Dear Health Care Professional Letter - CO Memantine

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Contact: Bureau of Pharmaceutical Sciences

Date: November 12, 2009

Dear Health Care Professional:

Cobalt Pharmaceuticals Inc. is pleased to announce that Health Canada has issued a Notice of Compliance with Conditions (NOC/c) under the Notice of Compliance with Conditions Policy for CO Memantine (memantine hydrochloride) to be used as monotherapy for the symptomatic treatment of patients with moderate to severe dementia of the Alzheimer's type. The issuance of the NOC/c for CO Memantine was based on pharmaceutical equivalence and bioequivalence to the Canadian Reference Product (CRP), Ebixa^® (memantine hydrochloride). As part of its conditions, Cobalt Pharmaceuticals Inc. has also undertaken to provide Health Canada with Periodic Safety Update Reports (PSUR-C's) on a semi-annual basis.

The CRP has been issued a NOC under the NOC/c Policy to reflect the promising nature of the clinical evidence for the CRP and the need for a confirmatory study to verify the clinical benefit of the memantine CRP.

Patients should be advised of the conditional nature of the market authorization for CO Memantine.

Persistent activation of the central nervous system N-methyl-D-aspartate (NMDA) receptors by the excitatory amino acid glutamate has been hypothesized to be involved in the pathogenesis of Alzheimer's disease. Memantine, a low to moderate affinity uncompetitive (open channel) NMDA receptor antagonist, binds preferentially to the NMDA receptor-operated cation channels. There is no clinical evidence that memantine prevents or slows neurodegeneration or that it alters the course of the underlying dementing process in patients with Alzheimer's disease.

CO Memantine is contraindicated in patients with known hypersensitivity to memantine hydrochloride or to any excipients used in the formulation.

Treatment emergent adverse events that were reported in at least 2% of patients receiving memantine hydrochloride in placebo-controlled dementia trials and for which the rate of occurrence was greater for patients treated with memantine hydrochloride than for those treated with placebo were anorexia, anxiety, back pain, confusion, constipation, dizziness, dyspnea, fatigue, hallucinations, headache, hypertension, nausea, pain, somnolence and vomiting. Other adverse events occurring with an incidence of at least 2% in memantine - treated patients but at an equal or lower rate than placebo were agitation, arthralgia, bronchitis, cataract, coughing, depression, diarrhea, fall, gait abnormal, inflicted injury, influenza-like symptoms, insomnia, urinary incontinence and urinary tract infection.

The risk/benefit of CO Memantine treatment for patients with a history of seizure disorder must be carefully evaluated. Caution should also be observed when memantine is initiated in patients with cardiovascular conditions.

CO Memantine should only be prescribed by (or following consultations with) clinicians who are experienced in the diagnosis and management of Alzheimer's disease. CO Memantine is available in 5 milligrams (mg) and 10 mg tablets, for oral use and at a recommended maintenance dose of 20 mg/day. In order to reduce the risk of side effects the maintenance dose is achieved by upward titration as follows: the usual starting dose is 5 mg/day. The dose should then be increased in 5 mg increments, as tolerated by the patient, to 10 mg/day (5 mg twice a day), 15 mg/day (10 mg and 5 mg as separate doses), and 20 mg/day (10 mg twice a day). The minimum recommended interval between dose increases is one week. In patients with moderate renal impairment (creatinine clearance 40 - 60 millilitres/minute/1.73 metres²) the daily dose should be reduced to 10 mg per day. In patients with severe renal impairment the use of memantine hydrochloride has not been systematically evaluated and is therefore not recommended in these patients. Please refer to the product monograph for further details.

Any questions from health care professionals may be directed to the customer service line at Cobalt Pharmaceuticals Inc. at Telephone Number 1-866-254-6111.

Sincerely,

Mr. Henry Koziarski
Chief Financial Officer