Memantine Mylan 10 mg film-coated tablets

4. CLINICAL PARTICULARS

4.2 Posology and method of administration

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 tablets (15 mg) per day for 7 days.

 

From Week 4 on:

The patient should take two 10 mg film-coated tablets (20 mg) or one 20 mg film-coated tablet 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 film-coated tablets or one 20 mg film-coated tablet once a day) as described above.

6.       PHARMACEUTICAL PARTICULARS

6.1     List of excipients

 

Tablet cores for 10/20 mg film-coated tablets:

Cellulose, microcrystalline

Croscarmellose sodium

Magnesium stearate

Talc

Silica, colloidal anhydrous

 

Tablet coat for 10/20 mg film-coated tablets:

Polydextrose (E1200)
Titanium dioxide (E171)
Hypromellose 3cP (E464)

Hypromellose 6cP (E464)

Hypromellose 50cP (E464)

Macrogol 400 (E1521)

Macrogol 8000 (E1521)

Iron oxide red (E172)

Additional for 10 mg film-coated tablets:

Titanium dioxide (E171)

Iron oxide yellow (E172)

Indigo carmine aluminium lake (E132)

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 22 April 2013
Date of latest renewal: DD MM YY

 

 

4. CLINICAL PARTICULARS

4.2 Posology and method of administration

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 tablets (15 mg) per day for 7 days.

 

From Week 4 on:

The patient should take two 10 mg film-coated tablets (20 mg) or one 20 mg film-coated tablet 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 film-coated tablets or one 20 mg film-coated tablet once a day) as described above.

6.       PHARMACEUTICAL PARTICULARS

6.1     List of excipients

 

Tablet cores for 10/20 mg film-coated tablets:

Cellulose, microcrystalline

Croscarmellose sodium

Magnesium stearate

Talc

Silica, colloidal anhydrous

 

Tablet coat for 10/20 mg film-coated tablets:

Polydextrose (E1200)
Titanium dioxide (E171)
Hypromellose 3cP (E464)

Hypromellose 6cP (E464)

Hypromellose 50cP (E464)

Macrogol 400 (E1521)

Macrogol 8000 (E1521)

Iron oxide red (E172)

Additional for 10 mg film-coated tablets:

Titanium dioxide (E171)

Iron oxide yellow (E172)

Indigo carmine aluminium lake (E132)

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 22 April 2013
Date of latest renewal: DD MM YY

 

 

$06.3 Shelf life$0$0$0$0$02 3 years$0$0$0$0

$06.3 Shelf life$0$0$0$0$02 3 years$0$0$0$0

Section 4.1:
Treatment of adult patients with moderate to severe Alzheimer’s disease.

Section 4.2:

Treatment should be initiated and supervised by a physician experienced in the diagnosis and treatment of Alzheimer’s dementia.

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 tablets (15 mg) per day for 7 days.

From Week 4 on:
The patient should take two 10 mg film-coated tablets (20 mg) per day.

Maintenance dose

The recommended maintenance dose is 20 mg per day.

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 film-coated tablets once a day) as described above.

Children and adolescents: Memantine Mylan is not recommended for use in children below 18 years due to a lack of data on safety and efficacy.

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 Mylan is not recommended in patients with severe hepatic impairment.

Paediatric population
No data available.

Method of administration

Memantine Mylan should be administered orally once a day and should be taken at the same time every day. The film-coated tablets can be taken with or without food.


Section 4.6:
Pregnancy
There are no or limited amount of data from the use of memantine in pregnant women.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 reactions of memantine were noted on male and female fertility.

Section 4.8:

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 Aadverse Rreactions 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.

Adverse reactions are ranked according to system organ class, using the following convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10), and 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.

[...]

Alzheimer’s disease has been associated with depression, suicidal ideation and suicide. In post-marketing experience these eventsreactions 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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; e-mail: medsafety@hpra.ie.

Section 5.2:
[...]

Linearity/non-linearity
Studies in volunteers have demonstrated linear pharmacokinetics in the dose range of 10 to 40 mg.

Section 6.1:

Tablet core
Microcrystalline cCellulose, microcrystalline
Croscarmellose sodium
Magnesium stearate
Talc
Silica, Ccolloidal anhydrous silica

Tablet coat
Polydextrose (E1200)
Titanium dioxide (E171)
Hypromellose 3cP (E464)
Hypromellose 6cP (E464)
Hypromellose 50cP (E464)
Iron oxide yellow (E172)
Macrogol 400 (E1521)
Macrogol 8000 (E1521)
Indigo carmine aluminium lake (E132)
Iron oxide red (E172)

Section 4.1:
Treatment of adult patients with moderate to severe Alzheimer’s disease.

Section 4.2:

Treatment should be initiated and supervised by a physician experienced in the diagnosis and treatment of Alzheimer’s dementia.

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 tablets (15 mg) per day for 7 days.

From Week 4 on:
The patient should take two 10 mg film-coated tablets (20 mg) per day.

Maintenance dose

The recommended maintenance dose is 20 mg per day.

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 film-coated tablets once a day) as described above.

Children and adolescents: Memantine Mylan is not recommended for use in children below 18 years due to a lack of data on safety and efficacy.

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 Mylan is not recommended in patients with severe hepatic impairment.

Paediatric population
No data available.

Method of administration

Memantine Mylan should be administered orally once a day and should be taken at the same time every day. The film-coated tablets can be taken with or without food.


Section 4.6:
Pregnancy
There are no or limited amount of data from the use of memantine in pregnant women.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 reactions of memantine were noted on male and female fertility.

Section 4.8:

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 Aadverse Rreactions 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.

Adverse reactions are ranked according to system organ class, using the following convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10), and 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.

[...]

Alzheimer’s disease has been associated with depression, suicidal ideation and suicide. In post-marketing experience these eventsreactions 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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; e-mail: medsafety@hpra.ie.

Section 5.2:
[...]

Linearity/non-linearity
Studies in volunteers have demonstrated linear pharmacokinetics in the dose range of 10 to 40 mg.

Section 6.1:

Tablet core
Microcrystalline cCellulose, microcrystalline
Croscarmellose sodium
Magnesium stearate
Talc
Silica, Ccolloidal anhydrous silica

Tablet coat
Polydextrose (E1200)
Titanium dioxide (E171)
Hypromellose 3cP (E464)
Hypromellose 6cP (E464)
Hypromellose 50cP (E464)
Iron oxide yellow (E172)
Macrogol 400 (E1521)
Macrogol 8000 (E1521)
Indigo carmine aluminium lake (E132)
Iron oxide red (E172)

None provided

None provided