OSMOLEX® ER (amantadine) Is Indicated for Both Parkinson's Disease and Drug-Induced Extrapyramidal Reactions1

Parkinson's Disease (PD)2

PD is a neurodegenerative disease
characterized by involuntary movement due
to neuronal death. It is the second most
frequently diagnosed neurodegenerative
disease after Alzheimer's disease. PD onset
usually occurs after age 60.

PD is primarily a movement disorder.
Motor system symptoms of
Parkinson's include:

Resting limb tremor icon

Resting limb tremors

Stiffness and rigidity icon

Stiffness and rigidity

Speedometer icon

Slowness of
intentional movement
(bradykinesia)

Balance icon

Disrupted balance

Forward pointing arrow icon

Characteristic
forward-falling gait

Drug-Induced Extrapyramidal Reactions (EPR)3,4

Drug-induced EPR are typically reversible effects to the nerves associated with motor activity. They are often caused by antipsychotic drug (APD) use, but may be associated with other medications as well. Symptoms can begin immediately after administration of an APD, or be delayed by hours or days. Drug-induced EPR are rarely life-threatening, but can cause distress for patients and their families.

Drug-induced EPR due to antipsychotic drug (APD) use:

Parkinsonism*

One of the more commonly observed movement disorders induced by APDs.5

  • Uncontrolled movement appearing within a few weeks of initation or dosage increase of an APD4
  • 50% of cases display additional signs of tardive dyskenisia or akathisia4

Tardive Dyskinesia

Involuntary movement that may be irreversible, occurring months to years after receiving APD therapy.5

  • Occurs in about 20%-30% of patients who receive long-term APD treatment for conditions such as schizophrenia, bipolar disorder, or major depressive disorder6

Dystonia

Involuntary movements that may appear in all muscle groups, but are observed mainly in the head and neck area.7

  • 95% of cases appear within 96 hours of starting treatment with APDs, or after a large increase in the dose7

*OSMOLEX ER was approved through the 505b(2) pathway where clinical trials evaluating the safety and efficacy in drug-induced EPR were not required for submission. OSMOLEX ER reflects similar labeling as SYMMETREL (amantadine IR) and is indicated for the treatment of drug-induced extrapyramidal reactions in adult patients.

References:

  1. OSMOLEX ER. Prescribing information. Vertical Pharmaceuticals, LLC; 2020.
  2. Parkinson’s Disease. MassGeneral Institute for Neurodegenerative Disease. http://mghmind.org/disease-research/parkinsons-disease. Accessed April 18, 2019.
  3. Extrapyramidal Symptoms – statPearls.
  4. Blanchet P, Kivenko V. Drug-induced parkinsonism: diagnosis and management. Journal of Parkinsonism and Restless Legs Syndrome. 2016;6:83-91.
  5. Ward KM, Citrome L. Antipsychotic-related movement disorders: drug-induced parkinsonism vs. tardive dyskinesia-key differences in pathophysiology and clinical management. Neurol Ther. 2018;7(2):233-248. DOI: 10.1007/s40120-018-0105-0.
  6. Carbon M, Hsieh CH, Kane JM, Correll CU. Tardive dyskinesia prevalence in the period of second-generation antipsychotic use: a meta-analysis. J Clin Psychiatry. 2017;78(3):e264-e278. DOI: 10.4088/JCP.16r10832.
  7. Harten PN, Hoek HW, Kahn RS: Acute dystonia induced by drug treatment. BMJ. 1999;319:623-626. DOI: 10.1136/bmj.319.7210.623.

INDICATION

OSMOLEX® ER (amantadine) extended-release tablets is indicated for the treatment of Parkinson’s disease and for the treatment of drug-induced extrapyramidal reactions in adult patients.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATION

OSMOLEX ER is contraindicated in patients with end-stage renal disease (i.e., creatinine clearance below 15 mL/min/1.73 m2).

WARNINGS AND PRECAUTIONS

Falling Asleep During Activities of Daily Living and Somnolence: Patients treated with amantadine have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles, which sometimes has resulted in accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Before initiating treatment with OSMOLEX ER, advise patients of the potential to develop drowsiness and specifically ask about factors that may increase the risk of somnolence with OSMOLEX ER, such as concomitant sedating medications, alcohol, or the presence of a sleep disorder. If a patient develops daytime sleepiness or episodes of falling asleep during activities that require full attention (eg, driving a motor vehicle, conversations, eating), OSMOLEX ER should ordinarily be discontinued. If a decision is made to continue OSMOLEX ER, advise patients not to drive and to avoid other potentially dangerous activities that might result in harm if they become somnolent.

Suicidality and Depression: Suicide, suicide attempts, and suicidal ideation have been reported in patients with and without prior history of psychiatric illness while treated with amantadine. Monitor patients for depression, including suicidal ideation or behavior. Prescribers should consider whether the benefits of treatment with OSMOLEX ER outweigh the risks in patients with a history of suicidality or depression.

Hallucinations/Psychotic Behavior: Patients with a major psychotic disorder should ordinarily not be treated with OSMOLEX ER due to the risk of exacerbating psychosis. Monitor patients for hallucinations throughout treatment but especially after initiation and after the dose of OSMOLEX ER is increased or decreased.

Dizziness and Orthostatic Hypotension: Patients should be monitored for these adverse reactions, especially after starting OSMOLEX ER or increasing the dose.

Withdrawal-Emergent Hyperpyrexia and Confusion: Abrupt discontinuation of OSMOLEX ER may cause an increase in the symptoms of Parkinson’s disease or cause delirium, agitation, delusions, hallucinations, paranoid reaction, stupor, anxiety, depression, or slurred speech. It is recommended that patients avoid sudden discontinuation of OSMOLEX ER.

Impulse Control/Compulsive Behaviors: Patients can experience increased sexual urges, and intense urges to gamble, spend money, binge eat, and/or other intense urges, and the inability to control these urges while taking one or more medications that increase central dopaminergic tone, including OSMOLEX ER. It is important for prescribers to specifically ask patients or their caregivers about the development of new or increased urges while being treated with OSMOLEX ER. Consider dose reduction or stopping the medication if a patient develops such urges while taking OSMOLEX ER.

ADVERSE REACTIONS

The most common adverse reactions reported in ≥5% of patients at the recommended dosage of immediate-release amantadine were nausea, dizziness/lightheadedness, and insomnia.

DRUG INTERACTIONS

Other Anticholinergic Drugs: The dose of anticholinergic drugs or of OSMOLEX ER should be reduced if atropine-like effects appear when these drugs are used concurrently.

Drugs Affecting Urinary pH: The pH of urine has been reported to influence the excretion rate of amantadine. Alterations in urine pH towards the alkaline condition may lead to an accumulation of the drug with a possible increase in adverse reactions. Monitor for efficacy or adverse reactions under conditions that alter the urine pH to more acidic or alkaline, respectively.

Live Attenuated Influenza Vaccines: Amantadine may interfere with the efficacy of live attenuated influenza vaccines. Therefore, live vaccines are not recommended during treatment with OSMOLEX ER. Inactivated influenza vaccines may be used as appropriate.

Alcohol: Concomitant use with alcohol is not recommended, as it may increase the potential for central nervous system effects such as somnolence, dizziness, confusion, lightheadedness, and orthostatic hypotension.