INDICATIONS AND USAGE Rimantadine hydrochloride tablet is indicated for the prophylaxis and treatment of illness caused by various strains of influenza A virus in adults (17 years and older).

Rimantadine hydrochloride tablet is indicated for prophylaxis against influenza A virus in children (1 year to 16 years of age).

Prophylaxis In controlled studies of children (1 year to 16 years of age), healthy adults (17 years and older), and elderly patients (65 years of age and older), rimantadine hydrochloride has been shown to be safe and effective in preventing signs and symptoms of infection caused by various strains of influenza A virus.

Since rimantadine hydrochloride does not completely prevent the host immune response to influenza A infection, individuals who take this drug may still develop immune responses to natural disease or vaccination and may be protected when later exposed to antigenically-related viruses.

Following vaccination during an influenza outbreak, rimantadine hydrochloride prophylaxis should be considered for the 2 to 4 week time period required to develop an antibody response.

However, the safety and effectiveness of rimantadine hydrochloride prophylaxis have not been demonstrated for longer than 6 weeks.

Treatment Rimantadine hydrochloride therapy should be considered for adults (17 years and older) who develop an influenza-like illness during known or suspected influenza A infection in the community.

When administered within 48 hours after onset of signs and symptoms of infection caused by influenza A virus strains, rimantadine hydrochloride has been shown to reduce the duration of fever and systemic symptoms.

The following points should be considered before initiating treatment or prophylaxis with rimantadine hydrochloride: Rimantadine hydrochloride is not a substitute for early vaccination on an annual basis as recommended by the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices.

Influenza viruses change over time.

Emergence of resistance mutations could decrease drug effectiveness.

Other factors (for example, changes in viral virulence) might also diminish clinical benefit of antiviral drugs.

Prescribers should consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use rimantadine hydrochloride.

ADVERSE REACTIONS In 1,027 patients treated with rimantadine hydrochloride in controlled clinical trials at the recommended dose of 200 mg daily, the most frequently reported adverse events involved the gastrointestinal and nervous systems.

Incidence >1%: Adverse events reported most frequently (1 % to 3%) at the recommended dose in controlled clinical trials are shown in the table below.

Rimantadine (n=1,027) Control (n=986) Nervous System Insomnia 2.1% 0.9% Dizziness 1.9% 1.1% Headache 1.4% 1.3% Nervousness 1.3% 0.6% Fatigue 1.0% 0.9% Gastrointestinal System Nausea 2.8% 1.6% Vomiting 1.7% 0.6% Anorexia 1.6% 0.8% Dry mouth 1.5% 0.6% Abdominal Pain 1.4% 0.8% Body as a Whole Asthenia 1.4% 0.5% Less frequent adverse events (0.3 to 1%) at the recommended dose in controlled clinical trials were: Gastrointestinal System: diarrhea, dyspepsia; Nervous System: impairment of concentration, ataxia, somnolence, agitation, depression; Skin and Appendages: rash; Hearing and Vestibular: tinnitus; Respiratory: dyspnea.

Additional adverse events (less than 0.3%) reported at recommended doses in controlled clinical trials were: Nervous System: gait abnormality, euphoria, hyperkinesia, tremor, hallucination, confusion, convulsions; Respiratory: bronchospasm, cough; Cardiovascular: pallor, palpitation, hypertension, cerebrovascular disorder, cardiac failure, pedal edema, heart block, tachycardia, syncope; Reproduction: non-puerperal lactation; Special Senses: taste loss/change, parosmia.

Rates of adverse events, particularly those involving the gastrointestinal and nervous systems, increased significantly in controlled studies using higher than recommended doses of rimantadine hydrochloride.

In most cases, symptoms resolved rapidly with discontinuation of treatment.

In addition to the adverse events reported above, the following were also reported at higher than recommended doses: increased lacrimation, increased micturition frequency, fever, rigors, agitation, constipation, diaphoresis, dysphagia, stomatitis, hypesthesia and eye pain.

Adverse Reactions in Trials of Rimantadine and Amantadine: In a six-week prophylaxis study of 436 healthy adults comparing rimantadine with amantadine and placebo, the following adverse reactions were reported with an incidence >1%.

Rimantadine 200 mg/day (n=145) Placebo (n=143) Amantadine 200 mg/day (n=148) Nervous System Insomia 3.4% 0.7% 7.0% Nervousness 2.1% 0.7% 2.8% Impaired Concentration 2.1% 1.4% 2.1% Dizziness 0.7% 0.0% 2.1% Depression 0.7% 0.7% 3.5% Total % of subjects with adverse reactions 6.9% 4.1% 14.7% Total % of subjects withdrawn due to adverse reactions 6.9% 3.4% 14.0% Geriatric Use Approximately 200 patients over the age of 65 were evaluated for safety in controlled clinical trials with rimantadine hydrochloride.

Geriatric subjects who received either 200 mg or 400 mg of rimantadine daily for 1 to 50 days experienced considerably more central nervous system and gastrointestinal adverse events than comparable geriatric subjects receiving placebo.

Central nervous system events including dizziness, headache, anxiety, asthenia, and fatigue, occurred up to two times more often in subjects treated with rimantadine than in those treated with placebo.

Gastrointestinal symptoms, particularly nausea, vomiting, and abdominal pain occurred at least twice as frequently in subjects receiving rimantadine than in those receiving placebo.

The gastrointestinal symptoms appeared to be dose related.

In patients over 65, the recommended dose is 100 mg, daily (see CLINCAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION ).

To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.