Adult: As conventional tab or oral solution: 100 mg bid, may be increased to 300 mg daily. As extended-release tab: Initially, 129 mg once daily in the morning. Doses are titrated gradually at weekly intervals up to a Max dose of 322 mg daily (combination of 129 mg tab and 193 mg tab), depending on the patient's response and tolerability. Dosage and treatment recommendations may vary among countries and individual products (refer to specific product guidelines).
Oral Parkinson's disease
Adult: As conventional tab, conventional cap, oral solution or syrup: Initially, 100 mg once daily for 1 week, then may increase to the usual dose of 100 mg bid. Max: 400 mg daily. Doses are titrated gradually depending on the patient's response and tolerability, at intervals of not less than 1 week. If given in combination with other antiparkinson agents, the dosage of both agents may be continued and adjusted according to individual needs. As extended-release tab: Initially, 129 mg once daily in the morning. Doses are gradually titrated at weekly intervals up to a Max dose of 322 mg daily (combination of 129 mg tab and 193 mg tab), depending on the patient's response and tolerability. As an adjunct to levodopa/carbidopa for the treatment of patients experiencing "off" days: As extended-release cap: Initially, 137 mg once daily at bedtime, then may increase after 1 week to the usual dose of 274 mg once daily at bedtime. Dosage and treatment recommendations may vary among countries and individual products (refer to specific product guidelines). Elderly: >65 years Use of lowest effective dose is recommended.
Oral Dyskinesia
Adult: For the treatment of cases in patients with Parkinson's disease receiving levodopa-based therapy (with or without concurrent dopaminergic agents): As extended-release cap: Initially, 137 mg once daily at bedtime, then may increase after 1 week to the usual dose of 274 mg once daily at bedtime. Dosage and treatment recommendations may vary among countries and individual products (refer to specific product guidelines).
Oral Influenza A
Adult: As conventional tab, conventional cap, oral solution or syrup: 100 mg daily for 4-5 days. Alternatively, 200 mg daily as a single dose or in 2 divided doses for 24-48 hours until symptoms resolution. Treatment recommendations may vary among countries and individual products (refer to specific product guidelines). Elderly: >65 years Max: 100 mg daily. Child: <9 years As conventional tab, conventional cap, oral solution or syrup: 4.4-8.8 mg/kg daily in 2 divided doses. Max: 150 mg daily. ≥9 years As conventional tab, conventional cap, oral solution or syrup: 100 mg bid. All doses must be initiated as soon as possible and continued until symptom resolution for 24 to 48 hours. Treatment recommendations may vary among countries and individual products (refer to specific product guidelines).
Oral Prophylaxis of influenza A
Adult: As conventional tab, conventional cap, oral solution or syrup: 100 mg daily or 200 mg as a single dose or in 2 divided doses beginning from the anticipation of contact and continued for approx 6 weeks. When given with influenza vaccine, administration may be continued for up to 2-3 weeks after vaccination. Treatment recommendations may vary among countries and individual products (refer to specific product guidelines). Elderly: >65 years Max: 100 mg daily. Child: <9 years As conventional tab, conventional cap, oral solution or syrup: 4.4-8.8 mg/kg daily in 2 divided doses. Max: 150 mg daily. ≥9 years As conventional tab, conventional cap, oral solution or syrup: 100 mg bid. All doses must be initiated in anticipation of contact and continued for the duration of the influenza A outbreak. Treatment recommendations may vary among countries and individual products (refer to specific product guidelines).
Oral Herpes zoster
Adult: As conventional cap or oral syrup: 100 mg bid for 14 days. May continue treatment for another 14 days if post-herpetic pain persists. Treatment recommendations may vary among countries and individual products (refer to specific product guidelines).
Renal Impairment
Parkinson's disease; Influenza A; Prophylaxis of influenza A; Herpes zoster:
CrCl (mL/min)
Dosage
<15
Contraindicated.
15-35
100 mg every 2-3 days.
>30
100 mg daily.
Drug-induced extrapyramidal symptoms:
CrCl (mL/min)
Dosage
<15
Contraindicated.
15-29
Initially, 129 mg every 96 hours then increase every 4 weeks up to a Max dose of 322 mg daily.
30-59
Initially, 129 mg every 96 hours then increase every 3 weeks up to a Max dose of 322 mg daily.
Dyskinesia:
CrCl (mL/min)
Dosage
<15
Contraindicated.
15-29
68.5 mg once daily at bedtime.
30-59
Initially, 68.5 mg once daily at bedtime, then may increase after 1 week up to a max of 137 mg once daily at bedtime, as necessary.
Dosage and treatment recommendations may vary among countries and individual products (refer to specific product guidelines).
Administration
May be taken with or without food.
Contraindications
Hypersensitivity. Seizures/epilepsy; severe decompensated heart failure (stage NYHA IV), cardiomyopathies and myocarditis, 2nd- or 3rd-degree AV-block, existing bradycardia (<55 bpm), and known prolonged QT interval. History of gastric ulceration and serious ventricular arrhythmias (e.g. torsade de pointes, hypokalaemia, hypomagnesaemia). Severe renal impairment (CrCl <15 mL/min). Pregnancy.
Special Precautions
Patient with CV disease (e.g. heart failure, peripheral oedema, orthostatic hypotension), cardiac pacemaker; sleep disorders, history of or existing psychiatric illness, history of substance abuse, pre-existing psychotic disorders; history of seizure disorder, recurrent and eczematoid dermatitis. Not for use in patients with corneal oedema or untreated angle-closure glaucoma. Certain country guidelines prohibit the use of amantadine for the treatment of influenza A until susceptibility has been re-established in circulating influenza A viruses (refer to specific country guidelines prior to administration). Amantadine is available in multiple products and formulations; conventional formulations are interchangeable within one another, however conventional formulations are not interchangeable with extended-release formulations, and consequently extended-release formulations are not interchangeable within one another. Patients who are receiving other agents that have CNS effects. Avoid abrupt withdrawal or dose reduction. Hepatic and mild to moderate renal impairment. Children and elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Peripheral oedema; cardiac arrhythmias (e.g. ventricular tachycardia, fibrillation, torsade de pointes, QT prolongation), CHF; somnolence, syncope, orthostatic hypotension (may lead to dizziness and falls); depression; impulse control disorders (e.g. hypersexuality, increased libido, pathological gambling, compulsive spending or buying, binge or compulsive eating); visual problems (e.g. blurred vision); anticholinergic effects; melanoma; hypothermia (particularly in children); increased seizure frequency; hallucinations, confusion, nightmares; and livedo reticularis. Rarely, reversible increase in transaminases, livedo racemosa. Blood and lymphatic system disorders: Rarely, leucopenia or thrombocytopenia. Cardiac disorders: Palpitations. Gastrointestinal disorders: Nausea, vomiting, dry mouth, constipation, diarrhoea. Infections and infestations: UTI. Metabolism and nutrition disorders: Decreased appetite, anorexia. Musculoskeletal and connective tissue disorders: Myalgia, muscle pain, joint swelling. Nervous system disorders: Headache, lethargy, ataxia, dysarthria, tremor, dyskinesia. Psychiatric disorders: Anxiety, elevated mood, agitation, nervousness, insomnia, hypomania, mania. Renal and urinary disorders: Benign prostatic hypertrophy. Rarely, urinary retention or incontinence. Respiratory, thoracic, and mediastinal disorders: Cough. Skin and subcutaneous tissue disorders: Hyperhidrosis, bruises, eczema, rash. Vascular disorders: Orthostatic hypotension. Potentially Fatal: Withdrawal syndrome resembling NMS, suicidal attempt/ideation.
This drug may cause dizziness, somnolence, or blurred vision, if affected, do not drive or operate machinery.
Monitoring Parameters
Perform culture and susceptibility tests prior to treatment initiation as an antiviral; consult local institutional recommendations before treatment initiation due to antiviral resistance risks. Monitor blood pressure, kidney function (baseline and as clinically indicated), and ECG (baseline; 1 and 3 weeks after initiation; before dose increases, 2 weeks following increase; as clinically indicated). Evaluate mental status (e.g. depression, hallucinations, psychosis, suicidality) upon initiation or dose increase. Assess for signs of impulse control disorders.
Overdosage
Symptoms: Nausea, vomiting, dry mouth, hyperthermia, acute toxic psychosis, extrapyramidal symptoms (e.g. dilated pupils, dysphagia, torsion spasms, dystonic posturing), convulsions/seizures, hyperreflexia, motor restlessness, lethargy, somnolence, dysarthria, confusion, disorientation, delirium, visual hallucinations, myoclonus, aggression/hostility, depressed level of consciousness, hyperventilation, pulmonary oedema, respiratory distress (including adult respiratory distress syndrome), urinary retention, renal dysfunction (e.g. increased BUN, decreased CrCl), arrhythmia, hypertension, sinus tachycardia, cardiac arrest, coma, and death. Management: Symptomatic and supportive treatment. Maintain adequate airway, control of respiration, and administration of oxygen. Induce vomiting or perform gastric aspiration or lavage if the patient is conscious; consider administering activated charcoal or saline cathartic, if suitable. To facilitate drug elimination, maintain renal function and copious diuresis (diuresis may be forced as necessary) or employ the acidification of the urine. Administer physostigmine to control CNS toxicity. Give anticonvulsants (e.g. IV diazepam, IM phenobarbital) for excessive motor restlessness or seizures. Administer adrenergic agents for arrhythmias and hypotension. Insert a catheter if with urinary retention. Monitor heart rate, respiration, blood pressure, body temperature, blood electrolytes, urine pH, and urinary output.
Drug Interactions
Enhanced anticholinergic or atropine-like effects with agents that have anticholinergic activity (e.g. benztropine, biperiden, orphenadrine, scopolamine, trihexyphenidyl) and levodopa. Increased risk of psychotic reactions with levodopa. Possible synergistic CNS stimulant effects with other CNS stimulants. Decreased renal clearance with quinidine or quinine. Increased occurrence of psychotic symptoms when concomitantly given with neuroleptic agents. Potentially Fatal: Increased risk of malignant neuroleptic syndrome with neuroleptic drugs.
Food Interaction
Enhanced CNS depressant effect with alcohol.
Lab Interference
May cause false-positive results with amphetamines/methamphetamines via urine detection.
Action
Description: Mechanism of Action: Amantadine, a weak dopamine agonist, is both an antiparkinson and antiviral agent. The exact mechanism of action in the treatment of Parkinson's disease is still unknown, however, studies show that it is a low-affinity antagonist of N-methyl-D-aspartate (NMDA) and has direct and indirect effects on dopamine neurons. As an antiviral, amantadine interferes with the transmembrane domain of the viral M2 protein function which primarily prevents infectious viral nucleic acid release into the host cell and additionally blocks virus assembly during virus replication. Synonym(s): Onset: Antidyskinetic: Withn 48 hours. Pharmacokinetics: Absorption: Well absorbed from the gastrointestinal tract. Bioavailability: 86-94% (conventional form). Time to peak concentration: 2-4 hours (conventional form); 12 hours (extended-release cap); 7.5 hours (extended-release tab). Distribution: Crosses the placenta and the blood-brain barrier; enters breast milk. Volume of distribution: 3-8 L/kg. Plasma protein binding: Approx 67%, with a substantial amount bound to erythrocytes. Metabolism: Metabolised to a minor extent, mainly via N-acetylation. Excretion: Mainly via urine (80-90% as unchanged drug). Elimination half-life: Approx 15 hours (range: 10-31 hours).
Chemical Structure
Amantadine Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 2130, Amantadine. https://pubchem.ncbi.nlm.nih.gov/compound/Amantadine. Accessed Apr. 26, 2024.
Storage
Store between 20-25°C. Storage recommendations may vary among countries and individual products (refer to specific product guidelines).
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