Medication Guide App

Rimantadine Hydrochloride

Class: Adamantanes
VA Class: AM800
Chemical Name: α-Methyl tricyclo[3.3.1.13,7]decane-1-methanamine hydrochloride
Molecular Formula: C12H21N•HCl
CAS Number: 1501-84-4
Brands: Flumadine

Introduction

Antiviral; adamantane derivative.1 3 10 13 15 16 40 42

Uses for Rimantadine Hydrochloride

Treatment of Seasonal Influenza A Virus Infections

Has been used for treatment of influenza caused by susceptible influenza A viruses in adults ≥17 years of age.1 2 3 5 11 13 15 16 33 37 61

Amantadine and rimantadine have little or no activity against influenza B; not used for treatment of influenza B infection.1 11 13 15 16 35 42

Beginning in the 2005–2006 influenza season, most influenza A (H3N2) strains circulating in the US were resistant to adamantanes (amantadine, rimantadine),121 and resistance to the drugs among seasonal influenza A (H3N2) isolates has remained high during subsequent influenza seasons.105 112 117 144 162 551 552 In addition, the influenza A (H1N1)pdm09 virus circulating during recent influenza seasons is resistant to amantadine and rimantadine.52 105 112 117 144 151 162 551 552

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CDC and other experts recommend that adamantanes (amantadine, rimantadine) not be used for treatment of seasonal influenza in the US until susceptibility to these antiviral agents has been reestablished in circulating influenza A viruses.112 144 488

Consider viral surveillance data available from local and state health departments and the CDC when selecting an antiviral for treatment of seasonal influenza.112 137 144 Strains of circulating influenza viruses and the antiviral susceptibility of these strains constantly evolve.144

CDC issues recommendations concerning use of antivirals for treatment of influenza, and these recommendations are updated as needed during each influenza season.137 144 Information regarding influenza surveillance and updated recommendations for treatment of seasonal influenza are available from CDC at .

Prevention of Seasonal Influenza A Virus Infections

Has been used for prophylaxis of influenza infection caused by susceptible influenza A viruses in adults, adolescents, and children ≥1 year of age.1 3 4 7 8 13 16 47

Amantadine and rimantadine have little or no activity against influenza B; not used for prevention of influenza B infection.1 11 13 15 16 35 42

Annual vaccination with seasonal influenza virus vaccine, as recommended by the US Public Health Service Advisory Committee on Immunization Practices (ACIP), is the primary means of preventing seasonal influenza and its severe complications.1 13 100 112 116 144 488 Prophylaxis with an appropriate antiviral active against circulating influenza strains is considered an adjunct to vaccination for control and prevention of influenza in certain individuals.1 13 105 112 116 144 488

CDC and other experts recommend that adamantanes (amantadine, rimantadine) not be used for prevention of influenza in the US until susceptibility to these antiviral agents has been reestablished in circulating influenza A viruses.112 144 488

Consider viral surveillance data available from local and state health departments and the CDC when selecting an antiviral for prophylaxis of influenza.112 137 144 Strains of circulating influenza viruses and the antiviral susceptibility of these strains constantly evolve.137 144

CDC issues recommendations concerning use of antivirals for prophylaxis of influenza, and these recommendations are updated as needed during each influenza season.137 144 Information regarding influenza surveillance and updated recommendations for prevention of seasonal influenza are available from CDC at .

Avian Influenza A Virus Infections

Has been recommended as alternative for treatment or prophylaxis of avian influenza A virus infections in certain situations.94

CDC and WHO recommend use of a neuraminidase inhibitor (oseltamivir, zanamivir) for treatment or prophylaxis of avian influenza A infections.50 94 104

If neuraminidase inhibitors unavailable, use of amantadine or rimantadine might be considered an alternative if local surveillance data indicate the strain is known or likely to be susceptible.94 Avian influenza A (H5N1) and avian influenza A (H7N9) generally have been resistant to adamantanes.50 94 104

Rimantadine Hydrochloride Dosage and Administration

Administration

Oral Administration

Administer orally.1 13

Commercially available as tablets.1 13

If necessary for use only during emergency situations for patients who cannot swallow tablets or when lower dosage needed, oral suspensions containing 10 mg/mL can be prepared extemporaneously using 100-mg tablets.1 13 Consult manufacturer's information for specific directions on how to prepare extemporaneous oral suspensions.1 13

Dosage

Available as rimantadine hydrochloride; dosage expressed in terms of rimantadine hydrochloride.1 13

Pediatric Patients

Treatment of Seasonal Influenza A Virus Infections
Oral

Children ≥13 years of age: AAP recommends 100 mg twice daily.105 Manufacturers state not indicated for treatment of influenza in pediatric patients ≤16 years of age.1 13

Initiate treatment as soon as possible, preferably within 48 hours after onset of symptoms.1 13

Prevention of Seasonal Influenza A Virus Infections
Oral

Children 1–9 years of age: 5 mg/kg (up to 150 mg) once daily.1 13 105

Children ≥10 years of age: 100 mg twice daily.1 13 AAP recommends 5 mg/kg (up to 150 mg) daily in those weighing <40 kg.105

Duration of prophylaxis in children in clinical studies ranged from 5–6 weeks.1 13 Manufacturers state safety and efficacy for >6 weeks not established.1 13

Adults

Treatment of Seasonal Influenza A Virus Infections
Oral

Adults ≥17 years of age: 100 mg twice daily for 7 days.1 13

Initiate treatment as soon as possible, preferably within 48 hours after onset of symptoms.1 13

Prevention of Seasonal Influenza A Virus Infections
Oral

Adults ≥17 years of age: 100 mg twice daily.1 13

Duration of prophylaxis in clinical studies in adults ranged from 11 days to 6 weeks.1 13 Manufacturers state safety and efficacy for >6 weeks not established.1 13

Prescribing Limits

Pediatric Patients

Prevention of Seasonal Influenza A Virus Infections
Oral

Children 1–9 years of age: Maximum 150 mg daily.1 13 105

Special Populations

Hepatic Impairment

Treatment or Prevention of Seasonal Influenza A Virus Infections

Severe hepatic impairment: 100 mg daily.1 13 144 Use with caution in patients with any degree of hepatic impairment; monitor for adverse effects.1 13

Renal Impairment

Treatment or Prevention of Seasonal Influenza A Virus Infections

Severe renal impairment (Clcr 5–29 mL/minute) or renal failure (Clcr ≤10 mL/minute): 100 mg daily.1 13 144 Use with caution in patients with any degree of renal impairment; monitor for adverse effects.1 13

Geriatric Patients

≥65 years of age (including those residing in nursing homes): 100 mg daily for treatment or prevention of influenza A virus infection.1 13 For treatment in those residing in the community, some clinicians suggest 100 mg twice daily can be considered; reduce dosage to 100 mg daily if adverse effects occur.144 (See Geriatric Use under Cautions.)

Cautions for Rimantadine Hydrochloride

Contraindications

  • Known hypersensitivity to adamantane derivatives (rimantadine, amantadine) or any ingredient in the formulation.1 13

Warnings/Precautions

CNS Effects

Seizure-like activity reported in a few patients with history of seizures who were not receiving anticonvulsants.1 13

Effect of rimantadine on incidence of seizures in individuals with seizure disorders not fully evaluated.144 Increased incidence of seizures reported when amantadine used in patients with history of epilepsy.1 13

Discontinue if seizures occur.1 13

Resistance

Seasonal influenza A (H3N2) and influenza A (H1N1)pdm09 viruses circulating during recent influenza seasons have been resistant to adamantanes (amantadine, rimantadine).105 112 144 488 551 552

CDC and other experts recommend that adamantanes (amantadine, rimantadine) not be used for treatment or prevention of influenza in the US until susceptibility to these antiviral agents has been reestablished in circulating influenza A viruses.112 144 488

Differential Diagnosis

Serious bacterial infections may begin with influenza-like symptoms or may coexist with or occur as complications of influenza.1 13 No evidence that rimantadine prevents such complications.1 13

Influenza Vaccination

Not a substitute for annual vaccination with a seasonal influenza vaccine (influenza virus vaccine inactivated, influenza vaccine recombinant, influenza vaccine live intranasal).1 13 144

Although antivirals used for treatment or prevention of influenza, including rimantadine, may be used concomitantly with or at any time before or after influenza virus vaccine inactivated,100 these antivirals may inhibit the vaccine virus contained in influenza vaccine live intranasal.1 13 100 (See Influenza Virus Vaccines under Interactions.)

Specific Populations

Pregnancy

Category C.1 13

Lactation

Do not use in nursing women.1 13

Distributed into milk in rats; adverse effects noted in offspring of rats given the drug during the nursing period.1 13

Pediatric Use

Safety and efficacy for treatment of influenza A virus infection not established in children ≤16 years of age.1 13 Has been used for the treatment of influenza A infection in children 1–15 years of age; safety and efficacy appears similar to that in adults.37 59 61

Safety and efficacy for prophylaxis of influenza A virus infection not established in children <1 year of age.1 13

Geriatric Use

Incidence of CNS and GI effects in elderly chronically ill adults receiving 200 mg daily is higher than that reported in younger healthy adults.144

Because geriatric patients may have decreased renal function and may be at increased risk of rimantadine-induced toxicity, reduced dosage usually recommended, especially for elderly nursing home patients.1 13 144 (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Use with caution and monitor for adverse effects.1 13 Use reduced dosage in those with severe hepatic impairment.1 13 (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Use with caution and monitor for adverse effects.1 13 Use reduced dosage in those with severe renal impairment (Clcr 5–29 mL/minute) or renal failure (Clcr ≤10 mL/minute).1 13 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Nausea,1 3 9 13 37 47 53 insomnia,1 3 13 40 47 53 dizziness.1 3 13 19 40 47 53

Interactions for Rimantadine Hydrochloride

Specific Drugs

Drug

Interaction

Comments

Acetaminophen

Slightly decreased rimantadine peak concentrations and AUC1 13

Aspirin

Slightly decreased rimantadine peak concentrations and AUC1 13

Cimetidine

No clinically important effect on rimantadine concentrations or AUC1 13

Influenza virus vaccines

Influenza virus vaccine inactivated: Rimantadine does not interfere with the antibody response to the vaccine1 13

Influenza vaccine live intranasal: Potential interference with antibody response to the live vaccine; no specific studies1 13 100

Influenza virus vaccine inactivated: May be administered concomitantly with or at any time before or after rimantadine1 13 100

Influenza vaccine live intranasal: Do not administer the live vaccine until ≥48 hours after rimantadine is discontinued; do not administer rimantadine until ≥2 weeks after administration of the vaccine, unless medically indicated;1 13 100 if rimantadine given within 2 weeks after the vaccine, repeat vaccine dose ≥48 hours after last antiviral dose;100 alternatively, if rimantadine given 2 days before to 14 days after the vaccine, revaccinate using the parenteral inactivated vaccine or parenteral recombinant vaccine100

Rimantadine Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Well absorbed from GI tract; peak plasma concentrations usually attained within 6 hours.1 13 14 40 49 51

Special Populations

Healthy geriatric adults 71–79 years of age: Steady-state peak plasma concentrations and AUC are 20–30% higher than in adults 50–70 years of age.1 13

Geriatric nursing home patients 68–102 years of age: Steady-state concentrations are up to fourfold higher than in healthy young and elderly adults.1 13

Severe hepatic impairment: AUC is threefold higher than in healthy individuals.1 13

Severe renal impairment (Clcr 5–29 mL/minute): Peak plasma concentrations are 75% higher and AUC is 81% higher than in healthy individuals.1 13

Distribution

Extent

Not fully characterized.1 13 Distributed into nasal secretions.40 51 54

Crosses the placenta in rats; distributed into milk in rats.1 13 Not known whether rimantadine crosses the placenta or is distributed into human milk.1 13

Plasma Protein Binding

40%.1 13 40

Elimination

Metabolism

Extensively metabolized in the liver to at least 3 hydroxylated metabolites.1 13 40 55

Elimination Route

Principally excreted in urine (<25% as unchanged drug).1 13 40 55

Not removed by hemodialysis.1 13

Half-life

25–38 hours in adults and children.1 13 40 49 51 54 60

Special Populations

Chronic liver disease (mainly stabilized cirrhosis): No appreciable change in half-life compared with healthy individuals.1 13

Severe hepatic impairment: Clearance reduced 50% and half-life increased twofold compared with healthy individuals.1 13

Mild or moderate renal impairment (Clcr 30–80 mL/minute): Half-life only slightly prolonged (≤18%) compared with healthy individuals.1 13

Severe renal impairment (Clcr 5–29 mL/minute): Half-life increased 49% compared with healthy individuals.1 13

Stability

Storage

Oral

Tablets

20–25°C (may be exposed to 15–30°C), depending on manufacturer.1 13

Extemporaneous Oral Suspension

Room temperature for up to 14 days.1 13

Actions and Spectrum

  • Adamantane-derivative (a symmetric tricyclic amine);1 3 10 13 15 16 40 42 structurally related to amantadine.2 3 4 5 8 10 15 16 17 40 42

  • Has antiviral activity against some strains of influenza A, including susceptible H1N1, H2N2, and H3N2.1 4 5 11 12 13 16 42 45

  • Has little or no activity against influenza B.1 11 13 15 16 35 42 551

  • Beginning in the 2005–2006 influenza season, most influenza A (H3N2) strains circulating in the US were resistant to amantadine and rimantadine.121 Resistance to amantadine and rimantadine among seasonal influenza A (H3N2) circulating during recent influenza seasons has remained high.93 105 112 117 144 162 551 552

  • Although amantadine and rimantadine were active against most seasonal influenza A (H1N1) viruses circulating in the US during the 2008–2009 and 2009–2010 influenza seasons,117 139 162 the influenza A (H1N1)pdm09 virus circulating during recent influenza seasons is resistant to amantadine and rimantadine.52 105 117 144 151 162 551 552

  • Although some strains of avian influenza A (H5N1) have been susceptible to rimantadine,38 39 most avian influenza A virus strains tested (including H5N1 and H7N9) are resistant to adamantanes (amantadine, rimantadine).76 50 104

  • Inhibits viral replication by interfering with the influenza A virus M2 protein, an integral membrane protein.1 11 13 15 16 41 42 46

  • Strains of influenza A virus with reduced susceptibility to rimantadine have been produced in vitro and have emerged during therapy with the drug.1 6 8 9 10 11 12 13 41 42 43 46

  • Rimantadine-resistant influenza A viruses also are resistant to amantadine and vice versa.9 10 13 16 41 42 43 46 48

Advice to Patients

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products, as well as any concomitant illnesses.1 13

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 13

  • Importance of advising patients of other important precautionary information.1 13 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Rimantadine Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

100 mg*

Flumadine

Forest

Rimantadine Hydrochloride Tablets

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 05/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Flumadine 100MG Tablets (CARACO): 14/$43.99 or 42/$109.97

Rimantadine HCl 100MG Tablets (GLOBAL PHARMACEUTICAL CORP): 30/$69.99 or 90/$195.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions April 25, 2014. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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