MYLAN-AMLODIPINE/ATORVASTATIN

). 1 Pediatrics Based on the data submitted and reviewed by Health Canada, the safety and efficacy of MYLAN- AMLODIPINE/ATORVASTATIN in pediatric patients has not been established; therefore, Health Canada has not authorized an indication for pediatric use.

3 Pediatrics). 4 Geriatrics). 2 CONTRAINDICATIONS MYLAN-AMLODIPINE/ATORVASTATIN (amlodipine besylate/atorvastatin calcium) is contraindicated in: • patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medical ingredient, or component of the container.

For a complete listing, see

1 Adverse Reaction Overview Amlodipine The most serious adverse reaction associated with the amlodipine component of MYLAN- AMLODIPINE/ATORVASTATIN is hypotension (including syncope) especially under gross overdose (see 5 OVERDOSAGE).

2 Clinical Trial Adverse Reactions). 5 Post-Market Adverse Reactions). 2 Clinical Trial Adverse Reactions). 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates of adverse drug reactions in real- world use. For amlodipine/atorvastatin, itself Amlodipine/atorvastatin (amlodipine besylate /atorvastatin calcium) has been evaluated for safety in 1,092 patients in two double-blind, placebo-controlled studies treated for co-morbid hypertension and dyslipidemia.

In these studies, no unexpected adverse experiences particular to this combination have been observed. Adverse experiences have been limited to those that were reported previously with amlodipine and/or atorvastatin. For the most part, adverse experiences with amlodipine/atorvastatin have been mild or moderate in severity.

0% of patients given placebo. The most common safety-related reasons for discontinuation from these studies in the combination treatment groups were headache and peripheral edema. In a double-blind, controlled clinical trial of all available amlodipine/atorvastatin doses (5/10 mg to 10/80 mg amlodipine/atorvastatin respectively), the incidences of treatment-emergent adverse events (all causalities) that occurred in at least 1% of all combination treatment groups, pooled across all the combination doses, are summarized below.

2 Breast-feeding). 4 Drug-Drug Interactions). 4 Drug-Drug Interactions). 1 Dosing Considerations • MYLAN-AMLODIPINE/ATORVASTATIN is a combination product containing amlodipine besylate and atorvastatin calcium • MYLAN-AMLODIPINE/ATORVASTATIN is not intended for initial therapy.

• The dosage of atorvastatin should be individualized according the baseline LDL-C, total-C/HDL-C ratio and/or TG levels to achieve the recommended desired lipid values at the lowest dose needed MYLAN-AMLODIPINE/ATORVASTATIN (amlodipine besylate and atorvastatin calcium) – Product Monograph Page 5 of 67 to achieve LDL-C desired level.

Lipid levels should be monitored periodically and, if necessary, the dose of atorvastatin adjusted based on desired lipid levels recommended by guidelines. • Patients should be placed on a standard cholesterol-lowering diet before receiving atorvastatin, and should continue on this diet during treatment with atorvastatin.

If appropriate, a program of weight control and physical exercise should be implemented. • Prior to initiating therapy with atorvastatin, secondary causes for elevations in plasma lipid levels should be excluded. A lipid profile should also be performed.

2 Recommended Dose and Dosage Adjustment The dosage of MYLAN-AMLODIPINE/ATORVASTATIN in adults must be individualized on the basis of both effectiveness and tolerance for each component which should be determined by titration as described below.

MYLAN-AMLODIPINE/ATORVASTATIN is not indicated for pediatric use. Amlodipine • For Adults For both hypertension and angina, the recommended initial dose of amlodipine besylate is 5 mg once daily. If necessary, dose can be increased after 1-2 weeks to a maximum dose of 10 mg once daily.

• For Elderly or in Patients with Impaired Renal Function The recommended initial dose in patients over 65 years of age or patients with impaired renal function is 5 mg once daily. 4 Geriatrics). • Patients with Impaired Hepatic Function Dosage requirements have not been established in patients with impaired hepatic function.

MYLAN-AMLODIPINE/ATORVASTATIN (amlodipine besylate/atorvastatin calcium) is contraindicated in: • patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medical ingredient, or component of the container.

For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING. • patients with severe hypotension (less than 90 mmHg systolic) and in patients with active liver disease or unexplained persistent elevations of serum transaminases exceeding 3 times the upper limit of normal.

2 Breast-feeding). 4 Drug-Drug Interactions). 4 Drug-Drug Interactions).