Regulatory Decision Summary for Mint-Citalopram Solution

This New Drug Submission (NDS) was filed by Mint Pharmaceuticals Inc. to obtain market authorization for Mint-Citalopram Solution (citalopram hydrobromide oral solution) for the symptomatic relief of depressive illness in adults. This submission proposes to rely on the safety and efficacy characterized for the innovator product Celexa (citalopram hydrobromide tablets) by bridging the Mint oral solution to the innovator tablet via a comparative bioavailability study. Since the oral solution and the tablet are not considered comparable dosage forms, this submission was filed as a NDS.

Citalopram is an antidepressant of the selective serotonin reuptake inhibitor class, first authorised in Canada as Celexa (citalopram hydrobromide tablets) for an indication in major depressive disorder (MDD) in 1999. This submission proposes to rely on the safety and efficacy characterised for the innovator product Celexa (citalopram hydrobromide tablets) by bridging the proposed citalopram oral solution formulation to the Celexa tablet by a comparative bioavailability study. Therefore, the sponsor did not conduct new non-clinical or clinical safety and efficacy studies with their product.

The only study conducted by the sponsor was the comparative bioavailability study of the proposed oral solution formulation against the reference product, Celexa tablets (Study 23-VIN-0236). Results of Study 23-VIN-0236 demonstrated comparative bioavailability between the proposed Mint-Citalopram Solution 10 milligram (mg) per 5 millilitre (mL) and Celexa tablets, administered as a 40 mg dose under fasting conditions. As a result, the safety and efficacy characterised for the innovator product, Celexa, was used to support the authorisation of Mint-Citalopram Solution. The sponsor’s proposed Mint-Citalopram Solution Product Monograph (PM) was based on the Celexa PM.

The sponsor provided a non-clinical overview that summarized information from the literature and from pharmacology, pharmacokinetics and toxicology studies conducted with citalopram, mostly good laboratory practice studies conducted during the initial drug development. No non-clinical information from these publications was considered relevant for inclusion to the PM, as the information either related to safety issues already described or was addressed by current risk management strategies in labelling for citalopram.

There were no impurity concerns related to the drug product or container closure system, including leachable/extractable impurities. Furthermore, there were no outstanding issues with excipients. The submitted chemistry and manufacturing information demonstrated that the drug substance and drug product can be consistently manufactured to meet approved specifications.

The sponsor also provided a clinical overview summarising safety and efficacy information for citalopram from a literature review up to February 2025.

For the review of efficacy, a total of seventeen published studies with citalopram were described, including some of the studies submitted to Health Canada in support of approval of the MDD indication for Celexa. The other studies used active comparators (tricyclic antidepressants, sertraline) or were conducted in special populations (elderly, with or without comorbid dementia) or in different patient populations (obsessive-compulsive disorder; bipolar depression as adjunct therapy; depression and epilepsy; depression and asthma). All studies showed significant improvements in the citalopram arm, with demonstrated superiority to placebo or similar efficacy to the active comparator. No information from these studies was considered relevant for inclusion in the citalopram labelling.

The safety information summarised from the literature was consistent with the safety profile already labelled for citalopram products in Canada. Generally, information provided in the summary did not warrant revisions to the PM, as they were consistent with information or with recommendations for risk minimisation already in the innovator (Celexa) PM.

Safety results from the comparative bioavailability Study 23-VIN-0236 did not raise any new safety concern. This was not unexpected due to limitations of the study to characterise safety (small population of healthy participants and low exposure from two citalopram doses with a washout period of 21 days between them).

The final Mint-Citalopram Solution PM was aligned with the latest PM for the innovator product Celexa, whose characterised safety and efficacy are relied upon, and to provide current evidence-based information and recommendations for optimal use and risk minimisation appropriate for this citalopram product.

Overall, the benefit-harm-uncertainty profile was favourable for Mint-Citalopram Solution for the authorized indication when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance was recommended.

For further details about Mint-Citalopram Solution, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.