AMANTADINE HYDROCHLORIDE

Posology Parkinson's disease:

Initially 100 mg daily for the first week, increasing to 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. 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, “Special warnings and precautions for use”). 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: 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. 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 Amantadine contra-indicated. 15 – 35 100 mg every 2 to 3 days.

> 35 100 mg every day 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.

Summary of the safety profile 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.

Tabulated list of adverse reactions The following list of adverse reactions is based on clinical trial experience and/or postmarketing use via spontaneous case reports and literature cases. The frequency of adverse reactions reported during post-marketing use cannot be determined as they are derived from spontaneous reports.

Consequently, the frequency of these adverse events is qualified as “not known”. Undesirable effects are listed by MedDRA System Organ Classes. Within each system organ class, ADRs are presented in order of decreasing seriousness.

Assessment of undesirable effects is based on the following frequency groupings:

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. 4), visual acuity reduced Very common oedema peripheral Common palpitations Cardiac disorders Very rare cardiac failure Vascular disorders Common orthostatic hypotension Common dry mouth, decreased appetite, nausea, vomiting, constipation Gastrointestinal disorders Rare diarrhoea Very common livedo reticularis* Common hyperhidrosis Rare rash Skin and subcutaneous tissue disorders Very rare photosensitivity reaction Musculoskeletal and connective tissue disorders Common myalgia System Organ Class Adverse Drug Reactions Renal and urinary disorders Rare urinary retention, urinary incontinence Investigations Very rare hepatic enzyme increased *See section ‘Description of selected adverse reactions’ Description of selected adverse reactions Nightmares are more common when amantadine is administered concurrently with anticholinergic agents or when the patient has an underlying psychiatric disorder.

4 Special warnings and precautions for use). Corneal lesions such as punctate subepithelial opacities which might be associated with superficial punctate keratitis. Livedo reticularis can develop usually after very high doses or use over many months.

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, Interactions with other medicaments and other forms of interaction). 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.

Some individuals have attempted suicide and 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. 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, increased 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. Patients with rare hereditary problems of galactose intolerance, the total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

1. Individuals subject to convulsions. A history of gastric ulceration. Severe renal disease. Pregnancy.