This information is intended for US healthcare professionals to access current scientific information about J&J Innovative Medicine products. It is prepared by Medical Information and is not intended for promotional purposes, nor to provide medical advice.
There have been no safety or efficacy studies conducted with INVOKAMET®; however, bioequivalence of INVOKAMET® to canagliflozin (CANA) and metformin coadministered as individual tablets was demonstrated in healthy subjects. Coadministration of CANA and metformin has been studied in type 2 diabetes mellitus (T2DM) patients inadequately controlled on diet and exercise and in combination with other antihyperglycemic agents (AHAs).1
Summary
- INVOKAMET® is supplied as film-coated tablets for oral administration. 1
- CANA and metformin HCl tablets are immediate-release tablets formulated with croscarmellose which1 ensures the break-up of the tablet matrix upon ingestion.2
- There were no relevant studies or case reports identified regarding crushing of INVOKAMET tablets for oral or enteral feeding tube administration.
CLINICAL STUDIES
According to unpublished protocols for 4 phase 1 bioequivalence studies3-6 and 1 food effects study7, INVOKAMET fixed dose combination (FDC) tablets were to be taken orally and swallowed whole with 240 mL of water in all 5 studies.
FORMULATION CONSIDERATIONS
- INVOKAMET® tablets, for oral use, are formulated to provide immediate-release upon swallowing.8 Tablets are not enteric-coated, delayed-release, extended-release, or controlled-release.
- Tablets are formulated with croscarmellose sodium8 which serves as a disintegrant to prepare the product for immediate-release upon swallowing.1
- Based on its solubility and intestinal permeability, the drug substance, CANA, is categorized under the Biopharmaceutics Classification System9 as BCS Class 4: Low Solubility and Low Permeability Drugs. Metformin is categorized as BCS Class 3: High Solubility and Low Permeability Drugs.10
Crushing Tablets to Mix with Food
- While INVOKAMET® tablets are to be administered orally with food8, no studies have been conducted to assess plasma concentrations using crushed tablets mixed with food.
Crushing Tablets to Make an Extemporaneous Oral Liquid
- There were no recipes identified in published literature describing extemporaneous compounding of crushed INVOKAMET tablets into liquid formulation, or storage and stability of a compounded liquid preparation.
- The drug substance CANA is practically insoluble in aqueous media from pH 1.1 to 12.9.8
- The drug substance metformin HCl is freely soluble in water. The pH of a 1% aqueous solution of metformin HCl is 6.68.11
- INVOKAMET® tablets contain the excipient, microcrystalline cellulose,8 which is insoluble in aqueous media.
Crushing Tablets to Administer via Enteral Feeding Tube
- No published reports were identified describing safety, efficacy, or pharmacokinetics of INVOKAMET tablets when crushed and administered via enteral feeding tube (e.g., Gtube, NG-tube, ND-tube, PEG-tube, J-tube).
REVIEW ARTICLES
While there is no published information regarding crushing INVOKAMET tablets for oral or enteral administration, there are references that offer general considerations regarding crushing tablets and/or administration via enteral feeding tubes.12-17
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 20 November 2024. No published reports of crushing INVOKAMET tablets prior to oral ingestion or administration via enteral feeding tube (e.g., gastric [G-tube], nasogastric [NG-tube], nasoduodenal [ND-tube], percutaneous endoscopic gastrostomy [PEG-tube], jejunostomy [J-tube]) were identified.
| 1 | INVOKAMET (canagliflozin and metformin hydrochloride) / INVOKAMET XR (canagliflozin and metformin hydrochloride extended-release) [Prescribing Information]. Titsuville, NJ: Janssen Pharmaceuticals, Inc; https://imedicalknowledge.veevavault.com/ui/approved_viewer?token=7994-1f749c73-ec3a-43a2-9b03-b61e1eb82a5d. |
| 2 | Desai PM, Liew CV, Heng PWS. Review of disintegrants and the disintegration phenomena. J Pharm Sci. 2016;105(9):2545-2555. |
| 3 | Janssen Research & Development, LLC. (Posted 2012). A study of canagliflozin and metformin immediate release (50 mg/500 mg) FDC tablets in healthy volunteers. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2024 November 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT01508195 NLM Identifier: NCT01508195. |
| 4 | Janssen Research & Development, LLC. (Posted 2011). A study to assess the bioequivalence of 2 fixed dose combination (FDC) tablets of canagliflozin and metformin immediate release (IR) (50 mg/1,000 mg) with respect to the individual components of canagliflozin (1 x 100 mg) and metformin IR tablets (2 x 1,000 mg) in healthy volunteers. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2024 November 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT01454622 NLM Identifier: NCT01454622. |
| 5 | Janssen Research & Development, LLC. (Posted 2011). A study to assess the bioequivalence of fixed dose combination (FDC) tablets of canagliflozin and metformin immediate release (IR) with respect to the individual components of canagliflozin and metformin IR tablets in healthy volunteers. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2024 November 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT01463228 NLM Identifier: NCT01463228. |
| 6 | Janssen Research & Development, LLC. (Posted 2012). A study of canagliflozin and metformin immediate release (150 mg/500 mg) FDC tablets in healthy volunteers. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2024 November 20]. Available from: https://clinicaltrials.gov/study/NCT01508182 NLM Identifier: NCT01508182. |
| 7 | Janssen Research & Development, LLC. (Posted 2011). Effect of food on a fixed dose combination tablet of canagliflozin and metformin immediate release in healthy volunteers. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2024 November 20]. Available from: https://clinicaltrials.gov/study/NCT01459094 NLM Identifier: NCT01459094. |
| 8 | INVOKAMET (canagliflozin and metformin hydrochloride) [Prescribing Information]. Titusville, NJ: Janssen Pharmaceuticals, Inc; https://imedicalknowledge.veevavault.com/ui/approved_viewer?token=7994-1f749c73-ec3a-43a2-9b03-b61e1eb82a5d. |
| 9 | Food and Drug Administration, Center for Drug Evaluation and Research (CDER). The Biopharmaceutics Classification System (BCS) Guidance. Food and Drug Administration; 2009. https://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm128219.htm Accessed November 20, 2024. |
| 10 | Center for Drug Evaluation and Research (CDER). Canagliflozin-Metformin - Clinical Pharmacology and Biopharmaceutics Review(s). Food and Drug Administration (FDA); 2014. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204353Orig1s000ClinPharmR.pdf Accessed November 20, 2024. |
| 11 | GLUCOPHAGE (metformin hydrochloride) [Prescribing Information]. Princeton, NJ: Bristol-Myers Squibb Company. |
| 12 | Miller D, Miller H. To crush or not to crush? What to consider before giving medications to a patient with a tube or who has trouble swallowing. Nursing. 2000;30(2):50-52. |
| 13 | James A. The legal and clinical implications of crushing tablet medication. Nurs Times. 2004;100(50):28-29. |
| 14 | Cornish P. “Avoid the crush”: hazards of medication administration in patients with dysphagia or a feeding tube. CMAJ. 2005;172(7):871-872. |
| 15 | Williams NT. Medication administration through enteral feeding tubes. Am J Health Syst Pharm. 2008;65(24):2347-2357. |
| 16 | Guenter P. Administering medications via feeding tubes: what consultant pharmacists need to know. Consult Pharm. 1999;14:41-48. |
| 17 | Mitchell J. Oral dosage forms that should not be crushed. Institute for Safe Medication Practices; http://www.ismp.org/tools/donotcrush.pdf |
