Amantadine was discontinued as a flu treatment in 2006 because the influenza A virus became almost completely resistant to it. The CDC issued a health alert that year advising doctors to stop prescribing it for influenza entirely. The drug itself, however, was never pulled from the market. It remains available and is still prescribed for Parkinson’s disease and related movement disorders.
How Influenza Outsmarted Amantadine
Amantadine works by blocking a tiny channel on the surface of influenza A virus particles. This channel lets the virus release its genetic material once it gets inside your cells. Block the channel, and the virus can’t replicate. The problem is that a single genetic change in the virus is enough to make the drug useless.
That’s exactly what happened. Resistance rates climbed from 1.8% during the 2001-02 flu season to 12.3% by 2003-04. Then, during the 2005-06 season, the CDC tested 120 circulating H3N2 flu samples and found that 109 of them, 91%, carried the specific mutation (called S31N) that renders both amantadine and its close relative rimantadine completely ineffective. By comparison, resistance to the newer flu drug oseltamivir (Tamiflu) was below 0.5% among thousands of samples tested during its early years on the market.
The speed of this resistance wasn’t entirely surprising. Studies had already shown that 30% to 80% of patients treated with amantadine shed resistant virus during their illness, and those resistant strains spread easily through communities. In January 2006, the CDC told clinicians to stop using amantadine and rimantadine for flu altogether and to prescribe neuraminidase inhibitors like oseltamivir and zanamivir instead.
It Never Worked Against All Flu Strains
Even before resistance became a crisis, amantadine had a fundamental limitation: it only worked against influenza A. Influenza B viruses have a structurally different version of the ion channel that amantadine targets. Lab testing confirmed that amantadine inhibited the influenza A channel by about 94%, while it had essentially zero effect on the influenza B channel. So during any flu season dominated by influenza B strains, amantadine offered no protection at all. This narrow coverage made it even less useful as resistance eroded its effectiveness against the one virus type it could treat.
The Brand Name Disappeared, Not the Drug
Some of the confusion around amantadine being “discontinued” comes from the fate of Symmetrel, the original brand-name version. The FDA placed Symmetrel’s syrup formulation on its Discontinued Drug Product List, but the agency explicitly confirmed this was not due to safety or effectiveness concerns. The manufacturer simply stopped marketing that particular product. Generic versions of amantadine remained available, and the FDA continued approving new generic applications referencing the original Symmetrel approval.
In 2017, the FDA approved Gocovri, an extended-release formulation of amantadine specifically for treating involuntary movements (dyskinesia) in people with Parkinson’s disease who take levodopa. This approval reinforced that amantadine as a molecule is very much still in clinical use.
Why Amantadine Still Matters in Neurology
Amantadine’s second life is in treating Parkinson’s disease. The drug blocks a receptor in the brain called NMDA, which plays a role in the involuntary, jerky movements that many Parkinson’s patients develop after years on levodopa. By dampening overactive signaling through this receptor, amantadine can reduce those movements without worsening the stiffness and slowness that levodopa is treating in the first place. It also has mild effects that boost dopamine activity, which provides some additional benefit for core Parkinson’s symptoms.
Amantadine is also sometimes used in traumatic brain injury rehabilitation and for fatigue in multiple sclerosis, though these uses are less well established than its role in Parkinson’s.
Side Effects Worth Knowing About
Amantadine is generally tolerable, but it does come with notable side effects, particularly for people taking it long-term for neurological conditions. Up to 40% of patients develop livedo reticularis, a mottled, net-like purple discoloration of the skin, most commonly on the legs and trunk. It’s more frequent in women. The discoloration is caused by spasm of small blood vessels and usually resolves after stopping the drug, though in rare cases it can progress to skin ulceration.
Because amantadine has anticholinergic properties, it can also cause dry mouth, constipation, urinary retention, and blurred vision. Some patients experience dizziness, insomnia, or difficulty concentrating. In older adults or those with kidney problems (since the drug is cleared almost entirely by the kidneys), higher blood levels can accumulate and cause confusion, hallucinations, or agitation. These psychiatric effects are the most serious concern and are the main reason dosing needs to be adjusted carefully in people with reduced kidney function.
The Bottom Line on Its Flu Use
Amantadine’s story as an antiviral is essentially over. Resistance among circulating influenza A strains remains high worldwide, and no mechanism exists to reverse it since the mutation that confers resistance doesn’t significantly weaken the virus. The CDC’s 2006 recommendation against using amantadine for flu has never been reversed. Unless a future pandemic strain happens to be sensitive to the drug, amantadine’s role in infectious disease is a historical footnote, while its role in neurology continues to grow.