Chemical formula: C₁₄H₇Cl₂NO₃ Molecular mass: 308.116 g/mol PubChem compound: 11001318
Tafamidis interacts in the following cases:
Tafamidis inhibits the uptake transporters OAT1 and OAT3 (organic anion transporters) with IC50=2.9 µM and IC50=2.36 µM, respectively, and may cause drug-drug interactions at clinically relevant concentrations with substrates of these transporters (e.g. non-steroidal anti-inflammatory drugs, bumetanide, furosemide, lamivudine, methotrexate, oseltamivir, tenofovir, ganciclovir, adefovir, cidofovir, zidovudine, zalcitabine). Based on in vitro data, the maximal predicted changes in AUC of OAT1 and OAT3 substrates were determined to be less than 1.25 for the tafamidis meglumine 20 mg dose, therefore, inhibition of OAT1 or OAT3 transporters by tafamidis is not expected to result in clinically significant interactions.
In vitro tafamidis inhibits the efflux transporter BCRP (breast cancer resistant protein) with IC50=1.16 µM and may cause drug-drug interactions at clinically relevant concentrations with substrates of this transporter (e.g. methotrexate, rosuvastatin, imatinib) following a 20 mg tafamidis meglumine dose.
Limited data are available in patients with severe renal impairment (creatinine clearance less than or equal to 30 mL/min).
Tafamidis meglumine has not been studied in patients with severe hepatic impairment and caution is recommended.
There are no data on the use of tafamidis meglumine in pregnant women. Studies in animals have shown developmental toxicity. Tafamidis meglumine is not recommended during pregnancy and in women of childbearing potential not using contraception.
Available data in animals have shown excretion of tafamidis in milk. A risk to the newborns/infants cannot be excluded. Tafamidis meglumine should not be used during breast-feeding.
Contraceptive measures should be used by women of childbearing potential during treatment with tafamidis meglumine, and for one month after stopping treatment, due to the prolonged half-life.
No impairment of fertility has been observed in nonclinical studies.
On the basis of the pharmacodynamic and pharmacokinetic profile, tafamidis meglumine is believed to have no or negligible influence on the ability to drive or use machines.
The overall clinical data reflect exposure of 127 patients with ATTR-PN to 20 mg of tafamidis meglumine administered daily for an average of 538 days (ranging from 15 to 994 days). The adverse reactions were generally mild or moderate in severity.
Adverse reactions are listed below by MedDRA System Organ Class (SOC) and frequency categories using the standard convention: Very common (≥1/10), Common (≥1/100 to <1/10), and Uncommon (≥1/1,000 to <1/100). Within the frequency group, adverse reactions are presented in order of decreasing seriousness. Adverse reactions reported from the clinical programme in the listing below reflect the rates at which they occurred in the Phase 3, double-blind, placebo-controlled study (Fx-005).
Very Common: Urinary tract infection, Vaginal infection
Very Common: Diarrhoea, Upper abdominal pain
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