Summary

• Canagliflozin is supplied as film-coated tablets for oral administration.¹ INVOKANA tablets are immediate-release tablets formulated with croscarmellose which acts as a disintegrant.²
• In phase 3 clinical trials, the INVOKANA study drug was to be swallowed whole with liquid and not crushed or dissolved.²
• There were no relevant studies identified regarding crushing of INVOKANA tablets for oral or enteral feeding tube administration.

CLINICAL STUDIES

• According to the unpublished protocols for the nine phase 3 clinical efficacy studies described in the CLINICAL STUDIES section of the INVOKANA^® Prescribing Information, the INVOKANA study drug was to be taken orally and was to be swallowed whole with liquid and not crushed or dissolved.²
• In a definitive food-effect study, co-administration of a single canagliflozin 300 mg tablet with a high-fat meal had no effect on the pharmacokinetics of canagliflozin; therefore, canagliflozin may be taken with or without food.^1,3 In this study, the tablets were swallowed whole.

FORMULATION CONSIDERATIONS

• INVOKANA tablets, for oral use, are formulated to provide immediate-release upon swallowing.² The tablets are not enteric-coated, delayed-release, extended-release, or controlled-release.
• The tablets are formulated with croscarmellose sodium¹ which serves as a disintegrant.² INVOKANA tablets are formulated to have an in vitro disintegration time of 0-15 minutes.²
• Based on its solubility and intestinal permeability, the drug substance, INVOKANA, is categorized under the Biopharmaceutics Classification System⁴ as BCS Class 4: Low Solubility and Low Permeability Drugs.²
• No studies have been conducted by Johnson & Johnson to establish bioequivalence between crushed and intact INVOKANA tablets.²

Crushing Tablets to Make an Extemporaneous Oral Liquid

• The drug substance canagliflozin is practically insoluble in aqueous media from pH 1.1 to 12.9.¹ Additionally, canagliflozin tablets contain the excipient, microcrystalline cellulose,¹ which is insoluble in aqueous media.
• Initial phase 1 studies^5-7 were conducted using an oral suspension of canagliflozin (5 mg/mL or 50 mg/mL prepared in 0.5% w/w hypromellose) to facilitate flexibility of a broad range of dosing. Subsequently, a solid oral dosage form (tablet) was developed for ease of administration and large-scale production.²

Crushing Tablets to Administer via Enteral Feeding Tube

• No published reports were identified describing the safety, efficacy, or pharmacokinetics of canagliflozin tablets when crushed and administered via enteral feeding tube (e.g., G-tube, NG-tube, ND-tube, PEG-tube, J-tube).

REVIEW ARTICLES

While there is no published information regarding crushing INVOKANA tablets for oral or enteral administration, there are a number of references that offer general considerations regarding the practice of crushing tablets and/or administration via enteral feeding tubes.^8-13

LITERATURE SEARCH

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 14 October 2024. No published reports were identified.