AMANTADINE HYDROCHLORIDE

Posology 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.

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 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.

Infection caused by Influenza A virus Treatment:

It is advisable to start treating influenza 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 for as long as protection from infection is required. In most instances 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: 100mg daily for the recommended period.

Paediatric population with infection caused by Influenza A virus Children aged 10-15 years: 100mg daily for the recommended period.

Children under 10 years of age:

Dosage not established. Special populations Elderly patients over 65 years of age with infection caused by Influenza A virus 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.

A daily dose of less than 100mg, or 100mg given at intervals of greater than one day, may be appropriate. Renal Impairment in Parkinson’s disease, herpes zoster and infection caused by Influenza A virus 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 Amantadine contraindicated 15-35 100mg every 2-3 days >35 100mg daily The above recommendations are for guidance only and physicians should continue to monitor their patients for signs of unwanted effects.

Method of administration For oral administration

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. The following undesired events, listed by MedDRA system organ class, have been reported.

The following definitions of frequencies are used:

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.

4), visual acuity reduced Cardiac disorders Very common Oedema peripheral Common Palpitations Very Rare Cardiac failure Vascular disorders Common Orthostatic hypotension Common Dry mouth, decreased appetite, nausea, vomiting, constipation Gastrointestinal disorders Rare Diarrhoea System Organ Class Frequency Undesirable effect Very common Livedo reticularis3 Common Hyperhidrosis Rare Rash Skin and subcutaneous tissue disorders Very Rare Photosensitivity reaction Musculoskeletal and connective tissue disorders Common Myalgia Renal and urinary disorders Rare Urinary retention, urinary incontinence General disorders Not known Hypothermia4 Investigations Very rare Hepatic enzyme increased 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). 6 Corneal lesions such as punctate subepithelial opacities which might be associated with superficial punctate keratitis 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.

Amantadine 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.

5). g. catatonia, confusion, disorientation, worsening of mental status, delirium). Amantadine 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 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.

Cases of suicidal ideation and behaviour have been reported during treatment with amantadine. Patients should be monitored for signs of suicidal ideation and behaviour and treatment initiated as needed. Patients (and caregivers of patients) should be advised to seek medical advice if any signs of suicidal ideation or behaviour emerge.

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 Amantadine.

This should be taken into account in patients with congestive heart failure. Anticholinergic effects Amantadine 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. 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, increase libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with products with a dopaminergic effect, including amantadine.

Dose reduction or tapered discontinuation should be considered if such symptoms develop. Paediatric population Hypothermia has been observed in children, especially in those younger than 5 years of age. 2). Excipient warnings This medicinal product contains lactose monohydrate.

Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take this medicine.

1 • Individuals subject to convulsions • History of gastric ulceration • Severe renal disease • Pregnancy