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  • CLASSES

    Anti-Alzheimer Products, Cholinesterase Inhibitors

    DEA CLASS

    Rx

    DESCRIPTION

    Oral cholinesterase (ChE) inhibitor
    Used for mild to moderate Alzheimer's disease; ineffective for Mild Cognitive Impairment (MCI)
    Improves cognitive functioning but does not alter degenerative process

    COMMON BRAND NAMES

    Razadyne, Reminyl

    HOW SUPPLIED

    Galantamine/Galantamine Hydrobromide/Razadyne/Reminyl 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; i.e., Razadyne)
    Adults

    Initially, 4 mg PO twice daily with food. If this dose is well tolerated after a minimum of 4 weeks, the dose may be increased to 8 mg PO twice daily. A subsequent increase to 12 mg PO twice daily may be considered after at least 4 weeks of the previous dose, if well-tolerated. However, the benefit of 24 mg/day vs. 16 mg/day in clinical trials was not statistically significant. Max: 24 mg/day PO. If treatment is interrupted for more than 3 days and then re-initiated, re-initiate with the lowest dose (i.e., 4 mg PO twice daily) and slowly re-titrate to the current dose. To achieve maximum therapeutic benefit, patients should be maintained on their highest well-tolerated dose. Periodic evaluation after initiation and during continuation of therapy may be helpful in deciding treatment duration (i.e., continue treatment if improvement or stability in functional, cognitive or behavioral status continues). Patients and caregivers should be advised to ensure adequate fluid intake during treatment. The oral solution dosage should be diluted into 3 to 4 ounces of non-alcoholic beverage.

    Oral dosage (i.e., extended-release capsules; i.e., Razadyne ER)
    Adults

    Initially, 8 mg PO once daily in the morning with food. After a minimum of 4 weeks, may increase to the recommended initial maintenance dosage of 16 mg PO once daily in the morning. Another increase may be considered after at least 4 weeks of the previous dose, if well-tolerated. Max: 24 mg PO once daily. If treatment is interrupted for more than 3 days and then re-initiated, clinicians should re-initiate with the lowest dose (i.e., 8 mg PO once daily) and slowly re-titrate to the current dose. To achieve maximum therapeutic benefit, patients should be maintained on their highest well-tolerated dose. Periodic evaluation after initiation and during continuation of therapy may be helpful to the clinician in deciding treatment duration (i.e., continue treatment if improvement or stability in functional, cognitive or behavioral status continues). Patients and caregivers should be advised to ensure adequate fluid intake during treatment.

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

    One multi-national trial evaluated the safety and efficacy of galantamine in 788 patients with probable vascular dementia using escalating doses of galantamine compared to placebo. Galantamine was initiated at 4 mg PO twice daily for 4 weeks, then titrated to 8 mg twice daily for 4 weeks. Thereafter, the dose could be maintained at 8 mg twice daily or increased to 12 mg twice daily for the next 4 weeks based upon tolerability and efficacy. At week 12, the dose could be maintained or reduced to 8 mg twice daily based upon tolerability. The dosage selected at week 12 was maintained for the remainder of the trial. Significant improvement in the galantamine group was noted at 26 weeks in 1 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 galantamine and placebo groups. A subgroup analysis revealed that subjects treated with galantamine who had a baseline Mini Mental State Examination (MMSE) score of less than 18 showed a greater effect at study endpoint on the ADAS-cog/11 than those with a baseline MMSE score of 18 or higher. Discontinuation due to adverse effects occurred in 13% of those receiving galantamine versus 6% of those receiving placebo.

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

    An open-label study (n = 50) suggests that galantamine may be effective for treating mild to moderately severe Dementia with Lewy bodies (DLB). Initially, 4 mg PO twice daily for 4 weeks, then 8 mg PO twice daily for 4 weeks, then 24 mg/day or previous highest tolerated dose (in divided doses) until the end of the 24-week study period. 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 show significant changes from baseline. Statistically significant improvement was observed in the mean cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog), a secondary efficacy measure, while the mean Mini Mental State Examination (MMSE) showed a slight decline from baseline (mean change from 20.8 to 20.4). Adverse events (AEs) were reported in 86% of the patients during the 24-week study period, with the most frequent events including nausea (24%), fatigue (20%), anorexia (10%), somnolence (10%), agitation (10%), and vomiting (6%). Most AEs were considered mild and transient with the exception of one myocardial infarction, although the patient recovered and continued in the study. Four patients discontinued treatment due to nausea (n = 2) or anorexia (n = 2).

    †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 is not recommended.

    Renal Impairment

    Moderate renal impairment (CrCl 9 to 59 mL/minute): The dose should generally not exceed 16 mg/day PO.
    Severe renal impairment (CrCl less than 9 mL/minute): Use is 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

    Patients and caregivers should be advised to ensure adequate fluid intake during treatment.
    If therapy has been interrupted for more than 3 days, the patient should be restarted at the lowest dose and the dose escalated to the current dose.

    Oral Solid Formulations

    Galantamine immediate release tablets: Administered twice per day, preferably with food to minimize cholinergic side effects.
    Extended-release capsules (Razadyne ER): Should be administered once daily in the morning, preferably with food.

    Oral Liquid Formulations

    Instructions for preparation and use of galantamine oral solution:
    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 medication and liquid mixture well before administering to the patient.
    The patient should swallow the prepared liquid to get the full dose. Do not store for later use.
    Replace bottle cap by turning it clockwise.
    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 controlled room temperature (between 68 and 77 degrees F)
    Reminyl:
    - 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 severe renal impairment (i.e., CrCl less than 9 mL/min) or in those with renal failure. Use galantamine cautiously and with careful dosage titration in those with moderate renal impairment.

    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, myocardial infarction, sick sinus syndrome, stroke, 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, post-marketing 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. The vagotonic effects of galantamine may be increased when given with other medications known to cause bradycardia such as digoxin or beta blockers. In clinical trials, however, bradycardia was rarely reported as severe. Deaths have occurred during randomized controlled trials evaluating galantamine in mild cognitive impairment (MCI). Individuals with mild cognitive impairment demonstrate isolated memory impairment greater than expected for their age and education, but do not meet current diagnostic criteria for Alzheimer's disease. In two randomized, placebo-controlled trials of 2 years duration in subjects with mild cognitive impairment (MCI), a total of 13 subjects on galantamine (n = 1026) and 1 subject on placebo (n = 1022) died. 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 statistically this mortality difference was significant, causality is difficult to assign as pooled studies evaluating Alzheimer's and other dementia patients (as opposed to MCI patients) have noted higher death rates in placebo vs. galantamine groups.

    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.

    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.

    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 during anesthesia. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade. In addition, the use of galantamine is not recommended in those recovering from gastrointestinal surgery due to various effects on the GI tract resulting from the cholinergic action of the drug.

    Pregnancy

    Galantamine is classified as FDA pregnancy risk category C. It is not known whether galantamine causes harm to the human fetus or influences reproductive capacity in pregnant females. Because there are no adequate and well-controlled studies of galantamine in pregnant women, the drug should be used during pregnancy only if the potential maternal benefit clearly justifies the potential fetal risk. In animal studies, developmental toxicity (increased incidence of morphological abnormalities and decreased offspring growth) was observed during use of doses similar to or greater than therapeutic human doses. The effects of galantamine in labor and delivery are unknown.

    Breast-feeding

    According to the manufacturer, it is not known whether galantamine is excreted in human breast milk. According to the manufacturer, caution is advisable when galantamine is administered to a breast-feeding woman. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Geriatric

    Data from clinical trials in patients with Alzheimer's disease indicate that galantamine concentrations are 30–40% higher in geriatric patients than in healthy young adults. Because adherence to dosage and titration instructions is essential to reduce the risk of certain adverse effects, geriatric patients or caregivers should be able to follow the recommended dosing titration and ensure adequate fluid intake prior to initiation of the drug. According to the Beers Criteria, acetylcholinesterase inhibitors are considered potentially inappropriate medications (PIMs) in geriatric patients with syncope and should be avoided in this patient population due to an increased risk of orthostatic hypotension or bradycardia. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to OBRA guidelines, the continued use of galantamine for the treatment of a cognitive disorder in residents of a LTCF should be re-evaluated as the underlying 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, and weight loss. Cardiac conduction may be affected, particularly in patients who already have a cardiac conduction disorder or who are taking other medications that affect heart rate.

    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
    erythema multiforme / Delayed / Incidence not known
    acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known

    Moderate

    depression / Delayed / 3.6-3.6
    hallucinations / Early / Incidence not known
    hypertension / Early / Incidence not known
    palpitations / Early / Incidence not known
    hypotension / Rapid / Incidence not known
    dehydration / Delayed / Incidence not known
    urinary retention / Early / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    hepatitis / 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
    paresthesias / Delayed / Incidence not known
    dysgeusia / Early / 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; Butalbital: (Moderate) Monitor for reduced efficacy of galantamine during concurrent use of barbiturates. Galantamine is a substrate for CYP3A4 and CYP2D6. The effectiveness of the drug could theoretically be reduced by the concomitant administration of strong CYP3A4 inducers such as barbiturates.
    Acetaminophen; Butalbital; Caffeine: (Moderate) Monitor for reduced efficacy of galantamine during concurrent use of barbiturates. Galantamine is a substrate for CYP3A4 and CYP2D6. The effectiveness of the drug could theoretically be reduced by the concomitant administration of strong CYP3A4 inducers such as barbiturates.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Moderate) Monitor for reduced efficacy of galantamine during concurrent use of barbiturates. Galantamine is a substrate for CYP3A4 and CYP2D6. The effectiveness of the drug could theoretically be reduced by the concomitant administration of strong CYP3A4 inducers such as barbiturates.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (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; Phenyltoloxamine; Salicylamide: (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; Phenyltoloxamine: (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.
    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.
    Amitriptyline: (Moderate) The therapeutic benefits of galantamine may be diminished when coadministered with drugs known to exhibit anticholinergic properties including tricyclic antidepressants. When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy. A population pharmacokinetic analysis showed that the clearance of galantamine was decreased by 25% to 33% during coadministration of certain CYP2D6 inhibitors including amitriptyline (n = 17). The CYP2D6 isoenzyme is partially involved in the metabolism of galantamine. The clinical relevance of this interaction is unknown; however, increased galantamine concentrations could potentially result in dose-related toxicity.
    Amitriptyline; Chlordiazepoxide: (Moderate) The therapeutic benefits of galantamine may be diminished when coadministered with drugs known to exhibit anticholinergic properties including tricyclic antidepressants. When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy. A population pharmacokinetic analysis showed that the clearance of galantamine was decreased by 25% to 33% during coadministration of certain CYP2D6 inhibitors including amitriptyline (n = 17). The CYP2D6 isoenzyme is partially involved in the metabolism of galantamine. The clinical relevance of this interaction is unknown; however, increased galantamine concentrations could potentially result in dose-related toxicity.
    Amobarbital: (Moderate) Monitor for reduced efficacy of galantamine during concurrent use of barbiturates. Galantamine is a substrate for CYP3A4 and CYP2D6. The effectiveness of the drug could theoretically be reduced by the concomitant administration of strong CYP3A4 inducers such as barbiturates.
    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.
    Amoxicillin; Clarithromycin; Lansoprazole: (Moderate) Galantamine is a primary substrate for CYP3A4 and the bioavailability of galantamine may be increased when coadministered with potent inhibitors of CYP3A4 such as clarithromycin. Monitor for galantamine-related adverse effects such as nausea, vomiting, loss of appetite, diarrhea, headache, confusion, and excessive sweating.
    Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Galantamine is a primary substrate for CYP3A4 and the bioavailability of galantamine may be increased when coadministered with potent inhibitors of CYP3A4 such as clarithromycin. Monitor for galantamine-related adverse effects such as nausea, vomiting, loss of appetite, diarrhea, headache, confusion, and excessive sweating.
    Amprenavir: (Moderate) The plasma concentrations of galantamine, a partial CYP3A4 substrate, may be elevated when administered with protease inhibitors, which are strong CYP3A4 inhibitors. If this combination is required, monitor for galantamine-related adverse effects such as nausea, vomiting, diarrhea, increased urination, decreased appetite, confusion, dizziness, bradycardia, and excessive sweating.
    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.
    Artemether; Lumefantrine: (Moderate) Lumefantrine is a potent inhibitor of CYP2D6 in vitro and galantamine is a partial substrate of CYP2D6; therefore, coadministration may lead to increased galantamine concentrations. Monitor for galantamine-related adverse effects such as nausea, vomiting, loss of appetite, diarrhea, confusion, and excessive sweating.
    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; Butalbital; Caffeine: (Moderate) Monitor for reduced efficacy of galantamine during concurrent use of barbiturates. Galantamine is a substrate for CYP3A4 and CYP2D6. The effectiveness of the drug could theoretically be reduced by the concomitant administration of strong CYP3A4 inducers such as barbiturates.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Monitor for reduced efficacy of galantamine during concurrent use of barbiturates. Galantamine is a substrate for CYP3A4 and CYP2D6. The effectiveness of the drug could theoretically be reduced by the concomitant administration of strong CYP3A4 inducers such as barbiturates.
    Atazanavir: (Moderate) The plasma concentrations of galantamine, a partial CYP3A4 substrate, may be elevated when administered with protease inhibitors, which are strong CYP3A4 inhibitors. If this combination is required, monitor for galantamine-related adverse effects such as nausea, vomiting, diarrhea, increased urination, decreased appetite, confusion, dizziness, bradycardia, and excessive sweating.
    Atazanavir; Cobicistat: (Moderate) The plasma concentrations of galantamine, a CYP3A4 and CYP2D6 substrate, may be elevated when administered with cobicistat, a moderate CYP2D6 inhibitor and strong CYP3A4 inhibitor. Monitor for galantamine-related adverse effects such as nausea, vomiting, diarrhea, increased urination, decreased appetite, confusion, dizziness, and excessive sweating. (Moderate) The plasma concentrations of galantamine, a partial CYP3A4 substrate, may be elevated when administered with protease inhibitors, which are strong CYP3A4 inhibitors. If this combination is required, monitor for galantamine-related adverse effects such as nausea, vomiting, diarrhea, increased urination, decreased appetite, confusion, dizziness, bradycardia, and excessive sweating.
    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.
    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; Diphenoxylate: (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.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Moderate) Monitor for reduced efficacy of galantamine during concurrent use of barbiturates. Galantamine is a substrate for CYP3A4 and CYP2D6. The effectiveness of the drug could theoretically be reduced by the concomitant administration of strong CYP3A4 inducers such as barbiturates. (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.
    Barbiturates: (Moderate) Monitor for reduced efficacy of galantamine during concurrent use of barbiturates. Galantamine is a substrate for CYP3A4 and CYP2D6. The effectiveness of the drug could theoretically be reduced by the concomitant administration of strong CYP3A4 inducers such as barbiturates.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Monitor for reduced efficacy of galantamine during concurrent use of barbiturates. Galantamine is a substrate for CYP3A4 and CYP2D6. The effectiveness of the drug could theoretically be reduced by the concomitant administration of strong CYP3A4 inducers such as barbiturates. (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.
    Benzonatate: (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.
    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.
    Boceprevir: (Moderate) Close clinical monitoring is advised when administering galantamine with boceprevir due to an increased potential for galantamine-related adverse events. If galantamine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of galantamine. Galantamine is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated galantamine plasma concentrations.
    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; Carbetapentane; 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; 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; Guaifenesin; 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.
    Brompheniramine; Hydrocodone; 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: (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.
    Bupivacaine Liposomal: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Bupivacaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Bupivacaine; Lidocaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary. (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
    Butabarbital: (Moderate) Monitor for reduced efficacy of galantamine during concurrent use of barbiturates. Galantamine is a substrate for CYP3A4 and CYP2D6. The effectiveness of the drug could theoretically be reduced by the concomitant administration of strong CYP3A4 inducers such as barbiturates.
    Carbamazepine: (Moderate) Galantamine is a substrate for CYP3A4 and CYP2D6. The effectiveness of the drug could theoretically be reduced by the concomitant administration of CYP3A4 inducers such as carbamazepine.
    Carbetapentane; 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.
    Carbetapentane; 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.
    Carbetapentane; 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.
    Carbetapentane; Phenylephrine; 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.
    Carbetapentane; 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.
    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; Hydrocodone; 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; Hydrocodone; 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; 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; 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; 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; Dihydrocodeine; 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; Guaifenesin; Hydrocodone; 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; 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; Hydrocodone; 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; 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.
    Cimetidine: (Minor) Galantamine is metabolized by CYP3A4 and CYP2D6 and systemic exposure may be increased by coadministration with CYP3A4 and CYP2D6 inhibitors, including cimetidine. An increase in cholinergic side effects may occur, particularly nausea, vomiting, diarrhea, dizziness, headache, and loss of appetite. In one pharmacokinetic study, galantamine was administered as a single dose of 4 mg on Day 2 of a 3-day treatment with cimetidine 800 mg daily. The bioavailability of galantamine was increased by approximately 16%. The clinical significance of this interaction, if any, is unknown.
    Clarithromycin: (Moderate) Galantamine is a primary substrate for CYP3A4 and the bioavailability of galantamine may be increased when coadministered with potent inhibitors of CYP3A4 such as clarithromycin. Monitor for galantamine-related adverse effects such as nausea, vomiting, loss of appetite, diarrhea, headache, confusion, and excessive sweating.
    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. When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy. A population pharmacokinetic analysis showed that the clearance of galantamine was decreased by 25% to 33% during coadministration of certain CYP2D6 inhibitors including amitriptyline (n = 17). The CYP2D6 isoenzyme is partially involved in the metabolism of galantamine. The clinical relevance of this interaction is unknown; however, increased galantamine concentrations could potentially result in dose-related toxicity.
    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.
    Cobicistat: (Moderate) The plasma concentrations of galantamine, a CYP3A4 and CYP2D6 substrate, may be elevated when administered with cobicistat, a moderate CYP2D6 inhibitor and strong CYP3A4 inhibitor. Monitor for galantamine-related adverse effects such as nausea, vomiting, diarrhea, increased urination, decreased appetite, confusion, dizziness, and excessive sweating.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) The plasma concentrations of galantamine, a CYP3A4 and CYP2D6 substrate, may be elevated when administered with cobicistat, a moderate CYP2D6 inhibitor and strong CYP3A4 inhibitor. Monitor for galantamine-related adverse effects such as nausea, vomiting, diarrhea, increased urination, decreased appetite, confusion, dizziness, and excessive sweating.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) The plasma concentrations of galantamine, a CYP3A4 and CYP2D6 substrate, may be elevated when administered with cobicistat, a moderate CYP2D6 inhibitor and strong CYP3A4 inhibitor. Monitor for galantamine-related adverse effects such as nausea, vomiting, diarrhea, increased urination, decreased appetite, confusion, dizziness, and excessive sweating.
    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.
    Conivaptan: (Major) According to the manufacturer of conivaptan, concomitant use of conivaptan, a strong CYP3A4 inhibitor, and CYP3A substrates, such as galantamine, should be avoided. Coadministration of conivaptan with other CYP3A substrates has resulted in increased mean AUC values (2 to 3 times). Theoretically, similar pharmacokinetic effects could be seen with galantamine. Treatment with galantamine may be initiated no sooner than 1 week after completion of conivaptan therapy.
    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.
    Darifenacin: (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.
    Darunavir: (Moderate) The plasma concentrations of galantamine, a partial CYP3A4 substrate, may be elevated when administered with protease inhibitors, which are strong CYP3A4 inhibitors. If this combination is required, monitor for galantamine-related adverse effects such as nausea, vomiting, diarrhea, increased urination, decreased appetite, confusion, dizziness, bradycardia, and excessive sweating.
    Darunavir; Cobicistat: (Moderate) The plasma concentrations of galantamine, a CYP3A4 and CYP2D6 substrate, may be elevated when administered with cobicistat, a moderate CYP2D6 inhibitor and strong CYP3A4 inhibitor. Monitor for galantamine-related adverse effects such as nausea, vomiting, diarrhea, increased urination, decreased appetite, confusion, dizziness, and excessive sweating. (Moderate) The plasma concentrations of galantamine, a partial CYP3A4 substrate, may be elevated when administered with protease inhibitors, which are strong CYP3A4 inhibitors. If this combination is required, monitor for galantamine-related adverse effects such as nausea, vomiting, diarrhea, increased urination, decreased appetite, confusion, dizziness, bradycardia, and excessive sweating.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) The plasma concentrations of galantamine, a partial CYP3A4 substrate, may be elevated when administered with protease inhibitors, which are strong CYP3A4 inhibitors. If this combination is required, monitor for galantamine-related adverse effects such as nausea, vomiting, diarrhea, increased urination, decreased appetite, confusion, dizziness, bradycardia, and excessive sweating.
    Desipramine: (Moderate) The therapeutic benefits of galantamine may be diminished when coadministered with drugs known to exhibit anticholinergic properties including tricyclic antidepressants. When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy. A population pharmacokinetic analysis showed that the clearance of galantamine was decreased by 25% to 33% during coadministration of certain CYP2D6 inhibitors including amitriptyline (n = 17). The CYP2D6 isoenzyme is partially involved in the metabolism of galantamine. The clinical relevance of this interaction is unknown; however, increased galantamine concentrations could potentially result in dose-related toxicity.
    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.
    Dextromethorphan; 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.
    Dextromethorphan; Quinidine: (Moderate) A population pharmacokinetic analysis showed that the clearance of galantamine was decreased by 25% to 33% during coadministration of certain CYP2D6 inhibitors including quinidine. The CYP2D6 isoenzyme is partially involved in the metabolism of galantamine. The clinical relevance of this interaction is unknown; however, increased galantamine concentrations could potentially result in dose-related toxicity.
    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; Hydrocodone; 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.
    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.
    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. When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy. A population pharmacokinetic analysis showed that the clearance of galantamine was decreased by 25% to 33% during coadministration of certain CYP2D6 inhibitors including amitriptyline (n = 17). The CYP2D6 isoenzyme is partially involved in the metabolism of galantamine. The clinical relevance of this interaction is unknown; however, increased galantamine concentrations could potentially result in dose-related toxicity.
    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.
    Erythromycin: (Minor) Galantamine is a primary substrate of CYP3A4 and coadministration with CYP3A4 inhibitors may increase the systemic exposure of galantamine. In one pharmacokinetic study, coadministration of galantamine with the moderate CYP3A4 inhibitor erythromycin at a dose of 500 mg four times a day for 4 days resulted in a minimal increase in the AUC of galantamine (10% increase). The clinical significance of this interaction, if any, is unknown.
    Erythromycin; Sulfisoxazole: (Minor) Galantamine is a primary substrate of CYP3A4 and coadministration with CYP3A4 inhibitors may increase the systemic exposure of galantamine. In one pharmacokinetic study, coadministration of galantamine with the moderate CYP3A4 inhibitor erythromycin at a dose of 500 mg four times a day for 4 days resulted in a minimal increase in the AUC of galantamine (10% increase). The clinical significance of this interaction, if any, is unknown.
    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.
    Fesoterodine: (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.
    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.
    Fluoxetine: (Moderate) A population pharmacokinetic analysis showed that the clearance of galantamine was decreased by 25% to 33% during coadministration of certain CYP2D6 inhibitors including fluoxetine (n = 48). The CYP2D6 isoenzyme is partially involved in the metabolism of galantamine. The clinical relevance of this interaction is unknown; however, increased galantamine concentrations could potentially result in dose-related toxicity.
    Fluoxetine; Olanzapine: (Moderate) A population pharmacokinetic analysis showed that the clearance of galantamine was decreased by 25% to 33% during coadministration of certain CYP2D6 inhibitors including fluoxetine (n = 48). The CYP2D6 isoenzyme is partially involved in the metabolism of galantamine. The clinical relevance of this interaction is unknown; however, increased galantamine concentrations could potentially result in dose-related toxicity. (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.
    Fluvoxamine: (Moderate) A population pharmacokinetic analysis showed that the clearance of galantamine was decreased by 25% to 33% during coadministration of certain CYP2D6 inhibitors including fluvoxamine (n = 14). The CYP2D6 isoenzyme is partially involved in the metabolism of galantamine. The clinical relevance of this interaction is unknown; however, increased galantamine concentrations could potentially result in dose-related toxicity.
    Fosamprenavir: (Moderate) The plasma concentrations of galantamine, a partial CYP3A4 substrate, may be elevated when administered with protease inhibitors, which are strong CYP3A4 inhibitors. If this combination is required, monitor for galantamine-related adverse effects such as nausea, vomiting, diarrhea, increased urination, decreased appetite, confusion, dizziness, bradycardia, and excessive sweating.
    Fosphenytoin: (Moderate) Galantamine is a substrate for CYP3A4 and CYP2D6. The effectiveness of the drug could theoretically be reduced by the concomitant administration of CYP3A4 inducers such as fosphenytoin.
    Fospropofol: (Moderate) Muscle relaxation produced by succinylcholine can be prolonged when the drug is administered with a cholinesterase inhibitor. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade. Other neuromuscular blockers may interact with cholinesterase inhibitors in a similar fashion. Cholinesterase inhibitors are therefore also likely to exaggerate muscle relaxation under general anesthetics.
    Glycopyrrolate: (Moderate) The therapeutic benefits of 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.
    Hydrochlorothiazide, HCTZ; 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.
    Hydrochlorothiazide, HCTZ; 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.
    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.
    Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with galantamine, a primary CYP3A substrate, as galantamine toxicity may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Imatinib: (Moderate) Imatinib is a potent inhibitor of cytochrome P450 3A4 and may increase concentrations of other drugs metabolized by this enzyme including galantamine.
    Imipramine: (Moderate) The therapeutic benefits of galantamine may be diminished when coadministered with drugs known to exhibit anticholinergic properties including tricyclic antidepressants. When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy. A population pharmacokinetic analysis showed that the clearance of galantamine was decreased by 25% to 33% during coadministration of certain CYP2D6 inhibitors including amitriptyline (n = 17). The CYP2D6 isoenzyme is partially involved in the metabolism of galantamine. The clinical relevance of this interaction is unknown; however, increased galantamine concentrations could potentially result in dose-related toxicity.
    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.
    Indinavir: (Moderate) The plasma concentrations of galantamine, a partial CYP3A4 substrate, may be elevated when administered with protease inhibitors, which are strong CYP3A4 inhibitors. If this combination is required, monitor for galantamine-related adverse effects such as nausea, vomiting, diarrhea, increased urination, decreased appetite, confusion, dizziness, bradycardia, and excessive sweating.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Galantamine is a substrate for CYP3A4 and CYP2D6. The effectiveness of the drug could theoretically be reduced by the concomitant administration of inducers of both CYP3A4 and CYP2D6 such as rifamycins.
    Isoniazid, INH; Rifampin: (Moderate) Galantamine is a substrate for CYP3A4 and CYP2D6. The effectiveness of the drug could theoretically be reduced by the concomitant administration of inducers of both CYP3A4 and CYP2D6 such as rifamycins.
    Itraconazole: (Moderate) Galantamine is a primary substrate of CYP3A4 and the bioavailability of galantamine may be increased when coadministered with strong CYP3A4 inhibitors, such as itraconazole. Monitor patients for galantamine-related adverse effects such as nausea, vomiting, diarrhea, headache, loss of appetite, excess sweating, and confusion.
    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.
    Ketoconazole: (Moderate) Galantamine is a primary substrate of CYP3A4 and the bioavailability of galantamine may be increased when coadministered with strong CYP3A4 inhibitors, such as ketoconazole. In one pharmacokinetic study, ketoconazole administered at a dose of 200 mg two times a day for 4 days increased the AUC of galantamine by 30%. Monitor patients for galantamine-related adverse effects such as nausea, vomiting, diarrhea, headache, loss of appetite, excess sweating, and confusion during use of this combination.
    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.
    Levobupivacaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Lidocaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
    Lopinavir; Ritonavir: (Moderate) The plasma concentrations of galantamine, a partial CYP3A4 substrate, may be elevated when administered with protease inhibitors, which are strong CYP3A4 inhibitors. If this combination is required, monitor for galantamine-related adverse effects such as nausea, vomiting, diarrhea, increased urination, decreased appetite, confusion, dizziness, bradycardia, and excessive sweating.
    Lumacaftor; Ivacaftor: (Minor) Lumacaftor; ivacaftor may decrease the systemic exposure and therapeutic efficacy of galantamine. Galantamine is a CYP3A substrate. Lumacaftor is a strong CYP3A inducer.
    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.
    Mepenzolate: (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.
    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.
    Mephobarbital: (Moderate) Monitor for reduced efficacy of galantamine during concurrent use of barbiturates. Galantamine is a substrate for CYP3A4 and CYP2D6. The effectiveness of the drug could theoretically be reduced by the concomitant administration of strong CYP3A4 inducers such as barbiturates.
    Mepivacaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Mepivacaine; Levonordefrin: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) The therapeutic benefits of 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: (Major) The effects of cholinesterase inhibitors may be inhibited by methocarbamol. Therefore, methocarbamol should be used with caution in patients with myasthenia gravis receiving cholinesterase inhibitors.
    Methohexital: (Moderate) Monitor for reduced efficacy of galantamine during concurrent use of barbiturates. Galantamine is a substrate for CYP3A4 and CYP2D6. The effectiveness of the drug could theoretically be reduced by the concomitant administration of strong CYP3A4 inducers such as barbiturates.
    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.
    Mitotane: (Moderate) Use caution if mitotane and galantamine are used concomitantly, and monitor for decreased efficacy of galantamine which may require a change in dosage. Mitotane is a strong CYP3A4 inducer and galantamine is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of 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.
    Nefazodone: (Moderate) Hepatic CYP3A4 is partially responsible for the metabolism of galantamine. The bioavailability of galantamine may be increased when co-administered with an inhibitor of this enzyme, including nefazodone.
    Nelfinavir: (Moderate) The plasma concentrations of galantamine, a partial CYP3A4 substrate, may be elevated when administered with protease inhibitors, which are strong CYP3A4 inhibitors. If this combination is required, monitor for galantamine-related adverse effects such as nausea, vomiting, diarrhea, increased urination, decreased appetite, confusion, dizziness, bradycardia, and excessive sweating.
    Neuromuscular blockers: (Major) Cholinesterase inhibitors may be used to reverse the actions of nondepolarizing neuromuscular blockers; however, cholinesterase inhibitors may also prolong the neuromuscular blocking effects if given with depolarizing neuromuscular blockers, as these drugs are metabolized by acetylcholinesterase. In addition, neuromuscular blocking agents can antagonize the effects of the cholinesterase inhibitors; temporary dosage adjustment following surgery may be necessary.
    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. When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy. A population pharmacokinetic analysis showed that the clearance of galantamine was decreased by 25% to 33% during coadministration of certain CYP2D6 inhibitors including amitriptyline (n = 17). The CYP2D6 isoenzyme is partially involved in the metabolism of galantamine. The clinical relevance of this interaction is unknown; however, increased galantamine concentrations could potentially result in dose-related toxicity.
    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.
    Ombitasvir; Paritaprevir; Ritonavir: (Moderate) The plasma concentrations of galantamine, a partial CYP3A4 substrate, may be elevated when administered with protease inhibitors, which are strong CYP3A4 inhibitors. If this combination is required, monitor for galantamine-related adverse effects such as nausea, vomiting, diarrhea, increased urination, decreased appetite, confusion, dizziness, bradycardia, and excessive sweating.
    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.
    Paroxetine: (Moderate) Galantamine is partially metabolized by CYP2D6 and systemic exposure may be increased during concurrent use of a strong CYP2D6 inhibitor, such as paroxetine. In one pharmacokinetic study, the bioavailability of galantamine was increased by about 40% when coadministered with paroxetine at a dose of 20 mg/day for 16 days. Monitor for galantamine-related adverse effects such as nausea, vomiting, loss of appetite, diarrhea, headache, confusion, and excessive sweating during concurrent use of these drugs.
    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.
    Pentobarbital: (Moderate) Monitor for reduced efficacy of galantamine during concurrent use of barbiturates. Galantamine is a substrate for CYP3A4 and CYP2D6. The effectiveness of the drug could theoretically be reduced by the concomitant administration of strong CYP3A4 inducers such as barbiturates.
    Perphenazine; Amitriptyline: (Moderate) The therapeutic benefits of galantamine may be diminished when coadministered with drugs known to exhibit anticholinergic properties including tricyclic antidepressants. When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy. A population pharmacokinetic analysis showed that the clearance of galantamine was decreased by 25% to 33% during coadministration of certain CYP2D6 inhibitors including amitriptyline (n = 17). The CYP2D6 isoenzyme is partially involved in the metabolism of galantamine. The clinical relevance of this interaction is unknown; however, increased galantamine concentrations could potentially result in dose-related toxicity.
    Phenobarbital: (Moderate) Monitor for reduced efficacy of galantamine during concurrent use of barbiturates. Galantamine is a substrate for CYP3A4 and CYP2D6. The effectiveness of the drug could theoretically be reduced by the concomitant administration of strong CYP3A4 inducers such as barbiturates.
    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.
    Phenytoin: (Moderate) Galantamine is a substrate for CYP3A4 and CYP2D6. The effectiveness of the drug could theoretically be reduced by the concomitant administration of CYP3A4 inducers such as phenytoin.
    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.
    Posaconazole: (Moderate) Posaconazole and galantamine should be coadministered with caution due to an increased potential for galantamine-related adverse events. Posaconazole is a potent inhibitor of CYP3A4 and galantamine is a primary substrate of CYP3A4. Monitor for galantamine-related adverse effects such as nausea, vomiting, loss of appetite, diarrhea, headache, confusion, and excessive sweating during concurrent use of these drugs.
    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.
    Primidone: (Moderate) Monitor for reduced efficacy of galantamine during concurrent use of barbiturates. Galantamine is a substrate for CYP3A4 and CYP2D6. The effectiveness of the drug could theoretically be reduced by the concomitant administration of strong CYP3A4 inducers such as barbiturates.
    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.
    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.
    Protease inhibitors: (Moderate) The plasma concentrations of galantamine, a partial CYP3A4 substrate, may be elevated when administered with protease inhibitors, which are strong CYP3A4 inhibitors. If this combination is required, monitor for galantamine-related adverse effects such as nausea, vomiting, diarrhea, increased urination, decreased appetite, confusion, dizziness, bradycardia, and excessive sweating.
    Protriptyline: (Moderate) The therapeutic benefits of galantamine may be diminished when coadministered with drugs known to exhibit anticholinergic properties including tricyclic antidepressants. When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy. A population pharmacokinetic analysis showed that the clearance of galantamine was decreased by 25% to 33% during coadministration of certain CYP2D6 inhibitors including amitriptyline (n = 17). The CYP2D6 isoenzyme is partially involved in the metabolism of galantamine. The clinical relevance of this interaction is unknown; however, increased galantamine concentrations could potentially result in dose-related toxicity.
    Quinidine: (Moderate) A population pharmacokinetic analysis showed that the clearance of galantamine was decreased by 25% to 33% during coadministration of certain CYP2D6 inhibitors including quinidine. The CYP2D6 isoenzyme is partially involved in the metabolism of galantamine. The clinical relevance of this interaction is unknown; however, increased galantamine concentrations could potentially result in dose-related toxicity.
    Rifabutin: (Moderate) Galantamine is a substrate for CYP3A4 and CYP2D6. The effectiveness of the drug could theoretically be reduced by the concomitant administration of inducers of both CYP3A4 and CYP2D6 such as rifamycins.
    Rifampin: (Moderate) Galantamine is a substrate for CYP3A4 and CYP2D6. The effectiveness of the drug could theoretically be reduced by the concomitant administration of inducers of both CYP3A4 and CYP2D6 such as rifamycins.
    Rifamycins: (Moderate) Galantamine is a substrate for CYP3A4 and CYP2D6. The effectiveness of the drug could theoretically be reduced by the concomitant administration of inducers of both CYP3A4 and CYP2D6 such as rifamycins.
    Rifapentine: (Moderate) Galantamine is a substrate for CYP3A4 and CYP2D6. The effectiveness of the drug could theoretically be reduced by the concomitant administration of inducers of both CYP3A4 and CYP2D6 such as rifamycins.
    Ritonavir: (Moderate) The plasma concentrations of galantamine, a partial CYP3A4 substrate, may be elevated when administered with protease inhibitors, which are strong CYP3A4 inhibitors. If this combination is required, monitor for galantamine-related adverse effects such as nausea, vomiting, diarrhea, increased urination, decreased appetite, confusion, dizziness, bradycardia, and excessive sweating.
    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.
    Saquinavir: (Moderate) The plasma concentrations of galantamine, a partial CYP3A4 substrate, may be elevated when administered with protease inhibitors, which are strong CYP3A4 inhibitors. If this combination is required, monitor for galantamine-related adverse effects such as nausea, vomiting, diarrhea, increased urination, decreased appetite, confusion, dizziness, bradycardia, and excessive sweating.
    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.
    Secobarbital: (Moderate) Monitor for reduced efficacy of galantamine during concurrent use of barbiturates. Galantamine is a substrate for CYP3A4 and CYP2D6. The effectiveness of the drug could theoretically be reduced by the concomitant administration of strong CYP3A4 inducers such as barbiturates.
    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.
    St. John's Wort, Hypericum perforatum: (Moderate) St. John's Wort appears to induce several isoenzymes of the hepatic cytochrome P450 enzyme system. Co-administration of St. John's wort could decrease the efficacy of some medications metabolized by these enzymes including galantamine.
    Telaprevir: (Moderate) Close clinical monitoring is advised when administering galantamine with telaprevir due to an increased potential for galantamine-related adverse events. If galantamine dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of galantamine. Galantamine is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated galantamine plasma concentrations.
    Telithromycin: (Moderate) Concentrations of galantamine may be increased with concomitant use of telithromycin. Galantamine is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects of galantamine including nausea, vomiting, diarrhea, increased urination, decreased appetite, excessive sweating, dizziness, or confusion.
    Tetracaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
    Thiopental: (Moderate) Monitor for reduced efficacy of galantamine during concurrent use of barbiturates. Galantamine is a substrate for CYP3A4 and CYP2D6. The effectiveness of the drug could theoretically be reduced by the concomitant administration of strong CYP3A4 inducers such as barbiturates.
    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.
    Tipranavir: (Moderate) The plasma concentrations of galantamine, a partial CYP3A4 substrate, may be elevated when administered with protease inhibitors, which are strong CYP3A4 inhibitors. If this combination is required, monitor for galantamine-related adverse effects such as nausea, vomiting, diarrhea, increased urination, decreased appetite, confusion, dizziness, bradycardia, and excessive sweating.
    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. When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy. A population pharmacokinetic analysis showed that the clearance of galantamine was decreased by 25% to 33% during coadministration of certain CYP2D6 inhibitors including amitriptyline (n = 17). The CYP2D6 isoenzyme is partially involved in the metabolism of galantamine. The clinical relevance of this interaction is unknown; however, increased galantamine concentrations could potentially result in dose-related toxicity.
    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. When concurrent use cannot be avoided, monitor the patient for reduced galantamine efficacy. A population pharmacokinetic analysis showed that the clearance of galantamine was decreased by 25% to 33% during coadministration of certain CYP2D6 inhibitors including amitriptyline (n = 17). The CYP2D6 isoenzyme is partially involved in the metabolism of galantamine. The clinical relevance of this interaction is unknown; however, increased galantamine concentrations could potentially result in dose-related toxicity.
    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.
    Voriconazole: (Minor) Galantamine is a substrate for CYP3A4 and CYP2D6. The bioavailability of galantamine is expected to increase when coadministered with the CYP3A4 inhibitor voriconazole. An increase in cholinergic side effects may occur, particularly nausea and vomiting.

    PREGNANCY AND LACTATION

    Pregnancy

    Galantamine is classified as FDA pregnancy risk category C. It is not known whether galantamine causes harm to the human fetus or influences reproductive capacity in pregnant females. Because there are no adequate and well-controlled studies of galantamine in pregnant women, the drug should be used during pregnancy only if the potential maternal benefit clearly justifies the potential fetal risk. In animal studies, developmental toxicity (increased incidence of morphological abnormalities and decreased offspring growth) was observed during use of doses similar to or greater than therapeutic human doses. The effects of galantamine in labor and delivery are unknown.

    According to the manufacturer, it is not known whether galantamine is excreted in human breast milk. According to the manufacturer, caution is advisable when galantamine is administered to a breast-feeding woman. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    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.