TRILASYM Oral solution Ref.[8673] Active ingredients: Amantadine

Trilasym should be used with caution in:

• patients with confusional or hallucinatory states or underlying psychiatric disorders
• patients with liver or kidney disorders
• patients suffering from, or who have a history of, cardiovascular disorders.
• when prescribing Trilasym with other medications having an effect on the CNS (see section 4.5).

Abrupt discontinuation

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).

Trilasym 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.

Resistance

Resistance to amantadine occurs during serial passage of influenza virus strains in vitro or in vivo in the presence of the drug. Apparent transmission of drug-resistant viruses may have been the cause of failure of prophylaxis and treatment in household contacts and in nursing-home patients.

However, there is no evidence to date that the resistant virus produces a disease that is in any way different from that produced by sensitive viruses.

Attempted suicide

The smallest quantity consistent with good patient management should be prescribed, as there have been cases of attempted suicide with amantadine

Peripheral oedema/Glaucoma

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 4 weeks) with amantadine. This should be taken into account in patients with congestive heart failure. Trilasym has anticholinergic effects, it should not be given to patients with untreated angle closure glaucoma.

If blurred vision or other visual problems occur an ophthalmologist should be contacted to exclude corneal oedema. In case that corneal oedema is diagnosed treatment with amantadine should be discontinued.

Paediatric population

This medicine should not be used in children under the age of 3 years old.

Hypothermia- Hypothermia has been observed in children, especially in those younger than 5 years of age. Caution is advised when prescribing amantadine to children for the prevention and treatment of influenza type A virus (see also section 4.2).

Impulse control disorders

Patients should be regularly monitored for the development of impulse control disorders. Patients and carers should be made aware that behavioural symptoms of impulse control disorders, including pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with products with a dopaminergic effect, including Trilasym. Dose reduction or tapered discontinuation should be considered if such symptoms develop.

This medicinal product contains Benzyl alcohol, which has been linked with the risk of severe side effects including breathing problems (called “gasping syndrome”) in young children.

Anticholinergic agents or levodopa

Concurrent administration 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.

Drugs or substances acting on the CNS (e.g. alcohol)

Concomitant use may result in additive CNS toxicity. Close observation is recommended (see section 4.9).

Combination diuretics (hydrochlorothiazide + potassium sparing diuretics)

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).

Pregnancy

Amantadine-related complications during pregnancy have been reported. Trilasym is contraindicated during pregnancy and in women trying to become pregnant.

Breastfeeding

Trilasym is excreted in human milk. Undesirable effects have been reported in breastfed infants. Trilasym should not be used during breast-feeding.

Fertility

There are insufficient data to adequately assess effects on the reproductive system.

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.

The side effects reported after the pivotal clinical studies in influenza in over 1200 patients receiving amantadine at 100mg daily were mostly mild, transient, and equivalent to placebo. Only 7% of subjects reported adverse events, many being similar to the effects of influenza itself. The most commonly reported effects were gastro-intestinal disturbances (anorexia, nausea), CNS effects (loss of concentration, dizziness, agitation, nervousness, depression, insomnia, fatigue, weakness), or myalgia.

Adverse reactions (Table 1) are ranked under heading of frequency, the most frequent first, using the following convention: very common (≥1/10); common (≥1/100 to ≤1/10); uncommon (≥1/1,000 to ≤1/100); rare (≥1/10,000 to ≤1/1,000) very rare (≤1/10,000), not known (cannot be estimated from the available data).

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: leukopenia, hepatic enzyme increased (reversible)

Psychiatric disorders

Not known: Impulse control disorders⁵

Nervous system disorders

Common: anxiety, euphoric mood, dizziness, headache, lethargy, hallucination, nightmare, ataxia, dysarthria, vision blurred, disturbance in attention, nervousness, depression, insomnia, myalgia, confusional state¹

Rare: confusion, disorientation, psychotic disorder, tremor, dyskinesia, seizure, neuroleptic malignant syndrome

Not known: delirium, hypomania and mania²

Eye disorders

Uncommon: blurred vision

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 peripheral, livedo reticularis³

Common: palpitations, orthostatic hypotension

Very rare: cardiac insufficiency/failure

Gastrointestinal disorders

Common: dry mouth, decreased appetite, nausea, vomiting, constipation

Rare: diarrhoea

Skin and subcutaneous tissue disorders

Common: Hyperhidrosis

Rare: rash

Very rare: photosensitivity reaction

Renal and urinary disorders

Rare: urinary retention, urinary incontinence

General disorders and administration site conditions

Not known: hypothermia⁴

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.
⁴ In post-marketing exposure hypothermia has been reported in children mainly those younger than 5 years of age (see also section 4.4). The frequency cannot be established.
⁵ Pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with products with a dopaminergic effect, including Trilasym (see section 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

None known.