EVISTA TABLET 60mg

Product Information

Registration Status: Active

EVISTA TABLET 60mg is approved to be sold in Singapore with effective from 1999-09-04. It is marketed by ALVOGEN SINGAPORE PTE LTD, with the registration number of SIN10872P.

This product contains Raloxifene 60mg in the form of TABLET, FILM-COATED. It is approved for ORAL use.

This product is manufactured by LILLY SA in SPAIN, andBushu Pharmaceuticals Ltd. in JAPAN.

It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.

Raloxifene

Description

A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue. [PubChem]

Indication

For the prevention and treatment of osteoporosis in post-menopausal women, as well as prevention and treatment of corticosteroid-induced bone loss. Also for the reduction in the incidence of invasive breast cancer in postmenopausal women with osteoporosis or have a high risk for developing breast cancer.

Mechanism of Action

Raloxifene binds to estrogen receptors, resulting in differential expression of multiple estrogen-regulated genes in different tissues. Raloxifene produces estrogen-like effects on bone, reducing resorption of bone and increasing bone mineral density in postmenopausal women, thus slowing the rate of bone loss. The maintenance of bone mass by raloxifene and estrogens is, in part, through the regulation of the gene-encoding transforming growth factor-β3 (TGF-β3), which is a bone matrix protein with antiosteoclastic properties. Raloxifene activates TGF-β3 through pathways that are estrogen receptor-mediated but involve DNA sequences distinct from the estrogen response element. The drug also binds to the estrogen receptor and acts as an estrogen agonist in preosteoclastic cells, which results in the inhibtion of their proliferative capacity. This inhibition is thought to contribute to the drug's effect on bone resorption. Other mechanisms include the suppression of activity of the bone-resorbing cytokine interleukin-6 promoter activity. Raloxifene also antagonizes the effects of estrogen on mammary tissue and blocks uterotrophic responses to estrogen. By competing with estrogens for the estrogen receptors in reproductive tissue, raloxifene prevents the transcriptional activation of genes containing the estrogen response element. As well, raloxifene inhibits the estradiol-dependent proliferation of MCF-7 human mammary tumor cells in vitro. The mechansim of action of raloxifene has not been fully determined, but evidence suggests that the drug's tissue-specific estrogen agonist or antagonist activity is related to the structural differences between the raloxifene-estrogen receptor complex (specifically the surface topography of AF-2) and the estrogen-estrogen receptor complex. Also, the existence of at least 2 estrogen receptors (ERα, ERβ) may contribute to the tissue specificity of raloxifene.

Pharmacokinetics

Absorption
Approximately 60% of an oral dose is absorbed, but presystemic glucuronide conjugation is extensive. Absolute bioavailability of raloxifene is 2.0%
Distribution
* 2348 L/kg [oral administration of single doses ranging from 30 to 150 mg]
Metabolism
Hepatic, raloxifene undergoes extensive first-pass metabolism to the glucuronide conjugates: raloxifene-4'-glucuronide, raloxifene-6-glucuronide, and raloxifene-6, 4'-diglucuronide. No other metabolites have been detected, providing strong evidence that raloxifene is not metabolized by cytochrome P450 pathways
Elimination

Clearance

* 44.1 L/kg•hr [Healthy Postmenopausal Woman with Single Dose] * 47.4 L/kg•hr [Healthy Postmenopausal Woman with Multiple Dose] * Oral cl=44.1 L/kg•hr

Active Ingredient/Synonyms

(2-(4-Hydroxyphenyl)-6-hydroxybenzo(b)thien-3-yl)(4-(2-(1-piperidinyl)ethoxy)phenyl)methanone | Raloxifène | Raloxifeno | Raloxifenum | Raloxifene |


Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.

References

  1. Health Science Authority of Singapore - Reclassified POM
  2. Drugbank