Symmetrel Capsules Ref.[2494] Active ingredients: Amantadine

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 (See section 4.5, Interactions with other medicaments and other forms of interaction).

Abrupt discontinuation of amantadine may result in worsening of Parkinsonism or in symptoms resembling neuroleptic malignant syndrome (NMS), as well as in cognitive manifestations (e.g. catatonia, confusion, disorientation, worsening of mental status, delirium). 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.

Amantadine has anticholinergic effects, it should not be given to patients with untreated angle closure glaucoma.

Concurrent administration of amantadine and anticholinergic agents or levodopa may increase confusion, hallucinations, nightmares, gastro-intestinal disturbances, or other atropine-like side effects (see Section 4.9 “Overdose”). 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 (see Section 4.9 “Overdose”).

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-related complications during pregnancy have been reported. Symmetrel is contra-indicated during pregnancy and in women trying to become pregnant. Amantadine passes into breast milk. Undesirable effects have been reported in breast-fed infants.

Nursing mothers should not take Symmetrel.

Patients should be warned of the potential hazards of driving or operating machinery if they experience side effects such as dizziness or blurred vision.

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.

Adverse reactions (Table 1) are ranked under heading of frequency, the most frequent first, using the following convention: very common (greater than or equal to 1 in 10); common (less than or equal to 1 in 100, less than 1 in 10); uncommon (greater than or equal to 1 in 1,000, less than 1 in 100); rare (greater than or less than 1 in 10,000, less than 1 in 1,000) very rare (less than 1 in 10,000), not known (where no valid estimate of the incidence has been derived).

NB: The incidence and severity of some of the adverse reactions, noted below, varies according to the dosage and nature of the disease under treatment.

Table 1:

Blood and lymphatic system disorders

Very rare: leucopenia, reversible elevation of liver enzymes

Nervous system disorders

Common: anxiety, elevation of mood, lightheadedness, headache, lethargy, hallucinations, nightmares, ataxia, slurred speech, blurred vision, loss of concentration, nervousness, depression, insomnia, myalgia. Hallucinations, confusion and nightmares¹

Uncommon: confusion, disorientation, psychosis, tremor, dyskinesia, convulsions, neuroleptic malignant-like syndrome

Not known: Delirium, hypomanic state and mania²

Eye disorders

Rare: corneal lesions, e.g. punctate subepithelial opacities which might be associated with superficial punctate keratitis, corneal epithelial oedema, and markedly reduced visual acuity

Cardiac disorders

Very common: oedema of ankles, livedo reticularis³

Common: palpitations, orthostatic hypotension

Very rare: heart insufficiency/failure

Gastrointestinal disorders

Common: dry mouth, anorexia, nausea, vomiting, constipation

Rare: diarrhoea

Skin and subcutaneous tissue disorders

Common: diaphoresis

Rare: exanthema

Very rare: photosensitisation

Renal and urinary disorders

Rare: urinary retention, urinary incontinence

1 more common when amantadine is administered concurrently with anticholinergic agents or when the patient has an underlying psychiatric disorder.
2 reported but their incidence cannot be readily deduced from the literature.
3 usually after very high doses or use over many months.

None known.