Lasofoxifene

Lasofoxifene Uses, Dosage, Side Effects, Food Interaction and all others data.

Lasofoxifene is a non-steroidal 3rd generation selective estrogen receptor modulator (SERM) that selectively binds to both ERα and ERβ with high affinity. It is a naphthalene derivative marketed for prevention and treatment of osteoporosis and for the treatment of vaginal atrophy. It was initially developed as Oporia by Pfizer as a treatment for postmenopausal osteoporosis and vaginal atrophy, in which were both rejected for approval by FDA. Later Fablyn was developed as a result of a research collaboration between Pfizer and Ligand Pharmaceuticals with a newly submitted New Drug Application in 2008. It gained approval by European Commission in March 2009. Ligand Pharmaceuticals signed a license agreement with Sermonix Pharmaceuticals for the development and commercialization of oral lasofoxifene in the USA.

Lasofoxifene exhibits both significant estrogenic and antiestrogenic activity both in vitro and in vivo, targeting any tissues that possess ERs, such as bone, uterus, breast, blood vessels, and liver. Binding assays demonstrated high affinity of the compound for both ERα and ERβ in a tissue-dependent manner. It mimics the effects of estradiol with varying agonist and antagonist effects.

Lasofoxifene
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Lasofoxifene
Generic	Lasofoxifene
Lasofoxifene Other Names	Lasofoxifene
Type
Formula	C₂₈H₃₁NO₂
Weight	Average: 413.5512 Monoisotopic: 413.235479241
Protein binding	Lasofoxifene is highly bound to plasma proteins (>99%) where it predominantly binds to albumin and α1-acid glycoprotein .
Groups	Approved, Investigational
Therapeutic Class
Manufacturer
Available Country
Last Updated:	September 19, 2023 at 7:00 am

Uses

Investigated for use/treatment in postmenopausal osteoporosis to reduce the risk of both vertebral and novertebral fractures, as well as address other postmenopausal conditions, including reduction in risk of breast cancer and treatment of vulvar and vaginal atrophy (VVA)

How Lasofoxifene works

Lasofoxifene mediates an agonist effect on estrogen receptors expressed on bone to mimic the positive effects of estrogen to reduce the production and lifespan of osteoclasts via altering the NF-kappaB ligand (RANKL)/RANK/osteoprotegerin system, stimulation of osteoblast (the bone forming cells) activity and additional effects on calcium homeostasis . It acts as an antagonist at uterus and mammary glands by suppressing the estrogen signaling in oncogenic pathways and inhibits the downstream gene transcription . A study also suggests that lasofoxifene may also act as an inverse agonist at CB2 cannabinoid receptor which is expressed in bone to inhibit osteoclast formation and resorptive activity.

Toxicity

Lasofoxifene increases the risk of venous thromboembolism driven by increased risk of deep vein thrombosis. Other adverse effects include hot flushes, muscle spasms and vaginal bleeding.

Volume of Distribution

The apparent volume of distribution in postmenopausal women is 1350L .

Elimination Route

Peak plasma concentrations (Cmax) were reached in about 6.0 to 7.3 hours . Displays higher oral bioavailability compared to other SERMs with increased resistance to intestinal glucuronidation due to nonpolar tetrahydronaphthalene structure . In a comparative study in the rat, lasofoxifene showed bioavailability of 62% .