Livedo reticularis amantadine

Type B effects are rare but should be recognized. They include oedema of the lower limbs (bromocriptine, amantadine), livedo reticularis (amantadine), diarrhoea (tolcapone, entacapone), paroxysmal hypertension and dysregulation of blood pressure control (selegiline), narcoleptic phenomena (pramipex-ole), and insomnia (all dopaminergic agonists). 

Paulson GW, Brandt JT. Amantadine, livedo reticularis, and antiphospholipid antibodies. Clin Neuropharmacol 1995 18(5) 466-7. 

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. 

D. Although not widely used, amantadine may be useful in the early stages of Parkinson s disease or as an adjunct to other agents. Livedo reticularis is a characteristic purple mottling of the skin associated with amantadine. 

Livedo reticularis sometimes occurs in patients taking amantadine and usually clears within 1 month after the drug is withdrawn.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). 

The primary adverse effects associated with amantadine are orthostatic hypotension, CNS disturbance (e.g., depression, confusion, hallucinations), and patches of skin discoloration on the lower extremities (livedo reticularis). However, these side effects are relatively mild compared to those of other anti-Parkinson drugs and are usually reversed by altering the drug dosage. 

A 48-year-old woman with a 17-year history of Parkinson s disease developed a sensorimotor peripheral neuropathy after taking amantadine 300 mg/day for 8 years (12). She had livedo reticularis after only 1 year of treatment and this had become increasingly extensive. Attempts to withdraw the drug resulted in worsening Parkinsonian symptoms. However, after the neuropathy had been diagnosed, amantadine was withdrawn, with improvement of the neurological symptoms within 6 weeks and complete resolution after 6 months. However, the livedo reticularis was still present 18 months after withdrawal. 

Silver DE, Sahs AL. Livedo reticularis in Parkinson s disease patients treated with amantadine hydrochloride. Neurology 1972 22(7) 665-9. 

Note Fifty to 90% of patients receiving amantadine for Parkinsonism develop a more or less livedo reticularis ... 

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 is generally well tolerated in most patients ) and causes fewer side effects than levodopa or anticholinergics. Some reported side effects may be due to concurrent anticholinergic medication or to amantadine intensification of their effects, but this is not yet clearly established. Livedo reticularis has been reported. ... 

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 ]. 

Minutilli E, Pompili M, Pelecca G, Rapaccini GL, Gasbarrini G, Castagneto M. Amantadine-induced livedo reticularis occurring during treatment of chronic hepatitis C. J Eur Acad Dermatol Venereol 2008 22(11) 1368-70. 

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