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Raloxifene Hydrochloride

Pronunciation

Pronunciation: ral-OX-i-FEEN HYE-droe-KLOR-ide
Class: Selective estrogen receptor modulator

Trade Names

Evista
- Tablets 60 mg

Pharmacology

Actions mediated largely through binding to estrogen receptors, which results in activation of certain estrogenic pathways and blockade of others. Appears to act as an estrogen agonist in bone. Decreases bone resorption and turnover, increases bone mineral density.

Slideshow: Flashback: FDA Drug Approvals 2013

Pharmacokinetics

Absorption

Absorbed rapidly after oral administration. Bioavailability is 2%.

Distribution

Vd is 2348 L/kg. Protein binding is 95%. Binds albumin and alpha-1 acid glycoprotein.

Metabolism

Extensive first-pass metabolism to glucuronide conjugates.

Elimination

Primarily excreted in feces. Less than 0.2% is excreted unchanged in urine. Cl (oral) is 44.1 L/kg•h and half-life is 27.7 to 32.5 h. Chronic dosing Cl is 40 to 60 L/kg•h.

Special Populations

Renal Function Impairment

Raloxifene concentrations are elevated in renal impairment. Use with caution.

Hepatic Function Impairment

Raloxifene Cl is reduced in patients with hepatic impairment; the pharmacokinetics were not studied in patients with moderate or severe hepatic impairment. Use with caution.

Elderly

No differences in pharmacokinetics were found in the age range 42 to 84 yr.

Gender

No differences in pharmacokinetics between men and women.

Race

No differences in pharmacokinetics have been identified based on race.

Cirrhosis

Plasma concentrations increase 2.5 times. Safety and efficacy have not been evaluated any further.

Indications and Usage

For the prevention and treatment of osteoporosis in postmenopausal women; reduction in the risk of invasive breast cancer in postmenopausal women with osteoporosis; reduction in the risk of invasive breast cancer in postmenopausal women at high risk of invasive breast cancer.

Unlabeled Uses

Treatment of uterine leiomyomas; treatment of pubertal gynecomastia; prevention of bone loss in men with prostate cancer.

Contraindications

Women who are or may become pregnant; breast-feeding mothers; women with active or history of venous thromboembolic events, including deep vein thrombosis (DVT), pulmonary embolism, and retinal vein thrombosis; allergy to raloxifene or other constituents of the product.

Dosage and Administration

Adult women

PO 60 mg every day.

General Advice

  • May be taken any time of day without regard to meals.
  • For reduction in risk of invasive breast cancer, the optimum duration of treatment is not known.
  • For osteoporosis treatment or prevention, add supplemental calcium and/or vitamin D to the diet if daily intake is inadequate.

Storage/Stability

Store at 59° to 86°F.

Drug Interactions

Cholestyramine

Major reduction in absorption and enterohepatic cycling of raloxifene; avoid concurrent use.

Estrogens

Safety and efficacy of coadministration not established; concurrent use is not recommended.

Highly protein-bound drugs (eg, clofibrate, diazepam, diazoxide, ibuprofen, indomethacin, naproxen)

May displace raloxifene from protein-binding sites, increasing the effects of raloxifene.

Warfarin

Raloxifene may decrease anticoagulant effect.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hot flashes (29%); migraine, syncope, varicose vein (2%); stroke, venous thromboembolism sometimes fatal (postmarketing).

CNS

Headache (9%); depression, insomnia (6%); vertigo (4%); hypesthesia, neuralgia (2%).

Dermatologic

Rash (6%); sweating (3%).

EENT

Pharyngitis (7%); conjunctivitis, laryngitis (2%); retinal vein occlusion (postmarketing).

GI

Nausea (9%); abdominal pain, diarrhea (7%); dyspepsia (6%); vomiting (5%); flatulence, gastroenteritis, GI disorder (3%).

Genitourinary

Cystitis (5%); breast pain, UTI, vaginal bleeding, vaginitis (4%); endometrial disorder, leucorrhea, urinary tract disorder, uterine disorder, vaginal hemorrhage (3%).

Metabolic-Nutritional

Weight gain (9%); peripheral edema (5%).

Musculoskeletal

Arthralgia (16%); myalgia (8%); leg cramps (7%); arthritis, tendon disorder (4%).

Respiratory

Bronchitis, rhinitis, sinusitis (10%); increased cough (9%); pneumonia (3%).

Miscellaneous

Flu syndrome (15%); infection (11%); chest pain, fever (4%); chest pain (3%).

Precautions

Warnings

Venous thrombosis

Increased risk of DVT and pulmonary embolism have been reported. Women with active or past history of venous thrombosis should not take raloxifene.

Stroke

The risk of death due to stroke may be increased in postmenopausal women with documented coronary heart disease or at increased risk of major coronary events.


Monitor

Monitor triglyceride plasma levels in women with a history of marked hypertriglyceridemia in response to treatment with oral estrogen or estrogen plus progestin.


Pregnancy

Category X .

Lactation

Contraindicated in breast-feeding women.

Children

Safety and efficacy not established.

Elderly

No overall differences in safety and efficacy have been reported between patients older than 65 yr of age and younger subjects.

Renal Function

Use with caution in patients with moderate or severe renal impairment.

Hepatic Function

Use with caution in patients with hepatic impairment.

Breast abnormality

Investigate any unexplained breast abnormality during therapy.

CV disease

Not for use for the primary or secondary prevention of CV disease.

Concurrent estrogen therapy

Concurrent use with systemic estrogens is not recommended.

History of breast cancer

Raloxifene has not been adequately studied in women with history of breast cancer.

Hypertriglyceridemia

Women with a history of marked hypertriglyceridemia in response to treatment with oral estrogen or estrogen plus progestin may develop increased triglyceride levels with raloxifene therapy.

Premenopausal use

Safety and efficacy not established. Use is not recommended.

Use in men

Safety and efficacy not established.

Venous thromboembolic events

Increased risk of thromboembolic events.

Overdosage

Symptoms

Dizziness, leg cramps.

Patient Information

  • Advise patient to read package insert before starting therapy and each time the prescription is refilled.
  • Advise patient that drug is taken once a day without regard to meals.
  • Advise patient that this drug is for postmenopausal women only. It should not be given to men or premenopausal women to prevent osteoporosis.
  • Advise patient that estrogen therapy comes as a pill, patch, or injection, and should not be used in conjunction with this drug.
  • Advise patient that drug does not reduce hot flashes and may actually cause hot flashes in women who are closer to menopause.
  • Instruct patient to take supplemental calcium (1,500 mg) and vitamin D (400 international units) daily if dietary intake is not adequate.
  • Encourage patient to perform weight-bearing exercises and avoid behaviors that promote osteoporosis (eg, alcohol consumption, cigarette smoking).
  • Advise patient to avoid prolonged restrictions of movement during travel.
  • Advise patient that medication will need to be discontinued 72 h or more prior to any event that would cause prolonged immobilization (eg, postsurgical recovery) and can only be restarted once patient is fully mobile.
  • Instruct patient to report the following symptoms to health care provider: abnormal vaginal bleeding, breast lumps, leg swelling, pain in groin or calves, shortness of breath or coughing up blood, sudden chest pain, sudden vision problems.
  • Advise patients to have breast exams and mammograms performed before starting therapy and regularly thereafter.

Copyright © 2009 Wolters Kluwer Health.

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