EL is available as:
tafamidis meglumine 20 mg: yellow, opaque, oblong capsule, printed with “VYN 20” in red.
VYNDAMAX is available as:
tafamidis 61 mg: reddish brown, opaque, oblong capsule, printed with “VYN 61” in white.
4. CONTRAINDICATIONS
None.
6. ADVERSE REACTIONS
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in theclinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may notreflect the rates observed in practice.
The data reflect exposure of 377 ATTR-CM patients to 20 mg or 80 mg (administered as four 20-mg capsules)of VYNDAQEL administered daily for an average of 24.5 months (ranging from 1 day to 111 months).
Adverse events were assessed from ATTR-CM clinical trials with VYNDAQEL, primarily a 30-monthplacebo-controlled trial [see Clinical Studies (14)]. The frequency of adverse events in patients treated withVYNDAQEL 20 mg (n=88) or 80 mg (n=176; administered as four 20-mg capsules) was similar to that withplacebo (n=177).
In the 30-month placebo-controlled trial, similar proportions of VYNDAQEL-treated patients andplacebo-treated patients discontinued the study drug because of an adverse event: 12 (7%), 5 (6%), and 11 (6%)from the VYNDAQEL 80-mg, VYNDAQEL 20-mg, and placebo groups, respectively.
7. DRUG INTERACTIONS
7.1 BCRP Substrates
Tafamidis inhibits breast cancer resistant protein (BCRP) in vitro and may increase exposure of substrates ofthis transporter (e.g., methotrexate, rosuvastatin, imatinib) following VYNDAQEL 80 mg or VYNDAMAX61 mg. Dose adjustment may be needed for these substrates.
8. USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Based on findings from animal studies, VYNDAQEL and VYNDAMAX may cause fetal harm whenadministered to a pregnant woman. However, limited available human data with VYNDAQEL use in pregnantwomen (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 oftafamidis meglumine to pregnant rabbits during organogenesis resulted in adverse effects on development(embryofetal mortality, fetal body weight reduction and fetal malformation) at a dosage providingapproximately 9 times the human exposure (AUC) at the maximum recommended human dose (MRHD) ofVYNDAQEL (80 mg), and increased incidence of fetal skeletal variation at a dosage providing equivalenthuman exposure (AUC) at the MRHD. Postnatal mortality, growth retardation, and impaired learning andmemory were observed in offspring of pregnant rats administered tafamidis meglumine during gestation andlactation at a dosage approximately 2 times the MRHD based on body surface area (mg/m2) (see Data). Advisepregnant women of the potential risk to a fetus. Report pregnancies to the Pfizer reporting line at1-800-438-1985.
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. generalpopulation, the estimated background risk of major birth defects and miscarriage in clinically recognizedpregnancies is 2% to 4% and 15% to 20%, respectively.
Data
Animal Data
In pregnant rats, oral administration of tafamidis me |
