raloxifene hydrochloride
Evista

Available forms
Available by prescription only
Tablets: 60 mg

Indications and dosages
 Prevention and treatment of osteoporosis in postmenopausal women. Adults: 60 mg P.O. once daily.

Pharmacodynamics
Antiosteoporotic action: Decreases bone turnover and reduces bone resorption, evidenced as reduced serum and urine levels of bone turnover markers and increased bone mineral density. Biological actions of drug are mediated through binding to estrogen receptors resulting in differential expression of multiple estrogen-regulated genes in different tissues.

Pharmacokinetics
Absorption: Rapidly absorbed. Peak levels depend on systemic interconversion and enterohepatic cycling of drug and its metabolites. After oral administration, about 60% of raloxifene is absorbed. Absolute bioavailability is 2%.
Distribution: Apparent volume of distribution is 2,348 L/kg, independent of dose administered. Drug is highly bound to plasma proteins, both albumin and α1-acid glycoprotein, but it doesn’t appear to interact with the binding of warfarin, phenytoin, or tamoxifen to plasma proteins.
Metabolism: Undergoes extensive first-pass metabolism to glucuronide conjugates.
Excretion: Primarily excreted in feces, with less than 6% of dose eliminated as glucuronide conjugates in urine. Less than 0.2% of dose is excreted unchanged in urine.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug or constituents of tablet. Also contraindicated in pregnant women or those planning pregnancy and in women with history of or currently active venous thromboembolic events, including pulmonary embolism, retinal vein thrombosis, and deep vein thrombosis. Use with hormone replacement therapy or systemic estrogen hasn’t been evaluated and isn’t recommended.
  Use cautiously in patients with severe hepatic impairment. Assess risks and benefits in women at high risk for thromboembolic disease secondary to heart failure, superficial thrombophlebitis, or active malignancy.

Interactions
Drug-drug. Cholestyramine: Significantly reduces raloxifene absorption. Don’t use together.
Highly protein-bound drugs, such as clofibrate, diazepam, diazoxide, ibuprofen, indomethacin, and naproxen: May interfere with binding sites. Use together cautiously.
Warfarin: Decreases PT. Monitor PT and INR.
Drug-lifestyle. Alcohol use: May decrease bone formation and reduce bone’s ability to absorb calcium. Discourage alcohol use.
Smoking: Interferes with the absorption of calcium. Discourage smoking.

Adverse reactions
CNS: depression, insomnia, headache, migraine, fever.
CV: hot flashes, chest pain, peripheral edema.
EENT: sinusitis, pharyngitis, laryngitis.
GI: nausea, dyspepsia, vomiting, flatulence, GI disorder, gastroenteritis, diarrhea, abdominal pain.
GU: vaginitis, urinary tract infection, cystitis, leukorrhea, endometrial disorder, vaginal bleeding.
Metabolic: weight gain.
Musculoskeletal: arthralgia, myalgia, arthritis, leg cramps.
Respiratory: increased cough, pneumonia.
Skin: rash, sweating.
Other: breast pain, infection, flu syndrome.

Effects on lab test results
• May increase calcium, inorganic phosphate, total protein, albumin, hormone-binding globulin, and apolipoprotein A-I levels. May decrease total and LDL cholesterol levels, fibrinogen, lipoprotein(a), and apolipoprotein B levels.

Overdose and treatment
There have been no reports of overdose.
 No specific antidote exists for raloxifene overdose.

Special considerations
• Discontinue drug at least 72 hours before prolonged immobilization.
• The greatest risk for thromboembolic events (deep vein thrombosis, pulmonary embolism, retinal vein thrombosis) occurs during first 4 months of treatment.
• No link has been shown between therapy and breast enlargement, breast pain, or an increased risk of breast cancer. Evaluate breast abnormalities that occur during treatment.
• Endometrial proliferation hasn’t been linked to drug use. Evaluate unexplained uterine bleeding.
• A decrease in total cholesterol and LDL levels (by 6% and 11%, respectively) has been reported. No effect on high-density lipoprotein or triglycerides has been shown.
• There are no data to support drug use in premenopausal women; avoid use in this population.
• Safety and efficacy haven’t been evaluated in men.
• Effect on bone mineral density beyond 2 years of therapy isn’t known. Safety and efficacy haven’t been established beyond 2 years.
Breast-feeding patients
• It isn’t known if drug appears in breast milk. Don’t use in breast-feeding women.
Pediatric patients
• Drug hasn’t been evaluated in children. Don’t use in this population.
Geriatric patients
• No age-related differences have been observed in patients ages 42 to 84.

Patient education
• Tell patient to avoid long periods of restricted movement (such as during traveling) because of an increased risk of venous thromboembolic events, such as deep vein thrombosis and pulmonary embolism.
• Inform patient that hot flashes or flushing may occur and will not disappear with continued drug use.
• Tell patient to take supplemental calcium and vitamin D if dietary intake is inadequate.
• Encourage patient to perform weight-bearing exercises. Also, advise her to stop drinking alcohol and smoking.
• Tell patient that drug may be taken without regard for food.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use