Memantine Accord

1

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



 2

1. NAME OF THE MEDICINAL PRODUCT 
 
Memantine Accord 10 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 10 mg of memantine hydrochloride equivalent to 8.31 mg 
memantine. 
 
Excipientwith known effect: each film coated tablet contains 183.13 mg lactose (as monohydrate).  
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet. 
White, oblong, coated and scored tablet, debossed with “MT” divided by the score on one side and 
"10" divided by the score on the other side. 
The tablet can be divided into equal doses. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Treatment of patients with moderate to severe Alzheimer's disease. 
 
4.2 Posology and method of administration 
 
Posology 
 
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. 
 
Adults 
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. 



 3

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. 
 
Elderly  
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. 
 
Renal impairment 
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. 
 
Hepatic impairment  
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 Memantine Accord is not recommended in patients with severe hepatic 
impairment. 
 
Children and adolescents 
Memantine Accord is not recommended for use in children below 18 years due to a lack of data on 
safety and efficacy. 
 
Method of administration 
 
Memantine Accord 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. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 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. These compounds act at the same receptor system as 
memantine, and therefore adverse reactions (mainly central nervous system (CNS)-related) may be 
more frequent or more pronounced (see also section 4.5). 
 
Some factors that may raise urine pH (see section 5.2 'Elimination') may necessitate careful 
monitoring of the patient. These factors include drastic changes in diet, e.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 



 4

Memantine Accord contains lactose. Patients with rare hereditary problems of galactose intolerance, 
the Lapp lactase deficiency or glucose-galactosemalabsorption should not take this medicinal product. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Due to the pharmacological effects and the mechanism of action of memantine the following 
interactions may occur: 
 
 The mode of action suggests that the effects of L-dopa, dopaminergic agonists, and 

anticholinergics may be enhanced by concomitant treatment with NMDA-antagonists such as 
memantine. The effects of barbiturates and neuroleptics may be reduced. Concomitant 
administration of memantine with the antispasmodic agents, dantrolene or baclofen, can modify 
their effects and a dose adjustment may be necessary. 

 Concomitant use of memantine and amantadine should be avoided, owing to the risk of 
pharmacotoxic psychosis. Both compounds are chemically related NMDA-antagonists. The 
same may be true for ketamine and dextromethorphan (see also section 4.4). There is one 
published case report on a possible risk also for the combination of memantine and phenytoin. 

 Other active substances such as cimetidine, ranitidine, procainamide, quinidine, quinine and 
nicotine that use the same renal cationic transport system as amantadine may also possibly 
interact with memantine leading to a potential risk of increased plasma levels. 

 There may be a possibility of reduced serum level of hydrochlorothiazide (HCT) when 
memantine is co-administered with HCT or any combination with HCT. 

 In post-marketing experience, isolated cases with international normalized ratio (INR) increases 
have been reported in patients concomitantly treated with warfarin. Although no causal 
relationship has been established, close monitoring of prothrombin time or INR is advisable for 
patients concomitantly treated with oral anticoagulants. 

 
In single-dose pharmacokinetic (PK) studies in young healthy subjects, no relevant active substance-
active substance interaction of memantine with glyburide/metformin or donepezil was observed. 
 
In a clinical study in young healthy subjects, no relevant effect of memantine on the pharmacokinetics 
of galantamine was observed. 
 
Memantine did not inhibit CYP 1A2, 2A6, 2C9, 2D6, 2E1, 3A, flavin containing monooxygenase, 
epoxide hydrolase or sulphation in vitro. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
For memantine, no clinical data on exposed pregnancies are available. Animal studies indicate a 
potential for reducing intrauterine growth at exposure levels, which are identical or slightly higher 
than at human exposure (see section 5.3). The potential risk for humans is unknown. Memantine 
should not be used during pregnancy unless clearly necessary. 
 
Breast-feeding 
 
It is not known whether memantine is excreted in human breast milk but, taking into consideration the 
lipophilicity of the substance, this probably occurs. Women taking memantine should not breast-feed. 
 
Fertility 
 
No adverse effects of memantine were noted on non-clinical male and female fertility studies. 
 
4.7 Effects on ability to drive and use machines 
 



 5

Moderate to severe Alzheimer's disease usually causes impairment of driving performance and 
compromises the ability to use machinery. Furthermore, memantine has minor to moderate 
influenceon the ability to drive and use machines such that outpatients should be warned to take 
special care. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
In clinical trials in mild to severe dementia, involving 1,784 patients treated with memantine and 
1,595 patients treated with placebo, the overall incidence rate of adverse reactions with memantine did 
not differ from those with placebo; the adverse reactions were usually mild to moderate in severity. 
The most frequently occurring adverse reactions with a higher incidence in the memantine group than 
in the placebo group were dizziness (6.3 % vs 5.6 %, respectively), headache (5.2 % vs 3.9 %), 
constipation (4.6 % vs 2.6 %), somnolence (3.4 % vs 2.2 %) and hypertension (4.1 % vs 2.8 %). 
 
The following adverse reactions listed in the table below have been accumulated in clinical studies 
with memantine and since its introduction in the market. Within each frequency grouping, undesirable 
effects are presented in order of decreasing seriousness. 
 
Tabulated list of adverse reactions 
 
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). 
 
System Organ Class Frequency Adverse Reaction 
Infections and infestations Uncommon Fungal infections 
Immune systeme disorders Common Drug hypersensitivity 
Psychiatric disorders Common Somnolence 

Uncommon Confusion 
Uncommon Hallucinations1 
Not known Psychotic reactions2 

Nervous system disorders Common Dizziness 
Common Balance disorders 
Uncommon Gait abnormal 
Very rare Seizures 

Cardiac disorders Uncommon Cardiac failure 
Vascular disorders Common Hypertension 

Uncommon Venous thrombosis/thromboembolism 
Respiratory, thoracic and 
mediastinal disorders 

Common Dyspnoea 

Gastrointestinal disorders Common Constipation 
Uncommon Vomiting 
Not known Pancreatitis2 

Hepatobiliary disorders Common Elevated liver function test 
Not known Hepatitis 

General disorders and 
administration site conditions 

Common Headache 
Uncommon Fatigue 

 
1 Hallucinations have mainly been observed in patients with severe Alzheimer's disease. 
2 Isolated cases reported in post-marketing experience. 
 
Description of selected adverse reactions 
 



 6

Alzheimer's disease has been associated with depression, suicidal ideation and suicide. In post-
marketing experience these events have been reported in patients treated with memantine. 
 
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 national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
Only limited experience with overdose is available from clinical studies and post-marketing 
experience. 
 
Symptoms 
 
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 of gastrointestinal origin (vomiting and diarrhoea). 
 
In the most extreme case of overdose, the patient survived the oral intake of a total of 2,000 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. 
 
Treatment 
 
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, carbomedicinalis (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. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other Anti-dementia drugs, ATC code: N06DX01. 
 
There is increasing evidence that malfunctioning of glutamatergic neurotransmission, in particular at 
NMDA-receptors, contributes to both expression of symptoms and disease progression in 
neurodegenerative dementia. 
 
Memantine is a voltage-dependent, moderate-affinity uncompetitive NMDA-receptor antagonist. It 
modulates the effects of pathologically elevated tonic levels of glutamate that may lead to neuronal 
dysfunction. 



 7

 
Clinical studies 
 
A pivotal monotherapy study in a population of patients suffering from moderate to severe 
Alzheimer's disease (mini mental state examination (MMSE) total scores at baseline of 3-14) included 
a total of 252 outpatients. The study showed beneficial effects of memantine treatment in comparison 
to placebo at 6 months (observed cases analysis for the clinician´s interview based impression of 
change (CIBIC-plus): p = 0.025; Alzheimer´s disease cooperative study – activities of daily living 
(ADCS-ADLsev): p = 0.003; severe impairment battery (SIB): p = 0.002). 
 
A pivotal monotherapy study of memantine in the treatment of mild to moderate Alzheimer's disease 
(MMSE total scores at baseline of 10-22) included 403 patients. Memantine-treated patients showed a 
statistically significantly better effect than placebo-treated patients on the primary endpoints: 
Alzheimer´s disease assessment scale (ADAS-cog) (p = 0.003) and CIBIC-plus (p = 0.004) at week 24 
last observation carried forward (LOCF). In another monotherapy study in mild to moderate 
Alzheimer's disease a total of 470 patients (MMSE total scores at baseline of 11-23) were randomised. 
In the prospectively defined primary analysis statistical significance was not reached at the primary 
efficacy endpoint at week 24. 
 
A meta-analysis of patients with moderate to severe Alzheimer's disease (MMSE total scores < 20) 
from the six phase III, placebo-controlled, 6-month studies (including monotherapy studies and studies 
with patients on a stable dose of acetylcholinesterase inhibitors) showed that there was a statistically 
significant effect in favour of memantine treatment for the cognitive, global, and functional domains. 
When patients were identified with concurrent worsening in all three domains, results showed a 
statistically significant effect of memantine in preventing worsening, as twice as many placebo-treated 
7 patients as memantine-treated patients showed worsening in all three domains (21 % vs. 11 %, 
p < 0.0001). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
Memantine has an absolute bioavailability of approximately 100 %. tmax is between 3 and 8 hours. 
There is no indication that food influences the absorption of memantine. 
 
Distribution  
 
Daily doses of 20 mg lead to steady-state plasma concentrations of memantine ranging from 
70-150 ng/ml (0.5-1μmol) with large interindividual variations. When daily doses of 5-30 mg were 
administered, a mean cerebrospinal fluid (CSF)/serum ratio of 0.52 was calculated. The volume of 
distribution is around 10 l/kg. About 45 % of memantine is bound to plasma-proteins. 
 
Biotransformation  
 
In man, about 80 % of the circulating memantine-related material is present as the parent compound. 
Main human metabolites are N-3,5-dimethyl-gludantan, the isomeric mixture of 4-and 6-hydroxy-
memantine, and 1-nitroso-3,5-dimethyl-adamantane. None of these metabolites exhibit 
NMDA-antagonistic activity. No cytochrome P 450 catalysed metabolism has been detected in vitro. 
 
In a study using orally administered 14C-memantine, a mean of 84 % of the dose was recovered within 
20 days, more than 99 % being excreted renally. 
 
Elimination  
 
Memantine is eliminated in a monoexponential manner with a terminal t½ of 60-100hours. In 
volunteers with normal kidney function, total clearance (Cltot) amounts to 170 ml/min/1.73 m² and part 
of total renal clearance is achieved by tubular secretion. 



 8

 
Renal handling also involves tubular reabsorption, probably mediated by cation transport proteins. The 
renal elimination rate of memantine under alkaline urine conditions may be reduced by a factor of 7-9 
(see section 4.4). Alkalisation of urine may result from drastic changes in diet, e.g. from a carnivore to 
a vegetarian diet, or from the massive ingestion of alkalising gastric buffers. 
 
Linearity 
 
Studies in volunteers have demonstrated linear pharmacokinetics in the dose range of 10-40 mg. 
 
Pharmacokinetic/pharmacodynamic relationship 
 
At a dose of memantine of 20 mg per day the CSF levels match the ki-value (ki = inhibition constant) 
of memantine, which is 0.5 μmol in human frontal cortex. 
 
5.3 Preclinical safety data 
 
In short term studies in rats, memantine like other NMDA-antagonists have induced neuronal 
vacuolisation and necrosis (Olney lesions) only after doses leading to very high peak serum 
concentrations. Ataxia and other preclinical signs have preceded the vacuolisation and necrosis. As the 
effects have neither been observed in long term studies in rodents nor in non-rodents, the clinical 
relevance of these findings is unknown. 
 
Ocular changes were inconsistently observed in repeat dose toxicity studies in rodents and dogs, but 
not in monkeys. Specific ophthalmoscopic examinations in clinical studies with memantine did not 
disclose any ocular changes. 
 
Phospholipidosis in pulmonary macrophages due to accumulation of memantine in lysosomes was 
observed in rodents. This effect is known from other active substances with cationic amphiphilic 
properties. There is a possible relationship between this accumulation and the vacuolisation observed 
in lungs. This effect was only observed at high doses in rodents. The clinical relevance of these 
findings is unknown. 
 
No genotoxicity has been observed following testing of memantine in standard assays. There was no 
evidence of any carcinogenicity in life long studies in mice and rats. Memantine was not teratogenic in 
rats and rabbits, even at maternally toxic doses, and no adverse effects of memantine were noted on 
fertility. In rats, foetal growth reduction was noted at exposure levels, which are identical or slightly 
higher than at human exposure. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core 
 
Lactose monohydrate 
Microcrystalline cellulose 
Silica, colloidal anhydrous 
Crospovidone 
Magnesium stearate 
 
Tablet coat 
 
Hypromellose 
Polysorbate 80 
Macrogol 400 



 9

Titanium dioxide (E 171) 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5 Nature and contents of container 
 
PVC/PE/PVDC-aluminium blister. 
Pack sizes of 14, 28, 30, 42, 50, 56, 98, 100 and 112 tablets are presented. 
 
Memantine Accord 10 mg tablets are also available in perforated unit dose calendar blister in 
pack-sizes of 14x1, 28x1, 56x1 or 98x1 tablet. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
No special requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Accord Healthcare S.L.U.  
World Trade Center, Moll de Barcelona, s/n,  
Edifici Est 6ª planta,  
08039 Barcelona,  
Spain 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/13/880/001 
EU/1/13/880/002 
EU/1/13/880/003 
EU/1/13/880/004 
EU/1/13/880/005 
EU/1/13/880/006 
EU/1/13/880/007 
EU/1/13/880/008 
EU/1/13/880/014 
EU/1/13/880/016 
EU/1/13/880/017 
EU/1/13/880/018 
EU/1/13/880/019 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 04 December 2013 



 10

Date of latest renewal: 3rd August 2018 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 



 11

1. NAME OF THE MEDICINAL PRODUCT 
 
Memantine Accord 20 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 20 mg of memantine hydrochloride equivalent to 16.62 mg 
memantine.  
 
Excipientwith known effect: each film-coated tablet contains 295.18 mg lactose (as monohydrate). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet. 
Pale red to grey-red, oblong, scored, coated tablet, debossed with “MT” divided by the score on one 
side and "20" divided by the score on the other side. 
The tablet can be divided into equal doses. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Treatment of patients with moderate to severe Alzheimer's disease. 
 
4.2 Posology and method of administration 
 
Posology 
 
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. 
 
Adults 
 
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): 



 12

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 for 7 days. 
 
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 as described above. 
 
Renal impairment 
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. 
 
Hepatic impairment 
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 Memantine Accord is not recommended in patients with severe hepatic 
impairment. 
 
Children and adolescents 
Memantine Accord is not recommended for use in children below 18 years due to a lack of data on 
safety and efficacy. 
 
Method of administration 
 
Memantine Accord 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. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 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. These compounds act at the same receptor system as 
memantine, and therefore adverse reactions (mainly central nervous system (CNS)-related) may be 
more frequent or more pronounced (see also section 4.5). 
 
Some factors that may raise urine pH (see section 5.2 'Elimination') may necessitate careful 
monitoring of the patient. These factors include drastic changes in diet, e.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. 
 



 13

Excipients 
Memantine Accord contains lactose. Patients with rare hereditary problems of galactose intolerance, 
the Lapp lactase deficiency or glucose-galactosemalabsorption should not take this medicinal product. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Due to the pharmacological effects and the mechanism of action of memantine the following 
interactions may occur: 
 
 The mode of action suggests that the effects of L-dopa, dopaminergic agonists, and 

anticholinergics may be enhanced by concomitant treatment with NMDA-antagonists such as 
memantine. The effects of barbiturates and neuroleptics may be reduced. Concomitant 
administration of memantine with the antispasmodic agents, dantrolene or baclofen, can modify 
their effects and a dose adjustment may be necessary. 

 Concomitant use of memantine and amantadine should be avoided, owing to the risk of 
pharmacotoxic psychosis. Both compounds are chemically related NMDA-antagonists. The 
same may be true for ketamine and dextromethorphan (see also section 4.4). There is one 
published case report on a possible risk also for the combination of memantine and phenytoin. 

 Other active substances such as cimetidine, ranitidine, procainamide, quinidine, quinine and 
nicotine that use the same renal cationic transport system as amantadine may also possibly 
interact with memantine leading to a potential risk of increased plasma levels. 

 There may be a possibility of reduced serum level of hydrochlorothiazide (HCT) when 
memantine is co-administered with HCT or any combination with HCT. 

 In post-marketing experience, isolated cases with international normalized ratio (INR) increases 
have been reported in patients concomitantly treated with warfarin. Although no causal 
relationship has been established, close monitoring of prothrombin time or INR is advisable for 
patients concomitantly treated with oral anticoagulants. 

 
In single-dose pharmacokinetic (PK) studies in young healthy subjects, no relevant active substance-
active substance interaction of memantine with glyburide/metformin or donepezil was observed. 
 
In a clinical study in young healthy subjects, no relevant effect of memantine on the pharmacokinetics 
of galantamine was observed. 
 
Memantine did not inhibit CYP 1A2, 2A6, 2C9, 2D6, 2E1, 3A, flavin containing monooxygenase, 
epoxide hydrolase or sulphation in vitro. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
For memantine, no clinical data on exposed pregnancies are available. Animal studies indicate a 
potential for reducing intrauterine growth at exposure levels, which are identical or slightly higher 
than at human exposure (see section 5.3). The potential risk for humans is unknown. Memantine 
should not be used during pregnancy unless clearly necessary. 
 
Breast-feeding 
 
It is not known whether memantine is excreted in human breast milk but, taking into consideration the 
lipophilicity of the substance, this probably occurs. Women taking memantine should not breast-feed. 
 
Fertility 
 
No adverse effects of memantine were noted on non-clinical male and female fertility studies. 
 
4.7 Effects on ability to drive and use machines 
 



 14

Moderate to severe Alzheimer's disease usually causes impairment of driving performance and 
compromises the ability to use machinery. Furthermore, memantine has minor to moderate influence 
on the ability to drive and use machines such that outpatients should be warned to take special care. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
In clinical trials in mild to severe dementia, involving 1,784 patients treated with memantine and 
1,595 patients treated with placebo, the overall incidence rate of adverse reactions with memantine did 
not differ from those with placebo; the adverse reactions were usually mild to moderate in severity. 
The most frequently occurring adverse reactions with a higher incidence in the memantine group than 
in the placebo group were dizziness (6.3 % vs 5.6 %, respectively), headache (5.2 % vs 3.9 %), 
constipation (4.6 % vs 2.6 %), somnolence (3.4 % vs 2.2 %) and hypertension (4.1 % vs 2.8 %). 
 
The following adverse reactions listed in the table below have been accumulated in clinical studies 
with memantine and since its introduction in the market. Within each frequency grouping, undesirable 
effects are presented in order of decreasing seriousness. 
 
Tabulated list of adverse reactions 
 
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). 
 
System Organ Class Frequency Adverse Reaction 
Infections and infestations Uncommon Fungal infections 
Immune systeme disorders Common Drug hypersensitivity 
Psychiatric disorders Common Somnolence 

Uncommon Confusion 
Uncommon Hallucinations1 
Not known Psychotic reactions2 

Nervous system disorders Common Dizziness 
Common Balance disorders 
Uncommon Gait abnormal 
Very rare Seizures 

Cardiac disorders Uncommon Cardiac failure 
Vascular disorders Common Hypertension 

Uncommon Venous thrombosis/thromboembolism 
Respiratory, thoracic and 
mediastinal disorders 

Common Dyspnoea 

Gastrointestinal disorders Common Constipation 
Uncommon Vomiting 
Not known Pancreatitis2 

Hepatobiliary disorders Common Elevated liver function test 
Not known Hepatitis 

General disorders and 
administration site conditions 

Common Headache 
Uncommon Fatigue 

 
1 Hallucinations have mainly been observed in patients with severe Alzheimer's disease. 
2 Isolated cases reported in post-marketing experience. 
 
Description of selected adverse reactions 
 
Alzheimer's disease has been associated with depression, suicidal ideation and suicide. In 
post-marketing experience these events have been reported in patients treated with memantine. 



 15

 
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 national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
Only limited experience with overdose is available from clinical studies and post-marketing 
experience. 
 
Symptoms 
 
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 of gastrointestinal origin (vomiting and diarrhoea). 
 
In the most extreme case of overdose, the patient survived the oral intake of a total of 2,000 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. 
 
Treatment  
 
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, carbomedicinalis (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. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other Anti-dementia drugs, ATC code: N06DX01. 
 
There is increasing evidence that malfunctioning of glutamatergic neurotransmission, in particular at 
NMDA-receptors, contributes to both expression of symptoms and disease progression in 
neurodegenerative dementia. 
 
Memantine is a voltage-dependent, moderate-affinity uncompetitive NMDA-receptor antagonist. It 
modulates the effects of pathologically elevated tonic levels of glutamate that may lead to neuronal 
dysfunction. 
 
Clinical studies 



 16

 
A pivotal monotherapy study in a population of patients suffering from moderate to severe 
Alzheimer's disease (mini mental state examination (MMSE) total scores at baseline of 3-14) included 
a total of 252 outpatients. The study showed beneficial effects of memantine treatment in comparison 
to placebo at 6 months (observed cases analysis for the clinician´s interview based impression of 
change (CIBIC-plus): p = 0.025; Alzheimer´s disease cooperative study – activities of daily living 
(ADCS-ADLsev): p = 0.003; severe impairment battery (SIB): p = 0.002). 
 
A pivotal monotherapy study of memantine in the treatment of mild to moderate Alzheimer's disease 
(MMSE total scores at baseline of 10-22) included 403 patients. Memantine-treated patients showed a 
statistically significantly better effect than placebo-treated patients on the primary endpoints: 
Alzheimer´s disease assessment scale (ADAS-cog) (p = 0.003) and CIBIC-plus (p = 0.004) at week 24 
last observation carried forward (LOCF). In another monotherapy study in mild to moderate 
Alzheimer's disease a total of 470 patients (MMSE total scores at baseline of 11-23) were randomised. 
 
In the prospectively defined primary analysis statistical significance was not reached at the 
primaryefficacy endpoint at week 24. 
 
A meta-analysis of patients with moderate to severe Alzheimer's disease (MMSE total scores < 20) 
from the six phase III, placebo-controlled, 6-month studies (including monotherapy studies and studies 
with patients on a stable dose of acetylcholinesterase inhibitors) showed that there was a statistically 
significant effect in favour of memantine treatment for the cognitive, global, and functional domains. 
When patients were identified with concurrent worsening in all three domains, results showed a 
statistically significant effect of memantine in preventing worsening, as twice as many placebo-treated 
7 patients as memantine-treated patients showed worsening in all three domains (21 % vs. 11 %, 
p < 0.0001). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
Memantine has an absolute bioavailability of approximately 100 %. tmax is between 3 and 8 hours. 
There is no indication that food influences the absorption of memantine. 
 
Distribution  
 
Daily doses of 20 mg lead to steady-state plasma concentrations of memantine ranging from 
70-150 ng/ml (0.5-1μmol) with large interindividual variations. When daily doses of 5-30 mg were 
administered, a mean cerebrospinal fluid (CSF)/serum ratio of 0.52 was calculated. The volume of 
distribution is around 10 l/kg. About 45 % of memantine is bound to plasma-proteins. 
 
Biotransformation: 
 
In man, about 80 % of the circulating memantine-related material is present as the parent compound. 
Main human metabolites are N-3,5-dimethyl-gludantan, the isomeric mixture of 4-and 6-hydroxy-
memantine, and 1-nitroso-3,5-dimethyl-adamantane. None of these metabolites exhibit 
NMDA-antagonistic activity. No cytochrome P 450 catalysed metabolism has been detected in vitro. 
 
In a study using orally administered 14C-memantine, a mean of 84 % of the dose was recovered within 
20days, more than 99 % being excreted renally. 
 
Elimination 
 
Memantine is eliminated in a monoexponential manner with a terminal t½ of 60-100hours. In 
volunteers with normal kidney function, total clearance (Cltot) amounts to 170 ml/min/1.73 m² and part 
of total renal clearance is achieved by tubular secretion. 
 



 17

Renal handling also involves tubular reabsorption, probably mediated by cation transport proteins. The 
renal elimination rate of memantine under alkaline urine conditions may be reduced by a factor of 7-9 
(see section 4.4). Alkalisation of urine may result from drastic changes in diet, e.g. from a carnivore to 
a vegetarian diet, or from the massive ingestion of alkalising gastric buffers. 
 
Linearity 
 
Studies in volunteers have demonstrated linear pharmacokinetics in the dose range of 10-40 mg. 
 
Pharmacokinetic/pharmacodynamic relationship  
 
At a dose of memantine of 20 mg per day the CSF levels match the ki-value (ki = inhibition constant) 
of memantine, which is 0.5 μmol in human frontal cortex. 
 
5.3 Preclinical safety data 
 
In short term studies in rats, memantine like other NMDA-antagonists have induced neuronal 
vacuolisation and necrosis (Olney lesions) only after doses leading to very high peak serum 
concentrations. Ataxia and other preclinical signs have preceded the vacuolisation and necrosis. As the 
effects have neither been observed in long term studies in rodents nor in non-rodents, the clinical 
relevance of these findings is unknown. 
 
Ocular changes were inconsistently observed in repeat dose toxicity studies in rodents and dogs, but 
not in monkeys. Specific ophthalmoscopic examinations in clinical studies with memantine did not 
disclose any ocular changes. 
 
Phospholipidosis in pulmonary macrophages due to accumulation of memantine in lysosomes was 
observed in rodents. This effect is known from other active substances with cationic amphiphilic 
properties. There is a possible relationship between this accumulation and the vacuolisation observed 
in lungs. This effect was only observed at high doses in rodents. The clinical relevance of these 
findings is unknown. 
 
No genotoxicity has been observed following testing of memantine in standard assays. There was no 
evidence of any carcinogenicity in life long studies in mice and rats. Memantine was not teratogenic in 
rats and rabbits, even at maternally toxic doses, and no adverse effects of memantine were noted on 
fertility. In rats, foetal growth reduction was noted at exposure levels, which are identical or slightly 
higher than at human exposure. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core 
 
Lactose monohydrate 
Microcrystalline cellulose 
Silica, colloidal anhydrous 
Crospovidone 
Magnesium stearate 
 
Tablet coat 
 
Hypromellose 
Polysorbate 80 
Macrogol 400 
Titanium dioxide (E 171) 



 18

Iron oxide yellow and red (E 172) 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5 Nature and contents of container 
 
PVC/PE/PVDC-aluminium blister.  
Pack sizes of 14, 28, 42, 56 and 98 tablets are presented. 
 
Memantine Accord 20 mg tablets are also available in perforated unit dose calendar blister in pack-
sizes of 14x1, 28x1, 56x1 or 98x1 tablet. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
No special requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Accord Healthcare S.L.U.  
World Trade Center, Moll de Barcelona, s/n,  
Edifici Est 6ª planta,  
08039 Barcelona,  
Spain 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/13/880/009 
EU/1/13/880/010 
EU/1/13/880/011 
EU/1/13/880/012 
EU/1/13/880/015 
EU/1/13/880/020 
EU/1/13/880/021 
EU/1/13/880/022 
EU/1/13/880/023 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 04 December 2013 
Date of latest renewal: 3rd August 2018 
 
 
10. DATE OF REVISION OF THE TEXT 



 19

 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



 20

1. NAME OF THE MEDICINAL PRODUCT 
 
Memantine Accord 5 mg film-coated tablets 
Memantine Accord 10 mg film-coated tablets 
Memantine Accord 15 mg film-coated tablets 
Memantine Accord 20 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 5 mg of memantine hydrochloride equivalent to 4.15 mg memantine. 
 
Excipientwith known effect: each film-coated tablet contains 73.80 mg lactose (as monohydrate). 
 
Each film-coated tablet contains 10 mg of memantine hydrochloride equivalent to 8.31 mg 
memantine. 
 
Excipientwith known effect: each film-coated tablet contains 183.13 mg lactose (as monohydrate) 
 
Each film-coated tablet contains 15 mg of memantine hydrochloride equivalent to 12.46 mg 
memantine. 
 
Excipientwith known effect: each film-coated tablet contains 221.39 mg lactose (as monohydrate) 
 
Each film-coated tablet contains 20 mg of memantine hydrochloride equivalent to 16.62 mg 
memantine. 
 
Excipientwith known effect: each film-coated tablet contains 295.18 mg lactose (as monohydrate). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet. 
The 5 mg film-coated tablets are white, oblong, coated tablets, debossed with "MT" on one side and 
"5" on the other side. 
 
The 10 mg film-coated tablets are white, oblong, coated and scored tablets, debossed with "MT" 
divided by the score on one side and "10" divided by the score on the other side. The tablets can be 
divided into equal doses. 
 
The 15 mg film-coated tablets are orange to grey-orange, oblong, coated tablets debossedwith "MT" 
on one side and "15" on the other side. 
 
The 20 mg film-coated tablets are pale red to grey-red, oblong, scored, coated tablets, debossed with 
"MT" divided by the score on one side and "20" divided by the score on the other side. The tablets can 
be divided into equal doses. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Treatment of patients with moderate to severe Alzheimer's disease. 
 
4.2 Posology and method of administration 



 21

 
Posology 
 
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. 
 
Adults 
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) for 7 days. 
 
Week 2 (day 8-14): 
The patient should take one 10 mg film-coated tablet per day (white, scored) for 7 days. 
 
Week 3 (day 15-21): 
The patient should take one 15 mg film-coated tablet per day (orange to grey-orange) for 7 days. 
 
Week 4 (day 22-28): 
The patient should take one 20 mg film-coated tablet per day (pale red to grey-red, scored) for 7 days. 
 
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 (20 mg tablets once a day) as described above. 
 
Renal impairment 
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. 
 
Hepatic impairment 
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 Memantine Accord is not recommended in patients with severe hepatic 
impairment. 
 
Children and adolescents 
Memantine Accord is not recommended for use in children below 18 years due to a lack of data on 
safety and efficacy. 
 
Method of administration 
 



 22

Memantine Accord 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. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 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. These compounds act at the same receptor system as 
memantine, and therefore adverse reactions (mainly central nervous system (CNS)-related) may be 
more frequent or more pronounced (see also section 4.5). 
 
Some factors that may raise urine pH (see section 5.2 'Elimination') may necessitate careful 
monitoring of the patient. These factors include drastic changes in diet, e.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 
Memantine Accord contains lactose. Patients with rare hereditary problems of galactose intolerance, 
the Lapp lactase deficiency or glucose-galactosemalabsorption should not take this medicinal product. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Due to the pharmacological effects and the mechanism of action of memantine the following 
interactions may occur: 
 
 The mode of action suggests that the effects of L-dopa, dopaminergic agonists, and 

anticholinergics may be enhanced by concomitant treatment with NMDA-antagonists such as 
memantine. The effects of barbiturates and neuroleptics may be reduced. Concomitant 
administration of memantine with the antispasmodic agents, dantrolene or baclofen, can modify 
their effects and a dose adjustment may be necessary. 

 Concomitant use of memantine and amantadine should be avoided, owing to the risk of 
pharmacotoxic psychosis. Both compounds are chemically related NMDA-antagonists. The 
same may be true for ketamine and dextromethorphan (see also section 4.4). There is one 
published case report on a possible risk also for the combination of memantine and phenytoin. 

 Other active substances such as cimetidine, ranitidine, procainamide, quinidine, quinine and 
nicotine that use the same renal cationic transport system as amantadine may also possibly 
interact with memantine leading to a potential risk of increased plasma levels. 

 There may be a possibility of reduced serum level of hydrochlorothiazide (HCT) when 
memantine is co-administered with HCT or any combination with HCT. 

 In post-marketing experience, isolated cases with international normalized ratio (INR) increases 
have been reported in patients concomitantly treated with warfarin. Although no causal 
relationship has been established, close monitoring of prothrombin time or INR is advisable for 
patients concomitantly treated with oral anticoagulants. 

 
In single-dose pharmacokinetic (PK) studies in young healthy subjects, no relevant active substance-
active substance interaction of memantine with glyburide/metformin or donepezil was observed. 
 



 23

In a clinical study in young healthy subjects, no relevant effect of memantine on the pharmacokinetics 
of galantamine was observed. 
 
Memantine did not inhibit CYP 1A2, 2A6, 2C9, 2D6, 2E1, 3A, flavin containing monooxygenase, 
epoxide hydrolase or sulphation in vitro. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
For memantine, no clinical data on exposed pregnancies are available. Animal studies indicate a 
potential for reducing intrauterine growth at exposure levels, which are identical or slightly higher 
than at human exposure (see section 5.3). The potential risk for humans is unknown. Memantine 
should not be used during pregnancy unless clearly necessary. 
 
Breast-feeding 
 
It is not known whether memantine is excreted in human breast milk but, taking into consideration the 
lipophilicity of the substance, this probably occurs. Women taking memantine should not breast-feed. 
 
Fertility 
 
No adverse effects of memantine were noted on non-clinical male and female fertility studies. 
 
4.7 Effects on ability to drive and use machines 
 
Moderate to severe Alzheimer's disease usually causes impairment of driving performance and 
compromises the ability to use machinery. Furthermore, memantine has minor to moderate influence 
on the ability to drive and use machines such that outpatients should be warned to take special care. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
In clinical trials in mild to severe dementia, involving 1,784 patients treated with memantine and 
1,595 patients treated with placebo, the overall incidence rate of adverse reactions with memantine did 
not differ from those with placebo; the adverse reactions were usually mild to moderate in severity. 
The most frequently occurring adverse reactions with a higher incidence in the memantine group than 
in the placebo group were dizziness (6.3 % vs 5.6 %, respectively), headache (5.2 % vs 3.9 %), 
constipation (4.6 % vs 2.6 %), somnolence (3.4 % vs 2.2 %) and hypertension (4.1 % vs 2.8 %). 
 
The following adverse reactions listed in the table below have been accumulated in clinical studies 
with memantine and since its introduction in the market. Within each frequency grouping, undesirable 
effects are presented in order of decreasing seriousness. 
 
Tabulated list of adverse reactions 
 
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). 
 
System Organ Class Frequency Adverse Reaction 
Infections and infestations Uncommon Fungal infections 
Immune systeme disorders Common Drug hypersensitivity 
Psychiatric disorders Common Somnolence 

Uncommon Confusion
Uncommon Hallucinations1



 24

Not known Psychotic reactions2 
Nervous system disorders Common Dizziness 

Common Balance disorders
Uncommon Gait abnormal 
Very rare Seizures 

Cardiac disorders Uncommon Cardiac failure 
Vascular disorders Common Hypertension 

Uncommon Venous thrombosis/thromboembolism 
Respiratory, thoracic and 
mediastinal disorders 

Common Dyspnoea 

Gastrointestinal disorders Common Constipation 
Uncommon Vomiting 
Not known Pancreatitis2 

Hepatobiliary disorders Common Elevated liver function test 
Not known Hepatitis 

General disorders and 
administration site conditions 

Common Headache 
Uncommon Fatigue 

 
1 Hallucinations have mainly been observed in patients with severe Alzheimer's disease. 
2 Isolated cases reported in post-marketing experience. 
 
Description of selected adverse reactions 
 
Alzheimer's disease has been associated with depression, suicidal ideation and suicide. In 
post-marketing experience these events have been reported in patients treated with memantine. 
 
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 national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
Only limited experience with overdose is available from clinical studies and post-marketing 
experience. 
 
Symptoms 
 
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 of gastrointestinal origin (vomiting and diarrhoea). 
 
In the most extreme case of overdose, the patient survived the oral intake of a total of 2,000 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. 
 



 25

Treatment 
 
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, carbomedicinalis (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. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other Anti-dementia drugs, ATC code: N06DX01. 
 
There is increasing evidence that malfunctioning of glutamatergic neurotransmission, in particular at 
 NMDA-receptors, contributes to both expression of symptoms and disease progression 
inneurodegenerative dementia. 
 
Memantine is a voltage-dependent, moderate-affinity uncompetitive NMDA-receptor antagonist. It 
modulates the effects of pathologically elevated tonic levels of glutamate that may lead to neuronal 
dysfunction. 
 
Clinical studies 
 
A pivotal monotherapy study in a population of patients suffering from moderate to severe 
Alzheimer's disease (mini mental state examination (MMSE) total scores at baseline of 3-14) included 
a total of 252 outpatients. The study showed beneficial effects of memantine treatment in comparison 
to placebo at 6 months (observed cases analysis for the clinician´s interview based impression of 
change (CIBIC-plus): p = 0.025; Alzheimer´s disease cooperative study – activities of daily living 
(ADCS-ADLsev): p = 0.003; severe impairment battery (SIB): p = 0.002). 
 
A pivotal monotherapy study of memantine in the treatment of mild to moderate Alzheimer's disease 
(MMSE total scores at baseline of 10-22) included 403 patients. Memantine-treated patients showed a 
statistically significantly better effect than placebo-treated patients on the primary endpoints: 
Alzheimer´s disease assessment scale (ADAS-cog) (p = 0.003) and CIBIC-plus (p = 0.004) at week 24 
last observation carried forward (LOCF). In another monotherapy study in mild to moderate 
Alzheimer's disease a total of 470 patients (MMSE total scores at baseline of 11-23) were randomised. 
In the prospectively defined primary analysis statistical significance was not reached at the primary 
efficacy endpoint at week 24. 
 
A meta-analysis of patients with moderate to severe Alzheimer's disease (MMSE total scores <20) 
from the six phase III, placebo-controlled, 6-month studies (including monotherapy studies and studies 
with patients on a stable dose of acetylcholinesterase inhibitors) showed that there was a statistically 
significant effect in favour of memantine treatment for the cognitive, global, and functional domains. 
When patients were identified with concurrent worsening in all three domains, results showed a 
statistically significant effect of memantine in preventing worsening, as twice as many placebo-treated 
7 patients as memantine-treated patients showed worsening in all three domains (21 % vs. 11 %, 
p < 0.0001). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 



 26

Memantine has an absolute bioavailability of approximately 100 %. tmax is between 3 and 8 hours. 
There is no indication that food influences the absorption of memantine. 
 
Distribution 
 
Daily doses of 20 mg lead to steady-state plasma concentrations of memantine ranging from 
70-150 ng/ml (0.5-1 μmol) with large interindividual variations. When daily doses of 5-30 mg were 
administered, a mean cerebrospinal fluid (CSF)/serum ratio of 0.52 was calculated. The volume of 
distribution is around 10 l/kg. About 45 % of memantine is bound to plasma-proteins. 
 
Biotransformation 
 
In man, about 80 % of the circulating memantine-related material is present as the parent compound. 
Main human metabolites are N-3,5-dimethyl-gludantan, the isomeric mixture of 4-and 6-hydroxy-
memantine, and 1-nitroso-3,5-dimethyl-adamantane. None of these metabolites exhibit 
NMDA-antagonistic activity. No cytochrome P 450 catalysed metabolism has been detected in vitro. 
 
In a study using orally administered 14C-memantine, a mean of 84 % of the dose was recovered within 
20 days, more than 99 % being excreted renally. 
 
Elimination 
 
Memantine is eliminated in a monoexponential manner with a terminal t½ of 60-100hours. In 
volunteers with normal kidney function, total clearance (Cltot) amounts to 170 ml/min/1.73 m² and part 
of total renal clearance is achieved by tubular secretion. 
 
Renal handling also involves tubular reabsorption, probably mediated by cation transport proteins. The 
renal elimination rate of memantine under alkaline urine conditions may be reduced by a factor of 7-9 
(see section 4.4). Alkalisation of urine may result from drastic changes in diet, e.g. from a carnivore to 
a vegetarian diet, or from the massive ingestion of alkalising gastric buffers. 
 
Linearity 
 
Studies in volunteers have demonstrated linear pharmacokinetics in the dose range of 10-40 mg. 
 
Pharmacokinetic/pharmacodynamic relationship 
 
At a dose of memantine of 20 mg per day the CSF levels match the ki-value (ki = inhibition constant) 
of memantine, which is 0.5 μmol in human frontal cortex. 
 
5.3 Preclinical safety data 
 
In short term studies in rats, memantine like other NMDA-antagonists have induced neuronal 
vacuolisation and necrosis (Olney lesions) only after doses leading to very high peak serum 
concentrations. Ataxia and other preclinical signs have preceded the vacuolisation and necrosis. As the 
effects have neither been observed in long term studies in rodents nor in non-rodents, the clinical 
relevance of these findings is unknown. 
 
Ocular changes were inconsistently observed in repeat dose toxicity studies in rodents and dogs, but 
not in monkeys. Specific ophthalmoscopic examinations in clinical studies with memantine did not 
disclose any ocular changes. 
 
Phospholipidosis in pulmonary macrophages due to accumulation of memantine in lysosomes was 
observed in rodents. This effect is known from other active substances with cationic amphiphilic 
properties. There is a possible relationship between this accumulation and the vacuolisation observed 
in lungs. This effect was only observed at high doses in rodents. The clinical relevance of these 
findings is unknown. 



 27

 
No genotoxicity has been observed following testing of memantine in standard assays. There was no 
evidence of any carcinogenicity in life long studies in mice and rats. Memantine was not teratogenic in 
rats and rabbits, even at maternally toxic doses, and no adverse effects of memantine were noted on 
fertility. In rats, foetal growth reduction was noted at exposure levels, which are identical or slightly 
higher than at human exposure. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet cores for 5/10/15/20 mg film-coated tablets 
 
Lactose monohydrate 
Microcrystalline cellulose 
Silica, colloidal anhydrous 
Crospovidone 
Magnesium stearate 
 
Tablet coat for 5/10/15/20 mg film-coated tablets 
 
Hypromellose 
Polysorbate 80 
Macrogol 400 
Titanium dioxide (E 171) 
 
Additional for 15 mg and 20 mg film-coated tablets 
 
Iron oxide yellow and red (E 172) 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5 Nature and contents of container 
 
PVC/PE/PVDC-aluminium blister 
Blister packs containing 28 tablets with 7 tablets of 5 mg, 7 tablets of 10 mg, 7 tablets of 15 mg and 
7 tablets of 20 mg. 
 
6.6 Special precautions for disposal 
 
No special requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Accord Healthcare S.L.U.  



 28

World Trade Center, Moll de Barcelona, s/n,  
Edifici Est 6ª planta,  
08039 Barcelona,  
Spain 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/13/880/013 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 04 December 2013 
Date of latest renewal: 3rd August 2018 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 

 



 29

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
ANNEX II 

 
A. MANUFACTURERS RESPONSIBLE FOR BATCH 

RELEASE 
 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE 

 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 
THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 



 30

A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturers responsible for batch release 

Delorbis Pharmaceuticals Ltd 
17 Athinon Street 
Ergates Industrial Area 
Nicosia 
2643 
Cyprus 
 
Accord Healthcare Limited 
Sage House 
319 Pinner Road 
North Harrow 
Middlesex, HA1 4HF 
United Kingdom 
 
Accord Healthcare Polska Sp.z o.o., 
ul. Lutomierska 50,95-200 Pabianice, Poland 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal products subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
 Periodic safety update reports  
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
 Risk Management Plan (RMP) 
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in 
the agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed 
subsequent updates of the RMP. 
 
An updated RMP should be submitted: 

 At the request of the European Medicines Agency; 
 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 



 31

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
 
 



 32

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



 33

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON FOR BLISTER PACK 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Memantine Accord 10 mg film-coated tablets 
memantine hydrochloride 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 10 mg memantine hydrochloride equivalent to 8.31 mg memantine. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablets. 
14 film-coated tablets 
28 film-coated tablets 
30 film-coated tablets 
42 film-coated tablets 
50 film-coated tablets 
56 film-coated tablets 
98 film-coated tablets 
100 film-coated tablets 
112 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
Once daily. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP: 



 34

 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Accord Healthcare S.L.U.  
World Trade Center, Moll de Barcelona, s/n,  
Edifici Est 6ª planta,  
08039 Barcelona,  
Spain 
 

 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/13/880/001 28 film-coated tablets 
EU/1/13/880/002 30 film-coated tablets 
EU/1/13/880/003 42 film-coated tablets 
EU/1/13/880/004 50 film-coated tablets 
EU/1/13/880/005 56 film-coated tablets 
EU/1/13/880/006 98 film-coated tablets 
EU/1/13/880/007 100 film-coated tablets 
EU/1/13/880/008 112 film-coated tablets 
EU/1/13/880/014 14 film-coated tablets  
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Memantine Accord 10 mg film-coated tablets 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 



 35

SN: 
NN: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



 36

 
 
 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER FOR TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Memantine Accord 10 mg film-coated tablets 
memantine hydrochloride 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Accord 
 
 
3. EXPIRY DATE 
 
EXP: 
 
 
4. BATCH NUMBER 
 
Lot: 
 
 
5. OTHER 
 
 
 
 



 37

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON FOR BLISTER PACK 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Memantine Accord 10 mg film-coated tablets 
memantine hydrochloride 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 10 mg memantine hydrochloride equivalent to 8.31 mg memantine. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablets. 
14 x 1 film-coated tablets 
28 x 1 film-coated tablets 
56 x 1 film-coated tablets 
98 x 1 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
Once daily. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP: 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 



 38

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Accord Healthcare S.L.U.  
World Trade Center, Moll de Barcelona, s/n,  
Edifici Est 6ª planta,  
08039 Barcelona,  
Spain 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/13/880/016 14 x 1 film-coated tablets 
EU/1/13/880/017 28 x 1 film-coated tablets 
EU/1/13/880/018 56 x 1film-coated tablets 
EU/1/13/880/019 98 x 1film-coated tablets 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Memantine Accord 10 mg film-coated tablets 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
 
 



 39

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER FOR TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Memantine Accord 10 mg film-coated tablets 
memantine hydrochloride 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Accord 
 
 
3. EXPIRY DATE 
 
EXP: 
 
 
4. BATCH NUMBER 
 
Lot: 
 
 
5. OTHER 
 
Monday 
Tuesday 
Wednesday 
Thursday 
Friday 
Saturday 
Sunday 
 
 



 40

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON FOR BLISTER PACK 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Memantine Accord 20 mg film-coated tablets 
memantine hydrochloride 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 20 mg memantine hydrochloride equivalent to 16.62 mg memantine. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablets 
14 film-coated tablets 
28 film-coated tablets 
42 film-coated tablets 
56 film-coated tablets 
98 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
Once daily. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP: 
 
 
9. SPECIAL STORAGE CONDITIONS 



 41

 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Accord Healthcare S.L.U.  
World Trade Center, Moll de Barcelona, s/n,  
Edifici Est 6ª planta,  
08039 Barcelona,  
Spain 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/13/880/009 28 fim-coated tablets 
EU/1/13/880/010 42 fim-coated tablets 
EU/1/13/880/011 56 fim-coated tablets 
EU/1/13/880/012 98 fim-coated tablets 
EU/1/13/880/015 14 fim-coated tablets 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Memantine Accord 20 mg film-coated tablets 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
 
 
 



 42

 
 
 
 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER FOR TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Memantine Accord 20 mg film-coated tablets 
memantine hydrochloride 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Accord 
 
 
3. EXPIRY DATE 
 
EXP: 
 
 
4. BATCH NUMBER 
 
Lot: 
 
 
5. OTHER 
 
 



 43

 
 
 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON FOR BLISTER PACK 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Memantine Accord 20 mg film-coated tablets 
memantine hydrochloride 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 20 mg memantine hydrochloride equivalent to 16.62 mg memantine. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablets 
14 x 1 film-coated tablets 
28 x 1 film-coated tablets 
56 x 1 film-coated tablets 
98 x 1 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
Once daily. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP: 
 
 



 44

9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Accord Healthcare S.L.U.  
World Trade Center, Moll de Barcelona, s/n,  
Edifici Est 6ª planta,  
08039 Barcelona,  
Spain 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/13/880/020 14 x 1 film-coated tablets 
EU/1/13/880/021 28 x 1 film-coated tablets 
EU/1/13/880/022 56 x 1 film-coated tablets 
EU/1/13/880/023 98 x 1 film-coated tablets 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Memantine Accord 20 mg film-coated tablets 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
 
 
 
 
 



 45

 
 
 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER FOR TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Memantine Accord 20 mg film-coated tablets 
memantine hydrochloride 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Accord 
 
 
3. EXPIRY DATE 
 
EXP: 
 
 
4. BATCH NUMBER 
 
Lot: 
 
 
5. OTHER 
 
Monday 
Tuesday 
Wednesday 
Thursday 
Friday 
Saturday 
Sunday 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



 46

 
 
 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON FOR 28 TABLETS – TREATMENT INITIATION PACK – 
4 WEEK TREATMENT SCHEDULE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Memantine Accord 5 mg film-coated tablets 
Memantine Accord 10 mg film-coated tablets 
Memantine Accord 15 mg film-coated tablets 
Memantine Accord 20 mg film-coated tablets 
memantine hydrochloride 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 5 mg memantine hydrochloride equivalent to 4.15 mg memantine. 
Each film-coated tablet contains 10 mg memantine hydrochloride equivalent to 8.31 mg memantine. 
Each film-coated tablet contains 15 mg memantine hydrochloride equivalent to 12.46 mg memantine. 
Each film-coated tablet contains 20 mg memantine hydrochloride equivalent to 16.62 mg memantine. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Treatment initiation pack 
Each pack with 28 film-coated tablets for a 4 week treatment schedule contains: 
7 x Memantine Accord 5 mg 
7 x Memantine Accord 10 mg 
7 x Memantine Accord 15 mg 
7 x Memantine Accord 20 mg 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
Once daily. 
 
For continuation of your treatment please consult your doctor. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 



 47

 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP: 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Accord Healthcare S.L.U.  
World Trade Center, Moll de Barcelona, s/n,  
Edifici Est 6ª planta,  
08039 Barcelona,  
Spain 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/13/880/013 28 film-coated tablets 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Memantine Accord 5 mg, 10 mg, 15 mg; 20 mg film-coated tablets 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 



 48

PC: 
SN: 
NN: 



 49

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
INNER CARTON FOR BLISTER PACK 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Memantine Accord 5 mg film-coated tablets 
Memantine Accord 10 mg film-coated tablets 
Memantine Accord 15 mg film-coated tablets 
Memantine Accord 20 mg film-coated tablets 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
memantine hydrochloride 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
7 film-coated tablets, Memantine Accord 5 mg 
7 film-coated tablets, Memantine Accord 10 mg 
7 film-coated tablets, Memantine Accord 15 mg 
7 film-coated tablets, Memantine Accord 20 mg 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
One tablet daily. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP: 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 



 50

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
Week 1 
Week 2 
Week 3 
Week 4 
 
 
16. INFORMATION IN BRAILLE 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 



 51

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER FOR TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Memantine Accord 5 mg film-coated tablets 
Memantine Accord 10 mg film-coated tablets 
Memantine Accord 15 mg film-coated tablets 
Memantine Accord 20 mg film-coated tablets 
memantine hydrochloride 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Accord 
 
 
3. EXPIRY DATE 
 
EXP: 
 
 
4. BATCH NUMBER 
 
Lot: 
 
 
5. OTHER 
 
 



 52

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 B. PACKAGE LEAFLET 



 53

Package leaflet: Information for the user 
 

Memantine Accord 10 mg film-coated tablets 
memantine hydrochloride 

 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet.See section 4. 
 
What is in this leaflet 
 
1. What Memantine Accord is and what it is used for 
2. What you need to know before you take Memantine Accord  
3. How to take Memantine Accord  
4. Possible side effects 
5. How to store Memantine Accord  
6. Contents of the pack and other information 
 
 
1. What Memantine Accord is and what it is used for 
 
How does Memantine Accord work 
 
Memantine Accord contains the active substance memantine hydrochloride. 
Memantine Accordbelongs to a group of medicines known as anti-dementia medicines. 
Memory loss in Alzheimer’s disease is due to a disturbance of message signals in the brain. The brain 
contains so-called N-methyl-D-aspartate (NMDA)-receptors that are involved in transmitting nerve 
signals important in learning and memory. Memantine Accord belongs to a group of medicines called 
NMDA-receptor antagonists. Memantine Accord acts on these NMDA-receptors improving the 
transmission of nerve signals and the memory. 
 
What is Memantine Accord used for 
 
Memantine Accordis used for the treatment of patients with moderate to severe Alzheimer’s disease. 
 
 
2. What you need to know before you take Memantine Accord 
 
Do not take Memantine Accord: 
 
- if you are allergic to memantine hydrochloride or any of the other ingredients of this medicine 

(listed in section 6). 
 
Warnings and precautions 
 
Talk to your doctor or pharmacist before taking Memantine Accord 
- if you have a history of epileptic seizures 
- if you have recently experienced a myocardial infarction (heart attack), or if you are suffering 

rom congestive heart failure or from an uncontrolled hypertension (high blood pressure). 
 
In these situations the treatment should be carefully supervised, and the clinical benefit of Memantine 
Accord assessed by your doctor on a regular basis. 



 54

If you suffer from renal impairment (kidney problems), your doctor should closely monitor your 
kidney function and if necessary adapt the memantine doses accordingly. 
 
The use of medicinal products called amantadine (for the treatment of Parkinson´s disease), ketamine 
(a substance generally used as an anaesthetic), dextromethorphan (generally used to treat cough) and 
other NMDA-antagonists at the same time should be avoided. 
 
Children and adolescents 
 
Memantine Accord is not recommended for children and adolescents under the age of 18 years. 
 
Other medicines and Memantine Accord 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
In particular, Memantine Accord may change the effects of the following medicines and their dose 
may need to be adjusted by your doctor: 
 
amantadine, ketamine, dextromethorphan 
dantrolene, baclofen 
cimetidine, ranitidine, procainamide, quinidine, quinine, nicotine 
hydrochlorothiazide (or any combination with hydrochlorothiazide) 
anticholinergics (substances generally used to treat movement disorders or intestinal cramps) 
anticonvulsants (substances used to prevent and relieve seizures) 
barbiturates (substances generally used to induce sleep) 
dopaminergic agonists (substances such as L-dopa, bromocriptine) 
neuroleptics (substances used in the treatment of mental disorders) 
oral anticoagulants 
 
If you go into hospital, let your doctor know that you are taking Memantine Accord. 
 
Memantine Accord with food and drink 
 
You should inform your doctor if you have recently changed or intend to change your diet 
substantially (e.g. from normal diet to strict vegetarian diet) or if you are suffering from states of renal 
tubulary acidosis (RTA, an excess of acid-forming substances in the blood due to renal dysfunction 
(poor kidney function)) or severe infections of the urinary tract (structure that carries urine), as your 
doctor may need to adjust the dose of your medicine. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Pregnancy 
The use of memantine in pregnant women is not recommended. 
 
Breast-Feeding 
Women taking Memantine Accord should not breast-feed. 
 
Driving and using machines 
 
Your doctor will tell you whether your illness allows you to drive and to use machines safely.Also, 
Memantine Accord may change your reactivity, making driving or operating machinery inappropriate. 
 
Memantine Accord contains lactose 



 55

This medicinal product contains lactose. If you have been told by your doctor that you have an 
intolerance to some sugars, please contact your doctor before taking this medicinal product. Your 
doctor will advise you. 
 
 
3. How to take Memantine Accord 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 
if you are not sure. 
 
Dosage 
 
The recommended dose of Memantine Accord for adults and older people is 20 mg once a day. In 
order to reduce the risk of side effects this dose is achieved gradually by the following daily treatment 
scheme: 
 

week 1 half a 10 mg tablet
week 2 one 10 mg tablet 
week 3 one and a half 10 mg tablet 
week 4 and beyond two 10 mg tablets once a day 

 
The usual starting dose is half a tablet once a day (1 x 5 mg) for the first week. This is increased to one 
tablet once a day (1 x 10 mg) in the second week and to 1 and a half tablet once a day (1 x 15 mg) in 
the third week. From the fourth week on, the usual dose is 2tablets once a day (1 x 20 mg). 
 
Dosage in patients with impaired kidney function 
 
If you have impaired kidney function, your doctor will decide upon a dose that suits your condition. In 
this case, monitoring of your kidney function should be performed by your doctor at specified 
intervals. 
 
Administration 
 
Memantine Accord should be administered orally once a day. To benefit from your medicine you 
should take it regularly every day at the same time of the day. The tablets should be swallowed with a 
little water. The tablets can be taken with or without food. 
 
Duration of treatment 
 
Continue to take Memantine Accord as long as it is of benefit to you. Your doctor should assess your 
treatment on a regular basis. 
 
If you take more Memantine Accord than you should 
 
- In general, taking too much Memantine Accord should not result in any harm to you. You may 

experience increased symptoms as described in section 4. 'Possible side effects'. 
- If you take a large overdose of Memantine Accord, contact your doctor or get medical advice, as 

you may need medical attention. 
 
If you forget to take Memantine Accord 
 
- If you find you have forgotten to take your dose of Memantine Accord, wait and take your next 

dose at the usual time. 
- Do not take a double dose to make up for a forgotten dose. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 



 56

 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
In general, the observed side effects are mild to moderate. 
 
Common (may affect up to 1 in 10 people): 
 Headache, sleepiness, constipation, elevated liver function test, dizziness, balance disorders, 

shortness of breath, high blood pressure and drug hypersensitivity 
 
Uncommon (may affect up to 1 in 100 people): 
 Tiredness, fungal infections, confusion, hallucinations, vomiting, abnormal gait, heart failure 

and venous blood clotting (thrombosis/thromboembolism). 
 
Very Rare (may affect up to 1 in 10,000 people): 
 Seizures 
 
Not known (frequency cannot be estimated from the available data): 
 Inflammation of the pancreas, inflammation of the liver and psychotic reactions 
 
Alzheimer's disease has been associated with depression, suicidal ideation and suicide. These events 
have been reported in patients treated with memantine. 
 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety 
of this medicine. 
 
  
5. How to store Memantine Accord 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use Memantine Accord after the expiry date which is stated on the carton and the blister after 
EXP. The expiry date refers to the last day of that month. 
 
This medicinal product does not require any special storage conditions. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Memantine Accord contains 
 
- The active substance is memantine hydrochloride. Each film-coated tablet contains 10 mg of 

memantine hydrochloride equivalent to 8.31 mg memantine 
- The other ingredients are lactose monohydrate, microcrystalline cellulose, colloidal anhydrous 

silica, crospovidone, magnesium stearate, all in the tablet core; hypromellose, polysorbate 80, 
macrogol 400, titanium dioxide (E 171), all in the tablet coating 



 57

 
What Memantine Accord looks like and contents of the pack 
 
Memantine Accord film-coated tablets are presented as white, oblong, coated and scored 
tablet,debossed with "MT" divided by the score on one side and “10” divided by the score on the other 
side. The tablet can be divided into equal doses. 
 
Memantine Accord film-coated tablets are available in blister packs (PVC/PE/PVDC-aluminium 
blister) of 14 tablets, 28 tablets, 30 tablets, 42 tablets, 50 tablets, 56 tablets, 98 tablets, 100 tablets and 
112 tablets. Memantine Accord film-coated tablets are also available in perforated unit dose calendar 
blister in pack-sizes of 14x1, 28x1, 56x1 or 98x1 tablet. 
 
Not all pack sizes may be marketed 
 
Marketing Authorisation Holder 
 
Accord Healthcare S.L.U.  
World Trade Center, Moll de Barcelona, s/n,  
Edifici Est 6ª planta,  
08039 Barcelona,  
Spain 
 
Manufacturer 
 
Delorbis Pharmaceuticals Ltd 
17, Athinon Street 
Ergates Industrial Area, 2643 Nicosia 
Cyprus 
 
Accord Healthcare Limited 
Sage house, 319 Pinner road 
North Harrow, Middlesex, HA1 4HF 
United Kingdom 
 
Accord Healthcare Polska Sp.z o.o., 
ul. Lutomierska 50,95-200 Pabianice, Poland 
 
This leaflet was last revised in 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
 
 
 



 58

Package leaflet: Information for the user 
 

Memantine Accord 20 mg film-coated tablets 
memantine hydrochloride 

 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet.See section 4. 
 
What is in this leaflet 
 
1. What Memantine Accord is and what it is used for 
2. What you need to know before you take Memantine Accord  
3. How to take Memantine Accord  
4. Possible side effects 
5. How to store Memantine Accord  
6. Contents of the pack and other information 
 
 
1. What Memantine Accord is and what it is used for 
 
How does Memantine Accord work 
 
Memantine Accord contains the active substance memantine hydrochloride. 
Memantine Accord belongs to a group of medicines known as anti-dementia medicines. 
Memory loss in Alzheimer’s disease is due to a disturbance of message signals in the brain. The brain 
contains so-called N-methyl-D-aspartate (NMDA)-receptors that are involved in transmitting nerve 
signals important in learning and memory. Memantine Accord belongs to a group of medicines called 
NMDA-receptor antagonists. Memantine Accord acts on these NMDA-receptors improving the 
transmission of nerve signals and the memory. 
 
What is Memantine Accord used for 
 
Memantine Accordis used for the treatment of patients with moderate to severe Alzheimer’s disease. 
 
 
2. What you need to know before you take Memantine Accord 
 
Do not take Memantine Accord: 
 
- if you are allergic to memantine hydrochloride or any of the other ingredients of this medicine 

(listed in section 6). 
 
Warnings and precautions 
 
Talk to your doctor or pharmacist before taking Memantine Accord 
- if you have a history of epileptic seizures 
- if you have recently experienced a myocardial infarction (heart attack), or if you are suffering 

rom congestive heart failure or from an uncontrolled hypertension (high blood pressure). 
 
In these situations the treatment should be carefully supervised, and the clinical benefit of Memantine 
Accord assessed by your doctor on a regular basis. 



 59

If you suffer from renal impairment (kidney problems), your doctor should closely monitor 
yourkidney function and if necessary adapt the memantine doses accordingly. 
 
The use of medicinal products called amantadine (for the treatment of Parkinson´s disease), ketamine 
(a substance generally used as an anaesthetic), dextromethorphan (generally used to treat cough) and 
other NMDA-antagonists at the same time should be avoided. 
 
Children and adolescents 
 
Memantine Accord is not recommended for children and adolescents under the age of 18 years. 
 
Other medicines and Memantine Accord 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
In particular, Memantine Accord may change the effects of the following medicines and their dose 
may need to be adjusted by your doctor: 
 
amantadine, ketamine, dextromethorphan 
dantrolene, baclofen 
cimetidine, ranitidine, procainamide, quinidine, quinine, nicotine 
hydrochlorothiazide (or any combination with hydrochlorothiazide) 
anticholinergics (substances generally used to treat movement disorders or intestinal cramps) 
anticonvulsants (substances used to prevent and relieve seizures) 
barbiturates (substances generally used to induce sleep) 
dopaminergic agonists (substances such as L-dopa, bromocriptine) 
neuroleptics (substances used in the treatment of mental disorders) 
oral anticoagulants 
 
If you go into hospital, let your doctor know that you are taking Memantine Accord. 
 
Memantine Accord with food and drink 
 
You should inform your doctor if you have recently changed or intend to change your diet 
substantially (e.g. from normal diet to strict vegetarian diet) or if you are suffering from states of renal 
tubulary acidosis (RTA, an excess of acid-forming substances in the blood due to renal dysfunction 
(poor kidney function)) or severe infections of the urinary tract (structure that carries urine),as your 
doctor may need to adjust the dose of your medicine. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Pregnancy  
The use of memantine in pregnant women is not recommended. 
 
Breast-Feeding 
Women taking Memantine Accord should not breast-feed. 
 
Driving and using machines 
 
Your doctor will tell you whether your illness allows you to drive and to use machines safely.Also, 
Memantine Accord may change your reactivity, making driving or operating machinery inappropriate. 
 
Memantine Accord contains lactose 



 60

 
This medicinal product contains lactose. If you have been told by your doctor that you have an 
intolerance to some sugars, please contact your doctor before taking this medicinal product. Your 
doctor will advise you. 
 
 
3. How to take Memantine Accord 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 
if you are not sure. 
 
Dosage 
 
The recommended dose of Memantine Accord for adults and older people is 20 mg once a day. In 
order to reduce the risk of side effects this dose is achieved gradually by the following daily treatment 
scheme. For up-titration other tablet strengths are available. 
 
At the beginning of treatment you will start by using Memantine Accord 5 mg film-coated ablets once 
a day. This dose will be increased weekly by 5 mg until the recommended (maintenance) dose is 
reached. The recommended maintenance dose is 20 mg once a day, which is reached at the beginning 
of the 4th week. 
 
Dosage in patients with impaired kidney function 
 
If you have impaired kidney function, your doctor will decide upon a dose that suits your condition. In 
this case, monitoring of your kidney function should be performed by your doctor at specified 
intervals. 
 
Administration 
 
Memantine Accord should be administered orally once a day. To benefit from your medicine you 
should take it regularly every day at the same time of the day. The tablets should be swallowed with a 
little water. The tablets can be taken with or without food. 
 
Duration of treatment 
 
Continue to take Memantine Accord as long as it is of benefit to you. Your doctor should assess your 
treatment on a regular basis. 
 
If you take more Memantine Accord than you should 
 
- In general, taking too much Memantine Accord should not result in any harm to you. You may 

experience increased symptoms as described in section 4. 'Possible side effects'. 
- If you take a large overdose of Memantine Accord, contact your doctor or get medical advice, as 

you may need medical attention. 
 
If you forget to take Memantine Accord 
 
- If you find you have forgotten to take your dose of Memantine Accord, wait and take your next 

dose at the usual time. 
- Do not take a double dose to make up for a forgotten dose. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 



 61

4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
In general, the observed side effects are mild to moderate. 
Common (may affect up to 1 in 10 people): 
 Headache, sleepiness, constipation, elevated liver function test, dizziness, balance disorders, 

shortness of breath, high blood pressure and drug hypersensitivity 
 
Uncommon (may affect up to 1 in 100 people): 
 Tiredness, fungal infections, confusion, hallucinations, vomiting, abnormal gait, heart failure 

and venous blood clotting (thrombosis/thromboembolism). 
 
Very Rare (may affect up to 1 in 10,000 people): 
 Seizures 
 
Not known (frequency cannot be estimated from the available data): 
 Inflammation of the pancreas, inflammation of the liver and psychotic reactions 
 
Alzheimer's disease has been associated with depression, suicidal ideation and suicide. These events 
have been reported in patients treated with memantine. 
 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Memantine Accord 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use Memantine Accord after the expiry date which is stated on the carton and the blister after 
EXP. The expiry date refers to the last day of that month. 
 
This medicinal product does not require any special storage conditions. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Memantine Accord contains 
 
- The active substance is memantine hydrochloride. Each film-coated tablet contains 20 mg of 

memantine hydrochloride equivalent to 16.62 mg memantine 
- The other ingredients are lactose monohydrate, microcrystalline cellulose, colloidal anhydrous 

silica, crospovidone, magnesium stearate, all in the tablet core; hypromellose, polysorbate 80, 
macrogol 400, titanium dioxide (E 171), iron oxide red (E 172), iron oxide yellow (E 172) all in 
the tablet coating 

 
What Memantine Accord looks like and contents of the pack 



 62

 
Memantine Accord film-coated tablets are presented as pale red to greyred, oblong, coated and scored 
tablet, debossed with "MT" divided by the score on one side and “20” divided by the score on the 
other side. The tablet can be divided into equal doses. 
Memantine Accord film-coated tablets are available in blister packs (PVC/PE/PVDC-aluminium 
blister) of 14 tablets, 28 tablets, 42 tablets, 56 tablets and 98 tablets. Memantine Accord film-coated 
tablets are also available in perforated unit dose calendar blister in pack-sizes of 14x1, 28x1, 56x1 or 
98x1 tablet. 
 
Not all pack sizes may be marketed 
 
Marketing Authorisation Holder 
 
Accord Healthcare S.L.U.  
World Trade Center, Moll de Barcelona, s/n,  
Edifici Est 6ª planta,  
08039 Barcelona,  
Spain 
Manufacturer 
 
Delorbis Pharmaceuticals Ltd 
17, Athinon Street 
Ergates Industrial Area, 2643 Nicosia 
Cyprus 
 
Accord Healthcare Limited 
Sage house, 319 Pinner road 
North Harrow, Middlesex, HA1 4HF 
United Kingdom 
 
Accord Healthcare Polska Sp.z o.o., 
ul. Lutomierska 50,95-200 Pabianice, Poland 
 
This leaflet was last revised in 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



 63

 



 64

Package leaflet: Information for the user 
 

Memantine Accord 5 mg film-coated tablets 
Memantine Accord 10 mg film-coated tablets 
Memantine Accord 15 mg film-coated tablets 
Memantine Accord 20 mg film-coated tablets 

memantine hydrochloride 
 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet.See section 4. 
 
What is in this leaflet 
 
1. What Memantine Accord is and what it is used for  
2. What you need to know before you take Memantine Accord  
3. How to take Memantine Accord  
4. Possible side effects 
5. How to store Memantine Accord  
6. Contents of the pack and other information 
 
 
1. What Memantine Accord is and what it is used for 
 
How does Memantine Accord work 
 
Memantine Accord contains the active substance memantine hydrochloride. 
Memantine Accord belongs to a group of medicines known as anti-dementia medicines. 
Memory loss in Alzheimer’s disease is due to a disturbance of message signals in the brain. The brain 
contains so-called N-methyl-D-aspartate (NMDA)-receptors that are involved in transmitting nerve 
signals important in learning and memory. Memantine Accord belongs to a group of medicines called 
NMDA-receptor antagonists. Memantine Accord acts on these NMDA-receptors improving the 
transmission of nerve signals and the memory. 
 
What is Memantine Accord used for 
 
Memantine Accordis used for the treatment of patients with moderate to severe Alzheimer’s disease. 
 
 
2. What you need to know before you take Memantine Accord 
 
Do not take Memantine Accord: 
 
- if you are allergic to memantine hydrochloride or any of the other ingredients of this medicine 

(listed in section 6). 
 
Warnings and precautions 
 
Talk to your doctor or pharmacist before taking Memantine Accord 
- if you have a history of epileptic seizures 
- if you have recently experienced a myocardial infarction (heart attack), or if you are suffering 

rom congestive heart failure or from an uncontrolled hypertension (high blood pressure). 



 65

 
In these situations the treatment should be carefully supervised, and the clinical benefit of Memantine  
Accord assessed by your doctor on a regular basis. 
 
If you suffer from renal impairment (kidney problems), your doctor should closely monitor your 
kidney function and if necessary adapt the memantine doses accordingly. 
 
The use of medicinal products called amantadine (for the treatment of Parkinson´s disease), ketamine 
(a substance generally used as an anaesthetic), dextromethorphan (generally used to treat cough) and 
other NMDA-antagonists at the same time should be avoided. 
 
Children and adolescents 
 
Memantine Accord is not recommended for children and adolescents under the age of 18 years. 
 
Other medicines and Memantine Accord 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
In particular, Memantine Accord may change the effects of the following medicines and their dose 
may need to be adjusted by your doctor: 
 
amantadine, ketamine, dextromethorphan 
dantrolene, baclofen 
cimetidine, ranitidine, procainamide, quinidine, quinine, nicotine 
hydrochlorothiazide (or any combination with hydrochlorothiazide) 
anticholinergics (substances generally used to treat movement disorders or intestinal cramps) 
anticonvulsants (substances used to prevent and relieve seizures) 
barbiturates (substances generally used to induce sleep) 
dopaminergic agonists (substances such as L-dopa, bromocriptine) 
neuroleptics (substances used in the treatment of mental disorders) 
oral anticoagulants 
 
If you go into hospital, let your doctor know that you are taking Memantine Accord. 
 
Memantine Accord with food and drink 
 
You should inform your doctor if you have recently changed or intend to change your diet 
substantially (e.g. from normal diet to strict vegetarian diet) or if you are suffering from states of renal 
tubulary acidosis (RTA, an excess of acid-forming substances in the blood due to renal dysfunction 
(poor kidney function)) or severe infections of the urinary tract (structure that carries urine), as your 
doctor may need to adjust the dose of your medicine. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Pregnancy 
The use of memantine in pregnant women is not recommended. 
 
Breast-Feeding 
Women taking Memantine Accord should not breast-feed. 
 
Driving and using machines 
 



 66

Your doctor will tell you whether your illness allows you to drive and to use machines safely.Also, 
Memantine Accord may change your reactivity, making driving or operating machinery inappropriate. 
 
Memantine Accord contains lactose 
 
This medicinal product contains lactose. If you have been told by your doctor that you have an 
intolerance to some sugars, please contact your doctor before taking this medicinal product. Your 
doctor will advise you. 
 
 
3. How to take Memantine Accord 
 
The Memantine Accord treatment initiation pack is only to be used for the beginning of the treatment 
with Memantine Accord. 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 
if you are not sure. 
 
Dosage 
 
The recommended treatment dose of 20 mg per day is achieved by a gradual increase of the 
Memantine Accord dose during the first 3 weeks of treatment. The treatment scheme is also indicated 
on the treatment initiation pack. Take one tablet once a day. 
 
Week 1 (day 1-7): 
Take one 5 mg tablet once a day (white) for 7 days. 
Week 2 (day 8-14): 
Take one 10 mg tablet once a day (white, scored) for 7 days. 
Week 3 (day 15-21): 
Take one 15 mg tablet once a day (orange to grey-orange) for 7 days. 
Week 4 (day 22-28): 
Take one 20 mg tablet per day (pale red to greyred, scored) for 7 days. 
 
week 1 5 mg tablet 
week 2 10 mg tablet 
week 3 15 mg tablet 
week 4 and beyond 20 mg tablets once a day 

 
Maintenance dose 
The recommended daily dose is 20 mg once a day. 
For continuation of the treatment please consult your doctor. 
 
Dosage in patients with impaired kidney function 
 
If you have impaired kidney function, your doctor will decide upon a dose that suits your condition. In 
this case, monitoring of your kidney function should be performed by your doctor at specified 
intervals. 
 
Administration 
 
Memantine Accord should be administered orally once a day. To benefit from your medicine you 
should take it regularly every day at the same time of the day. The tablets should be swallowed with a 
little water. The tablets can be taken with or without food. 
 
Duration of treatment 
 



 67

Continue to take Memantine Accord as long as it is of benefit to you. Your doctor should assess your 
treatment on a regular basis. 
 
If you take more Memantine Accord than you should 
- In general, taking too much Memantine Accord should not result in any harm to you. You may 

experience increased symptoms as described in section 4. 'Possible side effects'. 
- If you take a large overdose of Memantine Accord, contact your doctor or get medical advice, as 

you may need medical attention. 
 
If you forget to take Memantine Accord 
 
- If you find you have forgotten to take your dose of Memantine Accord, wait and take your next 

dose at the usual time. 
- Do not take a double dose to make up for a forgotten dose. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
In general, the observed side effects are mild to moderate. 
 
Common (may affect up to 1 in 10 people): 
 Headache, sleepiness, constipation, elevated liver function test, dizziness, balance disorders, 

shortness of breath, high blood pressure and drug hypersensitivity 
 
Uncommon (may affect up to 1 in 100 people): 
 Tiredness, fungal infections, confusion, hallucinations, vomiting, abnormal gait, heart failure 

and venous blood clotting (thrombosis/thromboembolism). 
 
Very Rare (may affect up to 1 in 10,000 people): 
 Seizures 
 
Not known (frequency cannot be estimated from the available data): 
 Inflammation of the pancreas, inflammation of the liver and psychotic reactions 
 
Alzheimer's disease has been associated with depression, suicidal ideation and suicide. These events 
have been reported in patients treated with memantine. 
 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Memantine Accord 
 
Keep this medicine out of the sight and reach of children. 
 



 68

Do not use Memantine Accord after the expiry date which is stated on the carton and the blister after 
EXP. The expiry date refers to the last day of that month. 
 
This medicinal product does not require any special storage conditions. 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Memantine Accord contains 
 
- The active substance is memantine hydrochloride. Each film-coated tablet contains 

5/10/15/20 mg of memantine hydrochloride equivalent to 4.15/8.31/12.46/16.62 mg memantine 
- The other ingredients are lactose monohydrate, microcrystalline cellulose, colloidal anhydrous 

silica, crospovidone, magnesium stearate, all in the tablet core; hypromellose, polysorbate 80, 
macrogol 400, titanium dioxide (E 171), and additional for Memantine Accord 15 mg and 
Memantine Accord 20 mg film-coated tablets iron oxide yellow and red (E 172), all in the tablet 
coating 

 
What Memantine Accord looks like and contents of the pack 
 
Memantine Accord 5 mg film-coated tablets are presented as white, oblong, coated tablet, debossed 
with “MT” on one side and “5” on the other side. 
 
Memantine Accord 10 mg film-coated tablets are presented as white, oblong, coated and scored tablet, 
debossed with “MT” divided by the score on one side and “10” divided by the score on the other side. 
The tablet can be divided into equal doses. 
 
Memantine Accord 15 mg film-coated tablets are presented as orange to grey-orange, oblong, coated 
tablet, debossed with “MT” on one side and “15” on the other side. 
 
Memantine Accord 20 mg film-coated tablets are presented as pale red to greyred, oblong, coated and 
scored tablet, debossed with “MT” divided by the score on one side and “20” divided by the score on 
the other side. The tablet can be divided into equal doses. 
 
One treatment initiation pack contains 28 tablets in 4 blisters with 7 tablets of Memantine Accord 
5 mg, 7 tablets of Memantine Accord 10 mg, 7 tablets of Memantine Accord 15 mg and 7 tablets of 
Memantine Accord 20 mg. 
 
Marketing Authorisation Holder 
 
Accord Healthcare S.L.U.  
World Trade Center, Moll de Barcelona, s/n,  
Edifici Est 6ª planta,  
08039 Barcelona,  
Spain 
Manufacturer 
 
Delorbis Pharmaceuticals Ltd 
17, Athinon Street 
Ergates Industrial Area, 2643 Nicosia 
Cyprus 
 
Accord Healthcare Limited 
Sage house, 319 Pinner road 
North Harrow, Middlesex, HA1 4HF 



 69

United Kingdom 
 
Accord Healthcare Polska Sp.z o.o., 
ul. Lutomierska 50,95-200 Pabianice, Poland 
 
This leaflet was last revised in 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETINGAUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE ANDEFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET