Description

Simple

A medication used to prevent bone loss and treat breast cancer in postmenopausal women.

Clinical

A selective estrogen receptor modulator that is used to prevent and treat osteoporosis and reduce the risk of invasive breast cancer in high-risk postmenopausal women.

Overview

Raloxifene is a second generation selective estrogen receptor modulator (SERM) that mediates anti-estrogenic effects on breast and uterine tissues, and estrogenic effects on bone, lipid metabolism, and blood coagulation.[6,12] Exhibiting tissue-specific effects distinct from [estradiol], raloxifene is the first of the benzothiophene group of antiestrogens to be labelled a SERM.[7] Available in many countries worldwide, raloxifene was initially approved by the FDA in December, 1997 under the market name Evista® for the management and prevention of osteoporosis in postmenopausal women and reduction in risk for invasive breast cancer in postmenopausal women with osteoporosis or those who are at high risk for invasive breast cancer. However, it has a negligible effect on altering the development and progression of breast cancer itself.[label] The most common causes of osteoporosis include postmenopausal deficiency of estrogen and age-relate... Read more

Pharmacology

Indication

Indicated for the prevention and treatment of osteoporosis in postmenopausal women, as well as prevention and treatment of corticosteroid-induced bone loss.[label]

Indicated for the reduction in the risk of invasive breast cancer in postmenopausal women with osteoporosis or postmenopausal women w... Read more

Pharmacodynamic

Raloxifene belongs to the selective estrogen receptor modulator (SERM) drug class that exhibits estrogenic effects on bone and lipid metabolism while mediating anti-estrogenic effects on uterine endometrium and breast tissues.[ Read more

Mechanism of action

Raloxifene is a selective estrogen receptor modulator that acts as both an estrogen agonist and antagonist via differential effects on the tissue-specific estrogen receptors. Based on the findings of competitive binding assays, raloxifene displays binding affinity that is similar to that of [estradi... Read more

Absorption

Raloxifene is well absorbed from the gastrointestinal tract, with approximately 60% fo the drug being absorbed following oral administration.[ Read more

Protein binding

About 95% of raloxifene and its glucuronide metabolites are bound to plasma proteins.[label] Although this is a relatively high protein binding profile, _in vitro_ studies suggest that raloxifene and its metabolites do not significantly interact with binding of highly protein-bound drugs.[ Read more

Volume of distribution

Following oral administration of single doses randing from 30 to 150 mg in postmenopausal women, the volume of distribution was about 2348 L/kg. Following oral administration of multiple doses, the value increased to 2853 L/kg. Raloxifene is widely distributed in the tissues. It is not known whether... Read more

Clearance

Following intravenous administration, raloxifene was shown to be cleared at a rate approximating hepatic blood flow. The apparent oral clearance is reported to be 44.1 L/kgxhr. The clearance can range from 40 to 60L/kgxhr following chronic dosing. In healthy postmenopausal women receiving multiple o... Read more

Half life

The average plasma elimination half-life of raloxifene ranges from 27 to 32 hours.[7, Read more

Route of elimination

Raloxifene predominantly undergoes fecal excretion, with less than 0.2% of the dose being excreted in the urine as unchanged form of the compound and less than 6% of the dose being excreted as glucuronide conjugates. Co-administration with [cholestyramine], a bile acid sequestrant, was shown to redu... Read more

Toxicity

**LD50 and Overdose**

The oral LD50 value in rats is > 5000 mg/kg, which is about 810 times the human dose.[MSDS] In monkeys, no mortality was seen after a single oral dose of 1000 mg/kg.[label] No cases of raloxifene overdose have been reported during clinical trials. A rar... Read more

Adverse Effects

Contraindications

  • Sex Group: female
  • Regions: US
  • Age Groups:
    • postmenopausal
    • premenopausal
  • Patient Conditions:
      • Name: Nursing Women
      • Drugbank Id: DBCOND0050656
  • Sex Group: female
  • Regions: US
  • Age Groups:
    • postmenopausal
    • premenopausal
  • Patient Conditions:
      • Name: Potential for pregnancy
      • Drugbank Id: DBCOND0108358
      • Name: Pregnancy
      • Drugbank Id: DBCOND0018394
  • Sex Group: female
  • Regions: US
  • Age Groups:
    • postmenopausal
  • Patient Conditions:
      • Name: Venous Thromboembolism
      • Drugbank Id: DBCOND0000676
      • Name: Pulmonary Embolism
      • Drugbank Id: DBCOND0027915
      • Name: Deep Vein Thrombosis
      • Drugbank Id: DBCOND0029964
      • Name: Retinal Vein Thrombosis
      • Drugbank Id: DBCOND0037936

Food Interactions

  • Avoid excessive or chronic alcohol consumption. Excessive and chronic alcohol consumption may be associated with vitamin D deficiency.
  • Take with or without food. The absorption is unaffected by food.

Interactions

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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(R)-warfarin
The serum concentration of (R)-warfarin can be increased when it is combined with Raloxifene.
(S)-Warfarin
The serum concentration of (S)-Warfarin can be increased when it is combined with Raloxifene.
4-hydroxycoumarin
The metabolism of 4-hydroxycoumarin can be decreased when combined with Raloxifene.
9-aminocamptothecin
The metabolism of 9-aminocamptothecin can be decreased when combined with Raloxifene.
Abemaciclib
Abemaciclib may decrease the excretion rate of Raloxifene which could result in a higher serum level.
Acenocoumarol
The serum concentration of Acenocoumarol can be increased when it is combined with Raloxifene.
Acetylcysteine
The excretion of Raloxifene can be decreased when combined with Acetylcysteine.
Adenine
The metabolism of Raloxifene can be decreased when combined with Adenine.
Afatinib
Afatinib may decrease the excretion rate of Raloxifene which could result in a higher serum level.
Albendazole
The metabolism of Albendazole can be decreased when combined with Raloxifene.
Alectinib
Alectinib may decrease the excretion rate of Raloxifene which could result in a higher serum level.
Alfentanil
The metabolism of Raloxifene can be decreased when combined with Alfentanil.
Alfuzosin
The metabolism of Alfuzosin can be decreased when combined with Raloxifene.
Allylestrenol
The metabolism of Allylestrenol can be decreased when combined with Raloxifene.
Almotriptan
The metabolism of Almotriptan can be decreased when combined with Raloxifene.
Alpelisib
The metabolism of Alpelisib can be decreased when combined with Raloxifene.
Alprazolam
The metabolism of Alprazolam can be decreased when combined with Raloxifene.
Aminohippuric acid
The excretion of Raloxifene can be decreased when combined with Aminohippuric acid.
Aminophenazone
The metabolism of Aminophenazone can be decreased when combined with Raloxifene.
Aminophylline
The metabolism of Aminophylline can be decreased when combined with Raloxifene.
13 References
  1. 1 . Heringa M: Review on raloxifene: profile of a selective estrogen receptor modulator. Int J Clin Pharmacol Ther. 2003 Aug;41(8):331-45.PubMed: 12940590
  2. 2 . Cummings SR, Eckert S, Krueger KA, Grady D, Powles TJ, Cauley JA, Norton L, Nickelsen T, Bjarnason NH, Morrow M, Lippman ME, Black D, Glusman JE, Costa A, Jordan VC: The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. JAMA. 1999 Jun 16;281(23):2189-97.PubMed: 10376571
  3. 3 . Bryant HU, Glasebrook AL, Yang NN, Sato M: An estrogen receptor basis for raloxifene action in bone. J Steroid Biochem Mol Biol. 1999 Apr-Jun;69(1-6):37-44.PubMed: 10418979
  4. 4 . Balfour JA, Goa KL: Raloxifene. Drugs Aging. 1998 Apr;12(4):335-41; discussion 342.PubMed: 9571395
  5. 5 . Clemett D, Spencer CM: Raloxifene: a review of its use in postmenopausal osteoporosis. Drugs. 2000 Aug;60(2):379-411.PubMed: 10983739
  6. 6 . Moen MD, Keating GM: Raloxifene: a review of its use in the prevention of invasive breast cancer. Drugs. 2008;68(14):2059-83.PubMed: 18778124
  7. 7 . Scott JA, Da Camara CC, Early JE: Raloxifene: a selective estrogen receptor modulator. Am Fam Physician. 1999 Sep 15;60(4):1131-9.PubMed: 10507743
  8. 8 . Yang NN, Venugopalan M, Hardikar S, Glasebrook A: Identification of an estrogen response element activated by metabolites of 17beta-estradiol and raloxifene. Science. 1996 Aug 30;273(5279):1222-5.PubMed: 8703055
  9. 9 . Palmisano BT, Zhu L, Stafford JM: Role of Estrogens in the Regulation of Liver Lipid Metabolism. Adv Exp Med Biol. 2017;1043:227-256. doi: 10.1007/978-3-319-70178-3_12.PubMed: 29224098
  10. 10 . Yaghjyan L, Colditz GA: Estrogens in the breast tissue: a systematic review. Cancer Causes Control. 2011 Apr;22(4):529-40. doi: 10.1007/s10552-011-9729-4. Epub 2011 Feb 1.PubMed: 21286801
  11. 11 . Diez-Perez A: Selective estrogen receptor modulators (SERMS). Arq Bras Endocrinol Metabol. 2006 Aug;50(4):720-34.PubMed: 17117297
  12. 12 . 35. (2012). In Rang and Dale's Pharmacology (7th ed., pp. 438-439). Edinburgh: Elsevier/Churchill Livingstone.
  13. 13 . EVISTA (raloxifene hydrochloride) Tablet for Oral Use - FDA Label Link