Regulatory Decision Summary for Mar-Cidofovir
Review decision
The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.
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What was the purpose of this submission?
The New Drug Submission (NDS) was filed in order to obtain market authorisation for Mar-Cidofovir in the treatment of cytomegalovirus (CMV) retinitis in patients having acquired immunodeficiency syndrome (AIDS). This NDS is a Submission Relying on Third-Party Data (SRTD). Cidofovir injection is not a new active substance in Canada, having received a Notice of Compliance in 1999 for a comparable indication. Therefore this assessment also refers to the original review by the Bureau of Pharmaceutical Assessment, dated February 10, 1999.
Why was the decision issued?
Mar-Cidofovir is an intravenous formulation of cidofovir, a cytidine nucleotide analogue which inhibits cytomegalovirus (CMV) replication. Mar-Cidofovir is intended for treatment of CMV retinitis in patients with AIDS.
The efficacy of cidofovir injection in delaying the progression of retinitis was demonstrated based on two controlled clinical trials, Studies GS-93-105 and GS-93-106. Cidofovir, when administered concomitantly with probenecid and intravenous hydration for renal protection, was shown to significantly slow progression of CMV retinitis in patients with AIDS, given as an induction course of 5 mg/kg once a week for two weeks, followed by a dose of 5 mg/kg once every two weeks as maintenance treatment. Additionally, data from Study GS-93-107 support the efficacy of the maintenance treatment regimen of 5 mg/kg given once every two weeks.
The major risks associated with cidofovir treatment include nephrotoxicity, potential carcinogenicity and teratogenesis, hematological effects, and the occurrence of iritis, with or without ocular hypotony. Despite these risks, considering the seriousness of CMV retinitis in AIDS patients, the overall benefit-harm-uncertainty profile of Mar-Cidofovir is considered favourable.
The potential for nephrotoxicity with cidofovir is a major safety concern, and as a result the Product Monograph includes a contraindication in patients with moderate renal impairment (creatinine clearance ≤ 55 mL/min) or those taking other potentially nephrotoxic medication. The PM specifies that cidofovir must only be administered with probenecid and intravenous hydration, according to the protocol described. Careful monitoring of renal function in patients on treatment is advised, as is prompt discontinuation of therapy if significant renal dysfunction occurs. The PM also includes clear warnings regarding the need for careful monitoring of other risks associated with cidofovir, including uveitis/iritis, ocular hypotony, carcinogenesis, teratogenesis, and hematologic disorders, including neutropenia. These risks are prominently highlighted in a Serious Warnings and Precautions Box.
Decision issued
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.
Related Drug Products
| Product name | DIN | Company name | Active ingredient(s) & strength |
|---|---|---|---|
| MAR-CIDOFOVIR | 02473925 | MARCAN PHARMACEUTICALS INC | CIDOFOVIR (CIDOFOVIR DIHYDRATE) 375 MG / 5 ML |