Gocovri (amantadine HCl)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Amantadine hydrochloride, an adamantane derivative, is a synthetic antiviral agent that is active against influenza A virus.
Amantadine hydrochloride is a synthetic adamantane derivative that has pharmacologic activity as an anti-Parkinson and antiviral agent.
Amantadine is an adamantanederivative (a symmetric tricyclic amine) that is structurally related to rimantadine. The exact mechanism of antiviral activity of amantadine has not been fully elucidated. Amantadineinhibits viral replication by interfering with the influenza A virus M2 protein, an integral membrane protein.
The M2 protein of influenza A functions as an ion channel and is important in at least 2 aspects of virus replication, disassembly of the infecting virus particle and regulation of the ionic environment of the transport pathway. By interfering with the ion channel function of the M2 protein, amantadine inhibits 2 stages in the replicative cycle of influenza A. Early in the virus replicative cycle, amantadine inhibits uncoating of the virus particle, presumably by inhibiting the acid-mediated dissociation of the virion nucleic acid and proteins, which prevents nuclear transport of viral genome material.
Amantadine also prevents viral maturation in some strains of influenza A (e.g., H7 strains) by promoting pH-induced conformational changes in influenza A hemagglutinin during its intracellular transport late in the replicative cycle. Adsorption of the virus to and penetration into cells do not appear to be affected by amantadine. In addition, amantadine does not interfere with the synthesis of viral components (e.g., RNA-directed RNA polymerase activity).
Beginning in the 2005-2006 influenza season, most influenza A (H3N2) strains circulating in the US were resistant to amantadine and rimantadine. Resistance to amantadine and rimantadine among seasonal influenza A (H3N2) circulating during recent influenza seasons has remained high.
Amantadine treatment of established influenza A infection does not appear to interfere with antibody response to the infection; however, some reduction in local immune responses has been observed in some patients. Because prophylactic use of amantadine can prevent influenza illness and to a lesser extent subclinical infection, some individuals who take amantadine can still develop immune responses that may protect them when they are exposed to the same or antigenically related viruses following discontinuance of amantadine prophylaxis.
Amantadine hydrochloride is well absorbed from the GI tract. While peak plasma concentrations are directly related to amantadine hydrochloride dosage up to 200 mg daily, higher dosages may result in a greater than proportional increase in peak plasma concentration. While amantadine principally is excreted unchanged in urine by glomerular filtration and tubular secretion, at least 8 metabolites have been identified in urine.
The elimination half-life of amantadine has been variously reported as 9-37 hours, with an average of 24 hours or less. Amantadine is only minimally removed by hemodialysis.
The exact mechanism of action of amantadine hydrochloride in the treatment of parkinsonian syndrome and drug-induced extrapyramidal reactions is not known. Amantadine does not appear to have direct anticholinergic activity; however, the drug causes anticholinergic-like effects such as dry mouth, urinary retention, and constipation. Amantadine is a weak uncompetitive antagonist of the NMDA receptor and may have direct and indirect effects on the dopaminergic system.
Amantadine hydrochloride is well absorbed from the GI tract. While peak plasma concentrations are directly related to amantadine hydrochloride dosages up to 200 mg daily, dosages exceeding 200 mg daily may result in a greater than proportional increase in peak plasma concentration. While amantadine principally is excreted unchanged in urine by glomerular filtration and tubular secretion, at least 8 metabolites have been identified in urine.
The elimination half-life of amantadine has been variously reported as 9-37 hours, with an average of 24 hours or less. Amantadine is only minimally removed by hemodialysis; in patients with renal failure who received a single 300-mg oral dose of amantadine hydrochloride, only 5% or less of the dose was removed into the dialysate following a 4-hour period of hemodialysis.
Following oral administration of amantadine as the extended-release capsules, dose-proportional pharmacokinetics were observed over the dose range of 68.5-274 mg. Time to peak plasma concentration after a single dose is approximately 12 hours and steady-state concentrations are achieved in 4 days. Food does not affect amantadine pharmacokinetics when given as the extended-release capsules; administration of capsule contents with applesauce also did not affect pharmacokinetics of the drug.
USES: This medication is used to treat Parkinson's disease. It is also used to treat certain movement disorders caused by some drugs (extrapyramidal reactions). This medication is thought to work by restoring the balance of certain natural substances (neurotransmitters) in the brain.
Different brands of this medication may have different uses. Do not change brands of this medication unless directed by your doctor.
Generic name: amantadine HCl
Pronunciation: (a-MAN-ta-deen)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Gocovri
Indications
The following indications are listed for Gocovri:
- Idiopathic Parkinsonism
Also known as: Paralysis Agitans, Primary Parkinson's Disease.
Dosing
Dosage of amantadine hydrochloride conventional tablets, capsules, and oral solution is expressed in terms of amantadine hydrochloride; dosage of amantadine hydrochloride extended-release capsules is expressed in terms of amantadine.
Amantadine hydrochloride is administered orally. Adverse effects (e.g., CNS effects) may be minimized if the daily dosage is given in 2 equally divided doses.
Amantadine hydrochloride is commercially available as tablets or liquid-filled capsules containing 100 mg of the drug and as an oral solution containing 50 mg/5 mL.
Amantadine hydrochloride is administered orally as conventional (i.e., immediate-release) tablets, conventional capsules, extended-release capsules,or a conventional oral solution.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
In vitro studies indicate that amantadine does not significantly inhibit the enzyme activity of drug metabolizing cytochrome P-450 (CYP) isoenzymes 1A2, 2B6, 2C19, 2C8, 2C9, 2D6, 2E1, 3A4, and 3A5.
Amantadine has negligible or no inhibitory activity against cellular transporters (P-gp, BCRP, MATE2-K, OAT1, OAT3, OATP1B1, and OATP1B3) at clinically relevant plasma concentrations.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Patients with known hypersensitivity to amantadine hydrochloride or any ingredients in the formulations.
*Patients with known hypersensitivity to amantadine hydrochloride or any ingredients in the formulations.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
The most common adverse effects (5-10%) of amantadine include nausea, dizziness, and insomnia.
The most common adverse effects (5-10%) of amantadine administered as conventional (immediate-release) preparations include nausea, dizziness, and insomnia.
The most common adverse effects (>10%) with extended-release amantadine capsules include hallucination, dizziness, dry mouth, peripheral edema, constipation, fall, and orthostatic hypotension.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy of amantadine for the prevention or treatment of infections caused by influenza A viruses have not been established in neonates or children younger than 1 year of age.
Safety and efficacy of amantadine for the treatment of parkinson disease have not been established in pediatric patients; the majority of individuals with parkinson disease are 65 years of age or older. When used in children, amantadine has caused CNS symptoms, which resolved when the drug was discontinued. An increased incidence of seizures has been reported in children with an underlying seizure disorder receiving amantadine.
Amantadine has been reported to be embryotoxic/teratogenic in rats when administered in dosages of 50 and 100 mg/kg daily (1.5 and 3 times, respectively, the maximum recommended human dosage on a mg/m2 basis), but not when administered in a dosage of 37 mg/kg daily (the maximum recommended human dosage on a mg/m2 basis). One woman with a movement disorder similar to parkinsonian syndrome who may have been treated with amantadine hydrochloride (100 mg daily) during the first trimester of pregnancy delivered a child with a complex cardiovascular lesion (single ventricle and pulmonary atresia) that may have been caused by the drug. Fallot and tibial hemimelia (normal karyotype) were reported in an infant exposed to oral amantadine hydrochloride during the first trimester of pregnancy (100 mg daily for 7 days during week 6 and 7 of gestation). There are no adequate and well-controlled studies using amantadine in pregnant women, and the drug should be used during pregnancy only when the potential benefits outweigh the possible risks to the fetus.
Amantadine has been reported to be embryotoxic/teratogenic in rats when administered in dosages of 50 and 100 mg/kg daily (1.5 and 3 times, respectively, the maximum recommended human dosage on a mg/m2 basis), but not when administered in a dosage of 37 mg/kg daily (the maximum recommended human dosage on a mg/m2. One woman with a movement disorder similar to parkinsonian syndrome who may have been treated with amantadine hydrochloride (100 mg daily) during the first trimester of pregnancy delivered a child with a complex cardiovascular lesion (single ventricle and pulmonary atresia) that may have been caused by the drug. There are no adequate and well-controlled studies using amantadine in pregnant women, and the drug should be used during pregnancy only when the potential benefits outweigh the possible risks to the fetus.
Because amantadine is distributed into human milk, some manufacturers state that the drug should not be used in nursing women.
Because amantadine is distributed into human milk, some manufacturers state that the drug should not be used in nursing women.
The usual dosage of amantadine hydrochloride for the treatment or prophylaxis of influenza infection caused by susceptible influenza A viruses in adults 65 years of age or older without recognized renal disease is 100 mg daily.
Since renal function normally declines with age and amantadine-induced adverse effects have been reported more frequently in geriatric patients, some clinicians state that 100 mg daily should be the maximum dosage of amantadine hydrochloride for adults 65 years of age or older, and that dosage may need to be further reduced in some geriatric patients.
Dosage of amantadine conventional preparations should be reduced in geriatric patients 65 years of age or older. The manufacturer of the extended-release capsules states that no dosage adjustment is required based on age; however, because elderly patients are more likely to have decreased renal function, care should be taken to select dosage with caution and it may be useful to monitor renal function.
Geriatric adults may have decreased renal function and because individuals with renal impairment may be at increased risk of amantadine-induced toxicity, the dosage of amantadine hydrochloride for adults in this age group should not exceed 100 mg daily. This dosage may need to be reduced further in some geriatric patients.
The majority of individuals with parkinson disease are 65 years of age or older. Clearance of amantadine is reduced, plasma concentrations of the drug are increased, and elimination half-life may be prolonged in healthy geriatric adults compared with healthy young adults.
Reduced dosages may be needed in geriatric patients >=65 years of age because of renal decline in such patients.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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