Dopaminergics.

Amantadine Hydrochloride - parkinsonism

Amantadine hydrochloride PhEur 100mg.

Brownish-red, hard gelatin capsules imprinted SYMM in white on both cap and body.

Parkinson's disease. Herpes zoster. It is recommended that Symmetrel be given to elderly or debilitated patients in whom the physician suspects that a severe and painful rash could occur. Symmetrel can significantly reduce the proportion of patients experiencing pain of long duration.

Parkinson's disease: Initially 100mg daily for the first week, increasing to 100mg twice daily. The dose can be titrated against signs and symptoms. Doses exceeding 200mg daily may provide some additional relief, but may also be associated with increasing toxicity. A dose of 400mg/day should not be exceeded. The dose should be increased gradually, at intervals of not less than 1 week. Since patients over 65 years of age tend to show lower renal clearance and consequently higher plasma concentrations, the lowest effective dose should be used.

Amantadine acts within a few days, but may appear to lose efficacy within a few months of continuous treatment. Its effectiveness may be prolonged by withdrawal for three to four weeks, which seems to restore activity. During this time, existing concomitant antiparkinsonian therapy should be continued, or low dose L-dopa treatment initiated if clinically necessary.

Symmetrel withdrawal should be gradual, e.g. half the dose at weekly intervals. Abrupt discontinuation may exacerbate Parkinsonism, regardless of the patient's response to therapy. Combined treatment: any antiparkinson drug already in use should be continued during initial Symmetrel treatment. It may then be possible to reduce the other drug gradually. If increased side effects occur, the dosage should be reduced more quickly. In patients receiving large doses of anticholinergic agents or L-dopa, the initial phase of Symmetrel treatment should be extended to 15 days.

Herpes zoster: 100mg twice daily for 14 days. Treatment should be started as soon as possible after diagnosis. If post-herpetic pain persists treatment can be continued for a further 14 days.

In patients with renal impairment: the dose of amantadine should be reduced. This can be achieved by either reducing the total daily dose, or by increasing the dosage interval in accordance with the creatinine clearance. For example,

The above recommendations are for guidance only and physicians should continue to monitor their patients for signs of unwanted effects.

Not recommended.

100 mg daily.

Known hypersensitivity to amantadine or any of the excipients. Individuals subject to convulsions. A history of gastric ulceration. Severe renal disease. Pregnancy.

Symmetrel should be used with caution in patients with confusional or hallucinatory states or underlying psychiatric disorders, in patients with liver or kidney disorders, and those suffering from, or who have a history of, cardiovascular disorders. Caution should be applied when prescribing amantadine with other medications having an effect on the CNS.

Abrupt discontinuation of amantadine may result in worsening of Parkinsonism. Symmetrel should not be stopped abruptly in patients who are treated concurrently with neuroleptics. There have been isolated reports of precipitation or aggravation of neuroleptic malignant syndrome or neuroleptic-induced catatonia following the withdrawal of amantadine in patients taking neuroleptic agents. A similar syndrome has also been reported rarely following withdrawal of amantadine and other anti-parkinson agents in patients who were not taking concurrent psychoactive medication.

As some individuals have attempted suicide with amantadine, prescriptions should be written for the smallest quantity consistent with good patient management.

Peripheral oedema (thought to be due to an alteration in the responsiveness of peripheral vessels) may occur in some patients during chronic treatment (not usually before four weeks) with Symmetrel. This should be taken into account in patients with congestive heart failure.

Concurrent administration of amantadine and anticholinergic agents or levodopa may increase confusion, hallucinations, nightmares, gastro-intestinal disturbances, or other atropine-like side effects. Psychotic reactions have been observed in patients receiving amantadine and levodopa.

In isolated cases, worsening of psychotic symptoms has been reported in patients receiving amantadine and concomitant neuroleptic medication.

Concurrent administration of amantadine and drugs or substances (e.g. alcohol) acting on the CNS may result in additive CNS toxicity. Close observation is recommended.

There have been isolated reports of a suspected interaction between amantadine and combination diuretics (hydrochlorothiazide + potassium sparing diuretics). One or both of the components apparently reduce the clearance of amantadine, leading to higher plasma concentrations and toxic effects (confusion, hallucinations, ataxia, myoclonus).

Amantadine's undesirable effects are often mild and transient, usually appearing within the first 2 to 4 days of treatment and promptly disappearing 24 to 48 hours after discontinuation. A direct relationship between dose and incidence of side effects has not been demonstrated, although there seems to be a tendency towards more frequent undesirable effects (particularly affecting the CNS) with increasing doses.

Side effects reported include:

Frequency estimates: frequent > 10%, occasional 1%-10%, rare 0.001%-1%, isolated cases < 0.001%.

Central nervous system: Occasional: anxiety, elevation of mood, lightheadedness, headache, lethargy, hallucinations, nightmares, ataxia, slurred speech, blurred vision, loss of concentration, nervousness, depression, insomnia, myalgia. Hallucinations, confusion and nightmares are more common when amantadine is administered concurrently with anticholinergic agents or when the patient has an underlying psychiatric disorder. Rare: confusion, disorientation, psychosis, tremor, dyskinesia, convulsions, neuroleptic malignant-like syndrome. Delirium, hypomanic state and mania have been reported but their incidence cannot be readily deduced from the literature. Cardiovascular system: Frequent: oedema of ankles, livedo reticularis (usually after very high doses or use over many months). Occasional: palpitations, orthostatic hypotension. Isolated cases: heart insufficiency/failure. Blood: Isolated cases: leucopenia, reversible elevation of liver enzymes. Gastrointestinal tract: Occasional: dry mouth, anorexia, nausea, vomiting, constipation. Rare: diarrhoea. Skin and appendages: Occasional: diaphoresis. Rare: exanthema. Isolated cases: photosensitisation. Sense organs: Rare: corneal lesions, e.g. punctate subepithelial opacities which might be associated with superficial punctate keratitis, corneal epithelial oedema, and markedly reduced visual acuity. Urogenital tract: Rare: urinary retention, urinary incontinence.

Alliance Pharmaceuticals

(POM)

29 June 2009