symmetrel
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Amantadine hydrochloride, sold under the brand name Symmetrel among others, is a medication with a fascinating and somewhat convoluted history. Initially developed as an antiviral agent, its utility in Parkinson’s disease was discovered quite by accident, a classic example of serendipity in medicine. It functions primarily as a weak, non-competitive antagonist of the NMDA receptor, but its exact mechanism in Parkinsonism isn’t fully elucidated—it’s thought to promote dopamine release and possibly block dopamine reuptake in the nigrostriatal pathway. It’s also used for its antiviral properties against influenza A and, in some cases, for fatigue in multiple sclerosis. The standard formulation is a 100 mg capsule or tablet, and its bioavailability is good, nearly 90% after oral administration, with peak plasma concentrations reached in about 1-4 hours. It’s primarily excreted unchanged in the urine, so renal function is a critical consideration for dosing.
I remember when I first started using it in the late 90s, we were much more liberal with its use for influenza A prophylaxis in nursing homes. The thinking was different then. But over the years, the rise of resistant strains and the advent of neuraminidase inhibitors like oseltamivir have really pushed it to the sidelines for that indication. Its role in Parkinson’s, however, remains a valuable, if sometimes underutilized, tool, especially for dealing with the dyskinesias induced by levodopa.
1. Introduction: What is Symmetrel? Its Role in Modern Medicine
Symmetrel is the brand name for the drug amantadine hydrochloride. Classified as an adamantane antiviral and an antiparkinsonian agent, its journey in the pharmacopeia is a testament to how drug applications can evolve. What began as a prophylactic for Asian influenza in the 1960s soon revealed an unexpected benefit: patients with Parkinson’s disease who were taking it reported a significant improvement in their motor symptoms. This off-label observation was later confirmed through clinical studies, cementing its place in neurology. For healthcare professionals and informed patients, understanding Symmetrel is about appreciating its dual, though now diverging, roles: a secondary option for antiviral prophylaxis and a key adjunctive therapy in the management of Parkinson’s disease and drug-induced extrapyramidal symptoms.
2. Key Components and Bioavailability of Symmetrel
The active pharmaceutical ingredient in Symmetrel is amantadine hydrochloride, a synthetic tricyclic amine. It is not a naturally occurring compound but is synthesized in a laboratory setting. It is available in two primary forms for oral administration: 100 mg capsules and a syrup formulation (50 mg/5 mL).
A critical aspect of its pharmacology is its pharmacokinetic profile. Unlike many supplements or drugs that require special formulations for absorption, amantadine is well-absorbed from the gastrointestinal tract, with a bioavailability of approximately 90%. It is not significantly metabolized by the liver; about 90% of the administered dose is excreted unchanged in the urine via glomerular filtration and tubular secretion. This has profound implications for its use, making renal function the single most important factor in determining appropriate dosage and avoiding toxicity. The plasma half-life is around 11-15 hours in individuals with normal renal function, but this can extend dramatically to over a week in patients with end-stage renal disease.
3. Mechanism of Action of Symmetrel: Scientific Substantiation
The mechanism of action of Symmetrel is multifaceted and differs depending on its application.
- Antiparkinsonian Effects: The primary mechanism is believed to be the antagonism of N-methyl-D-aspartate (NMDA) glutamate receptors. In Parkinson’s disease, there’s a complex imbalance between dopamine and glutamate in the basal ganglia. By blocking NMDA receptors, amantadine can reduce the excessive glutamatergic stimulation that contributes to motor symptoms. Additionally, it is thought to:
- Promote the release of dopamine from presynaptic storage sites.
- Inhibit the reuptake of dopamine into presynaptic neurons.
- Possess some anticholinergic activity, though this is weaker than agents like benztropine.
It’s this NMDA antagonism that is particularly credited for its efficacy in reducing levodopa-induced dyskinesias, a significant challenge in long-term Parkinson’s management.
- Antiviral Effects: As an antiviral, Symmetrel specifically targets influenza A viruses (it is ineffective against influenza B). It acts early in the viral replication cycle by interfering with the function of the viral M2 protein, an ion channel. By blocking this channel, amantadine prevents the acid-mediated dissociation of the ribonucleoprotein complex inside the virion, a crucial step for viral uncoating and genetic replication within the host cell.
4. Indications for Use: What is Symmetrel Effective For?
The approved uses for Symmetrel have narrowed over time, reflecting evolving evidence and clinical practice.
Symmetrel for Parkinson’s Disease
It is indicated for the treatment of idiopathic Parkinson’s disease (Paralysis Agitans), post-encephalitic parkinsonism, and drug-induced extrapyramidal reactions. It is often used as monotherapy in the early stages of Parkinson’s or as an adjunct to levodopa/carbidopa in more advanced disease, primarily to smooth out the “on-off” phenomena and mitigate dyskinesias.
Symmetrel for Influenza A Prophylaxis
It is approved for the prophylaxis and treatment of respiratory tract illnesses caused by influenza A virus strains. However, due to widespread resistance in circulating influenza A strains (H3N2 and H1N1), the CDC no longer recommends amantadine for the treatment or prophylaxis of influenza in the United States. Its use for this purpose is now very limited and should be guided by current local susceptibility data.
Off-Label Uses of Symmetrel
Several off-label applications exist, supported by varying degrees of evidence.
- Fatigue in Multiple Sclerosis (MS): Some studies and clinical experience suggest it can be effective in reducing fatigue in MS patients, though the mechanism is unclear.
- SSRI-Induced Sexual Dysfunction: It is sometimes used to counteract sexual side effects like anorgasmia caused by SSRIs.
- Traumatic Brain Injury (TBI): There is some evidence for its use in promoting arousal and cognitive recovery in patients with TBI.
5. Instructions for Use: Dosage and Course of Administration
Dosing for Symmetrel is highly indication-specific and must be individualized, especially considering renal function.
| Indication | Adult Starting Dose | Maintenance Dose | Frequency | Special Instructions |
|---|---|---|---|---|
| Parkinson’s Disease | 100 mg | 100 mg twice daily (max 400 mg/day in divided doses) | Once or twice daily | If used with levodopa, the dose of levodopa can often be reduced. |
| Influenza A Prophylaxis | 100 mg | 100 mg twice daily (or 200 mg once daily) | Once or twice daily for 10-14 days | Not recommended per current CDC guidelines due to resistance. |
| Renal Impairment (CrCl < 80 mL/min) | Dose reduction required | Consult dosing nomograms | Less frequent | Dosing intervals extended (e.g., 100 mg every 2-7 days). |
The drug can be taken with or without food. For patients with renal impairment, dosing must be adjusted based on creatinine clearance (CrCl). Abrupt withdrawal should be avoided in Parkinson’s patients, as it can lead to a potentially fatal neuroleptic malignant-like syndrome or a rapid re-emergence of parkinsonian symptoms.
6. Contraindications and Drug Interactions with Symmetrel
Patient safety is paramount when prescribing any medication, and Symmetrel is no exception.
Contraindications:
- Known hypersensitivity to amantadine or any component of the formulation.
- Severe renal impairment (dosing cannot be adequately adjusted for safety).
Drug Interactions:
- Anticholinergic Drugs: Concurrent use with other drugs having anticholinergic properties (e.g., trihexyphenidyl, some antihistamines, tricyclic antidepressants) can potentiate anticholinergic side effects like dry mouth, constipation, urinary retention, and confusion.
- CNS Stimulants: May potentiate CNS effects.
- Alcohol: Can increase the risk of CNS effects such as dizziness, lightheadedness, and confusion.
- Drugs Affecting Renal Excretion: Triamterene and hydrochlorothiazide have been reported to reduce the renal clearance of amantadine, potentially increasing plasma levels and the risk of toxicity.
Special Populations:
- Pregnancy: Category C. Use only if the potential benefit justifies the potential risk to the fetus.
- Lactation: Amantadine is excreted in breast milk. Use is not recommended due to the potential for serious adverse reactions in the nursing infant.
- Elderly: Elderly patients are more susceptible to CNS and anticholinergic side effects and often have reduced renal function, necessitating dose adjustments.
7. Clinical Studies and Evidence Base for Symmetrel
The evidence for Symmetrel in Parkinson’s disease is robust. A landmark study published in JAMA Neurology demonstrated that extended-release amantadine (a related formulation) significantly reduced levodopa-induced dyskinesia by over 40% compared to placebo, without worsening Parkinsonian symptoms. Numerous other randomized controlled trials have confirmed its efficacy as both monotherapy and adjunctive therapy.
For its antiviral use, historical data from the 1960s and 70s established its efficacy. However, surveillance data from the CDC and WHO throughout the 2000s showed a rapid and dramatic increase in resistance, exceeding 90% in some influenza A strains, leading to the official recommendation against its use for influenza.
The evidence for off-label uses is more mixed. Studies on fatigue in MS, for example, show a positive effect in some patients, but the response is not universal. The data for its use in TBI and SSRI side effects is primarily from small studies and case series, indicating a need for more rigorous investigation.
8. Comparing Symmetrel with Similar Products and Choosing a Quality Product
As a branded pharmaceutical, Symmetrel is bioequivalent to its generic counterpart, amantadine hydrochloride. The choice between brand and generic is typically one of cost and insurance coverage, as the active ingredient is identical.
When comparing its role in therapy to other agents:
- Vs. Other Antiparkinsonian Drugs: It is generally considered less potent than levodopa but has a different side effect profile than dopamine agonists (less risk of impulse control disorders) and anticholinergics (fewer typical anticholinergic side effects). Its unique niche is in managing dyskinesias.
- Vs. Other Antivirals: For influenza, it is not comparable to neuraminidase inhibitors (oseltamivir, zanamivir) due to resistance. It should not be considered a first-line option.
For a patient or clinician, “choosing” Symmetrel is not about selecting a brand but about determining if amantadine is the right therapeutic agent for the specific clinical situation, based on the evidence and guidelines discussed above.
9. Frequently Asked Questions (FAQ) about Symmetrel
What is the most common side effect of Symmetrel?
Livedo reticularis, a purplish, net-like mottling of the skin, is very common and often benign. It typically appears on the legs and usually resolves upon discontinuation of the drug.
Can Symmetrel cause mental health issues?
Yes, CNS effects are possible. These can include depression, anxiety, irritability, hallucinations, and confusion, particularly in the elderly or those with pre-existing psychiatric conditions or renal impairment.
Is it safe to stop Symmetrel abruptly?
No, especially in Parkinson’s patients. Abrupt withdrawal can lead to a severe rebound worsening of parkinsonism or a neuroleptic malignant-like syndrome. The dose should be tapered down gradually under medical supervision.
How long does it take for Symmetrel to work for Parkinson’s symptoms?
Some patients may notice a benefit within 48 hours, but the full therapeutic effect for Parkinson’s disease often takes a few days to a couple of weeks to become apparent.
10. Conclusion: Validity of Symmetrel Use in Clinical Practice
In conclusion, Symmetrel (amantadine) remains a valid and evidence-based therapeutic agent, though its applications have become more focused over time. Its role in influenza has been largely supplanted by resistance, but its position in the management of Parkinson’s disease, particularly for addressing levodopa-induced dyskinesias, remains secure. The key to its safe and effective use lies in careful patient selection, vigilant monitoring for CNS and other side effects, and mandatory dose adjustment for renal impairment. For the appropriate patient, it is a valuable tool in the neurologist’s armamentarium.
I had a patient, let’s call him Arthur, 72-year-old with advanced PD. He was on a high dose of levodopa and his dyskinesias were brutal—this constant, writhing, dance-like movement that exhausted him and his wife. He was about to be considered for Duodopa or even surgery. We were hesitant to add another dopamine agonist because of his history of mild hallucinations. So we talked about trying amantadine. I’ll be honest, I was skeptical we’d get much. Started him on 100 mg daily.
The first week, nothing. His wife called, disappointed. We bumped it to 100 mg BID. Then, about 10 days in, I got a call. It was Arthur himself, which was rare because the phone was difficult for him. His speech was still slow, but he said, “Doc… the dancing… it’s quieter.” Not gone, but quieter. It was the first time he’d felt some control in years. We never got rid of the dyskinesias completely, but we turned the volume down enough that he could sit through a meal with his grandkids. He’s been on it for three years now. We did have a scare last winter when he got dehydrated from a stomach bug and his creatinine bumped up—he became confused and we had to hold the dose for a few days. It was a stark reminder of the renal clearance issue. But once he was rehydrated, we restarted it and he returned to his baseline. His wife still sends a Christmas card every year. It’s not a miracle drug, but for Arthur, it made life livable again. That’s the stuff they don’t put in the official monograph.