|
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or
standards of non-Merck sources.
Special Alerts
CDC Antiviral Treatment Recommendations for Novel H1N1 Influenza - Updated May 7, 2009
Updated interim guidance from the Centers for Disease Control (CDC) notes that the novel influenza A (H1N1) virus (formerly known as swine-origin influenza A) is resistant to amantadine and rimantadine. With the exception of areas with continued seasonal human influenza activity (particularly with known oseltamivir-resistance to human A [H1N1] viruses), these medications should NOT be used in the treatment of confirmed, probable, or suspected cases of novel (H1N1) influenza, or for chemoprophylaxis.
CDC recommendations are changing frequently as more information on antiviral susceptibilities and effectiveness becomes available. For the most recent recommendations and information from the CDC, please refer to http://www.cdc.gov/h1n1flu/recommendations.htm.
CDC Interim Recommendations Concerning Use of Antivirals During 2008-09 Influenza Season - December 2008
The Centers for Disease Control (CDC) has issued a Health Advisory with interim recommendations for chemoprophylaxis or influenza treatment with the following antiviral agents: Oseltamivir (Tamiflu®), zanamivir (Relenza®), rimantadine (Flumadine®), amantadine (Symmetrel®).
The recommendations were prompted by preliminary data in a limited number of states indicating a high prevalence of the oseltamivir-resistant influenza A (H1N1) strain. Influenza activity remains low at the present time, but of the 50 H1N1 isolates from 12 states tested between October 1 and December 19, 2008, 49 (98%) were resistant to oseltamivir. The CDC is unable to make any accurate predictions of which influenza virus types (A or B) or subtypes of influenza A (H1N1 or H3N2) will predominate during the 2008-09 season, but based on the current findings, the following recommendations have been made:
• Patients testing positive for influenza type B: If treatment is indicated, patients may receive either oseltamivir or zanamivir (no preference).
• Patients testing positive for influenza type A (or patients testing negative for influenza, but likelihood of influenza infection is high): If treatment is indicated, patient may receive zanamivir. If zanamivir therapy is inappropriate (eg, patients with chronic respiratory disease, patients <7 years of age) or zanamivir is unavailable, combination treatment with oseltamivir and rimantadine is acceptable (if rimantadine is unavailable, amantadine may be substituted). Oseltamivir monotherapy should only be used if local surveillance indicates that influenza A (H3N2) or influenza type B viruses are likely.
• If confirmatory diagnostic testing to distinguish between subtypes of influenza A (H1N1 or H3N2) is available, and treatment is indicated:
Patients testing positive for influenza A (H3N2): Use oseltamivir or zanamivir (no preference)
Patients testing positive for influenza A (H1N1): Use zanamivir (or combination treatment with oseltamivir and rimantadine as an alternative)
Patients requiring chemoprophylaxis due to potential exposure with laboratory-confirmed influenza A (H3N2) or influenza B should receive oseltamivir or zanamivir. Patients requiring chemoprophylaxis due to influenza A (H1N1) virus should receive zanamivir (or rimantadine, if zanamivir use contraindicated).
The CDC is reminding clinicians to continue to vaccinate patients using the influenza vaccine, which is expected to be effective against all circulating influenza viruses, including the oseltamivir-resistant strain.
For additional information, including the CDC Health Advisory, please refer to http://www2a.cdc.gov/HAN/ArchiveSys/ViewMsgV.asp?AlertNum=00279
Rimantadine ACIP 2008-2009 Influenza Guidelines (July 2008)
The Advisory Committee on Immunization Practices (ACIP), as part of their recommendations for the Prevention and Control of Influenza, do not recommend the use of amantadine or rimantadine for the treatment or chemoprophylaxis of influenza A infection. This recommendation is for the 2008-2009 season for residents of the United States and is based on current patterns of resistance to these medications. Oseltamivir or zanamivir are the recommended antiviral agents. In some areas, resistance is developing against oseltamivir. If resistance is suspected, amantadine or rimantadine may be used in combination with oseltamivir for the treatment or prophylaxis of influenza A infection when zanamivir therapy is not indicated (such as in children of certain ages).
For additional information, refer to the ACIP guidelines on the following CDC website: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr57e717a1.htm
Medication Safety Issues
Sound-alike/look-alike issues:
Rimantadine may be confused with amantadine, ranitidine, Rimactane®
Flumadine® may be confused with fludarabine, flunisolide, flutamide
Pronunciation
(ri MAN ta deen)
U.S. Brand Names
Index Terms
Generic Available
Yes: Tablet
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Prophylaxis (adults and children >1 year of age) and treatment (adults) of influenza A viral infection (per manufacturer labeling; also refer to current ACIP guidelines for recommendations during current flu season)
Note: In certain circumstances, the ACIP recommends use of rimantadine in combination with oseltamivir for the treatment or prophylaxis of influenza A infection when resistance to oseltamivir is suspected.
Pregnancy Risk Factor
C
Pregnancy Considerations
Animal data suggest embryotoxicity, maternal toxicity, and offspring mortality at doses 7-11 times the recommended human dose. There are no adequate and well-controlled studies in pregnant women.
Lactation
Excretion in breast milk unknown/ not recommended
Breast-Feeding Considerations
Do not use in nursing mothers due to potential adverse effect in infants.
Contraindications
Hypersensitivity to drugs of the adamantine class, including rimantadine and amantadine, or any component of the formulation
Warnings/Precautions
Disease-related concerns:
• Eczema: Avoid use, if possible, in patients with recurrent and eczematoid dermatitis.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Influenza A: Appropriate use: Consult current guidelines. Due to increased resistance, the ACIP has recommended that rimantadine and amantadine no longer be used for the treatment or prophylaxis of influenza A in the United States until susceptibility has been re-established.
• Psychosis: Avoid use, if possible, in patients with uncontrolled psychosis or severe psychoneurosis.
• Renal impairment: Use with caution in patients with renal impairment.
• Seizures: Use with caution in patients with a history of seizure disorder; an increase in seizure incidence may occur. Discontinue if seizures occur.
Other warnings/precautions:
• Resistance: May develop during treatment; viruses exhibit cross-resistance between amantadine and rimantadine.
Adverse Reactions
1% to 10%:
Central nervous system: Insomnia (2% to 3%), concentration impaired (2%), dizziness (1% to 2%), nervousness (1% to 2%), anxiety (1%), fatigue (1%), headache (1%)
Gastrointestinal: Nausea (3%), anorexia (2%), vomiting (2%), xerostomia (2%), abdominal pain (1%)
Neuromuscular & skeletal: Weakness (1%)
<1%: Agitation, ataxia, bronchospasm, cardiac failure, concentration impaired, confusion, convulsions, cough, depression, diarrhea, dyspepsia, dyspnea, euphoria, gait abnormality, hallucinations, heart block, hyperkinesias, hypertension, lactation, palpitation, pallor, parosmia, pedal edema, rash, somnolence, syncope, tachycardia, taste alteration, tinnitus, tremor
Drug Interactions
Influenza Virus Vaccine: Antiviral Agents (Influenza A and B) may diminish the therapeutic effect of Influenza Virus Vaccine. This only pertains to live, attentuated influenza virus vaccine. Risk D: Consider therapy modification
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Food: Food does not affect rate or extent of absorption
Storage
Store at 15°C to 30°C (59°F to 86°F).
Mechanism of Action
Exerts its inhibitory effect on three antigenic subtypes of influenza A virus (H1N1, H2N2, H3N2) early in the viral replicative cycle, possibly inhibiting the uncoating process; it has no activity against influenza B virus and is two- to eightfold more active than amantadine
Pharmacodynamics/Kinetics
Onset of action: Antiviral activity: No data exist establishing a correlation between plasma concentration and antiviral effect
Absorption: Tablet and syrup formulations are equally absorbed
Metabolism: Extensively hepatic
Half-life elimination: 25.4 hours; prolonged in elderly
Time to peak: 6 hours
Excretion: Urine (<25% as unchanged drug)
Clearance: Hemodialysis does not contribute to clearance
Dosage
Oral:
Prophylaxis:
Children 1-10 years: CDC recommendation: 5 mg/kg/day in 2 divided doses; maximum: 150 mg/day
Children >10 years and Adults: 100 mg twice daily
Elderly: 100 mg/day in nursing home patients or all elderly patients who may experience adverse effects using the adult dose
Treatment:
Adults: 100 mg twice daily
Elderly: 100 mg once daily in patients ?65 years
Dosage adjustment in renal impairment:
Clcr >10 mL/minute: Dose adjustment not required
Clcr ?10 mL/minute: 100 mg/day
Dosage adjustment in hepatic impairment: Severe dysfunction: 100 mg/day
Administration: Oral
Initiation of rimantadine within 48 hours of the onset of influenza A illness halves the duration of illness and significantly reduces the duration of viral shedding and increased peripheral airways resistance. Continue therapy for 5-7 days after symptoms begin.
Monitoring Parameters
Monitor for CNS or GI effects in elderly or patients with renal or hepatic impairment
Patient Education
Do not take any new medication during therapy unless approved by prescriber. Take as directed. Complete full course of therapy even if feeling better. Take a missed dose as soon as possible. If almost time for next dose, skip the missed dose and return to your regular schedule. Do not take a double dose. May cause dizziness, insomnia, fatigue, nervousness (use caution when driving or engaged in potentially hazardous tasks until response to medication is known); gastrointestinal upset (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help). Report rash, palpitations; severe nausea or vomiting; persistent CNS changes (eg, confusion, insomnia, anxiety, restlessness, irritability, hallucinations) or other persistent adverse reactions. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Do not breast-feed.
Geriatric Considerations
Rimantadine is no longer recommended for the treatment or chemoprophylaxis of influenza A infection. Adverse CNS and GI effects occur frequently if dosage is not adjusted. Monitor GI effects in the elderly or patients with renal or hepatic impairment. Dosing must be individualized (100 mg 1-2 times/day). It is recommended that nursing home patients receive 100 mg/day.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Infectious Diseases Comment
Consult current guidelines for appropriate use. Due to increased resistance the ACIP recommends that amantadine and rimantadine no longer be used for the treatment or prophylaxis of influenza A in the United States. If an antiviral medication is needed, oseltamivir or zanamivir should be used. In some areas, resistance is developing against oseltamivir. If resistance is suspected, amantadine or rimantadine may be used in combination with oseltamivir for the treatment or prophylaxis of influenza A infection when zanamivir therapy is not indicated (such as in children of certain ages).Amantadine may still be used for its other approved indications, such as in the treatment of Parkinson's disease.
For additional information, refer to the ACIP guidelines on the following CDC website: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr57e717a1.htm
Mental Health: Effects on Mental Status
May cause dizziness, anxiety, confusion, insomnia, restlessness, irritability, or hallucinations
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Use caution with hepatic or renal impairment, seizure disorders, uncontrolled psychoses, or severe psychoneurosis. Assess effectiveness (resolution of infection) and adverse reactions (eg, hypotension, CNS changes [confusion, anxiety, agitation], gastrointestinal upset, anticholinergic effects [dry mouth, urinary retention, mydriases]). Teach patient appropriate use, possible side effects/interventions (eg, postural hypotension), and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Syrup, as hydrochloride:
Flumadine®: 50 mg/5 mL (240 mL) [raspberry flavor] [DSC]
Tablet, as hydrochloride: 100 mg
Flumadine®: 100 mg
Pricing: U.S. (www.drugstore.com)
Syrup (Flumadine)
50 mg/5 mL (240): $55.99
Tablets (Flumadine)
100 mg (14): $43.99
References
Bentley DW, Karki SD, and Betts RF, “Rimantadine and Seizures,” Ann Intern Med, 1989, 110(4):323-4.
Centers for Disease Control, “Prevention and Control of Influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP),” MMWR Recomm Rep, 2008, 56 (early release):1-60. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr57e717a1.htm
Dolin R, Reichman RC, Madore HP, et al, “A Controlled Trial of Amantadine and Rimantadine in the Prophylaxis of Influenza A Infection,” N Engl J Med, 1982, 307(10):580-4.
Douglas RG Jr, “Prophylaxis and Treatment of Influenza,” N Engl J Med, 1990, 322(7):443-50.
“Drugs for Non-HIV Viral Infections,” Med Lett Drugs Ther, 1994, 36(919):27.
Guay DR, “Amantadine and Rimantadine Prophylaxis of Influenza A in Nursing Homes,” Drugs Aging, 1994, 5(1):8-19.
Keating MR, “Antiviral Agents,” Mayo Clin Proc, 1992, 67(2):160-78.
Patriarca PA, Kater NA, Kendal AP, et al, “Safety of Prolonged Administration of Rimantadine Hydrochloride in the Prophylaxis of Influenza A Virus Infections in Nursing Homes,” Antimicrob Agents Chemother, 1984, 26(1):101-3.
Wintermeyer SM and Nahata MC, “Rimantadine: A Clinical Perspective,” Ann Pharmacother, 1995, 29(3):299-310.
International Brand Names
Lexi-Comp.com
Last full review/revision June 2009
|
