MEMANTINE HYDROCHLORIDE

Treatment should be initiated and supervised by a physician experienced in the diagnosis and treatment of Alzheimer's dementia. Posology Therapy should only be started if a caregiver is available who will regularly monitor the intake of the medicinal product by the patient.

Diagnosis should be made according to current guidelines. The tolerance and dosing of memantine should be reassessed on a regular basis, preferably within three months after start of treatment. Thereafter, the clinical benefit of memantine and the patient’s tolerance of treatment should be reassessed on a regular basis according to current clinical guidelines.

Maintenance treatment can be continued for as long as a therapeutic benefit is favourable and the patient tolerates treatment with memantine. Discontinuation of memantine should be considered when evidence of a therapeutic effect is no longer present or if the patient does not tolerate treatment.

Adults Dose titration The maximum daily dose is 20 mg daily. 5 ml solution (5 mg) equivalent to one pump actuation, per day for 7 days.

Week 2 (day 8 14):

The patient should take 1 ml solution (10 mg) equivalent to two pump actuations, per day for 7 days. 5 ml solution (15 mg) equivalent to three pump actuations per day for 7 days.

From Week 4 on:

The patient should take 2 ml solution (20 mg) equivalent to four pump actuations, once a day. 5 ml solution (5 mg) for 7 days.

Week 2 (day 8 14):

The patient should take 1 ml solution (10 mg) for 7 days. 5 ml solution (15 mg) for 7 days.

From Week 4 on:

The patient should take 2 ml solution (20 mg) once a day. Maintenance dose The recommended maintenance dose is 20 mg per day. Elderly On the basis of the clinical studies, the recommended dose for patients over the age of 65 years is 20 mg per day (2 ml solution, equivalent to four pump actuations) as described above.

Renal impairment In patients with mildly impaired renal function (creatinine clearance 50 – 80 ml/min) no dosage adjustment is required. In patients with moderate renal impairment (creatinine clearance 30 - 49 ml/min) daily dose should be 10 mg (1 ml solution, equivalent to two pump actuations).

If tolerated well after at least 7 days of treatment, the dose could be increased up to 20 mg/day according to standard titration scheme. In patients with severe renal impairment (creatinine clearance 5 – 29 ml/min) daily dose should be 10 mg (1 ml solution, equivalent to two pump actuations) per day.

Hepatic impairment In patients with mild or moderate hepatic impaired function (Child-Pugh A and Child-Pugh B) no dosage adjustment is needed. No data on the use of memantine in patients with severe hepatic impairment are available.

Administration of this medicinal product is not recommended in patients with severe hepatic impairment. Paediatric population This medicinal product is not recommended for use in children below 18 years due to a lack of data on safety and efficacy.

Method of administration This medicinal product should be taken once daily at the same time each day. The solution can be taken with or without food. The solution must not be poured, pumped or pipetted into the mouth directly from the bottle, pump or pipette, but should be dosed onto a spoon or into a glass of water using the pump or pipette.

6.

Summary of the safety profile In clinical trials in mild to severe dementia, involving 1,784 patients treated with this memantine hydrochloride and 1,595 patients treated with placebo, the overall incidence rate of adverse reactions with this memantine hydrochloride did not differ from those with placebo; the adverse reactions were usually mild to moderate in severity.

8%). Tabulated list of adverse reactions The following Adverse Drug Reactions listed in the Table below have been accumulated in clinical studies with this memantine hydrochloride and since its introduction in the market. Adverse reactions are ranked according to system organ class, 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).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. System Organ Class Frequency Adverse Reaction Infections and infestations Uncommon Fungal Infections Immune system disorders Common Drug Hypersensitivity Psychiatric disorders Common Somnolence Uncommon Confusion Uncommon Hallucinations1 Not known Psychotic reactions2 Common Dizziness, balance disorders Uncommon Gait abnormal Nervous system disorders Very Rare Seizures Cardiac disorders Uncommon Cardiac Failure Vascular disorders Common Hypertension Uncommon Venous thrombosis/thromboemb olism Respiratory, thoracic and mediastinal disorders Common Dyspnoea Common Constipation Uncommon Vomiting Gastrointestinal disorders Not known Pancreatitis2 Common Elevated Liver Function Test Hepatobiliary disorders Not known Hepatitis Common HeadacheGeneral disorders and administration site conditions Uncommon Fatigue 1 Hallucinations have mainly been observed in patients with severe Alzheimer's disease.

2 Isolated cases reported in post-marketing experience. Alzheimer's disease has been associated with depression, suicidal ideation and suicide. In post-marketing experience these reactions have been reported in patients treated with this medicinal product.

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 the Yellow Card Scheme.

uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store

4. 1. 3 PHARMACEUTICAL FORM Oral Solution. 1 Therapeutic indications Treatment of patients with moderate to severe Alzheimer’s disease. 2 Posology and method of administration Treatment should be initiated and supervised by a physician experienced in the diagnosis and treatment of Alzheimer's dementia.

Posology Therapy should only be started if a caregiver is available who will regularly monitor the intake of the medicinal product by the patient. Diagnosis should be made according to current guidelines. The tolerance and dosing of memantine should be reassessed on a regular basis, preferably within three months after start of treatment.

Thereafter, the clinical benefit of memantine and the patient’s tolerance of treatment should be reassessed on a regular basis according to current clinical guidelines. Maintenance treatment can be continued for as long as a therapeutic benefit is favourable and the patient tolerates treatment with memantine.

Discontinuation of memantine should be considered when evidence of a therapeutic effect is no longer present or if the patient does not tolerate treatment. Adults Dose titration The maximum daily dose is 20 mg daily. 5 ml solution (5 mg) equivalent to one pump actuation, per day for 7 days.

Week 2 (day 8 14):

The patient should take 1 ml solution (10 mg) equivalent to two pump actuations, per day for 7 days. 5 ml solution (15 mg) equivalent to three pump actuations per day for 7 days.

From Week 4 on:

The patient should take 2 ml solution (20 mg) equivalent to four pump actuations, once a day. 5 ml solution (5 mg) for 7 days.

Week 2 (day 8 14):

The patient should take 1 ml solution (10 mg) for 7 days. 5 ml solution (15 mg) for 7 days.

From Week 4 on:

The patient should take 2 ml solution (20 mg) once a day. Maintenance dose The recommended maintenance dose is 20 mg per day. Elderly On the basis of the clinical studies, the recommended dose for patients over the age of 65 years is 20 mg per day (2 ml solution, equivalent to four pump actuations) as described above.

Renal impairment In patients with mildly impaired renal function (creatinine clearance 50 – 80 ml/min) no dosage adjustment is required. In patients with moderate renal impairment (creatinine clearance 30 - 49 ml/min) daily dose should be 10 mg (1 ml solution, equivalent to two pump actuations).

If tolerated well after at least 7 days of treatment, the dose could be increased up to 20 mg/day according to standard titration scheme. In patients with severe renal impairment (creatinine clearance 5 – 29 ml/min) daily dose should be 10 mg (1 ml solution, equivalent to two pump actuations) per day.

Hepatic impairment In patients with mild or moderate hepatic impaired function (Child-Pugh A and Child-Pugh B) no dosage adjustment is needed. No data on the use of memantine in patients with severe hepatic impairment are available.

Administration of this medicinal product is not recommended in patients with severe hepatic impairment. Paediatric population This medicinal product is not recommended for use in children below 18 years due to a lack of data on safety and efficacy.

Method of administration This medicinal product should be taken once daily at the same time each day. The solution can be taken with or without food. The solution must not be poured, pumped or pipetted into the mouth directly from the bottle, pump or pipette, but should be dosed onto a spoon or into a glass of water using the pump or pipette.

6. 1. 4 Special warnings and precautions for use Caution is recommended in patients with epilepsy, former history of convulsions or patients with predisposing factors for epilepsy. Concomitant use of N-methyl-D-aspartate (NMDA)-antagonists such as amantadine, ketamine or dextromethorphan should be avoided.

5). 2 “Elimination”) may necessitate careful monitoring of the patient. g. from a carnivore to a vegetarian diet, or a massive ingestion of alkalising gastric buffers. Also, urine pH may be elevated by states of renal tubulary acidosis (RTA) or severe infections of the urinary tract with Proteus bacteria.

In most clinical trials, patients with recent myocardial infarction, uncompensated congestive heart failure (NYHA III-IV), or uncontrolled hypertension were excluded. As a consequence, only limited data are available and patients with these conditions should be closely supervised.

Excipients:

This medicine contains 100mg sorbitol (E420) in each millilitre of solution. If your doctor has told you that you (or the person being treated) have an intolerance to some sugars or if you have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which a person cannot break down fructose, talk to your doctor before you take or receive this medicine.

This medicine contains potassium, less than 1 mmol (39 mg) per millilitre, that is to say essentially ‘potassium-free’.

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