Side Effects of Flumadine (rimantadine)

Flumadine (rimantadine) is an antiviral drug that can prevent viruses in cells from multiplying and is used to treat and prevent influenza A in adults, and to prevent the influenza A virus in children older than one year of age. 

Flumadine is chemically related to amantadine (Symmetrel), but Flumadine has fewer side effects on the nervous system. The Centers for Disease Control and Prevention (CDC) recommends Flumadine should not be used to replace the annual influenza vaccination. 

Prolonged and frequent use of Flumadine can cause it to be less effective in its activity against the influenza A virus. Flumadine is most effective when given within 48 hours of the start of symptoms associated with the influenza A. 

Common side effects of Flumadine include

• nausea,
• vomiting,
• sleep disturbances,
• lack of concentration,
• dizziness,
• loss of appetite,
• swelling (edema),
• anxiety,
• headaches, and
• weight loss.

Serious side effects of Flumadine include

• extreme drowsiness,
• lightheadedness,
• depression,
• agitation,
• aggression,
• behavior changes,
• hallucinations,
• thoughts of hurting yourself, and
• seizures.

Drug interactions of Flumadine include the influenza virus vaccine, because it may reduce the effectiveness of the vaccine. 

It is recommended Flumadine not be given 48 hours prior to and 14 days after administering the influenza virus vaccine. 

Flumadine may interact with monoamine oxidase inhibitors (MAOIs) and cause the blood pressure to drop suddenly.

There are no well-controlled studies of Flumadine in pregnant women and, therefore, Flumadine is not recommended during pregnancy. Other drugs including oseltamivir (Tamiflu) and zanamivir (Relenza) are recommended to prevent and treat influenza A virus illness in pregnant women.

Breastfeeding is not recommended while using Flumadine due to possible risks of adverse effects in infants.

The most common side effects of rimantadine are:

• nausea,
• vomiting,
• sleep disturbances,
• lack of concentration,
• dizziness, and
• loss of appetite.

Other side effects associated with rimantadine are:

• edema (swelling)
• anxiety
• headaches,
• and weight loss.

In 1,027 patients treated with Flumadine (rimantadine) 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 (1-3%) at the recommended dose in controlled clinical trials are shown in the table below.

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 Flumadine (rimantadine).

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 %.

Geriatric Use

Approximately 200 subjects over the age of 65 were evaluated for safety in controlled clinical trials with Flumadine (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.

Acetaminophen: Flumadine (rimantadine) , 100 mg, was given twice daily for 13 days to 12 healthy volunteers. On day 11, acetaminophen (650 mg four times daily) was started and continued for 8 days.

The pharmacokinetics of rimantadine were assessed on days 11 and 13. Coadministration with acetaminophen reduced the peak concentration and AUC values for rimantadine by approximately 11%.

Aspirin: Flumadine (rimantadine), 100 mg, was given twice daily for 13 days to 12 healthy volunteers. On day 11, aspirin (650 mg, four times daily) was started and continued for 8 days.

The pharmacokinetics of rimantadine were assessed on days 11 and 13. Peak plasma concentrations and AUC of rimantadine were reduced approximately 10% in the presence of aspirin.

Cimetidine: When a single 100 mg dose of Flumadine (rimantadine) was administered with steady-state cimetidine (300 mg four times a day), there were no statistically significant differences in rimantadine Cmax or AUC between Flumadine (rimantadine) alone and Flumadine (rimantadine) in the presence of cimetidine.

Live Attenuated Influenza Vaccine (LAIV): The concurrent use of Flumadine (rimantadine) with live attenuated intranasal influenza vaccine has not been evaluated. However, because of potential interference between these products, the live attenuated intranasal influenza vaccine should not be administered until 48 hours after cessation of Flumadine (rimantadine) and Flumadine (rimantadine) should not be administered until two weeks after the administration of live attenuated intranasal influenza vaccine unless medically indicated. The concern about potential interference arises principally from the potential for antiviral drugs to inhibit replication of live vaccine virus.