Ebixa 10mg FC Tablet

Treatment of patients with moderately severe to severe Alzheimeru2019s disease. Efficacy has not been established beyond 6 months.

Treatment should be initiated and supervised by a physician experienced in the diagnosis and treatment of Alzheimeru2019s dementia. Therapy should only be started if a caregiver is available who will regularly monitor drug intake by the patient. Diagnosis should be made according to current guidelines.

Adults: 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 the 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 is recommended (one tablet in the morning and half a tablet in the afternoon). From the 4th week on, treatment can be continued with the recommended maintenance dose of 20 mg per day (one tablet twice a day). The tablets can be taken with or without food.

Elderly: On the basis of the clinical studies the recommended dose for patients over the age of 65 years is 20 mg per day (10 mg twice a day) as described above.

Renal impairment: In patients with normal to mildly impaired renal function (serum creatinine levels of up to 130 u03bcmol/litre) no dose reduction is needed. In patients with moderate renal impairment (creatinine clearance 40 - 60 ml/min/1.73 mu00b2) daily dose should be reduced to 10 mg per day. No data are available for patients with severely reduced kidney function (see u201cWarningsu201d and u201cPharmacokinetic propertiesu201d).

Hepatic impairment: There are no data on the use of Ebixa in patients with hepatic impairment (see u201cPharmacokinetic propertiesu201d).

Hypersensitivity to the active substance or to any of the excipients. Children and adolescents under the age of 18 years, as safety and efficacy have not been established.

As no data are available for patients with severe renal impairment (creatinine clearance less than 9 ml/min/1.73 mu00b2) therapy is not recommended (see u201cDosage and Directions for Useu201d). Based on pharmacological considerations and single case reports, caution is recommended with patients suffering from epilepsy.

Due to the pharmacological effects and the mechanism of action of Ebixa 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 Ebixa with the antispasmodic agents, dantrolene or baclofen, can modify their effects and a dosage adjustment may be necessary.

Concomitant use of Ebixa 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 u201cSpecial Precautionsu201d). There is one published case report on a possible risk also for the combination of Ebixa and phenytoin.

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 Ebixa leading to a potential risk of increased plasma levels.

There may be a possibility of reduced diuretic effect of hydrochlorothiazide (HCT) when Ebixa is co-administered with HCT or any combination with HCT.

Ebixa did not inhibit CYP 1A2, 2A6, 2C9, 2D6, 2E1, 3A, flavin containing monoxygenase, epoxide hydrolase and sulphation in vitro.

The safety and efficacy of Ebixa in pregnant and lactating women have not been established.

Moderately severe to severe Alzheimeru2019s disease usually causes impairment of driving performance and compromises the ability to use machinery. Furthermore, Ebixa may change reactivity such that outpatients should be warned to take special care when driving a vehicle or operating machinery.

In clinical trials in moderately severe to severe dementia, overall incidence rates for adverse events did not differ from placebo treatment and adverse events were usually mild to moderate in severity. The following table gives an overview of the most frequent (> 4% for Ebixa) adverse events (irrespective of causal relationship) that were observed in the trial population of patients with moderately severe to severe dementia.

Preferred term (WHO ART) Memantine n=299 Placebo n=288 Agitation 27 (9.0%) 50 (17.4%) Inflicted Injury 20 (6.7%) 20 (6.9%) Urinary Incontinence 17 (5.7%) 21 (7.3%) Diarrhoea 16 (5.4%) 14 (4.9%) Insomnia 16 (5.4%) 14 (4.9%) Dizziness 15 (5.0%) 8 (2.8%) Headache 15 (5.0%) 9 (3.1%) Hallucination 15 (5.0%) 6 (2.1%) Fall 14 (4.7%) 14 (4.9%) Constipation 12 (4.0%) 13 (4.5%) Coughing 12 (4.0%) 17 (5.9%) Common adverse reactions (1-10% and more frequent than with placebo) for memantine and placebo patients respectively were: hallucinations (2.0 vs. 0.7%), confusion (1.3 vs. 0.3%), dizziness (1.7 vs. 1.0%), headache (1.7 vs. 1.4%) and tiredness (1.0 vs. 0.3%). Uncommon adverse reactions (0.1-1% and more frequent than with placebo) were anxiety, hypertonia (increased muscle tone), vomiting, cystitis and increased libido.

Treatment of overdosage should be symptomatic and supportive. In one case of suicidal overdosage the patient survived the oral intake of up to 400 mg memantine with effects on the central nervous system (e.g. restlessness, psychosis, visual hallucinations, proconvulsiveness, somnolence, stupor and unconsciousness) which resolved without permanent sequelae.