LIPFENDRA Film-coated tablet Ref.[116750] Active ingredients:

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adverse Reactions in Adults with Hypercholesterolemia

The safety of LIPFENDRA was evaluated in Trial 1 (CORALreef Lipids, NCT05952856), a 52-week, multicenter, double-blind, randomized, placebo-controlled trial in 2,904 patients with hypercholesterolemia (including those with and without HeFH) and a history of a major atherosclerotic cardiovascular disease (ASCVD) event or increased risk for development of a first major ASCVD event [see Clinical Studies (14)]. In Trial 1, the frequencies of adverse reactions in adults with hypercholesterolemia were similar between those treated with LIPFENDRA and those receiving placebo. Similar proportions of LIPFENDRA-treated patients and placebo-treated patients discontinued treatment because of an adverse reaction.

Adverse Reactions in Adults with HeFH

The safety of LIPFENDRA was evaluated in Trial 2 (CORALreef HeFH, NCT05952869), a 52-week multicenter, double-blind, randomized, placebo-controlled trial in 303 patients with HeFH [see Clinical Studies (14)]. In Trial 2, the most common adverse reactions in adults with HeFH treated with LIPFENDRA that occurred at higher frequencies compared to placebo were diarrhea (LIPFENDRA 7%, placebo 2%) and dizziness (LIPFENDRA 9%, placebo 4%). Similar proportions of LIPFENDRA-treated patients and placebo-treated patients discontinued treatment because of an adverse reaction. The safety profile observed in adults with HeFH in Trial 2 was otherwise generally consistent with that observed in adults with hypercholesterolemia in Trial 1.

Risk Summary

Discontinue LIPFENDRA when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus. Alternatively, consider the ongoing therapeutic needs of the individual patient. Enlicitide increases LDL-C uptake and lowers LDL-C levels in the circulation, thus decreasing cholesterol and possibly other biologically active substances derived from cholesterol; therefore, LIPFENDRA may cause fetal harm when administered to pregnant patients based on the mechanism of action [see Clinical Pharmacology (12.1)].

There are insufficient data on the use of LIPFENDRA in pregnant patients to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Consider the benefits and risks of LIPFENDRA when prescribing LIPFENDRA to pregnant women.

In animal reproduction studies, no adverse embryofetal developmental effects were observed in pregnant rats and rabbits administered enlicitide subcutaneously during organogenesis (up to 58- and 51-fold, respectively, the human exposure at the recommended human dose (RHD), based on AUC) (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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.

Data

Animal Data

In the embryofetal developmental rat toxicity study, pregnant rats were administered enlicitide subcutaneously at 0.5, 3, or 10 mg/kg/day during the period of organogenesis (Gestational Days (GD) 6 through 17). No adverse embryofetal or maternal effects were observed up to 10 mg/kg/day (58-fold the human exposure at the RHD, based on AUC).

In the embryofetal developmental rabbit toxicity study, pregnant rabbits were administered enlicitide subcutaneously at 0.2, 0.5, or 3 mg/kg/day during the period of organogenesis (GD7 through 19). No adverse embryofetal or maternal effects were observed up to 3 mg/kg/day (51-fold the human exposure at the RHD, based on AUC).

In the rat pre- and postnatal developmental toxicity study, enlicitide was administered subcutaneously at 0.5, 3, or 10 mg/kg/day daily from GD 6 through lactation day (LD) 20. No adverse developmental or maternal effects were observed up to 10 mg/kg/day (58-fold the human exposure at the RHD, based on AUC).

Enlicitide crosses the placenta and was detected in rat fetal plasma at concentrations that were 3 to 5% of mean maternal plasma concentrations.

Risk Summary

There is no information on the presence of enlicitide in human milk, the effects on the breastfed infant, or the effects on milk production. Enlicitide was detected at low concentrations in the plasma of nursing pups from lactating rats administered subcutaneous enlicitide (see Data).

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for LIPFENDRA and any potential adverse effects on the breastfed child from LIPFENDRA or from the underlying maternal condition [see Clinical Pharmacology (12.1)].

Data

Animal Data

Enlicitide was detected in the plasma of nursing pups (LD 7) from lactating rats administered enlicitide subcutaneously at 0.5, 3, and 10 mg/kg/day from GD 6 to LD 7, with the majority of individual pup-to-maternal plasma concentrations ≤0.7% across doses.

The safety and effectiveness of LIPFENDRA have not been established in pediatric patients.

Of the 2,137 patients treated with LIPFENDRA in placebo-controlled trials, 960 (45%) patients were 65 years of age and older, and 252 (12%) patients were 75 years of age and older. No overall differences in safety or effectiveness were observed between patients 65 years of age and older and younger adult patients.