ADVERSE REACTIONS In 1,0 27 patients treated with Flumadine in co ntro lled clinical trials at the reco mmended do se o f 20 0 mg daily, the mo st frequently repo rted adverse events invo lved the g astro intestinal and nervo us systems. Incidence >1%: Adverse events repo rted mo st frequently (1-3%) at the reco mmended do se in co ntro lled clinical trials are sho wn in the table belo w. Rimantadine Co ntro l (n=10 27) (n=9 8 6 ) N e r v ous s y s t e m Inso mnia 2.1% 0 9 % Dizziness 1.9% 1.1% Headache 1.4% 1.3% Nervo usness 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 % Abdo minal Pain 1.4% 0 .8 % Body as a Whole A s t h e n i a 1 .4 % 0 . 5 % Less frequent adverse events (0 .3 to 1%) at the reco mmended do se in co ntro lled clinical trials were: G a s t r o i n t e s ti na l S y s t e m : diarrhea, dyspepsia; N e r v ou s S y s t e m : impairment o f co ncentratio n, ataxia, so mno lence, ag itatio n, depressio n; S k i n an d A pp e ndag e s : rash; H e a r i n g an d V e s ti bu l a r : tinnitus; R e s p i r a t o r y : dyspnea. A dd iti ona l ad ve rs e eve n t s ( l e s s t ha n 0 . 3 % ) r e po r t e d a t r ec o mm e nd e d do s e s i n c on t r o ll e d c li n i c a l t r i a l s w e r e : Nervo us System: g ait abno rmality, eupho ria, hyperkinesia, tremo r, hallucinatio n, co nfusio n, co nvulsio ns; R e s p i r a t o r y : bro ncho spasm, co ug h; C a r d i o v a s c u l a r : pallo r, palpitatio n, hypertensio n, cerebro vascular diso rder, cardiac failure, pedal edema, heart blo ck, tachycardia, synco pe; R e p r odu c ti on : no n-puerperal lactatio n; Sp ec i a l S e n s e s : taste lo ss/chang e, paro smia. Rates o f adverse events, particularly tho se invo lving the g astro intestinal and nervo us systems, increased sig nificantly in co ntro lled studies using hig her than reco mmended do ses o f Flumadine. In mo st cases, sympto ms reso lved rapidly with disco ntinuatio n o f treatment. In additio n to the adverse events repo rted abo ve, the fo llo wing were also repo rted at hig her than reco mmended do ses: increased lacrimatio n, increased micturitio n frequency, fever, rig o rs, ag itatio n, co nstipatio n, diapho resis, dysphag ia, sto matitis, hypesthesia and eye pain. Adverse Reactio ns in T rials o f Rimantadine and Amantadine: In a six-week pro phylaxis study o f 4 36 healthy adults comparing rimantadine with amantadine and placebo , the fo llo wing adverse reactio ns were repo rted with an incidence >1 %. Rimantadine Placebo Amantadine 20 0 mg /day 20 0 mg /day ( n =1 4 5 ) ( n =1 4 3 ) ( n =1 4 8 ) N e r v ou s S y s t e m Inso mnia 3.4 % 0 .7% 7.0 % Nervo usness 2.1% 0 .7% 2.8 % Impaired Co ncentratio n 2.1% 1.4 % 2.1% Dizziness 0 .7% 0 .0 % 2.1% Depressio n 0 .7% 0 .7% 3.5% T o tal % o f subjects with adverse reactio ns 6 .9 % 4 .1% 14 .7% T o tal % o f subjects withdrawn due to adverse reactio ns 6 .9 % 3.4 % 14 .0 % G ER I A T R I C U S E : Appro ximately 20 0 patients o ver the ag e o f 6 4 were evaluated fo r safety in co ntro lled clinical trials with Flumadine® (rimantadine hydro chlo ride). Geriatric subjects who received either 20 0 mg o r 4 0 0 mg o f rimantadine daily fo r 1 to 50 days experienced co nsiderably mo re central nervo us system and g astro intestinal adverse events than co mparable g eriatric subjects receiving placebo . Central nervo us system events including dizziness, headache, anxiety, asthenia, and fatig ue, o ccurred up to two times mo re o ften in subjects treated with rimantadine than in tho se treated with placebo . Gastro intestinal sympto ms, particularly nausea, vo miting , and abdo minal pain o ccurred at least twice as frequently in subjects receiving rimantadine than in tho se receiving placebo . T he g astro intestinal sympto ms appeared to be do se related. In patients o ver 6 4 , the reco mmended do se is 10 0 mg , daily (see Clinical Pharmacology and Dosage and Administration ).