Actions and Spectrum: 

• amantadine is an antiviral and anti-Parkinson’s drug with a mechanism of action that involves blocking the function of viral proteins or increasing dopamine levels in the brain. The spectrum of activity of amantadine is limited to certain types of viruses, specifically the influenza A virus. 
• amantadine is a weak base thought to enter the virus particle through the M2 ion channel found on the surface of the influenza A virus. By blocking this ion channel, amantadine inhibits the acidification of the virus particle, which is necessary to release the viral RNA into the host cell. As a result, amantadine inhibits viral replication and prevents the spread of the virus. 

DRUG INTERACTION

Contraindicated  

Serious Use Alternative  

Monitor Closely  

Minor  

Frequency defined 

>10% 

Extended-release capsule 

Dizziness (16%) 

Peripheral edema (16%) 

Fall (13%) 

Hallucinations (21%) 

Dry mouth (16%) 

Constipation (13%) 

Orthostatic hypotension (13%)  

1-10% 

Extended-release capsule (Gocovri) 

Nausea (8%) 

Insomnia (7%) 

Livedo reticularis (6%) 

Depression/depressed mood (6%) 

Benign prostate hyperplasia (6%) 

Abnormal dreams (4%) 

Cough (3%) 

Dystonia (3%) 

Vomiting (3%) 

Cataract (3%) 

Joint swelling (3%) 

Urinary tract infection (10%) 

Anxiety (7%) 

Contusion (6%) 

Headache (6%) 

Decreased appetite (6%) 

Blurred vision (4%) 

Pigmentation disorder (3%) 

Confusional state (3%) 

Gait disturbance (3%) 

Dry eye (3%) 

Muscle spasms (3%) 

Immediate-release tablet/capsule or syrup 

5-10% 

Dizziness/lightheadedness 

Nausea 

Insomnia 

1-5% 

Anxiety and irritability 

Confusion 

Dry mouth 

Ataxia 

Peripheral edema 

Headache 

Nervousness 

Agitation 

Diarrhea 

Fatigue 

Depression 

Hallucinations 

Anorexia 

Constipation 

Livedo reticularis 

Orthostatic hypotension 

Somnolence 

Dream abnormality 

Dry nose 

<1% 

Immediate-release tablet/capsule or syrup 

Psychosis 

Dyspnea 

Vomiting 

Slurred speech 

Euphoria 

Thinking abnormality 

Hyperkinesia 

Congestive heart failure 

Urinary retention 

Skin rash 

Weakness 

Amnesia 

Hypertension  

Post-marketing reports 

Seizures 

Contraindications/caution: 

Contraindications: 

• Hypersensitivity: amantadine is contraindicated in individuals with a known hypersensitivity or allergic reaction to the drug or its components. 
• Severe renal impairment: amantadine is primarily eliminated through the kidneys, contraindicated in individuals with severe renal impairment. 
• Glaucoma: amantadine can increase intraocular pressure, which may exacerbate or precipitate an acute glaucoma attack. Therefore, it is contraindicated in individuals with glaucoma. 
• Psychiatric disorders: amantadine can cause or exacerbate psychiatric disorders such as anxiety, agitation, hallucinations, and depression. Therefore, it is contraindicated in individuals with a history of psychiatric disorders. 
• History of seizures: amantadine can lower the seizure threshold and increase the risk of seizures. Therefore, it is contraindicated in individuals with a history of seizures. 
• Breast-feeding: amantadine can be excreted in breast milk, which is contraindicated in breast-feeding women. 

Caution: 

• Central nervous system (CNS) side effects: amantadine can cause a range of CNS side effects, including nervousness, anxiety, insomnia, confusion, hallucinations, and delirium. Patients should be closely monitored for these side effects, especially at higher doses. 
• Kidney disease: amantadine is primarily eliminated from the body through the kidneys, so patients with kidney disease may need lower doses or more frequent monitoring. 
• History of seizures: amantadine can lower the seizure threshold, so patients with seizures should be closely monitored when taking this medication. 
• Heart disease: amantadine can cause changes in heart rhythm, so patients with a history of heart disease or arrhythmias should be closely monitored 
• Pregnancy and breast-feeding: The safety of amantadine in pregnancy and breast-feeding has not been established, so it should only be used if the potential benefits outweigh the risks. 

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast milk is known 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.   

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology: 

• amantadine is a medication with both antiviral and antiparkinsonian effects. It works by increasing dopamine levels in the brain and blocking the action of a glutamate neurotransmitter. 

• amantadine is a weak inhibitor of the reuptake of dopamine in the brain, increasing dopamine availability in the synapse and enhancing its activity. This leads to improvement in the symptoms of Parkinson’s disease, such as tremors, rigidity, and bradykinesia. 

Pharmacodynamics: 

The pharmacodynamics of amantadine is the study of how the drug interacts with the body and produces its therapeutic effects. amantadine is a dopaminergic and glutamatergic drug with antiviral and antiparkinsonian effects. 

• Antiparkinsonian effects: amantadine’s antiparkinsonian effects are primarily due to its ability to increase dopamine release and decrease dopamine reuptake in the brain. It acts as a weak NMDA receptor antagonist, which reduces the excitability of glutamatergic neurons, further enhancing dopamine release. 
• Antiviral effects: amantadine’s antiviral effects are due to its ability to inhibit the uncoating of the influenza A virus. The drug enters the virus particle and causes conformational changes in the viral matrix protein, which prevents the virus from releasing its RNA into the host cell. This prevents viral replication and spread. 

Pharmacokinetics: 

Absorption 

amantadine is well absorbed orally, with a bioavailability of 86-90%. Its onset of action is within 48 hours for its antidyskinetic effects, and peak plasma concentration is reached 2-4 hours after the oral administration of capsules, tablets, or syrup. The peak plasma concentration is 0.24 mcg/mL for a 100-mg single dose and 328 ng/mL for a 129-mg single extended-release tablet dose. The AUC is 20-30% higher for the steady state of a single extended-release capsule dose and 8263 ng·hr/mL for a single extended-release tablet dose. 

Distribution 

amantadine is extensively protein-bound, with 67% bound to plasma proteins. The volume of distribution is 1.5-6.1 L/kg for capsules, tablets, or syrup and 3-8 L/kg for IV administration. 

Metabolism 

amantadine is not appreciably metabolized, with only small amounts of an acetyl metabolite identified. 

Elimination and Excretion 

The elimination half-life of amantadine is 16 hours, and clearance is 0.2-0.3 L/hr/kg for capsules, tablets, or syrup and 0.27 L/hr/kg for capsules, extended-release. amantadine is primarily eliminated unchanged in the urine by glomerular filtration and tubular secretion, with 80-90% of the dose excreted unchanged in the urine. The extended-release tablets have a similar excretion pattern, with 85% of the dose excreted unchanged in the urine and 0-15% excreted as an N-acetylated compound. The metabolism of amantadine accounts for only 5-18% of its total clearance. Urine pH can influence the excretion rate of amantadine. 

Administration: 

amantadine can be taken with or without food. The capsules, tablets, or syrup should be swallowed whole with a full glass of water. The extended-release capsules should be swallowed whole and not crushed or chewed. 

Storage: 

Temperature excursions of 15-30°C (59-86°F) are permissible between 20-25°C (68-77°F). 

Patient information leaflet 

Generic Name: amantadine 

Why do we use amantadine? 

amantadine has several uses, including: 

• Treatment of Parkinson’s disease: amantadine is used to improve muscle control and reduce tremors, rigidity, and bradykinesia (slowness of movement) in patients with Parkinson’s disease. 
• Prevention and treatment of influenza A: amantadine is an antiviral drug effective against the influenza A virus. It can be used to prevent and treat influenza A infections but is not effective against the influenza B virus. 
• Treatment of drug-induced extrapyramidal symptoms: amantadine is sometimes used to treat extrapyramidal symptoms (EPS), which are side effects of certain medications used to treat mental health disorders. 
• Treatment of fatigue in multiple sclerosis: amantadine can improve fatigue in patients with multiple sclerosis, although the exact mechanism of action is poorly understood. 
• Treatment of other neurological conditions: amantadine has also been used to treat other neurological conditions, such as traumatic brain injury, dementia, and dyskinesia associated with levodopa therapy.