Tafamidis

Tafamidis is a selective transthyretin (TTR) stabilizer used in cardiology and neurology.

Pharmacology

  • Mechanism of Action: Tafamidis binds to the thyroxine-binding sites of transthyretin (TTR), stabilizing the tetramer structure.
    • Prevents dissociation of TTR into monomers.
    • Reduces misfolding and aggregation into amyloid fibrils.
    • Slows the progression of transthyretin amyloidosis (ATTR amyloidosis).

Indications

  1. Cardiology
    • Treatment of transthyretin amyloid cardiomyopathy (ATTR-CM), both hereditary and wild-type forms.
    • Reduces cardiovascular mortality and hospitalizations.
  2. Neurology
    • Treatment of polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR).

Formulations & Brand Names

  • Tafamidis meglumine (20 mg capsules) → Brand: Vyndaqel®
  • Tafamidis free acid (61 mg capsules) → Brand: Vyndamax®
    • Both provide equivalent tafamidis exposure, but not interchangeable mg-to-mg.

Dosing (Adults)

  • ATTR-CM:
    • Vyndaqel®: 80 mg orally once daily (four × 20 mg capsules).
    • Vyndamax®: 61 mg orally once daily (one capsule).
  • hATTR Polyneuropathy:
    • 20 mg orally once daily (in some regions; approval differs).

Pharmacokinetics

  • Oral absorption, highly protein bound.
  • Hepatic metabolism (glucuronidation).
  • Excretion mainly biliary/fecal.

Adverse Effects

  • Generally well tolerated.
  • Most common: diarrhea, urinary tract infection, abdominal pain.
  • Less common: fatigue, dizziness, headache.

Monitoring / Considerations

  • Monitor disease progression (neurologic exam, cardiac imaging, biomarkers).
  • No major drug–drug interactions (not CYP-mediated).
  • Contraindicated in pregnancy (risk of fetal harm).

For an oncology/clinical pharmacist perspective, tafamidis is important mainly in cardio-oncology, since some chemotherapy (e.g., anthracyclines, proteasome inhibitors) can worsen cardiac amyloidosis symptoms.

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