Enlicitide
LIPFENDRA
What it isOral macrocyclic peptide that blocks PCSK9–LDL-receptor binding (LIPFENDRA, 2026); hypercholesterolemia including HeFH.
Why this onePCSK9 blockade in a pill: placebo-adjusted LDL-C reductions of 56-59% at week 24, with very low CYP/transporter interaction potential.
What limits itThe catch is the empty stomach: food 30 minutes before cuts exposure roughly in half (AUC -48%); then 30 minutes of nothing else.
FDA-approved for
- hypercholesterolemia incl. HeFH (2026)
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Hypercholesterolemia (incl. HeFH), adjunct to diet/exercise to reduce LDL-C | Adults | 20 mg QD | 20 mg QD | 20 mg QD |
Renal Undefined
Hepatic Undefined
LDL-C-lowering effect measurable as early as 4 weeks after initiation; assess LDL-C when clinically appropriate
Instructions
- Take on an empty stomach in the morning with water, black coffee, or plain tea
- Swallow tablet whole; do not split, crush, or chew
- Wait ≥30 min after dose before eating or drinking anything other than water, black coffee, or plain tea
- Missed dose: take ASAP ≥30 min before next food/drink (other than water/black coffee/plain tea); never 2 doses same day
- Can be taken with other medications
Cautions
- May cause fetal harm based on mechanism (lowers cholesterol-derived substances); discontinue when pregnancy recognized unless benefit outweighs risk
Adverse reactions
- HeFH trial: diarrhea (7% vs 2% placebo), dizziness (9% vs 4%)
- General hypercholesterolemia trial: adverse reaction rates similar to placebo
Pregnancy Discontinue when pregnancy recognized unless benefit outweighs fetal risk; may cause fetal harm by mechanism of action; no adverse embryofetal effects in animals up to 51–58× human exposure
Lactation No human data on milk presence, infant effects, or milk production; weigh benefits of breastfeeding vs maternal need
NO BOXED WARNINGS
Classes and tags
Clinical profile
Mechanism of action: Enlicitide ballicule
Open Enlicitide in the interactive console ↗
Memory aids: mascots and interaction avatars
Pesky K-9 → PCSK9, which targets LDL receptors for destruction
Pill → the first ORAL PCSK9 inhibitor (2026)
