Vyndaqel Tafamidis Meglumine Soft Capsules

1. Indications and Usage
Transthyretin Amyloid Cardiomyopathy (ATTR-CM): Treatment of adult patients with transthyretin amyloid cardiomyopathy to reduce the risk of cardiovascular mortality and cardiovascular-related hospitalization.
Hereditary Transthyretin-mediated Amyloidosis (hATTR): Treatment of adults with stage 1 (symptomatic) hereditary transthyretin-mediated amyloidosis with polyneuropathy to slow peripheral nerve impairment.
2. Dosage and Administration
Administration: Oral administration. Capsules should be swallowed whole with water. Can be taken with or without food.
Standard Dose:
Recommended Dose: 61 mg once daily (equivalent to 20 mg of free base tafamidis).
Missed Dose: If a dose is missed, take it as soon as possible on the same day. Resume the usual schedule the next day. Do not take a double dose.
Dose Reduction: Not typically required, but if the 61 mg dose is not tolerated, a temporary reduction to 20 mg once daily may be considered.
3. Mechanism of Action
Tafamidis is a selective and high-affinity kinetic stabilizer of the transthyretin (TTR) tetramer.
It binds to the thyroxine-binding sites of the TTR tetramer, preventing its dissociation into monomers.
By stabilizing the tetramer, it inhibits the misfolding and subsequent aggregation of TTR into amyloid fibrils, thereby reducing amyloid deposition in tissues.
4. Safety and Warnings
Embryo-Fetal Toxicity: Based on animal data, tafamidis may cause fetal harm. Contraception is recommended for females of reproductive potential during treatment. Breastfeeding is not recommended.
Monitoring: Periodic monitoring of clinical symptoms and laboratory parameters (e.g., cardiac function, nerve conduction) is recommended to assess disease progression.
5. Adverse Reactions
Common adverse reactions (incidence >10%) include:
Gastrointestinal: Diarrhea, Nausea.
Urinary Tract: Urinary tract infection.
Neurologic: Headache.
Other: Rash, Pruritus.
6. Drug Interactions
BCRP Substrates: Tafamidis meglumine may inhibit Breast Cancer Resistance Protein (BCRP). Use caution when co-administering with BCRP substrates (e.g., methotrexate, rosuvastatin) as exposure to these drugs may increase.
Metabolism: Tafamidis is primarily metabolized by CYP2C9. Caution is advised when co-administering with strong CYP2C9 inhibitors (e.g., fluconazole), although dose adjustment is not typically required.
7. Pharmaceutical Information
Chemical Name: (2R,3R,4R,5S)-6-(methylamino)hexane-1,2,3,4,5-pentaol 2-(3,5-dichlorophenyl)benzo[d]oxazole-6-carboxylate.