Amantadine edema

CHF or peripheral edema Closely follow patients with a history of CHF or peripheral edema as there are patients who developed CHF while receiving amantadine. Glaucoma Because amantadine has anticholinergic effects and may cause mydriasis, do not give to patients with untreated angle closure glaucoma. 

Rimantadine (Flumadine) [Antiviral] Uses Prophylaxis Rx of influenza A viral Infxns but not for HlNl swine flu Action Antiviral Dose Adults Feds >9 y. 100 mg PO bid Feds 2-9 y. 5 mg/kg/d PO, 150 mg/d max daily w/ severe renal/hepatic impair elderly initiate w/in 48 h of Sx onset Caution [C, -] w/ cimetidine avoid w/ PRG, breast-feeding Contra Component amantadine allergy Disp Tabs SE Orthostatic X BP, edema, dizziness, GI upset, X Sz threshold Interactions T Effects W/ cimetidine i effects W/ acetaminophen, ASA EMS Concurrent EtOH usage may result in light-headedness, confusion, syncope, and hypotension OD May cause N/V, tremors, Szs, anticholinergic Sxs, ventricular arrhythmias give IV fluids... 

Amantadine was originally introduced as an antiviral compound (see Chapter 50), but it is modestly effective in treating symptoms of parkinsonism. It is useful in the early stages of parkinsonism or as an adjunct to levodopa therapy. Its mechanism of action in parkinsonism is not clear, but amantadine may affect dopamine release and reuptake. Additional sites of action may include antagonism at muscarinic and A-methyl-D-aspartate (NMDA) receptors. Adverse effects include nausea, dizziness, insomnia, confusion, hallucinations, ankle edema, and livedo reticularis. Amantadine and the anticholinergics may exert additive effects on mental functioning. 

Livedo reticularis sometimes occurs in patients taking amantadine and usually clears within 1 month after the drug is withdrawn. Other dermatologic reactions have also been described. Peripheral edema, another well-recognized complication, is not accompanied by signs of cardiac, hepatic, or renal disease and responds to diuretics. Other adverse reactions to amantadine include headache, heart failure, postural hypotension, urinary retention, and gastrointestinal disturbances (eg, anorexia, nausea, constipation, and dry mouth). 

Rarely, amantadine causes visual impairment due to corneal abrasions, local edema, and superficial keratitis (14). 

Cardiovascular Does the patient have atrial fibrillation, a coronary artery disease history, or hyperlipidemia increasing stroke risk Could orthostatic hypotension be due to medications for Parkinson s disease treatment Is a medication such as amantadine causing peripheral edema ... 

Toxicity Behavioral effects include restlessness, agitation, insomnia, confusion, hallucinations, and acute toxic psychosis. Dermatologic reactions include livedo reticularis. Miscellaneous effects may include gastrointestinal disturbances, urinary retention, and postural hypotension. Amantadine also causes peripheral edema that responds to diuretics. 

Amantadine has also been used for the treatment of PD-related dementia (Greulich and Fenger, 1995). Amantadine has been reported to reduce the duration of levodopa-induced dyskinesia and improves motor disability in PD. Although some beneficial effects are noted in patients after amantadine treatment, this drug is known to induce corneal edema that begins few months to several years after institutional therapy (Jeng et al., 2008). 

Ghaffariyeh A, Honarpisheh N. Amantadine-associated comeal edema. Parkinsonism Relat Disord 2010 16(6) 427. 

Deogaonkar M, Wilson K, Vitek J. Amantadine induced reversible comeal edema. J Clin Neurosci 2011 18(2) 298-9. 

Hood CT, Langston RH, Schoenfield LR, Dupps WJ Jr. Amantadine-associated corneal edema treated with Descemet s stripping automated endothelial keratoplasty. 

French DD, Margo CE. Postmarketing surveillance of corneal edema, Fuchs dystrophy, and amantadine use in the Veterans Health Administration. Cornea 2007 26 1087-9. 

Comeal edema has occasionally been attributed to amantadine, and since the first... 

Case reports Three patients who took amantadine developed diffuse corneal edema [272 ]. In two cases the symptoms started within a few weeks and in the third case after 6 years. In the first two cases withdrawal of amantadine resulted in resolution of the corneal edema. However, the other patient received a full-thickness corneal transplant while still taking amantadine, and edema developed in the grafted cornea withdrawal of amantadine then resulted in resolution of the comeal edema in both eyes, but the ungrafted comeal eventually also became edematous, requiring transplantation. Histopathology showed significant loss of endothelial cells. As in the last of these cases, another report documented comeal edema in a corneal transplant until amantadine withdrawn [273" ]. 

A 14-year-old boy with a tremor took amantadine and developed comeal edema. The corneal thickness was over 900 pm [274 ]. The edema rapidly resolved after withdrawal and the corneal thickness returned to normal. 

A 61-year-old man with Parkinson s disease took amantadine 300 mg/day for 8 months and developed comeal endothelial edema withdrawal of amantadine resulted in rapid improvement of visual acuity [275 ]. 

A 74-year-old woman took amantadine for 8 years without problems after a break she started taking it again and after a further 2 years developed bilateral corneal edema, which resolved within 1 month of withdrawal [276 ]. 

A 52-year-old woman with Parkinson s disease who had taken amantadine for 6 years developed bilateral comeal edema for 2 months amantadine was withdrawn and the edema resolved amantadine was reintroduced and the corneal edema recurred amantadine was then permanently withdrawn and the comeal edema again resolved [277 ]. 

A 12-year-old girl took amantadine HCl 100 mg bd for 4 months and developed bilateral blurred vision which progressed. She had corneal edema and the central corneal thicknesses were 851 pm in the right eye and 886 pm in the left eye (reference range 509-613) [278 ]. 

A 39-year-old woman developed bilateral corneal edema after taking amantadine for 2 months [279 ]. Corneal thicknesses were 940 pm in the right eye and 802 pm in the left. There was diffuse stromal edema, folds in Des-cemet s membrane, and microcystic subepithe-lial edema. Specular microscopy showed significant pleomorphism and polymegathism with an endothelial cell count of 1504 cells in the right eye and 1596 in the left eye. 

A 68-year-old woman with Parkinsonism took amantadine HCl 100 mg bd for 2 years and developed comeal edema, with central comeal thicknesses of 871 mm in the right eye and 746 mm in the left eye [280 ]. There was bilateral diffuse stromal and epithelial edema with marked folds in Descemet s membrane. The amantadine was withdrawn and topical prednisolone acetate 1 % and sodium chloride eye-drops were given. There was complete resolution within 3 weeks, and the comeal thicknesses resolved (592 mm in the right eye and 567 mm in the left eye). 

A 45-year-old woman developed amantadine-associated comeal edema, which did not resolve despite withdrawal of amantadine and treatment with glucocorticoids [281 ]. She therefore underwent sequential phakic Descemet s stripping automated endothelial keratoplasty (DSAEK), with significant. Histology of Descemet s membrane by light microscopy showed a paucity of endothelial cells. 

A 61-year-old woman with Parkinson s disease was given amantadine, followed over the next 6 years by pramipexole. ropinirole, co-careldopa, and entacapone [282 ]. She subsequently developed severe comeal edema. Amantadine was withdrawn and within 1 trwnth the comeal edema had completely resolved. The comeal thicknesses improved from 810 to 640 pm in the right eye and from 780 to 660 pm in the left eye. 

Post-marketing surveillance In a post-marketing surveillance study of patients with a new diagnosis of comeal disease and new prescriptions for amantadine over 2 years, 36 (0.27%) of 13 137 patients developed comeal edema [283 ]. The relative risk of comeal edema was 1.7 (95% Cl = 1.1, 2.8) in 12 patients (0.09%) the diagnosis was made in the first month. 

Skin Livedo reticularis has again been reported, in a 58-year-old woman with chronic genotype lb hepatitis C, who developed an asymptomatic, mild, mottled, reddish-brown eruption on the thighs and arms, associated with severe edema, after taking peginterferon alfa-2a 180 micro-grams/week, ribavirin 400 mg bd, and amantadine 100 mg bd it resolved when the amantadine was withdrawn and the other drugs were continued [290 ]. 

Blanchard DL. Amantadine caused corneal edema. Cornea 1990 9(2) 181. 

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