Amantadine

Amantadine was first developed as an antiviral, but its value in Parkinson's disease lies in its effect on dopamine: it appears to increase the release of this messenger in the brain and slow its reuptake, and it also has a mild blocking action on NMDA receptors. The result can be some easing of stiffness, slowness and tremor. In the UK, the SmPC for the 100 mg capsules names Parkinson's disease as the indication, and the medicine is often used alongside levodopa rather than on its own.

Each capsule contains 100 mg of amantadine hydrochloride, and pack sizes run from 30 up to 360 capsules. They are an imported generic, and this brand is not licensed in the UK. Medicines with a UK licence include generic 100 mg capsules from several manufacturers and a 50 mg/5 ml oral solution. Every one of them is a POM, so a prescription is required.

The SmPC recommends 100 mg once a day for the first week, then 100 mg twice daily, with any further changes made at least a week apart. Up to 400 mg a day may be used, although doses above 200 mg add to the risk of toxicity. People over 65 usually need the lowest effective amount because their kidneys clear the medicine more slowly. With creatinine clearance of 15 to 35 ml/min the dose is 100 mg every two to three days, and below 15 ml/min it should not be used. If a patient already takes high doses of levodopa or anticholinergics, the starting phase can be stretched to 15 days. Coming off treatment abruptly can make parkinsonism much worse or trigger a reaction resembling neuroleptic malignant syndrome, so the dose is reduced gradually, for instance halved each week.

Amantadine capsules are contraindicated in people who have had convulsions, a history of stomach ulcer, severe kidney disease, or an allergy to the ingredients, and in pregnancy. Breastfeeding is not advised. Caution is needed with confusion or hallucinations, psychiatric illness, heart failure and liver or kidney problems. Blurred vision should prompt an eye check, as corneal oedema has been reported. Impulse control problems such as compulsive gambling, spending or eating, or increased sex drive, can occur and should be raised with the specialist.

Taking amantadine with anticholinergics or levodopa may bring on confusion, nightmares, hallucinations and stomach upset. Antipsychotics have occasionally been linked to worsening psychosis. Alcohol and other sedating medicines can add to effects on the brain. Diuretic combinations containing hydrochlorothiazide with a potassium-sparing agent may reduce clearance and lead to toxicity.

Swollen ankles and livedo reticularis, a purplish net-like pattern on the skin, are very common, particularly with long-term use. Common effects include dry mouth, nausea, constipation, loss of appetite, dizziness on standing, palpitations, headache, sleeplessness, anxiety, low mood, sweating and muscle aches. Amantadine can cause dizziness or blurred vision, so driving needs care. Any change to treatment is a decision for the prescribing specialist or GP.