Regulatory Decision Summary for Pdp-Amlodipine

The present New Drug Submission for pdp-Amlodipine oral solution was based on a single bioequivalence study which demonstrated relative bioavailability of pdp-Amlodipine oral solution compared to a foreign reference product, ISTIN (amlodipine besylate) tablets. Because a foreign reference product was administered as the comparator in the pivotal bioequivalence study, the sponsor sought to bridge the proposed pdp-Amlodipine oral solution to the Canadian Reference Product (CRP), i.e., Norvasc tablets, by linking Istin Tablets to Norvasc Tablets. The link between the proposed pdp-Amlodipine oral solution and the existing Norvasc tablets was considered sufficient Having pdp-Amlodipine oral solution available to Canadians will allow more accurate dosing, which is particularly important in a vulnerable patient population such as pediatrics. This amlodipine oral solution will also be useful for adult patients with swallowing difficulties.

Although the Canadian labelling content of Norvasc tablets was deemed acceptable to be applied to pdp-Amlodipine, some revisions were made to reflect differences in drug formulation. These revisions aimed at informing the prescribers on the presence of liquid maltitol and glycerol as non-medicinal ingredients in the oral solution formulation and their associated risks; emphasizing that the long-term effects of pdp-Amlodipine on growth, puberty and general development have not been studied; describing signs, symptoms and treatment information obtained from pediatric case reports of amlodipine overdosing; and advising on how the product should be administered with regards to food. Two new contraindications for patients with hereditary fructose intolerance or with hyperglycerolemia / glycerol kinase deficiency, and a new cautionary statement were added in the Product Monograph of pdp-Amlodipine. Off-label use in patients below age of 6 years could potentially be increased with this new formulation. The Product Monograph clearly mentions that the use of pdp-Amlodipine in children less than 6 years of age is not recommended as the safety and efficacy have not been established in this patient population.

With all the above-mentioned aspects properly addressed, the benefit-harm-uncertainty assessment of pdp-Amlodipine oral solution was deemed positive.