Amantadine

Cardiovascular

Reversible congestive cardiac failure has been attributed to amantadine [ ].

Nervous system

Neurological effects of supposed amantadine toxicity have been reported [ ].

• A 70-year-old woman with Parkinson’s disease took amantadine hydrochloride 150 mg/day and levodopa 200 mg/day and developed poor communication, restlessness, disturbed concentration, impaired memory, visual hallucinations, gait disturbance, and general myoclonic jerks in her limbs and trunk; she had marked grasp reflexes. After withdrawal of oral amantadine, all of her symptoms and signs gradually improved; about 3 weeks later she was able to walk without aid.

• A 74-year-old woman had a right cerebellar hemorrhage and subsequently developed apathy, depression, and gait disturbance. She was given amantadine hydrochloride 200 mg/day and droxidopa 200 mg/day. Sometime later she began to have visual disturbances followed about a month later by fever, vomiting, and myoclonic jerks in her limbs, and she became unable to stand independently. She could not speak voluntarily and was bound to her wheelchair. She had myoclonic jerks in the limbs and marked grasp reflexes in both hands. Amantadine was withdrawn and her symptoms and signs gradually improved; after about 3 weeks, she was able to walk without aid.

• A 73-year-old woman with Parkinson’s disease and diabetic nephropathy started to take amantadine 300 mg/day and gradually developed somnolence and gait disturbance and became bedridden about 1 week later. Amantadine was withdrawn. Generalized myoclonic jerks appeared and she developed an acute high-grade fever, coma, and status epilepticus. Ashe was given dantrolene sodium without major benefit. She developed severe dementia and moderate parkinsonism. She had bilateral grasp reflexes, a mild left hemiparesis due to lacunar infarction in the right corona radiata, multiple cerebral infarctions in the right frontoparietal and occipital lobes, and multiple confluent white matter changes. Oral levodopa 450 mg/day and pramipexole 0.25 mg/day improved her parkinsonism, but her daily living skills did not improve.

Renal impairment may have contributed to amantadine toxicity in at least two of these cases.

Insomnia is common with amantadine [ ].

Myoclonus, especially vocal, can occur [ ].

• 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 [ ]. 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.

This is the first description of peripheral neuropathy in these circumstances, but it suggests that chronic livedo reticularis may be a forerunner of more severe problems.

Three Japanese women aged 78–87 years who had taken amantadine 100–200 mg/day for 1 month to 5 years, in two cases together with co-careldopa, developed multifocal myoclonus and two were confused [ ]. Amantadine concentrations were high in the two patients in whom they were measured, at over 3000 ng/ml; a concentration over 1000 ng/ml is regarded as toxic. Amantadine was withdrawn and the myoclonus disappeared within 1–2 weeks and did not recur. Cortical myoclonus has also been described with levodopa and bromocriptine, but the mechanism is not known.