OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Tafamidis – Vyndamax®, [Meglumine] Vyndaqel®

DRUG CLASS

Agents for genetic diseases

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Tafamidis	594839-88-0	C14-H7-Cl2-NO3

ANNOTATED BIBLIOGRAPHY

References updated: 20 February 2025

Abbreviations: siRNA, small interfering RNA.

• Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999.

  (Expert review of hepatotoxicity published in 1999 before the availability of antisense therapies such as eplontersen).
• FDA. Integrated Review. 2023. https://www​.accessdata​.fda.gov/drugsatfda_docs​/nda/2024/217388Orig1s000IntegratedR.pdf

  (FDA website with the product labels and integrated review of the data on efficacy and safety provided by the sponsor in support of approval of tafamidis as therapy of polyneuropathy due to transthyretin amyloidosis mentions that mild-to-moderate elevations in serum aminotransferase or alkaline phosphatase levels arose in 7.6% of tafamidis vs 6.7% of placebo recipients, but there were no ALT elevations above 3 times ULN and no cases of drug induced liver injury or aminotransferase elevations accompanied by jaundice).
• Maurer MS, Grogan DR, Judge DP, Mundayat R, Packman J, Lombardo I, Quyyumi AA, et al. Tafamidis in transthyretin amyloid cardiomyopathy: effects on transthyretin stabilization and clinical outcomes. Circ Heart Fail. 2015;8:519-26. [PubMed: 25872787]

  (Among 31 patients with wild-type transthyretin-mediated amyloidosis cardiomyopathy treated with tafamidis [20 mg daily] for 12 months, most patients had transthyretin stability and most adverse events were due to the underlying disease; no mention of ALT elevations or hepatotoxicity).
• Barroso FA, Judge DP, Ebede B, Li H, Stewart M, Amass L, Sultan MB. Long-term safety and efficacy of tafamidis for the treatment of hereditary transthyretin amyloid polyneuropathy: results up to 6 years. Amyloid. 2017;24:194-204. [PubMed: 28758793]

  (Among 93 patients with transthyretin-mediated amyloidosis with polyneuropathy enrolled in an 18 month controlled trial followed by an open label extension study for a total of up to 6 years, “therapy was generally well tolerated with no unexpected adverse events”, while ALT elevations occurred in only 3 patients [4%], none of which were accompanied with jaundice).
• Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M, Kristen AV, et al.; ATTR-ACT Study Investigators. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med. 2018;379:1007-1016. [PubMed: 30145929]

  (Among 441 patients with transthyretin-amyloidosis cardiomyopathy treated with tafamidis [20 or 80 mg] or placebo once daily, all-cause mortality was less with tafamidis [30% vs 43%] as was the worsening of signs and symptoms of cardiomyopathy, while adverse event rates were similar, and “results of laboratory analyses related to safety did not differ between the tafamidis and placebo groups” and “hepatobiliary disorders” arose in 9.5% vs 8.5% of patients [no details provided]).
• In brief: Tafamidis (Vyndaqel; Vyndamax) for transthyretin amyloid cardiomyopathy. Med Lett Drugs Ther. 2020;62(1590):16. [PubMed: 31999671]

  (Concise review of the mechanism of action, clinical efficacy, safety, and costs of tafamidis shortly after its approval in the US, mentions that the efficacy and adverse events of both doses of tafamidis [20 and 80 mg daily] were similar to those of placebo).
• Damy T, Garcia-Pavia P, Hanna M, Judge DP, Merlini G, Gundapaneni B, Patterson TA, et al. Efficacy and safety of tafamidis doses in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and long-term extension study. Eur J Heart Fail. 2021;23:277-285. [PMC free article: PMC8048553] [PubMed: 33070419]

  (Further follow up of patients enrolled in the registration trial of tafamidis vs placebo [Maurer 2018] showed a continued efficacy of the two doses of tafamidis and the “incidence of adverse events in both tafamidis doses were comparable to placebo”).
• Aimo A, Castiglione V, Rapezzi C, Franzini M, Panichella G, Vergaro G, Gillmore J, et al. RNA-targeting and gene editing therapies for transthyretin amyloidosis. Nat Rev Cardiol. 2022;19:655-667. [PubMed: 35322226]

  (Review of the molecular approaches to therapy of transthyretin related amyloidosis including small interfering RNA [siRNA, patisiran, vutrisiran], antisense RNA [inotersen, eplontersen], CRISPR-Cas9 therapy, and molecular stabilization agents [acoramidis, tafamidis], some of which have been linked to minor serum aminotransferase elevations during therapy [vutrisiran, eplontersen], but not to clinically apparent liver injury).
• Maurer MS. Overview of current and emerging therapies for amyloid transthyretin cardiomyopathy. Am J Cardiol. 2022;185 Suppl 1:S23-S34. [PubMed: 36371281]

  (Review of approaches to therapy of amyloid transthyretin cardiomyopathy including the transthyretin stabilizers [tafamidis, acoramidis] and transthyretin gene silencing or knockdown agents [patisiran, vutrisiran, inotersen, eplontersen, CRISPR-Cas9]; no mention of liver related adverse events).
• Ruberg FL, Maurer MS. Cardiac amyloidosis due to transthyretin protein: a review. JAMA. 2024;331:778-791. [PMC free article: PMC11167454] [PubMed: 38441582]

  (Review of the pathogenesis, genetics, clinical features, diagnosis, and treatment of transthyretin-mediated amyloidosis cardiomyopathy; no mention of ALT elevations or hepatotoxicity).