    hypertension / Early / Incidence not known
    palpitations / Early / Incidence not known
    urinary retention / Early / Incidence not known
    dehydration / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    blurred vision / Early / Incidence not known
    myasthenia / Delayed / Incidence not known

    Mild

    nausea / Early / 20.7-20.7
    vomiting / Early / 10.5-10.5
    dizziness / Early / 7.5-7.5
    diarrhea / Early / 7.4-7.4
    headache / Early / 7.1-7.1
    weight loss / Delayed / 4.7-4.7
    abdominal pain / Early / 3.8-3.8
    fatigue / Early / 3.5-3.5
    syncope / Early / 0.4-2.2
    asthenia / Delayed / 2.0-2.0
    tremor / Early / 1.6-1.6
    dyspepsia / Early / 1.5-1.5
    drowsiness / Early / 1.5-1.5
    lethargy / Early / 1.3-1.3
    muscle cramps / Delayed / 1.2-1.2
    malaise / Early / 1.1-1.1
    anorexia / Delayed / Incidence not known
    dysgeusia / Early / Incidence not known
    paresthesias / Delayed / Incidence not known
    tinnitus / Delayed / Incidence not known
    flushing / Rapid / Incidence not known
    hyperhidrosis / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acebutolol: (Moderate) The increase in vagal tone induced by cholinesterase inhibitors, such as galantamine, may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with beta-blockers.
    Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Acetaminophen; Caffeine; Pyrilamine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Acetaminophen; Chlorpheniramine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Acetaminophen; Diphenhydramine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Acrivastine; Pseudoephedrine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Amantadine: (Moderate) The therapeutic benefits of cholinesterase inhibitors may be diminished when co-administered with drugs known to exhibit anticholinergic properties like amantadine.
    Ambenonium Chloride: (Major) Ambenonium chloride is a slowly reversible anticholinesterase agent and other cholinesterase inhibitors, such as galantamine, can produce additive pharmacodynamic effects if used concomitantly with ambenonium. If coadministration is necessary, patients should be monitored for adverse effects such as nausea, vomiting, loss of appetite, diarrhea, and excess sweating.
    Amifampridine: (Moderate) Coaministration of amifampridine and galantamine may increase the risk for adverse reactions due to additive cholinergic effects. Monitor patients closely for new or worsening side effects such as headache, visual disturbances, watery eyes, excessive sweating, shortness of breath, nausea, vomiting, diarrhea, bradycardia, loss of bladder control, confusion, or tremors.
    Amitriptyline: (Moderate) The therapeutic benefits of galantamine may be diminished when coadministered with drugs known to exhibit anticholinergic properties including tricyclic antidepressants (TCAs). When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy, and consider use of secondary TCAs (e.g., desipramine, nortriptyline), which generally have less potent anticholinergic effects than tertiary TCAs (e.g., amitriptyline, clomipramine).
    Amoxapine: (Moderate) Due to their anticholinergic actions, some cyclic antidepressants, including amoxapine, may antagonize the therapeutic actions of the cholinesterase-inhibitors such as galantamine, which are used for the treatment of dementia. Consider alternatives if concurrent therapy is needed. If alternative therapy is not possible, monitor for deceased efficacy of galantamine.
    Anticholinergics: (Moderate) The therapeutic benefits of galantamine, 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) The therapeutic benefits of galantamine may be diminished when co-administered with drugs known to exhibit anticholinergic properties, such as orphenadrine.
    Atenolol: (Moderate) The increase in vagal tone induced by cholinesterase inhibitors, such as galantamine, may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with beta-blockers.
    Atenolol; Chlorthalidone: (Moderate) The increase in vagal tone induced by cholinesterase inhibitors, such as galantamine, may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with beta-blockers.
    Atracurium: (Moderate) A higher atracurium dose may be required to achieve neuromuscular block with concomitant use of a cholinesterase inhibitor, such as galantamine.
    Atropine: (Moderate) The therapeutic benefits of galantamine, 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 galantamine, 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 galantamine, 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 galantamine, 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 galantamine, 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 cholinesterase inhibitors, such as galantamine, may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with beta-blockers.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) The therapeutic benefits of galantamine, 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 galantamine, 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-adrenergic blockers: (Moderate) The increase in vagal tone induced by cholinesterase inhibitors, such as galantamine, may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with beta-blockers.
    Betaxolol: (Moderate) The increase in vagal tone induced by cholinesterase inhibitors, such as galantamine, may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with beta-blockers.
    Bisoprolol: (Moderate) The increase in vagal tone induced by cholinesterase inhibitors, such as galantamine, may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with beta-blockers.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) The increase in vagal tone induced by cholinesterase inhibitors, such as galantamine, may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with beta-blockers.
    Brimonidine; Timolol: (Moderate) The increase in vagal tone induced by cholinesterase inhibitors, such as galantamine, may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with beta-blockers.
    Brompheniramine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Brompheniramine; Phenylephrine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Brompheniramine; Pseudoephedrine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Budesonide; Glycopyrrolate; Formoterol: (Moderate) The therapeutic benefits of galantamine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Bupivacaine Liposomal: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Bupivacaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Bupivacaine; Epinephrine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Bupivacaine; Lidocaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary. (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
    Bupivacaine; Meloxicam: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Carbinoxamine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Carbinoxamine; Phenylephrine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Carbinoxamine; Pseudoephedrine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Carteolol: (Moderate) The increase in vagal tone induced by cholinesterase inhibitors, such as galantamine, may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with beta-blockers.
    Carvedilol: (Moderate) The increase in vagal tone induced by cholinesterase inhibitors, such as galantamine, may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with beta-blockers.
    Chlophedianol; Dexbrompheniramine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Chlorcyclizine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Chlordiazepoxide; Amitriptyline: (Moderate) The therapeutic benefits of galantamine may be diminished when coadministered with drugs known to exhibit anticholinergic properties including tricyclic antidepressants (TCAs). When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy, and consider use of secondary TCAs (e.g., desipramine, nortriptyline), which generally have less potent anticholinergic effects than tertiary TCAs (e.g., amitriptyline, clomipramine).
    Chlordiazepoxide; Clidinium: (Moderate) The therapeutic benefits of galantamine, 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 galantamine should be avoided if possible. Galantamine 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 galantamine.
    Chlorpheniramine; Codeine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Chlorpheniramine; Dextromethorphan: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Chlorpheniramine; Hydrocodone: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Chlorpheniramine; Phenylephrine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Chlorpheniramine; Pseudoephedrine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Chlorpromazine: (Moderate) Conventional antipsychotics with significant anticholinergic effects, such as chlorpromazine, are more likely than other conventional antipsychotics to diminish the therapeutic action of galantamine, and use of an alternative antipsychotic should be considered. Galantamine 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 galantamine.
    Clemastine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Clomipramine: (Moderate) The therapeutic benefits of galantamine may be diminished when coadministered with drugs known to exhibit anticholinergic properties including tricyclic antidepressants (TCAs). When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy, and consider use of secondary TCAs (e.g., desipramine, nortriptyline), which generally have less potent anticholinergic effects than tertiary TCAs (e.g., amitriptyline, clomipramine).
    Clozapine: (Moderate) The anticholinergic activity of clozapine may interfere with the action of cholinergic medications such as galantamine. Atypical antipsychotics with significant anticholinergic effects, such clozapine, are more likely than other atypical antipsychotics to diminish the therapeutic action of galantamine in treating dementia. Use of an alternative antipsychotic should be considered. Galantamine 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.
    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 galantamine. When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy.
    Codeine; Promethazine: (Moderate) Promethazine exhibits anticholinergic properties that could potentially interfere with the cholinesterase inhibitor activity of galantamine. When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy.
    Cyclizine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Cyclobenzaprine: (Moderate) Concurrent use of certain muscle relaxants, such as cyclobenzaprine with galantamine should be avoided if possible. Galantamine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Use of cyclobenzaprine may result in significant anticholinergic activity, thereby interfering with the therapeutic effect of galantamine.
    Cyproheptadine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Desipramine: (Moderate) The therapeutic benefits of galantamine may be diminished when coadministered with drugs known to exhibit anticholinergic properties including tricyclic antidepressants (TCAs). When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy, and consider use of secondary TCAs (e.g., desipramine, nortriptyline), which generally have less potent anticholinergic effects than tertiary TCAs (e.g., amitriptyline, clomipramine).
    Dexbrompheniramine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Dexbrompheniramine; Pseudoephedrine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Dexchlorpheniramine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Dicyclomine: (Moderate) The therapeutic benefits of galantamine, 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 galantamine should be avoided if possible. Galantamine 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 galantamine.
    Diphenhydramine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Diphenhydramine; Ibuprofen: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Diphenhydramine; Naproxen: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Diphenhydramine; Phenylephrine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Diphenoxylate; Atropine: (Moderate) The therapeutic benefits of galantamine, 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) The therapeutic benefits of galantamine may be diminished when co-administered with the antimuscarinics, such as disopyramide. When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy.
    Dorzolamide; Timolol: (Moderate) The increase in vagal tone induced by cholinesterase inhibitors, such as galantamine, may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with beta-blockers.
    Doxepin: (Moderate) The therapeutic benefits of galantamine may be diminished when coadministered with drugs known to exhibit anticholinergic properties including tricyclic antidepressants (TCAs). When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy, and consider use of secondary TCAs (e.g., desipramine, nortriptyline), which generally have less potent anticholinergic effects than tertiary TCAs (e.g., amitriptyline, clomipramine).
    Doxylamine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Doxylamine; Pyridoxine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Esmolol: (Moderate) The increase in vagal tone induced by cholinesterase inhibitors, such as galantamine, may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with 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 galantamine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Glycopyrrolate: (Moderate) The therapeutic benefits of galantamine, 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 galantamine, 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 galantamine, 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 galantamine should be avoided if possible. Galantamine 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 galantamine.
    Hyoscyamine: (Moderate) The therapeutic benefits of galantamine, 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 galantamine, 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.
    Imipramine: (Moderate) The therapeutic benefits of galantamine may be diminished when coadministered with drugs known to exhibit anticholinergic properties including tricyclic antidepressants (TCAs). When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy, and consider use of secondary TCAs (e.g., desipramine, nortriptyline), which generally have less potent anticholinergic effects than tertiary TCAs (e.g., amitriptyline, clomipramine).
    Indacaterol; Glycopyrrolate: (Moderate) The therapeutic benefits of galantamine, 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 cholinesterase inhibitors, such as galantamine, may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with beta-blockers.
    Levobetaxolol: (Moderate) The increase in vagal tone induced by cholinesterase inhibitors, such as galantamine, may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with beta-blockers.
    Levobunolol: (Moderate) The increase in vagal tone induced by cholinesterase inhibitors, such as galantamine, may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with beta-blockers.
    Lidocaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
    Lidocaine; Epinephrine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
    Lidocaine; Prilocaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary. (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
    Maprotiline: (Moderate) Due to their anticholinergic actions, some cyclic antidepressants, including mapotiline, may antagonize the therapeutic actions of the cholinesterase-inhibitors such as galantamine, which are used for the treatment of dementia. Consider alternatives if concurrent therapy is needed. If alternative therapy is not possible, monitor for deceased efficacy of galantamine.
    Meclizine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Meperidine; Promethazine: (Moderate) Promethazine exhibits anticholinergic properties that could potentially interfere with the cholinesterase inhibitor activity of galantamine. When concurrent use cannot be avoided, monitor the patient for reduced galantamine 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.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) The therapeutic benefits of galantamine, 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.
    Methscopolamine: (Moderate) The therapeutic benefits of galantamine, 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.
    Metoprolol: (Moderate) The increase in vagal tone induced by cholinesterase inhibitors, such as galantamine, may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with beta-blockers.
    Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) The increase in vagal tone induced by cholinesterase inhibitors, such as galantamine, may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with beta-blockers.
    Mivacurium: (Moderate) A higher mivacurium dose may be required to achieve neuromuscular block with concomitant use of a cholinesterase inhibitor, such as galantamine.
    Nadolol: (Moderate) The increase in vagal tone induced by cholinesterase inhibitors, such as galantamine, may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with beta-blockers.
    Nebivolol: (Moderate) The increase in vagal tone induced by cholinesterase inhibitors, such as galantamine, may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with beta-blockers.
    Nebivolol; Valsartan: (Moderate) The increase in vagal tone induced by cholinesterase inhibitors, such as galantamine, may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with 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.
    Nortriptyline: (Moderate) The therapeutic benefits of galantamine may be diminished when coadministered with drugs known to exhibit anticholinergic properties including tricyclic antidepressants (TCAs). When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy, and consider use of secondary TCAs (e.g., desipramine, nortriptyline), which generally have less potent anticholinergic effects than tertiary TCAs (e.g., amitriptyline, clomipramine).
    Olanzapine: (Moderate) Atypical antipsychotics with significant anticholinergic effects, such olanzapine, are more likely than other atypical antipsychotics to diminish the therapeutic action of galantamine in treating dementia. Use of an alternative antipsychotic should be considered. Galantamine 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. Monitor for decreased clinical efficacy of galantamine if olanzapine must be used concurrently.
    Olanzapine; Fluoxetine: (Moderate) Atypical antipsychotics with significant anticholinergic effects, such olanzapine, are more likely than other atypical antipsychotics to diminish the therapeutic action of galantamine in treating dementia. Use of an alternative antipsychotic should be considered. Galantamine 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. Monitor for decreased clinical efficacy of galantamine if olanzapine must be used concurrently.
    Olanzapine; Samidorphan: (Moderate) Atypical antipsychotics with significant anticholinergic effects, such olanzapine, are more likely than other atypical antipsychotics to diminish the therapeutic action of galantamine in treating dementia. Use of an alternative antipsychotic should be considered. Galantamine 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. Monitor for decreased clinical efficacy of galantamine if olanzapine must be used concurrently.
    Orphenadrine: (Moderate) The therapeutic benefits of galantamine may be diminished when co-administered with drugs known to exhibit anticholinergic properties, such as orphenadrine.
    Oxybutynin: (Moderate) The therapeutic benefits of galantamine, 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 galantamine.
    Penbutolol: (Moderate) The increase in vagal tone induced by cholinesterase inhibitors, such as galantamine, may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with beta-blockers.
    Perphenazine; Amitriptyline: (Moderate) The therapeutic benefits of galantamine may be diminished when coadministered with drugs known to exhibit anticholinergic properties including tricyclic antidepressants (TCAs). When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy, and consider use of secondary TCAs (e.g., desipramine, nortriptyline), which generally have less potent anticholinergic effects than tertiary TCAs (e.g., amitriptyline, clomipramine).
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) The therapeutic benefits of galantamine, 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 cholinesterase inhibitors, such as galantamine, may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with 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 galantamine. When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy.
    Promethazine; Dextromethorphan: (Moderate) Promethazine exhibits anticholinergic properties that could potentially interfere with the cholinesterase inhibitor activity of galantamine. When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy.
    Promethazine; Phenylephrine: (Moderate) Promethazine exhibits anticholinergic properties that could potentially interfere with the cholinesterase inhibitor activity of galantamine. When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy.
    Propantheline: (Moderate) The therapeutic benefits of galantamine, 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 cholinesterase inhibitors, such as galantamine, may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with beta-blockers.
    Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) The increase in vagal tone induced by cholinesterase inhibitors, such as galantamine, may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with beta-blockers.
    Protriptyline: (Moderate) The therapeutic benefits of galantamine may be diminished when coadministered with drugs known to exhibit anticholinergic properties including tricyclic antidepressants (TCAs). When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy, and consider use of secondary TCAs (e.g., desipramine, nortriptyline), which generally have less potent anticholinergic effects than tertiary TCAs (e.g., amitriptyline, clomipramine).
    Pseudoephedrine; Triprolidine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Pyrilamine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    Rocuronium: (Moderate) A higher rocuronium dose may be required to achieve neuromuscular block with concomitant use of a cholinesterase inhibitor, such as galantamine.
    Ropivacaine: (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.
    Scopolamine: (Moderate) The therapeutic benefits of galantamine, 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 galantamine should be avoided if possible. Galantamine 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 galantamine.
    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 cholinesterase inhibitors such as galantamine may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with beta-blockers.
    Succinylcholine: (Moderate) A synergistic effect may be expected when succinylcholine is given concomitantly with a cholinesterase inhibitor, such as galantamine.
    Tetracaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Thioridazine: (Moderate) Conventional antipsychotics with significant anticholinergic effects, such thioridazine, are more likely than other conventional antipsychotics to diminish the therapeutic action of galantamine in treating dementia. Use of an alternative antipsychotic should be considered. Galantamine 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 cholinesterase inhibitors, such as galantamine, may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with beta-blockers.
    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) The therapeutic benefits of galantamine may be diminished when coadministered with drugs known to exhibit anticholinergic properties including tricyclic antidepressants (TCAs). When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy, and consider use of secondary TCAs (e.g., desipramine, nortriptyline), which generally have less potent anticholinergic effects than tertiary TCAs (e.g., amitriptyline, clomipramine).
    Trihexyphenidyl: (Moderate) The therapeutic benefits of galantamine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Trimipramine: (Moderate) The therapeutic benefits of galantamine may be diminished when coadministered with drugs known to exhibit anticholinergic properties including tricyclic antidepressants (TCAs). When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy, and consider use of secondary TCAs (e.g., desipramine, nortriptyline), which generally have less potent anticholinergic effects than tertiary TCAs (e.g., amitriptyline, clomipramine).
    Triprolidine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine 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 galantamine.
    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 galantamine.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no adequate data on the developmental risk associated with the use of galantamine during human pregnancy. In animal studies, developmental toxicity (increased incidence of morphological abnormalities and decreased offspring growth) and maternal toxicity were observed during the use of doses similar to or greater than the maximum recommended human dose. The effects of galantamine in labor and delivery are unknown.

    The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for galantamine and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition. It is not known whether galantamine is excreted in human breast milk. There are no data regarding the effects of galantamine on the breastfed infant or the effects of the drug on milk production.

    MECHANISM OF ACTION

    Galantamine is a tertiary alkaloid that is a reversible inhibitor of acetylcholinesterase (AChE), one of the enzymes responsible for the degradation of the neurotransmitter acetylcholine. Since galantamine is tertiary in structure, it penetrates the CNS and can inhibit brain AChE. Patients with Alzheimer's disease show a slow decline in memory, learning, behavior, emotions, and social and executive functioning, partially related to cholinergic deficits. This cholinergic loss has been correlated with the degree of cognitive impairment and density of amyloid plaques (a neuropathological hallmark of Alzheimer’s disease). Cholinesterase inhibitors are designed to offset the loss of cholinergic neurons by symptomatically slowing the decline in memory and the ability to perform functions of daily living by increasing central synaptic concentrations of acetylcholine. This mechanism requires that intact cholinergic neurons be present. As Alzheimer's disease progresses, fewer intact cholinergic neurons remain, and cholinesterase inhibitors become less effective. In addition, there is no evidence to suggest that the drugs have an effect on the underlying neuropathology or progression of dementia. 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. Unlike other AChE inhibitors, galantamine enhances the effect of acetylcholine on nicotinic receptors, likely through binding to an allosteric site on the receptor; however, human data have not shown evidence that the nicotinic receptor activity of the drug results in clinically significant benefit over other AChE inhibitors.

    PHARMACOKINETICS

    Galantamine is administered orally. The plasma protein binding is 18% at therapeutically relevant concentrations. In whole blood, it is mainly distributed to blood cells (roughly 53%).
     
    Galantamine does not appear to be a significant inhibitor of the hepatic CYP450 microsomal enzymes; however, it is partially metabolized via this system. Multiple metabolic pathways and renal excretion are involved in elimination, so no single pathway appears predominant. Hepatic isoenzymes CYP2D6 and CYP3A4 are involved in the formation of the metabolites O-desmethylgalantamine and N-oxide-galantamine, respectively. O-demethylation, mediated by CYP2D6, is greater in extensive metabolizers of CYP2D6 than in poor metabolizers. Population pharmacokinetic analysis indicate that there is a 25% decrease in median clearance in poor metabolizers compared to extensive metabolizers. However, dosage adjustment is not necessary in patients identified as poor metabolizers as the dose of drug is individually titrated to tolerability. The elimination half-life averages 7 hours. Approximately 20% of a dose is excreted through the kidneys in 24 hours as unchanged galantamine. In studies of radiolabeled oral galantamine, unchanged galantamine and its glucuronide accounted for most of the plasma radioactivity. By 7 days, 93—99% of the total radioactivity was recovered, with about 95% in urine and about 5% in the feces.
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP2D6, CYP3A4
    Galantamine is partially metabolized by the cytochrome P450 system, specifically by isoenzymes CYP3A4 and CYP2D6. Agents that are inhibitors or inducers of CYP3A4 and/or CYP2D6 may alter serum concentrations of galantamine.

    Oral Route

    Galantamine is rapidly and completely absorbed following oral administration with time to peak concentration about 1 hour. Bioavailability of the immediate-release tablet is the same as an oral solution; bioavailability is roughly 90%. The rate of absorption is delayed by administration with food; however, the extent of absorption is not affected. Administration with food is recommended to limit drug intolerance.