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Home > Medications (Drugs) > Amantadine > Interactions with Amantadine

Interactions with Amantadine

If you are currently being treated with any of the following medications, you should not use Amantadine without reading these interactions.

Influenza virus vaccine (nasal)

ADJUST DOSING INTERVAL: Antiviral agents that are active against influenza A and/or B viruses may conceivably interfere with the immunogenicity of live influenza virus vaccine by inhibiting the replication of vaccine virus. However, the potential for interaction has not been evaluated.

MANAGEMENT: Live influenza virus vaccine should preferably not be administered until at least 48 hours after the cessation of antiviral therapy. Antiviral agents should not be administered until two weeks after immunization with live influenza virus vaccine unless medically indicated. The product labeling for zanamivir recommends waiting 24 hours after cessation of the drug before administration of live influenza virus vaccine.

Iopamidol

GENERALLY AVOID: Intrathecal administration of iodinated contrast media may induce seizures. Although clinical data are generally lacking, there may be a theoretical risk of increased seizure potential when used with selective serotonin reuptake inhibitors (SSRI antidepressants or anorectics), monoamine oxidase inhibitors, neuroleptic agents, central nervous system stimulants, opioids, tricyclic antidepressants, other tricyclic compounds (e.g., cyclobenzaprine, phenothiazines), and/or any substance that can reduce the seizure threshold (e.g., carbapenems, cholinergic agents, fluoroquinolones, interferons, chloroquine, mefloquine, lindane, theophylline). These agents are often individually epileptogenic and may have additive effects when combined.

MANAGEMENT: Drugs that can lower the seizure threshold should preferably be withheld for at least 48 hours prior to and 24 hours following intrathecal administration of iodinated contrast media, provided that temporary interruption of therapy does not pose an undue risk to the patient. Otherwise, close monitoring is advised during and after contrast administration. The manufacturers typically recommend avoiding concomitant administration of phenothiazines (including those used for their antihistamine properties), monoamine oxidase inhibitors, tricyclic antidepressants, central nervous system stimulants, and psychoactive drugs.

Chlorothiazide, Chlorthalidone, Hydrochlorothiazide, Indapamide, Metolazone, Triamterene

Limited data indicate that thiazide diuretics and/or triamterene may increase the probability of adverse reactions to amantadine. The mechanism is unknown but may be related to reduced clearance of amantadine, resulting in increased plasma levels. Possible reactions include ataxia, confusion, and agitation. If an interaction is suspected, the dosage of amantadine may be reduced or discontinued, or a different diuretic may be substituted.

Tramadol

MONITOR CLOSELY: The risk of seizures may be increased during coadministration of tramadol with selective serotonin reuptake inhibitors (SSRI antidepressants or anorectics), monoamine oxidase inhibitors, neuroleptic agents, central nervous system stimulants, opioids, tricyclic antidepressants, other tricyclic compounds (e.g., cyclobenzaprine, phenothiazines), and/or any substance that can reduce the seizure threshold (e.g., carbapenems, cholinergic agents, fluoroquinolones, interferons, chloroquine, mefloquine, lindane, theophylline). These agents are often individually epileptogenic and may have additive effects when combined. Many of these agents also exhibit CNS- and/or respiratory-depressant effects, which may be enhanced during their concomitant use with tramadol.

MANAGEMENT: Caution is advised if tramadol is administered with any substance that can reduce the seizure threshold, particularly in the elderly and in patients with epilepsy, a history of seizures, or other risk factors for seizures (e.g., head trauma, brain tumor, metabolic disorders, alcohol and drug withdrawal, CNS infections).

Bupropion (oral)

MONITOR CLOSELY: The use of bupropion is associated with a dose-related risk of seizures. The estimated incidence of seizures is approximately 0.1% at dosages up to 300 mg/day and 0.4% at dosages between 300 to 450 mg/day, but increases almost tenfold between 450 mg and 600 mg/day. The risk may also be increased during coadministration of bupropion with other potentially epileptogenic agents such as amantadine.

MONITOR CLOSELY: According to the product labeling for bupropion, limited clinical data suggest a higher incidence of adverse experiences in patients receiving bupropion concurrently with either levodopa or amantadine. Neither the mechanism of interaction nor specific adverse effects are cited. According to a published case report, neurotoxic effects including ataxia, dizziness, vertigo, agitation, tremors, and gait abnormalities occurred in 3 elderly patients following addition of amantadine to bupropion therapy. The symptoms resolved within 72 hours after discontinuation of both drugs. The authors theorize that additive central dopaminergic effects of the drugs may have caused the apparent interaction.

MANAGEMENT: Extreme caution is advised if bupropion is administered with amantadine, particularly in the elderly and in patients with a history of seizures or other risk factors for seizures (e.g., head trauma; brain tumor; severe hepatic cirrhosis; metabolic disorders; CNS infections; excessive use of alcohol or sedatives; addiction to opiates, cocaine, or stimulants; diabetes treated with oral hypoglycemic agents or insulin). The manufacturer recommends a lower initial dosage of bupropion and gradual dosage increments in patients receiving the drugs concurrently. The total dose of bupropion should generally not exceed 450 mg/day (or 150 mg every other day in patients with severe hepatic cirrhosis). Bupropion should be discontinued and not restarted in patients who experience a seizure during treatment.

Quinine

MONITOR: Coadministration with quinine or quinidine may decrease the renal clearance of amantadine. The proposed mechanism is quinine and quinidine inhibition of the renal tubular secretion of amantadine. In 18 healthy volunteers administered a single oral dose of amantadine (3 mg/kg), renal clearance of amantadine decreased by approximately 27% and 32% within 6 hours after ingestion of a 200 mg dose of quinine or quinidine, respectively. The interaction was reported only in the male subjects and was not influenced by age.

MANAGEMENT: The potential for increased pharmacologic effects of amantadine, including adverse effects such as dizziness, confusion, ataxia, orthostatic hypotension, dry mouth, nausea and constipation, should be considered during coadministration with quinine or quinidine.

Lindane topical

MONITOR: Lindane penetrates human skin and has the potential to cause central nervous system toxicity. Seizures have been reported after excessive use or oral ingestion of lindane. There may be a theoretical risk of increased seizure potential when lindane is used with selective serotonin reuptake inhibitors (SSRI antidepressants or anorectics), monoamine oxidase inhibitors, neuroleptic agents, central nervous system stimulants, opioids, tricyclic antidepressants, other tricyclic compounds (e.g., cyclobenzaprine, phenothiazines), and/or any substance that can reduce the seizure threshold (e.g., carbapenems, cholinergic agents, fluoroquinolones, interferons, chloroquine, mefloquine, theophylline). These agents are often individually epileptogenic and may have additive effects when combined.

MANAGEMENT: Caution is advised if lindane is used with any substance that can reduce the seizure threshold, particularly in the very young or the elderly and in patients with epilepsy, a history of seizures, or other risk factors for seizures (e.g., head trauma, brain tumor, metabolic disorders, alcohol and drug withdrawal, CNS infections). Lindane should be used according to recommended dosage and directions for application.

Nortriptyline, Desipramine, Amitriptyline, Atropine, Benztropine, Chlorpheniramine, Clozapine, Diphenhydramine, Disopyramide, Doxepin, Fluphenazine, Imipramine, Prochlorperazine, Propantheline, Thioridazine (oral), Thiothixene, Clemastine, Tripelennamine, Dexchlorpheniramine, Brompheniramine, Promethazine (oral), Cyproheptadine, Azatadine, Phenindamine, Perphenazine, Thiethylperazine, Cyclizine, Meclizine, Dimenhydrinate, Trimipramine, Amoxapine, Protriptyline, Clomipramine, Mesoridazine, Trifluoperazine, Molindone, Loxapine, Pimozide (oral), Hydroxyzine, Cyclobenzaprine, Orphenadrine, Procyclidine, Trihexyphenidyl, Biperiden, Hyoscyamine, Belladonna, Methscopolamine, Clidinium, Glycopyrrolate, Dicyclomine, Risperidone (oral), Olanzapine, Oxybutynin (oral), Oxybutynin (transdermal), Triprolidine, Promethazine (rectal), Promethazine (injection), Maprotiline, Scopolamine, Flavoxate, Carbinoxamine, Scopolamine topical, Quetiapine, Tolterodine, Ziprasidone, Aripiprazole, Trospium, Solifenacin, Darifenacin, Paliperidone

MONITOR: The anticholinergic-like adverse effects of amantadine may be potentiated by agents with anticholinergic properties such as antihistamines, antispasmodics, class IA antiarrhythmics, neuroleptics, phenothiazines, skeletal muscle relaxants, and tricyclic antidepressants. The cumulative parasympatholytic effects of these agents may produce paralytic ileus, hyperthermia, heat stroke, and the anticholinergic intoxication syndrome. Peripheral symptoms of intoxication commonly include mydriasis, blurred vision, flushed face, fever, dry skin and mucous membranes, tachycardia, urinary retention, and constipation. Central symptoms may include memory loss, disorientation, incoherence, hallucinations, psychosis, delirium, hyperactivity, twitching or jerking movements, stereotypy, and seizures.

MANAGEMENT: Caution is advised when amantadine is used in combination with anticholinergic agents, particularly in the elderly and those with underlying organic brain disease, who tend to be more sensitive to the central anticholinergic effects of these drugs and in whom toxicity symptoms may be easily overlooked. Patients should be advised to notify their physician promptly if they experience potential symptoms of anticholinergic intoxication such as abdominal pain, fever, heat intolerance, blurred vision, confusion, and/or hallucinations. Ambulatory patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them. A reduction in anticholinergic and/or amantadine dosage may be necessary if excessive adverse effects develop.

Memantine

The manufacturer recommends caution if other NMDA antagonists are used concomitantly with memantine. The clinical significance is unknown.

Trimethoprim

Trimethoprim may decrease the renal clearance of amantadine. Serum amantadine levels and the risk of mental confusion may be increased. Amantadine also may inhibit the renal clearance of trimethoprim. Serum trimethoprim levels may be increased. Management consists of monitoring for nervous system side effects during therapy.

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