These interactions are likely related to opposing dopaminergic mechanisms of action, which inhibits amantadines anti-Parkinson effects. Contraindications
Amantadine is contraindicated in persons with end stage kidney disease. The drug is renally cleared.Amantadine may have anticholinergic side effects. Thus, patients with an enlarged prostate or glaucoma should use with caution.Live attenuated vaccines are contraindicated while taking amantadine. It is possible that amantadine will inhibit viral replication and reduce the efficacy of administered vaccines. The U.S. Food and Drug Administration recommends avoiding amantadine for two weeks prior to vaccine administration and 48 hours afterward. History
Influenza A
Antiviral properties were first reported in 1963 at the University of Illinois Hospital in Chicago. In this amantadine trial study volunteer college students were exposed to a viral challenge. The group that received amantadine (100 milligrams 18 hours before viral challenge) had less Asia influenza infections than the placebo group. Amantadine received approval for the treatment of influenza virus A in adults in 1976. It was first used in West Germany in 1966. Amantadine was approved by the U.S. Food and Drug Administration in October 1968, as a prophylactic agent against Asian (H2N2) influenza and received approval for prophylactic use for influenza A in 1976.During the 1980 influenza A epidemic, the first amantadine-resistance influenza viruses were reported. The frequency of amantadine resistance among influenza A (H3N2) viruses from 1991 and 1995 was as low as 0.8%. In 2004 the resistance frequency increased to 12.3%. A year later resistance increase significantly to 96%, 72%, and 14.5% in China, South Korea, and the United States, respectively.
There are also reports of significantly improved consciousness in patients treated for non-traumatic cases of DoC, such as in the case of a subarachnoid hemorrhage, cerebral hemorrhage, and hypoxic encephalopathy. In 2018 the American Academy of Neurology (AAN) updated treatment guidelines on the use of amantadine for patients with prolonged DoC, recommending the use of amantadine (100–200 mg bid) for adults with DoC 4–16 weeks post injury to support early functional recovery and reduce disability. Neuroplasticity and overall functional recovery in patients with brain injury
In various studies, amantadine and memantine have been shown to accelerate the rate of recovery from a brain injury. The time-limited window following a brain injury is characterized by neuroplasticity, or the capacity of neurons in the brain to adapt and compensate after injury. Thus, physiatrists will often start patients on amantadine as soon as impairments are recognized. There are also case reports showing improved functional recovery with amantadine treatment occurring years after the initial brain injury. There is insufficient evidence to determine if the functional gains are a result of effects through the dopamine or norepinephrine pathways. Some patients may benefit from direct dopamine stimulation with amantadine, while others may benefit more from other stimulants that act more on the norepinephrine pathway, such as methylphenidate. It is unclear if treatment with amantadine improves long-term outcomes or simply accelerates recovery. Nonetheless, amantadine-induced acceleration of recovery reduces the burden of disability, lessens health care costs, and minimizes psychosocial stressors in patients. Adverse effects
Amantadine is generally well tolerated and has a mild side-effect profile.