Ravemantine

Each tablet contains:

Pharmacological Actions. 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.

• Memantine is indicated for treatment of moderate to severe Alzheimer's disease.

Memantine is contraindicated in patients with Known hypersensitivity to memantine hydrochloride or to any of the product excipients.

• The maximum daily dose is 20 mg per day in order to reduce the risk of side effects the maintenance dose is achieved by upward titration of 5 mg per week over the first 3 weeks as follows:
• Treatment should be started with 5 mg daily (half a tablet in the morning) during 1st week. In the 2nd week 10 mg per day (half a tablet twice a day) and in the 3rd week 15 mg per day (one tablet in the morning and half a tablet in the afternoon or evening) is recommended. From the 4th week on treatment can be continued with the recommended maintenance dose of 20 mg per day (one tablet twice a day).
• Tablets can be taken with or without food.
• Elderly: the recommended dose for patients over the age of 65 years is 20 mg per day (10 mg twice a day).
• Children and adolescent under the age of 18 years: not recommended for use in children below 18 years due to a lack of data on safety and efficacy.

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 agent, dantrolene or baclofen, can modify their effects and a dosage adjustment may be necessary.

Concomitant use of memantine and amantadine should be avoided, owing to the risk of pharmacotoxic psychosis. Other drugs 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 INR increases have been reported in patients concomitantly treated with warfarin , although no relationship has been established, close monitoring of prothrombin time or INR is advisable for patients concomitantly treated with oral anticoagulants.

• Caution is recommended in patients with epilepsy, former history of convulsions or patients with predisposing factors for epilepsy.
• Concomitant administration of N-methyl -D-aspartate (NMDA) antagonists such as amantadine, ketamine should be avoided.
• Patients with myocardial infarction, uncompensated congestive heart failure or uncontrolled hypertension were excluded as patients with these conditions should be closely supervised.

Pregnancy and Lactation:
Pregnancy:
No clinical data on exposed pregnancies are available. Memantine should not be used during pregnancy unless clearly necessary.

Lactation:
It is not known whether memantine is excreted in human breast milk. Memantine administration to nursing women should be avoided if clinically possible.

Keep in a cool dry place away from light, below 30 °C.

Pack of one or two blisters AL/PVC each of 10 tablets.