TRILASYM

Influenza A Treatment:

When treating influenza, the treatment should start as early as possible and to continue for 4 to 5 days. When amantadine is started within 48 hours of symptoms appearing, the duration of fever and other effects is reduced by one or two days and the inflammatory reaction of the bronchial tree that usually accompanies influenza resolves more quickly.

Prophylaxis:

Treat daily while the protection from infection is required. In most of the cases this is expected to be for 6 weeks. When used with inactivated influenza A vaccine, amantadine is continued for 2 to 3 weeks following inoculation. Adults: 10 m l (100 mg) daily for the recommended period.

Children aged 10-15 years: 10 m l (100 mg) daily for the recommended period.

Children under 10 years of age:

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

Adults over 65 years of age:

A daily dose of less than 10 m l (100 mg), or 10 ml (100 mg) given at intervals of greater than one day, may be appropriate, dependent on the renal function. Plasma amantadine concentrations are influenced by renal function. In elderly patients, the elimination half-life is longer and renal clearance of the compound is diminished in comparison to young people.

Parkinson's disease Initially 10 ml (100 mg) daily for the first week, increasing to 10 ml (100 mg) twice daily. The dose can be titrated against signs and symptoms. Doses exceeding 200 mg daily may provide some additional relief, but may also be associated with increasing toxicity.

A dose of 400 mg/day should not be exceeded. The dose should be increased gradually, at intervals of not less than 1 week.

Adults over 65 years of age:

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. Trilasym 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.

g. half the dose at weekly intervals. 4).

Combined treatment:

Any antiparkinson drug already in use should be continued during initial amantadine 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 amantadine treatment should be extended to 15 days.

Herpes zoster 10 ml (100 mg) 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. Special populations Renal impairment 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, Creatinine clearance ml/(min) Dose < 15 Trilasym contraindicated 15 – 35 10 ml (100 mg) every 2 to 3 days > 35 10 ml (100 mg) every day The above recommendations are for guidance only and physicians should continue to monitor their patients for signs of unwanted effects.

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. g. punctate subepithelial opacities which might be associated with superficial punctate keratitis, corneal epithelial oedema, and markedly reduced visual acuity Very common oedema peripheral, livedo reticularis3 Common palpitations, orthostatic hypotension Cardiac disorders Very rare cardiac insufficiency/failure Common dry mouth, decreased appetite, nausea, vomiting, constipationGastrointestinal disorders Rare diarrhoea Common Hyperhidrosis Rare rash Skin and subcutaneous tissue disorders 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). The frequency cannot be established. 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. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store

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.

5). 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.

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.

1 • Individuals subject to convulsions • A history of gastric ulceration • Severe renal disease • Pregnancy and breast-feeding