AMANTADINE HYDROCHLORIDE

Posology Parkinson's disease Initial dose: 10 ml (100 mg) daily after a meal, preferably in the morning. Maintenance dose: 10 ml (100 mg) twice daily after meals. The interval between the initial dose and the maintenance dose should be at least 7 days.

In individual cases, the dose can be increased further depending on the clinical picture. It is recommended that this should be done gradually with intervals of at least 1 week. The maximum dose of 40 ml (400 mg)/day should not be exceeded.

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

Combination treatment:

If Amantadine Oral Solution is added to existing treatment for Parkinson, it should be commenced at the lowest possible dose and the dosage should then be titrated slowly and carefully. Special populations Paediatric population This medicine is not indicated for use in paediatric population.

The safety and efficacy of this product in children aged below 10 years has not been established. No data are available.

Elderly (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. If the patient has a renal function disorder, the dosing interval should be adapted (see ‘Renal impairment’ below).

Renal impairment In patients with renal impairment, the clearance is significantly reduced, which results in elevated plasma concentrations of amantadine. The dosage should be carefully adjusted for these patients by extending the dosing interval depending on the creatinine clearance (see Table 1), after a loading dose on day 1 of the treatment.

When Parkinson’s disease is diagnosed in a patient who already has impaired renal function (with or without haemodialysis), treatment should be started with a loading dose of 10 ml (100 mg)/day on day 1 of the treatment. After the initial dose, the dosing interval should be monitored immediately, depending on the creatinine clearance (see Table 1).

If impaired renal function is diagnosed in patients with Parkinson’s disease who are already being treated with the maintenance dose of Amantadine Oral solution (100 mg twice daily), switching immediately to the dosing interval based on the creatinine clearance (see Table 1) is possible without any loading dose.

Table 1. 73 m²) Dosing interval 10ml (100 mg) < 15 7 days 15-25 3 days 25-35 2 days 35-75 1 day > 75 12 hours The above recommendations are for guidance only and physicians should continue to monitor their patients for signs of unwanted effects.

Method of administration This medicine should be taken orally after a meal.

Amantadine's undesirable effects are often mild and transient, usually appearing within the first 2 to 4 days of treatment and often disappearing within 24 to 48 hours after discontinuation of amantadine. A direct relationship between the dosage and the incidence of side effects has not been demonstrated, although there seems to be a tendency towards more frequent undesirable effects (particularly affecting the central nervous system) 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, < 1/10); uncommon (> 1/1,000, < 1/100); rare (> 1/10,000, < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data).

The side effects are shown within each frequency group in decreasing order of severity. 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 subepthelial opacities which might be associated with superficial punctate keratitis, corneal epithelial oedema, and markedly reduced visual acuity. Cardiac disorders oedema of ankles, livedo reticularis3 palpitations, orthostatic hypotension heart insufficiency/fai lure Gastrointestinal disorders dry mouth, decreased appetite, nausea, vomiting, constipation diarrhoea Skin and subcutaneous tissue disorders hyperhidrosis rash photosensitivity reaction Renal and urinary disorders urinary retention, urinary incontinence Psychiatric disorders Impulse control disorders4 General disorders and administration site conditions Peripheral edema hepatic enzyme increased (reversible) Hypotherm ia 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). 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.

There have been reports that patients with pre-existing epilepsy with seizures may develop an increased frequency of severe motor seizures during treatment with amantadine. Reducing the dose can minimise this risk. Such patients should be monitored carefully.

Amantadine is contraindicated for refractory epilepsy. An electrocardiographic control should be performed to detect a possible prolongation of the QT interval. 8). Because Amantadine oral solution does not completely inhibit the host’s immune response to an influenza A infection, people who use this medicinal product may still develop immune responses to the natural illness or vaccination later on and may be protected if they are exposed to antigen-related viruses at a later date.

Special care is needed in patients who are suffering from or who have suffered from recurrent eczema or cardiovascular conditions. This medicine should be used with caution in patients with hepatic or renal function disorders. Where renal function is reduced, the dose should be adjusted correspondingly and the amantadine plasma concentrations should ideally be monitored.

9). Caution is required in patients with hypotension and dopamine-related endocrine disorders. Exacerbation of hallucinations, confusion and nightmares can occur. Amantadine should be given with caution in these cases. Hallucinations, confusion and nightmares occur more often when amantadine is administered together with anticholinergic agents or if the patient has an underlying psychiatric disorder.

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. g. 2 (Withdrawal). Amantadine oral solution 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.

Attempted suicide Given the severity of the side effects of overdoses, caution should be exercised when prescribing this medicine to patients with an elevated risk of suicidal behaviour. 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.

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

Dose reduction or tapered discontinuation should be considered if such symptoms develop. 8). 1). This one parahydroxybenzoates can cause allergic reactions (possibly delayed). This medicine also contains sorbitol. Patients with rare hereditary disorders such as fructose intolerance must not use this medicinal product.

2 g sorbitol in each ml dose. This medicine contains 8 mg propylene glycol in each ml dose.

5) - Patients with electrolyte disorders (hypokalemia, hypomagnesemia) - Gastric ulceration - Individuals subject to uncontrolled convulsions - Psychosis - Untreated angle closure glaucoma.