Memantine LEK

1 

 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



2 

1.  NAME OF THE MEDICINAL PRODUCT 
 
Memantine LEK 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. 
 
For the full list of excipients, see section 6.1. 
 
 
3.  PHARMACEUTICAL FORM 
 
Film-coated tablet. 
 
Yellow, oval film-coated tablet scored in one side. 
The tablet can be divided into equal doses. 
 
 
4.  CLINICAL PARTICULARS 
 
4.1  Therapeutic indications 
 
Treatment of adult patients with moderate to severe Alzheimer’s disease. 
 
4.2  Posology and method of administration 
 
 
Treatment should be initiated and supervised by a physician experienced in the diagnosis and treatment of 
Alzheimer’s dementia. 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. 
 
Posology 
 
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. 
 
From Week 4 on: 
The patient should take two 10 mg film-coated tablets (20 mg) per day. 



3 

 
Maintenance dose 
The recommended maintenance dose is 20 mg per day. 
 
Special populations 
 
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 LEK is not recommended in patients with severe hepatic 
impairment. 
 
Paediatric population 
Memantine LEK is not recommended for use in children and adolescents below 18 years due to a lack of 
data on safety and efficacy. 
 
Method of administration 
 
Memantine LEK is for oral use. 
Memantine LEK 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 active substances 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. 
 
4.5  Interaction with other medicinal products and other forms of interaction 



4 

 
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 medicinal products, 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 active substances 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 
 
There are no or limited amount of data from the use of memantine in pregnant women. 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 reactions of memantine were noted on male and female fertility. 
 
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 LEK has minor or moderate influence on the ability to 
drive and use machines such that outpatients should be warned to take special care. 
 
4.8  Undesirable effects 



5 

 
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%). 
 
Tabulated list of adverse reactions 
 
The following Adverse Reactions listed in the Table below have been accumulated in clinical studies with 
memantine and since its introduction in the market.  
 
Adverse reactions are ranked according to system organ class, using the following convention: very common 
(≥1/10), common (≥1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥1/10,000 to <1/1,000), very 
rare (< 1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, 
undesirable effects are presented in order of decreasing seriousness. 
 
System organ class Frequency Adverse reaction 
Infections and infestations Uncommon Fungal infections 

 
Immune system disorders Common Drug hypersensitivity 

 
Psychiatric disorders Common  

Uncommon  
Uncommon  
Not known 

Somnolence 
Confusion 
Hallucinations1 
Psychotic reactions2 
 

Nervous system disorders Common  
Common 
Uncommon  
Very rare 

Dizziness 
Balance disorders 
Gait abnormal 
Seizures 
 

Cardiac disorders Uncommon Cardiac failure 
 

Vascular disorders Common  
Uncommon 

Hypertension 
Venous 
thrombosis/thromboembolism 
 

Respiratory, thoracic and 
mediastinal disorders 
 

Common Dyspnoea 
 

Gastrointestinal disorders Common  
Uncommon  
Not known 
 

Constipation 
Vomiting 
Pancreatitis2 

Hepatobiliary disorders Common 
Not known 

Elevated liver function test 
Hepatitis 

General disorders and 
administration site conditions 

Common  
Uncommon 

Headache  
Fatigue 

1Hallucinations have mainly been observed in patients with severe Alzheimer’s disease. 
2Isolated cases reported in post-marketing experience. 
 



6 

Alzheimer’s disease has been associated with depression, suicidal ideation and suicide. In post-marketing 
experience these reactions have been reported in patients treated with 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. 
 
Management  
 
In the event of overdose, treatment should be symptomatic. No specific antidote for intoxication or overdose 
is available. Standard clinical procedures to remove active substance material, e.g. gastric lavage, carbo 
medicinalis (interruption of potential entero-hepatic recirculation), acidification of urine, forced diuresis 
should be used as appropriate. 
 
In case of signs and symptoms of general central nervous system (CNS) overstimulation, careful 
symptomatic clinical treatment should be considered. 
 
 
5.  PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Psychoanaleptics; 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  

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


7 

 
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 to 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 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 to 150 
ng/mL (0.5 - 1 μmol) with large interindividual variations. When daily doses of 5 to 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 to 100 hours. 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 to 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. 



8 

 
Linearity  
 
Studies in volunteers have demonstrated linear pharmacokinetics in the dose range of 10 to 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 events 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 
 
Microcrystalline cellulose 
Croscarmellose sodium 
Colloidal anhydrous silica 
Magnesium stearate 
 
Tablet coat 
 
Polyvinyl alcohol 
Macrogol 3350 
Titanium dioxide (E 171) 
Talc 
Iron oxide yellow (E 172) 
 
6.2  Incompatibilities 
 
Not applicable. 
 



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6.3  Shelf life 
 
4 years. 
 
6.4  Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5  Nature and contents of container 
 
Aluminium-PVC/PVDC blisters placed into cardboard boxes containing 28, 30, 42, 50, 56, 60, 98, 100 and 
112 film-coated tablets. 
 
Not all pack sizes may be marketed. 
 
6.6  Special precautions for disposal 
 
No special requirements. 
 
 
7.  MARKETING AUTHORISATION HOLDER 
 
Pharmathen S.A. 
6, Dervenakion str.  
15351 Pallini, Attiki 
Greece 
 
 
8.  MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/13/826 /001 
EU/1/13/826 /002 
EU/1/13/826 /003 
EU/1/13/826 /004 
EU/1/13/826 /005 
EU/1/13/826 /006 
EU/1/13/826 /012 
EU/1/13/826 /013 
EU/1/13/826 /014 
 
 
9.  DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 22 April 2013 
Date of latest renewal: 
 
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. 

http://www.ema.europa.eu/


10 

1.  NAME OF THE MEDICINAL PRODUCT 
 
Memantine LEK 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. 
 
For the full list of excipients, see section 6.1. 
 
 
3.  PHARMACEUTICAL FORM 
 
Film-coated tablet. 
Pale red, oval film-coated tablet scored in one side. 
The score line is not intended for breaking the tablet. 
 
4.  CLINICAL PARTICULARS 
 
4.1  Therapeutic indications 
 
Treatment of adult patients with moderate to severe Alzheimer’s disease. 
 
4.2  Posology and method of administration 
 
Treatment should be initiated and supervised by a physician experienced in the diagnosis and treatment of 
Alzheimer’s dementia. 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. 
 
Posology 
 
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 5 mg per day for 7 days. 
 
Week 2 (day 8-14): 
The patient should take 10 mg per day for 7 days. 
 
Week 3 (day 15-21): 
The patient should take 15 mg per day for 7 days. 
 
From Week 4 on (day 22-28): 
The patient should take one 20 mg film-coated tablet (20 mg) per day for 7 days. 
The maximum daily dose is 20 mg per day. 
 
Maintenance dose 



11 

The recommended maintenance dose is 20 mg per day. 
 
Special populations 
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 LEK is not recommended in patients with severe hepatic 
impairment. 
 
Paediatric population 
Memantine LEK is not recommended for use in children and adolescents below 18 years due to a lack of 
data on safety and efficacy. 
 
Method of administration 
 
Memantine LEK is for oral use. 
Memantine LEK 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 active substances 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. 
 
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: 



12 

• 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 medicinal products, 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 active substances 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 
 
There are no or limited amount of data from the use of memantine in pregnant women. 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 reactions of memantine were noted on male and female fertility. 
 
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 LEK has minor or 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 
 



13 

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%). 
 
Tabulated list of adverse reactions 
 
The following Adverse Reactions listed in the Table below have been accumulated in clinical studies with 
memantine and since its introduction in the market.  
 
Adverse reactions are ranked according to system organ class, using the following convention: very common 
(≥1/10), common (≥1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥1/10,000 to <1/1,000), very 
rare (< 1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, 
undesirable effects are presented in order of decreasing seriousness. 
 
System organ class Frequency Adverse reaction 
Infections and infestations Uncommon Fungal infections 

 
Immune system disorders Common Drug hypersensitivity 

 
Psychiatric disorders Common  

Uncommon  
Uncommon  
Not known 

Somnolence 
Confusion 
Hallucinations1 
Psychotic reactions2 
 

Nervous system disorders Common  
Common 
Uncommon  
Very rare 

Dizziness 
Balance disorders 
Gait abnormal 
Seizures 
 

Cardiac disorders Uncommon Cardiac failure 
 

Vascular disorders Common  
Uncommon 

Hypertension 
Venous 
thrombosis/thromboembolism 
 

Respiratory, thoracic and 
mediastinal disorders 
 

Common Dyspnoea 
 

Hepatobiliary disorders Common 
Not known 

Elevated liver function test 
Hepatitis 

Gastrointestinal disorders Common  
Uncommon  
Not known 
 

Constipation 
Vomiting 
Pancreatitis2 

General disorders and 
administration site conditions 
 

Common  
Uncommon 

Headache  
Fatigue 
 

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



14 

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. 
 
Management  
 
In the event of overdose, treatment should be symptomatic. No specific antidote for intoxication or overdose 
is available. Standard clinical procedures to remove active substance material, e.g. gastric lavage, carbo 
medicinalis (interruption of potential entero-hepatic recirculation), acidification of urine, forced diuresis 
should be used as appropriate. 
 
In case of signs and symptoms of general central nervous system (CNS) overstimulation, careful 
symptomatic clinical treatment should be considered. 
 
 
5.  PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Psychoanaleptics; 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  
 
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): 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


15 

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 to 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 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 to 150 
ng/mL (0.5 - 1 μmol) with large interindividual variations. When daily doses of 5 to 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 to100 hours. 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 to 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 to 40 mg. 



16 

 
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 events 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 
 
Microcrystalline cellulose 
Croscarmellose sodium 
Colloidal anhydrous silica 
Magnesium stearate 
 
Tablet coat 
 
Polyvinyl alcohol 
Macrogol 3350 
Titanium dioxide (E 171) 
Talc 
Iron oxide yellow (E 172) 
Iron oxide red (E 172) 
 
6.2  Incompatibilities 
 
Not applicable. 
 
6.3  Shelf life 
 
4 years. 



17 

 
6.4  Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5  Nature and contents of container 
 
Aluminium-PVC/PVDC blisters placed into cardboard boxes containing 28, 30, 42, 56, 98 and 100 film-
coated tablets. 
 
Not all pack sizes may be marketed. 
 
6.6  Special precautions for disposal 
 
No special requirements. 
 
 
7.  MARKETING AUTHORISATION HOLDER 
 
Pharmathen S.A. 
6, Dervenakion str.  
15351 Pallini, Attiki 
Greece 
 
 
8.  MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/13/826 /007 
EU/1/13/826 /008 
EU/1/13/826 /009 
EU/1/13/826 /010 
EU/1/13/826 /011 
EU/1/13/826 /015 
 
 
9.  DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 22 April 2013 
Date of latest renewal: 

 
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. 

http://www.ema.europa.eu/


18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 
 
 

 



19 

A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 

Name and address of the manufacturers responsible for batch release 

Lek Pharmaceuticals d.d. 
Verovškova 57, 1526 Ljubljana 
Slovenia 
 
Pharmathen International S.A. 
Industrial Park Sapes 
Rodopi Prefecture 
Block No 5 
EL-69300 Rodopi 
Greece 
 
Pharmathen S.A. 
6 Dervenakion str. 
15351 Pallini, Attiki 
Greece 
 

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 product 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) 
 

Not applicable. 



20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 

 
 
 



21 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 



22 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
 
OUTER PACKING 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Memantine LEK 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 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablet. 
28 film-coated tablets 
30 film-coated tablets 
42 film-coated tablets 
50 film-coated tablets 
56 film-coated tablets 
60 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.  
 
 
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  
 
 



23 

9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IFAPPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Pharmathen S.A. 
6, Dervenakion str.  
15351 Pallini, Attiki 
Greece 
Tel.: +30 210 66 65 067 
Email: info@pharmathen.com 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/13/826 /001 28 film-coated tabletsEU/1/13/826 /002 30 film-coated tablets 
EU/1/13/826 /003 42 film-coated tablets 
EU/1/13/826 /004 50 film-coated tablets 
EU/1/13/826 /005 56 film-coated tablets 
EU/1/13/826 /006 60 film-coated tablets 
EU/1/13/826 /012 98 film-coated tablets 
EU/1/13/826 /013 100 film-coated tablets 
EU/1/13/826 /014 112 film-coated tablets 
 
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Memantine LEK 10 mg  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC:  



24 

SN:  
NN:  



25 

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



26 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER PACKING 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Memantine LEK 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 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablet. 
28 film-coated tablets 
30 film-coated tablets 
42 film-coated tablets 
56 film-coated tablets 
98 film-coated tablets 
100 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
Oral use.  
 
 
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 
 
 



27 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IFAPPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Pharmathen S.A. 
6, Dervenakion str.  
15351 Pallini, Attiki 
Greece 
Tel.: +30 210 66 65 067 
Email: info@pharmathen.com 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/13/826 /007 28 film-coated tablets 
EU/1/13/826 /008 30 film-coated tablets 
EU/1/13/826 /009 42 film-coated tablets 
EU/1/13/826 /010 56 film-coated tablets 
EU/1/13/826 /011 98 film-coated tablets 
EU/1/13/826 /015 100 film-coated tablets 
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Memantine LEK 20 mg  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  



28 

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

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 



29 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



30 

 
Package leaflet: Information for the user 

 
Memantine LEK 10 mg film-coated tablets 
Memantine LEK 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 LEK is and what it is used for 
2.  What you need to know before you take Memantine LEK 
3.  How to take Memantine LEK 
4.  Possible side effects 
5.  How to store Memantine LEK 
6.  Contents of the pack and other information 
 
 
1.  What Memantine LEK is and what it is used for 
 
How does Memantine LEK work 
Memantine LEK contains the active substance memantine hydrochloride. 
Memantine LEK 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 LEK belongs to a group of medicines called NMDA-receptor 
antagonists. Memantine LEK acts on these NMDA-receptors improving the transmission of nerve signals 
and the memory. 
 
What is Memantine LEK used for 
Memantine LEK is used for the treatment of adult patients with moderate to severe Alzheimer’s disease. 
 
 
2.  What you need to know before you take Memantine LEK 
 
Do not take Memantine LEK 
• 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 LEK  
• if you have a history of epileptic seizures. 
• if you have recently experienced a myocardial infarction (heart attack), or if you are suffering from 

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 LEK 
reassessed by your doctor on a regular basis. 



31 

 
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 LEK is not recommended for children and adolescents under the age of 18 years. 
 
Other medicines and Memantine LEK 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This 
includes medicines obtained without a prescription. 
 
In particular, Memantine LEK 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 LEK. 
 
Memantine LEK 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. 
 
The use of memantine in pregnant women is not recommended. 
 
Women taking Memantine LEK 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 LEK may change your reactivity, making driving or operating machinery inappropriate. 
 
 
3.  How to take Memantine LEK 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you 
are not sure. 
 



32 

Dose 
The recommended dose of Memantine LEK for adults and elderly patients 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 10 mg tablet 
week 2 one 10 mg tablet 
week 3 one and a half 10 mg tablets 
week 4 and beyond two 10 mg tablets or one 20 mg tablet once a 

day 
 
The usual starting dose is half a tablet of 10 mg once a day (1x 5 mg) for the first week. This is increased to 
one tablet of 10 mg once a day (1x 10 mg) in the second week and to 1 and a half tablet of 10 mg once a day 
in the third week. From the fourth week on, the usual dose is 2 tablets once a day (1 x 20 mg). 
 
Dose 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 LEK 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 some water. The 
tablets can be taken with or without food. 
 
Duration of treatment 
Continue to take Memantine LEK as long as it is of benefit to you. Your doctor should assess your treatment 
on a regular basis. 
 
If you take more Memantine LEK than you should 
- In general, taking too much Memantine LEK 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 LEK, contact your doctor or get medical advice, as you may 
need medical attention. 
 
If you forget to take Memantine LEK 
- If you find you have forgotten to take your dose of Memantine LEK, 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 tests, 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 
 



33 

Not known (frequency cannot be estimated from the available data): 
• Inflammation of the pancreas, inflammation of the liver (hepatitis) 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. 
 
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 LEK 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine 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 medicine 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 LEK contains 
• The active substance is memantine hydrochloride.  

Each 10 mg tablet contains 10 mg of memantine hydrochloride equivalent to 8.31 mg memantine. 
Each 20 mg tablet contains 20 mg of memantine hydrochloride equivalent to 16.62 mg memantine. 

 
• The other ingredients are: 

Tablet core: croscarmellose sodium, colloidal anhydrous silica, microcrystalline cellulose, magnesium 
stearate  
 
10 mg: 
Film-coating: polyvinyl alcohol, titanium dioxide (E-171), talc, macrogol 3350 and iron oxide yellow (E-
172) 
 
20 mg: 
Film-coating: polyvinyl alcohol, titanium dioxide (E-171), talc, macrogol 3350, iron oxide yellow (E-
172) and iron oxide red (E-172)  

 
What Memantine LEK looks like and contents of the pack 
Memantine LEK 10 mg film-coated tablets are presented as yellow, oval film-coated tablet scored in one 
side. The tablet can be divided into equal doses. 
Memantine LEK 20 mg film-coated tablets are presented as pale red, oval film-coated tablet scored in one 
side. The score line is not intended for breaking the tablet. 
 
Memantine LEK 10 mg film-coated tablets are available in PVC/PVDC–Aluminium blister packs of 28, 30, 
42, 50, 56, 60, 98, 100 and 112 tablets. 
 
Memantine LEK 20 mg film-coated tablets are available in PVC/PVDC–Aluminium blister packs of 28, 30, 
42, 56, 98 and 100 tablets. 
 
Not all pack sizes may be marketed. 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


34 

 
Marketing Authorisation Holder 
Pharmathen S.A., 6, Dervenakion str., 15351 Pallini, Attiki, Greece 
 
Manufacturers 
Pharmathen S.A , 6, Dervenakion str., 15351 Pallini, Attiki, Greece  
 
Pharmathen International S.A., Industrial Park Sapes, Rodopi Prefecture, Block No 5, Rodopi 69300, Greece  
Lek Pharmaceuticals d.d., Verovškova 57, 1526 Ljubljana, Slovenia 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sandoz n.v./s.a.  
Tél/Tel: +32 2 722 97 81 

Lietuva 
Sandoz Pharmaceuticals d.d. 
Tel: + 370 5 2636 037 
 

България 
Sandoz d.d Representative office  
Teл.: + 359 2 970 47 47 
 

Luxembourg/Luxemburg 
Sandoz n.v./s.a.  
Tel: + 32 2 722 97 81 
 

Česká republika 
Sandoz s.r.o. 
Tel: + +420 225 775 111  

Magyarország 
Sandoz Hungária Kft. 
Tel.: + 36 1 430 2896  
 

Danmark 
Sandoz A/S  
Tel: + 45 6395 1000  

Malta 
Cherubino LTD  
Tel: + 356 21 343 270 
 

Deutschland 
Sandoz Pharmaceuticals GmbH  
Tel: + 49 08024 902-4513 

Nederland 
Sandoz B.V. 
Tel: + 31 (0)36 5241600  
 

Eesti  
Sandoz d.d. Estonia  
Tel: + 372 6652405  

Norge 
Sandoz A/S  
Tlf: + 45 6395 1000  
 

Ελλάδα 
Sambrook Pharmaceuticals Med SA 
800 110 0333  (χωρίς χρέωση) / +30-210-
8194280 

Österreich 
Sandoz GmbH  
Tel: + 43 5338 200  
 

España 
Sandoz Farmacéutica, S.A. 
Tel: + 34 91 740 12 92  

Polska 
Lek S.A. 
Tel.: + 48 /22/ 549 15 43, +48 /22/ 549 07 24 
 

France 
Sandoz  
+33 1 49 64 48 21 

Portugal 
Sandoz Farmacêutica Lda. 
Tel: + 351 21 196 40 00  
 

Hrvatska 
Sandoz d.o.o. 
Tel: +385 1 23 53 111 
 

România 
Sandoz SRL Romania  
Tel: + 40 21 407 51 83 
 

Ireland 
ROWEX LTD 
Tel: + 353 27 50077 

Slovenija 
Lek Pharmaceuticals d.d.  
Tel: + 386 1 580 3327  
 



35 

Ísland 
Sandoz A/S  
Tel: + 45 6395 1000 

Slovenská republika 
Sandoz d.d. organizacna zlozka  
Tel: + 421-2/48 200 600  
 

Italia 
Sandoz S.p.A. 
Tel: + 39 02 96 54 3483 

Suomi/Finland 
Sandoz A/S 
Puh/Tel: + 45 6395 1000 
 

Κύπρος 
P.T.Hadjigeorgiou Co Ltd 
Τηλ: + 357 – 25372425 

Sverige 
Sandoz A/S  
Tel: + 45 6395 1000  
 

Latvija 
Sandoz d.d. representative office Latvia. 
Tel: + 371 6789 2006 

United Kingdom 
Sandoz Limited 
Tel: + 44 1276 698020 
 

 
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. 

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 MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET