Source: European Medicines Agency (EU) Revision Year: 2021 Publisher: Merz Pharmaceuticals GmbH, Eckenheimer Landstr. 100, D-60318 Frankfurt/Main, Germany
Treatment of patients with moderate to severe Alzheimer’s disease.
Treatment should be initiated and supervised by a physician experienced in the diagnosis and treatment of Alzheimer’s dementia.
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.
Dose titration:
The maximum daily dose is 20 mg per day. In order to reduce the risk of undesirable effects the maintenance dose is achieved by upward titration of 5 mg per week over the first 3 weeks as follows:
Week 1 (day 1-7): The patient should take half a 10 mg film-coated tablet (5 mg) per day for 7 days.
Week 2 (day 8-14): The patient should take one 10 mg film-coated tablet (10 mg) per day for 7 days.
Week 3 (day 15-21): The patient should take one and a half 10 mg film-coated tablet (15 mg) per day for 7 days.
From Week 4 on: The patient should take two 10 mg film-coated tablets (20 mg) per day.
Maintenance dose:
The recommended maintenance dose is 20 mg per day.
On the basis of the clinical studies, the recommended dose for patients over the age of 65 years is 20 mg per day (two 10 mg tablets once a day) as described above.
Dose titration:
The recommended starting dose is 5 mg per day which is stepwise increased over the first 4 weeks of treatment reaching the recommended maintenance dose as follows:
Week 1 (day 1-7): The patient should take one 5 mg film-coated tablet per day (white to off-white, oval-oblong) for 7 days.
Week 2 (day 8-14): The patient should take one 10 mg film-coated tablet per day (pale yellow to yellow, oval shaped) for 7 days.
Week 3 (day 15-21): The patient should take one 15 mg film-coated tablet per day (grey-orange, oval-oblong) for 7 days.
Week 4 (day 22-28): The patient should take one 20 mg film-coated tablet per day (grey-red, oval-oblong) for 7 days.
Maintenance dose:
The recommended maintenance dose is 20 mg per day.
On the basis of the clinical studies, the recommended dose for patients over the age of 65 years is 20 mg per day (20 mg once a day) as described above.
Dose titration:
The maximum daily dose is 20 mg per day. In order to reduce the risk of undesirable effects the maintenance dose is achieved by upward titration of 5 mg per week over the first 3 weeks as follows.
For up-titration other tablet strengths are available.
Week 1 (day 1-7): The patient should take one 5 mg film-coated tablet per day for 7 days.
Week 2 (day 8-14): The patient should take one 10 mg film-coated tablet per day for 7 days.
Week 3 (day 15-21): The patient should take one 15 mg film-coated tablet per day for 7 days.
From Week 4 on: The patient should take one 20 mg film-coated tablet per day.
Maintenance dose:
The recommended maintenance dose is 20 mg per day.
On the basis of the clinical studies, the recommended dose for patients over the age of 65 years is 20 mg per day as described above.
In patients with mildly impaired renal function (creatinine clearance 50-80 ml/min) no dose adjustment is required. In patients with moderate renal impairment (creatinine clearance 30-49 ml/min) daily dose should be 10 mg per day. 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 per day.
In patients with mild or moderate hepatic impaired function (Child-Pugh A and Child-Pugh B) no dose adjustment is needed. No data on the use of memantine in patients with severe hepatic impairment are available. Administration of Axura is not recommended in patients with severe hepatic impairment.
The safety and efficacy of Axura in children aged below 18 years has not been established. No data are available.
Axura should be administered once a day and should be taken at the same time every day. The film-coated tablets can be taken with or without food.
Only limited experience with overdose is available from clinical studies and post-marketing experience.
Relative large overdoses (200 mg and 105 mg/day for 3 days, respectively) have been associated with either only symptoms of tiredness, weakness and/or diarrhoea or no symptoms. In the overdose cases below 140 mg or unknown dose the patients revealed symptoms from central nervous system (confusion, drowsiness, somnolence, vertigo, agitation, aggression, hallucination, and gait disturbance) and/or gastrointestinal origin (vomiting and diarrhoea).
In the most extreme case of overdose, the patient survived the oral intake of a total of 2000 mg memantine with effects on the central nervous system (coma for 10 days, and later diplopia and agitation). The patient received symptomatic treatment and plasmapheresis. The patient recovered without permanent sequelae.
In another case of a large overdose, the patient also survived and recovered. The patient had received 400 mg memantine orally. The patient experienced central nervous system symptoms such as restlessness, psychosis, visual hallucinations, proconvulsiveness, somnolence, stupor, and unconsciousness.
In the event of overdose, treatment should be symptomatic. No specific antidote for intoxication or overdose is available. Standard clinical procedures to remove active substance material, e.g. gastric lavage, carbo medicinalis (interruption of potential entero-hepatic recirculation), acidification of urine, forced diuresis should be used as appropriate.
In case of signs and symptoms of general central nervous system (CNS) overstimulation, careful symptomatic clinical treatment should be considered.
4 years.
This medicinal product does not require any special storage conditions.
Axura 10 mg film-coated tablets:
Blister packs containing either 7, 10, 14 or 20 tablets per blister strip (Alu/PP). Pack sizes of 14, 28, 30, 42, 50, 56, 98, 100, 112, and multipacks containing 840 (20 × 42), 980 (10 × 98) or 1000 (20 × 50) tablets are presented.
Axura 5 mg+10 mg+15 mg+20 mg film-coated tablets:
Each pack contains 28 film-coated tablets in 4 PVDC/PE/PVC/Al-blister or PP/Al-blisters with 7 filmcoated tablets of 5 mg, 7 film-coated tablets of 10 mg, 7 film-coated tablets of 15 mg and 7 film-coated tablets of 20 mg.
Axura 20 mg film-coated tablets:
Blister packs containing 14 film-coated tablets per PVDC/PE/PVC/Al-blister or PP/Al-blister strip. Pack sizes of 14, 28, 42, 56, 98 or multipacks containing 840 (20 × 42) film-coated tablets are presented.
Not all pack sizes may be marketed.
No special requirements.
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