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Tafamidis

Class: Antiarrhythmics, Miscellaneous
Chemical Name: 2-(3,5-Dichlorophenyl)-6-benzoxazolecarboxylic acid
Molecular Formula: C14H7Cl2NO3C14H7Cl2NO3•C7H17NO5
CAS Number: 594839-88-0
Brands: Vyndamax, Vyndaqel

Medically reviewed by Drugs.com. Last updated on May 27, 2019.

Introduction

Tafamidis meglumine and tafamidis are antiarrhythmic agents.

Uses for Tafamidis

Tafamidis meglumine and tafamidis have the following uses:

Tafamidis meglumine and tafamidis are transthyretin (TTR) stabilizers indicated for the treatment of the cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization.1

Tafamidis Dosage and Administration

General

Tafamidis meglumine and tafamidis are available in the following dosage form(s) and strength(s):

Capsules: Tafamidis meglumine (Vyndaqel) 20 mg and tafamidis (Vyndamax) 61 mg.1

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

The recommended dosage is either:

  • Tafamidis meglumine (Vyndaqel) 80 mg orally once daily, or1

  • Tafamidis (Vyndamax) 61 mg orally once daily.1

  • Tafamidis (Vyndamax) and tafamidis meglumine (Vyndaqel) are not substitutable on a per mg basis.1

Cautions for Tafamidis

Contraindications

None.1

Warnings/Precautions

Specific Populations

Pregnancy

Risk Summary: Based on findings from animal studies, tafamidis meglumine and tafamidis may cause fetal harm when administered to a pregnant woman. However, limited available human data with tafamidis meglumine use in pregnant women (at a dose of 20 mg per day) have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproductive studies, oral administration of tafamidis meglumine to pregnant rabbits during organogenesis resulted in adverse effects on development (embryofetal mortality, fetal body weight reduction and fetal malformation) at a dosage providing approximately 9 times the human exposure (AUC) at the maximum recommended human dose (MRHD) of tafamidis meglumine (80 mg), and increased incidence of fetal skeletal variation at a dosage providing equivalent human exposure (AUC) at the MRHD. Postnatal mortality, growth retardation, and impaired learning and memory were observed in offspring of pregnant rats administered tafamidis meglumine during gestation and lactation at a dosage approximately 2 times the MRHD based on body surface area (mg/m2). Advise pregnant women of the potential risk to a fetus. Report pregnancies to the Pfizer reporting line at 1-800-438-1985.1

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.1

Animal Data: In pregnant rats, oral administration of tafamidis meglumine (0, 15, 30, and 45 mg/kg/day) throughout organogenesis resulted in decreased fetal body weights at ≥30 mg/kg/day (approximately 10 times the human exposure at the MRHD based on AUC). The no-observed-adverse-effect-level (NOAEL) for embryofetal development in rats was 15 mg/kg/day (approximately 7 times the human exposure at the MRHD based on AUC).1

In pregnant rabbits, oral administration of tafamidis meglumine (0, 0.5, 2, and 8 mg/kg/day) throughout organogenesis resulted in increased embryofetal mortality, reduced fetal body weights, and an increased incidence of fetal malformations at 8 mg/kg/day (approximately 9 times the human exposure at the MRHD based on AUC), which was also maternally toxic. Increased incidences of fetal skeletal variations were observed at doses ≥0.5 mg/kg/day (approximately equivalent to the human exposure at the MRHD based on AUC). 1

In the pre- and postnatal study, pregnant rats received oral administration of tafamidis meglumine at doses of 0, 5, 15, or 30 mg/kg/day throughout pregnancy and lactation (Gestation Day 7 to Lactation Day 20). Decreased survival and body weights, delayed male sexual maturation and neurobehavioral effects (learning and memory impairment) were observed in the offspring of dams treated at 15 mg/kg/day (approximately 2 times the MRHD on a mg/m2 basis). The NOAEL for pre- and postnatal development in rats was 5 mg/kg/day (approximately equivalent to the MRHD on a mg/m2 basis).1

Lactation

Risk Summary: There are no available data on the presence of tafamidis in human milk, the effect on the breastfed infant, or the effect on milk production. Tafamidis is present in rat milk. When a drug is present in animal milk, it is likely the drug will be present in human milk. Based on findings from animal studies which suggest the potential for serious adverse reactions in the breastfed infant, advise patients that breastfeeding is not recommended during treatment with tafamidis meglumine or tafamidis.1

Data: Pregnant and lactating female rats were administered repeated daily oral doses of tafamidis meglumine (15 mg/kg/day) followed by a single oral gavage dose of 14C-tafamidis meglumine on Lactation Day 4 or 12. Radioactivity was observed in milk by 1 hour post-dose and increased thereafter. The ratio of the highest radioactivity associated with 14C tafamidis meglumine in milk (8 hours post-dose) vs. plasma (1 hour post-dose) was approximately 1.6 on Day 12, indicating tafamidis meglumine is transferred to milk after oral administration.1

Females and Males of Reproductive Potential

Based on findings from animal studies, tafamidis meglumine and tafamidis may cause fetal harm when administered to a pregnant woman. Consider pregnancy planning and prevention for females of reproductive potential.1

Pediatric Use

The safety and effectiveness of tafamidis meglumine and tafamidis have not been established in pediatric patients. 1

Geriatric Use

No dosage adjustment is required for elderly patients (≥65 years). Of the total number of patients in the clinical study (n=441), 90.5% were 65 and over, with a median age of 75 years.1

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Tafamidis is a selective stabilizer of TTR. Tafamidis binds to TTR at the thyroxine binding sites, stabilizing the tetramer and slowing dissociation into monomers, the rate-limiting step in the amyloidogenic process.1

Advice to Patients

Advise the patient to read the FDA-approved patient labeling (Patient Information).1

Pregnancy

Report pregnancies to the Pfizer reporting line at 1-800-438-1985. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females to inform their healthcare provider of a known or suspected pregnancy. 1

Lactation

Advise females not to breastfeed during treatment with tafamidis meglumine or tafamidis.1

Transthyretin Amyloidosis Outcome Survey

Advise all patients prescribed tafamidis meglumine or tafamidis of the availability of the Transthyretin Amyloidosis Outcome Survey (THAOS) registry, that their participation is voluntary, and may involve long-term follow-up. THAOS is an international disease registry designed to assess disease progression, genotype/phenotype relationships, and the impact of interventions, including tafamidis meglumine and tafamidis on disease progression. For information regarding the registry, visit www.thaos.net.1

Additional Information

AHFSfirstRelease. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Tafamidis

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

61 mg

Vyndamax

Pfizer Laboratories Div Pfizer Inc

Tafamidis Meglumine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

20 mg

Vyndaqel

Pfizer Laboratories Div Pfizer Inc

AHFS Drug Information. © Copyright 2021, Selected Revisions May 27, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Pfizer Laboratories Div Pfizer Inc. Vyndaqel (tafamidis meglumine) and Vyndamax (tafamidis) ORAL prescribing information. 2019 May. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1b4121ee-a733-4456-a917-be2603477839