Gastrointestinal (GI) complaints were among the most common adverse events associated with the use of rimantadine during clinical trials. When compared with placebo, more patients who received rimantadine experienced episodes of nausea (2.8% vs. 1.6%), vomiting (1.7% vs. 0.6%), anorexia (1.6% vs. 0.8%), xerostomia or dry mouth (1.5% vs. 0.6%), and abdominal pain (1.4% vs. 0.8%). Other, less frequent, GI adverse events included diarrhea (0.3% to 1%), dyspepsia (0.3% to 1%), ageusia (less than 0.3%), and dysgeusia (less than 0.3%). At normal adult doses, GI symptoms, especially nausea, vomiting and abdominal pain, occur twice as frequently in elderly patients versus younger adults. Since GI adverse reactions appear to be dose-related, a lower rimantadine dose is recommended for patients 65 years or older. Additional GI adverse events (e.g., constipation, dysphagia, and stomatitis) were reported in clinical studies using higher than recommended doses of rimantadine. In the majority of cases, these GI symptoms rapidly resolved following treatment discontinuation.[31158] [46158]

Neurologic complaints were among the most common adverse events associated with the use of rimantadine during clinical trials. When compared with placebo, patients receiving rimantadine experienced more episodes of insomnia (2.1% to 3.4% vs. 0.7% to 0.9%), dizziness (0.7% to 1.9% vs. 1.1%), nervousness or anxiety (1.3% to 2.1% vs. 0.6% to 0.7%), concentration impairment (2.1% vs. 1.4%), headache (1.4% vs. 1.3%), asthenia (1.4% vs. 0.5%), and fatigue (1% vs. 0.9%). Other, less frequent, neurologic adverse events observed in rimantadine recipients included agitation (0.3% to 1%), ataxia (0.3% to 1%), depression (0.7%), and drowsiness (0.3% to 1%). Cases of convulsions or seizures, confusion, euphoria, gait abnormalities, hallucinations, hyperkinesis, and tremor were rarely reported (less than 0.3%) in patients receiving rimantadine treatment. In elderly patients, CNS reactions including dizziness, headache, anxiety, asthenia, and fatigue, occurred up to two-times more often in patients treated with rimantadine versus placebo. Additionally, the incidence of neurologic adverse events (e.g., rigors, agitation, and hypoesthesia) were significantly increased in clinical trials that employed higher than recommended doses of rimantadine. Health care providers are advised to comply with approved dosing regimens.[31158] [46158]

Antimicrobial resistance can occur during therapy with rimantadine due to the development of viral mutations. Drug effectiveness may be diminished by resistance mutations or other factors such as viral virulence. Drug susceptibility patterns should be assessed when determining appropriateness of treatment with rimantadine.[31158] [46158]

Rash developed in 0.3% to 1% of patients who received treatment with rimantadine during clinical trials. Additionally, in clinical trials that employed higher than recommended doses of rimantadine, episodes of diaphoresis and fever were observed. Health care providers are advised to comply with recommended dosing regimens.[31158] [46158]

Although infrequent, adverse events of the respiratory system were reported during rimantadine clinical trials, including dyspnea (0.3% to 1%), bronchospasm (less than 0.3%), and increased cough (less than 0.3%).[31158] [46158]

Adverse events of the cardiovascular system reported in less than 0.3% of patients receiving recommended doses of rimantadine in controlled clinical trials included pallor, palpitations, hypertension, cerebrovascular disorder, heart failure, pedal edema, heart block (AV block), sinus tachycardia, and syncope.[31158] [46158]

Parosmia (less than 0.3%) and tinnitus (0.3% to 1%) were reported in patients receiving recommended doses of rimantadine in controlled clinical trials. Additionally, cases of ocular pain and increased lacrimation were noted in clinical trials that employed higher than recommended doses of rimantadine. Health care providers are advised to comply with recommended dosing regimens.[31158] [46158]

Cases of non-puerperal lactation (galactorrhea) were noted in less than 0.3% of patients receiving treatment with recommended doses of rimantadine during controlled clinical trials. When higher than recommended doses were used in clinical trials, episodes of increased urinary frequency were reported. Health care providers are advised to comply with approved dosing regimens.[31158] [46158]

Rimantadine is contraindicated in patients with a known rimantadine hypersensitivity, amantadine hypersensitivity, or hypersensitivity to any agent in the adamantane class.[31158]

Rimantadine should be used cautiously in patients with a history of seizure disorder. The manufacturer reports that during clinical trials a small number of patients with a history of seizures who were not receiving anticonvulsant therapy developed seizure-like activity while receiving rimantadine. Rimantadine should be discontinued if seizures develop.[31158]

Geriatric patients receiving either 200 or 400 mg/day of rimantadine experience considerably more central nervous system and GI adverse reactions than those patients receiving placebo. The side-effects appear to be dose related; therefore in patients 65 years or older, the recommended dose of rimantadine is 100 mg/day.[31158]

The safe and effective use of rimantadine in infants and neonates has not been determined. In children and adolescents ages 1 to 16 years, rimantadine may be used for prophylaxis against influenza A; however, safety and efficacy of treating symptomatic influenza has not been established in this population.[31158]

Rimantadine is primarily excreted unchanged in the urine. Dose reductions are advised for patients with renal failure or severe renal impairment (CrCl less than 30 mL/min). Monitor renal function closely and the dose adjusted accordingly.[31158]

Use caution when administering rimantadine to patients with hepatic disease. Severe hepatic impairment reduces the clearance of rimantadine, accumulation and toxicity can occur.[31158]

Rimantadine is classified as an FDA pregnancy risk category C drug. No adequate and well-controlled studies have been conducted in pregnant women. In animal studies, rimantadine 200 mg/kg/day (11-time the maximum recommended human dose (MRHD)) was embryotoxic in rats, causing increased fetal resorption. In rabbits receiving 50 mg/kg/day (0.1-times MRHD), no embryotoxic events were observed. According to the manufacturer, use during pregnancy should be avoided unless the potential benefits outweigh the possible risks to the fetus.[31158] [46158]

It is unknown if rimantadine is excreted in human milk, and data regarding use during breast-feeding are limited; however, it is concentrated at amounts greater than maternal serum concentration in the milk of rats and adverse effects have been noted in rat offspring. Due to the potential for infant toxicities, the manufacturer advises against use in nursing mothers. Oseltamivir and zanamivir may be potential alternatives to consider during breast-feeding. However, patient factors, local susceptibility patterns, and specific microbial susceptibility should be assessed before choosing an alternative. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, health care providers are encouraged to report the adverse effect to the FDA.[46158] [46966] [46967]

A serious bacterial infection may begin with influenza-type symptoms or may coexist with or occur as complications of influenza. There are no data to suggest rimantadine is effective in preventing such complications or treating a viral infection other than influenza virus A.[31158]