DRUGS & SUPPLEMENTS

Raloxifene

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Raloxifene uses


WARNING: INCREASED RISK OF VENOUS THROMBOEMBOLISM AND DEATH FROM STROKE

  • Increased risk of deep vein thrombosis and pulmonary embolism have been reported with Raloxifene . Women with active or past history of venous thromboembolism should not take Raloxifene .
  • Increased risk of death due to stroke occurred in a trial in postmenopausal women with documented coronary heart disease or at increased risk for major coronary events. Consider risk-benefit balance in women at risk for stroke .

WARNING: INCREASED RISK OF VENOUS THROMBOEMBOLISM AND DEATH FROM STROKE

See full prescribing information for complete boxed warning.

  • Increased risk of deep vein thrombosis and pulmonary embolism have been reported with Raloxifene (5.1). Women with active or past history of venous thromboembolism should not take Raloxifene (4.1).
  • Increased risk of death due to stroke occurred in a trial in postmenopausal women with documented coronary heart disease or at increased risk for major coronary events. Consider risk-benefit balance in women at risk for stroke (5.2, 14.5).

None.

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1 INDICATIONS AND USAGE

Raloxifene® is an estrogen agonist/antagonist indicated for:

  • Treatment and prevention of osteoporosis in postmenopausal women.
  • Reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis. (1.2)
  • Reduction in risk of invasive breast cancer in postmenopausal women at high risk for invasive breast cancer. (1.3)

Important Limitations: Raloxifene is not indicated for the treatment of invasive breast cancer, reduction of the risk of recurrence of breast cancer, or reduction of risk of noninvasive breast cancer. (1.3)

1.1 Treatment and Prevention of Osteoporosis in Postmenopausal Women

Raloxifene is indicated for the treatment and prevention of osteoporosis in postmenopausal women .

1.2 Reduction in the Risk of Invasive Breast Cancer in Postmenopausal Women with Osteoporosis

Raloxifene is indicated for the reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis .

1.3 Reduction in the Risk of Invasive Breast Cancer in Postmenopausal Women at High Risk of Invasive Breast Cancer

Raloxifene is indicated for the reduction in risk of invasive breast cancer in postmenopausal women at high risk of invasive breast cancer .

The effect in the reduction in the incidence of breast cancer was shown in a study of postmenopausal women at high risk for breast cancer with a 5-year planned duration with a median follow-up of 4.3 years . Twenty-seven percent of the participants received drug for 5 years. The long-term effects and the recommended length of treatment are not known.

High risk of breast cancer is defined as at least one breast biopsy showing lobular carcinoma in situ (LCIS) or atypical hyperplasia, one or more first-degree relatives with breast cancer, or a 5-year predicted risk of breast cancer ≥1.66% (based on the modified Gail model). Among the factors included in the modified Gail model are the following: current age, number of first-degree relatives with breast cancer, number of breast biopsies, age at menarche, nulliparity or age of first live birth. Healthcare professionals can obtain a Gail Model Risk Assessment Tool by dialing 1-800-545-5979. Currently, no single clinical finding or test result can quantify risk of breast cancer with certainty.

After an assessment of the risk of developing breast cancer, the decision regarding therapy with Raloxifene should be based upon an individual assessment of the benefits and risks.

Raloxifene does not eliminate the risk of breast cancer. Patients should have breast exams and mammograms before starting Raloxifene and should continue regular breast exams and mammograms in keeping with good medical practice after beginning treatment with Raloxifene.

Important Limitations of Use for Breast Cancer Risk Reduction

  • There are no data available regarding the effect of Raloxifene on invasive breast cancer incidence in women with inherited mutations (BRCA1, BRCA2) to be able to make specific recommendations on the effectiveness of Raloxifene.
  • Raloxifene is not indicated for the treatment of invasive breast cancer or reduction of the risk of recurrence.
  • Raloxifene is not indicated for the reduction in the risk of noninvasive breast cancer.
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2 DOSAGE AND ADMINISTRATION

60 mg tablet orally once daily.

2.1 Recommended Dosing

The recommended dosage is one 60 mg Raloxifene (raloxifene hydrochloride tablets) tablet daily, which may be administered any time of day without regard to meals .

For the indications in risk of invasive breast cancer the optimum duration of treatment is not known .

2.2 Recommendations for Calcium and Vitamin D Supplementation

For either osteoporosis treatment or prevention, supplemental calcium and/or vitamin D should be added to the diet if daily intake is inadequate. Postmenopausal women require an average of 1500 mg/day of elemental calcium. Total daily intake of calcium above 1500 mg has not demonstrated additional bone benefits while daily intake above 2000 mg has been associated with increased risk of adverse effects, including hypercalcemia and kidney stones. The recommended intake of vitamin D is 400-800 IU daily. Patients at increased risk for vitamin D insufficiency (e.g., over the age of 70 years, nursing home bound, or chronically ill) may need additional vitamin D supplements. Patients with gastrointestinal malabsorption syndromes may require higher doses of vitamin D supplementation and measurement of 25-hydroxyvitamin D should be considered.

3 DOSAGE FORMS AND STRENGTHS

60 mg, white, elliptical, film-coated tablets (not scored). They are imprinted on one side with LILLY and the tablet code 4165 in edible blue ink.

Tablets (not scored): 60 mg (3)

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4 CONTRAINDICATIONS

  • Active or past history of venous thromboembolism, including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis.
  • Pregnancy, women who may become pregnant, and nursing mothers. (4.2, 8.1, 8.3)

4.1 Venous Thromboembolism

Raloxifene is contraindicated in women with active or past history of venous thromboembolism (VTE), including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis .

4.2 Pregnancy, Women Who May Become Pregnant, and Nursing Mothers

Raloxifene is contraindicated in pregnancy, in women who may become pregnant, and in nursing mothers . Raloxifene may cause fetal harm when administered to a pregnant woman. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

In rabbit studies, abortion and a low rate of fetal heart anomalies (ventricular septal defects) occurred in rabbits at doses ≥0.1 mg/kg (≥0.04 times the human dose based on surface area, mg/m2), and hydrocephaly was observed in fetuses at doses ≥10 mg/kg (≥4 times the human dose based on surface area, mg/m2). In rat studies, retardation of fetal development and developmental abnormalities (wavy ribs, kidney cavitation) occurred at doses ≥1 mg/kg (≥0.2 times the human dose based on surface area, mg/m2). Treatment of rats at doses of 0.1 to 10 mg/kg (0.02 to 1.6 times the human dose based on surface area, mg/m2) during gestation and lactation produced effects that included delayed and disrupted parturition; decreased neonatal survival and altered physical development; sex- and age-specific reductions in growth and changes in pituitary hormone content; and decreased lymphoid compartment size in offspring. At 10 mg/kg, raloxifene disrupted parturition, which resulted in maternal and progeny death and morbidity. Effects in adult offspring (4 months of age) included uterine hypoplasia and reduced fertility; however, no ovarian or vaginal pathology was observed.

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5 WARNINGS AND PRECAUTIONS

  • Venous Thromboembolism: Increased risk of deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis. Discontinue use 72 hours prior to and during prolonged immobilization.
  • Death Due to Stroke: Increased risk of death due to stroke occurred in a trial in postmenopausal women with documented coronary heart disease or at increased risk for major coronary events. No increased risk of stroke was seen in this trial. Consider risk-benefit balance in women at risk for stroke. (5.2, 14.5)
  • Cardiovascular Disease: Raloxifene should not be used for the primary or secondary prevention of cardiovascular disease. (5.3, 14.5)
  • Premenopausal Women: Use is not recommended. (5.4)
  • Hepatic Impairment: Use with caution. (5.5)
  • Concomitant Use with Systemic Estrogens: Not recommended. (5.6)
  • Hypertriglyceridemia: If previous treatment with estrogen resulted in hypertriglyceridemia, monitor serum triglycerides. (5.7)

5.1 Venous Thromboembolism

In clinical trials, EVISTA-treated women had an increased risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism). Other venous thromboembolic events also could occur. A less serious event, superficial thrombophlebitis, also has been reported more frequently with Raloxifene than with placebo. The greatest risk for deep vein thrombosis and pulmonary embolism occurs during the first 4 months of treatment, and the magnitude of risk appears to be similar to the reported risk associated with use of hormone therapy. Because immobilization increases the risk for venous thromboembolic events independent of therapy, Raloxifene should be discontinued at least 72 hours prior to and during prolonged immobilization (e.g., post-surgical recovery, prolonged bed rest), and Raloxifene therapy should be resumed only after the patient is fully ambulatory. In addition, women taking Raloxifene should be advised to move about periodically during prolonged travel. The risk-benefit balance should be considered in women at risk of thromboembolic disease for other reasons, such as congestive heart failure, superficial thrombophlebitis, and active malignancy .

5.2 Death Due to Stroke

In a clinical trial of postmenopausal women with documented coronary heart disease or at increased risk for coronary events, an increased risk of death due to stroke was observed after treatment with Raloxifene. During an average follow-up of 5.6 years, 59 EVISTA-treated women died due to a stroke compared to 39 (0.8%) placebo-treated women (22 versus 15 per 10,000 women-years; hazard ratio 1.49; 95% confidence interval, 1.00-2.24; p=0.0499). There was no statistically significant difference between treatment groups in the incidence of stroke (249 in Raloxifene [4.9%] versus 224 placebo [4.4%]). Raloxifene had no significant effect on all-cause mortality. The risk-benefit balance should be considered in women at risk for stroke, such as prior stroke or transient ischemic attack (TIA), atrial fibrillation, hypertension, or cigarette smoking .

5.3 Cardiovascular Disease

Raloxifene should not be used for the primary or secondary prevention of cardiovascular disease. In a clinical trial of postmenopausal women with documented coronary heart disease or at increased risk for coronary events, no cardiovascular benefit was demonstrated after treatment with raloxifene for 5 years .

5.4 Premenopausal Use

There is no indication for premenopausal use of Raloxifene. Safety of Raloxifene in premenopausal women has not been established and its use is not recommended.

5.5 Hepatic Impairment

Raloxifene should be used with caution in patients with hepatic impairment. Safety and efficacy have not been established in patients with hepatic impairment .

5.6 Concomitant Estrogen Therapy

The safety of concomitant use of Raloxifene with systemic estrogens has not been established and its use is not recommended.

5.7 History of Hypertriglyceridemia when Treated with Estrogens

Limited clinical data suggest that some women with a history of marked hypertriglyceridemia in response to treatment with oral estrogen or estrogen plus progestin may develop increased levels of triglycerides when treated with Raloxifene. Women with this medical history should have serum triglycerides monitored when taking Raloxifene.

5.8 Renal Impairment

Raloxifene should be used with caution in patients with moderate or severe renal impairment. Safety and efficacy have not been established in patients with moderate or severe renal impairment .

5.9 History of Breast Cancer

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

5.10 Use in Men

There is no indication for the use of Raloxifene in men. Raloxifene has not been adequately studied in men and its use is not recommended.

5.11 Unexplained Uterine Bleeding

Any unexplained uterine bleeding should be investigated as clinically indicated. EVISTA-treated and placebo-treated groups had similar incidences of endometrial proliferation .

5.12 Breast Abnormalities

Any unexplained breast abnormality occurring during Raloxifene therapy should be investigated. Raloxifene does not eliminate the risk of breast cancer .

6 ADVERSE REACTIONS

Adverse reactions include: hot flashes, leg cramps, peripheral edema, flu syndrome, arthralgia, sweating. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-545-5979 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

6.1 Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described below reflect exposure to Raloxifene in 8429 patients who were enrolled in placebo-controlled trials, including 6666 exposed for 1 year and 5685 for at least 3 years.

Osteoporosis Treatment Clinical Trial (MORE) - The safety of raloxifene in the treatment of osteoporosis was assessed in a large (7705 patients) multinational, placebo-controlled trial. Duration of treatment was 36 months, and 5129 postmenopausal women were exposed to Raloxifene (2557 received 60 mg/day, and 2572 received 120 mg/day). The incidence of all-cause mortality was similar among groups: 23 (0.9%) placebo, 13 (0.5%) EVISTA-treated (raloxifene HCl 60 mg), and 28 (1.1%) raloxifene HCl 120 mg women died. Therapy was discontinued due to an adverse reaction in 10.9% of EVISTA-treated women and 8.8% of placebo-treated women.

Venous Thromboembolism: The most serious adverse reaction related to Raloxifene was VTE (deep venous thrombosis, pulmonary embolism, and retinal vein thrombosis). During an average of study-drug exposure of 2.6 years, VTE occurred in about 1 out of 100 patients treated with Raloxifene. Twenty-six EVISTA-treated women had a VTE compared to 11 placebo-treated women, the hazard ratio was 2.4 (95% confidence interval, 1.2, 4.5), and the highest VTE risk was during the initial months of treatment.

Common adverse reactions considered to be related to Raloxifene therapy were hot flashes and leg cramps. Hot flashes occurred in about one in 10 patients on Raloxifene and were most commonly reported during the first 6 months of treatment and were not different from placebo thereafter. Leg cramps occurred in about one in 14 patients on Raloxifene.

Placebo-Controlled Osteoporosis Prevention Clinical Trials - The safety of raloxifene has been assessed primarily in 12 Phase 2 and Phase 3 studies with placebo, estrogen, and estrogen-progestin therapy control groups. The duration of treatment ranged from 2 to 30 months, and 2036 women were exposed to raloxifene HCl (371 patients received 10 to 50 mg/day, 828 received 60 mg/day, and 837 received from 120 to 600 mg/day).

Therapy was discontinued due to an adverse reaction in 11.4% of 581 EVISTA-treated women and 12.2% of 584 placebo-treated women. Discontinuation rates due to hot flashes did not differ significantly between Raloxifene and placebo groups (1.7% and 2.2%, respectively).

Common adverse reactions considered to be drug-related were hot flashes and leg cramps. Hot flashes occurred in about one in four patients on Raloxifene versus about one in six on placebo. The first occurrence of hot flashes was most commonly reported during the first 6 months of treatment.

Table 1 lists adverse reactions occurring in either the osteoporosis treatment or in five prevention placebo-controlled clinical trials at a frequency ≥2.0% in either group and in more EVISTA-treated women than in placebo-treated women. Adverse reactions are shown without attribution of causality. The majority of adverse reactions occurring during the studies were mild and generally did not require discontinuation of therapy.

Treatment Prevention
Raloxifene

(N=2557)

%

Placebo

(N=2576)

%

Raloxifene

(N=581)

%

Placebo

(N=584)

%

a A: Placebo incidence greater than or equal to Raloxifene incidence; B: Less than 2% incidence and more frequent with Raloxifene.

b Includes only patients with an intact uterus: Prevention Trials: Raloxifene, n=354, Placebo, n=364; Treatment Trial: Raloxifene, n=1948, Placebo, n=1999.

c Actual terms most frequently referred to endometrial fluid.

Body as a Whole
    Infection A A 15.1 14.6
    Flu Syndrome 13.5 11.4 14.6 13.5
    Headache 9.2 8.5 A A
    Leg Cramps 7.0 3.7 5.9 1.9
    Chest Pain A A 4.0 3.6
    Fever 3.9 3.8 3.1 2.6
Cardiovascular System
    Hot Flashes 9.7 6.4 24.6 18.3
    Migraine A A 2.4 2.1
    Syncope 2.3 2.1 B B
    Varicose Vein 2.2 1.5 A A
Digestive System
    Nausea 8.3 7.8 8.8 8.6
    Diarrhea 7.2 6.9 A A
    Dyspepsia A A 5.9 5.8
    Vomiting 4.8 4.3 3.4 3.3
    Flatulence A A 3.1 2.4
    Gastrointestinal Disorder A A 3.3 2.1
    Gastroenteritis B B 2.6 2.1
Metabolic and Nutritional
    Weight Gain A A 8.8 6.8
Peripheral Edema 5.2 4.4 3.3 1.9
Musculoskeletal System
    Arthralgia 15.5 14.0 10.7 10.1
    Myalgia A A 7.7 6.2
    Arthritis A A 4.0 3.6
    Tendon Disorder 3.6 3.1 A A
Nervous System
    Depression A A 6.4 6.0
    Insomnia A A 5.5 4.3
    Vertigo 4.1 3.7 A A
    Neuralgia 2.4 1.9 B B
    Hypesthesia 2.1 2.0 B B
Respiratory System
    Sinusitis 7.9 7.5 10.3 6.5
    Rhinitis 10.2 10.1 A A
    Bronchitis 9.5 8.6 A A
    Pharyngitis 5.3 5.1 7.6 7.2
    Cough Increased 9.3 9.2 6.0 5.7
    Pneumonia A A 2.6 1.5
    Laryngitis B B 2.2 1.4
Skin and Appendages
    Rash A A 5.5 3.8
    Sweating 2.5 2.0 3.1 1.7
Special Senses
    Conjunctivitis 2.2 1.7 A A
Urogenital System
    Vaginitis A A 4.3 3.6
    Urinary Tract Infection A A 4.0 3.9
    Cystitis 4.6 4.5 3.3 3.1
    Leukorrhea A A 3.3 1.7
    Uterine Disorderb, c 3.3 2.3 A A
    Endometrial Disorderb B B 3.1 1.9
    Vaginal Hemorrhage 2.5 2.4 A A
    Urinary Tract Disorder 2.5 2.1 A A

Comparison of Raloxifene and Hormone Therapy - Raloxifene was compared with estrogen-progestin therapy in three clinical trials for prevention of osteoporosis. Table 2 shows adverse reactions occurring more frequently in one treatment group and at an incidence ≥2.0% in any group. Adverse reactions are shown without attribution of causality.

Raloxifene

(N=317)

%

Hormone Therapy-Continuous Combined b

(N=96)

%

Hormone Therapy-Cyclic c

(N=219)

%

a These data are from both blinded and open-label studies.

b Continuous Combined Hormone Therapy = 0.625 mg conjugated estrogens plus 2.5 mg medroxyprogesterone acetate.

c Cyclic Hormone Therapy = 0.625 mg conjugated estrogens for 28 days with concomitant 5 mg medroxyprogesterone acetate or 0.15 mg norgestrel on Days 1 through 14 or 17 through 28.

d Includes only patients with an intact uterus: Raloxifene, n=290; Hormone Therapy-Continuous Combined, n=67; Hormone Therapy-Cyclic, n=217.

Urogenital
    Breast Pain 4.4 37.5 29.7
    Vaginal Bleedingd 6.2 64.2 88.5
Digestive
    Flatulence 1.6 12.5 6.4
Cardiovascular
    Hot Flashes 28.7 3.1 5.9
Body as a Whole
    Infection 11.0 0 6.8
    Abdominal Pain 6.6 10.4 18.7
    Chest Pain 2.8 0 0.5

Breast Pain - Across all placebo-controlled trials, Raloxifene was indistinguishable from placebo with regard to frequency and severity of breast pain and tenderness. Raloxifene was associated with less breast pain and tenderness than reported by women receiving estrogens with or without added progestin.

Gynecologic Cancers - EVISTA-treated and placebo-treated groups had similar incidences of endometrial cancer and ovarian cancer.

Placebo-Controlled Trial of Postmenopausal Women at Increased Risk for Major Coronary Events (RUTH) - The safety of Raloxifene (60 mg once daily) was assessed in a placebo-controlled multinational trial of 10,101 postmenopausal women (age range 55-92) with documented coronary heart disease (CHD) or multiple CHD risk factors. Median study drug exposure was 5.1 years for both treatment groups . Therapy was discontinued due to an adverse reaction in 25% of 5044 EVISTA-treated women and 24% of 5057 placebo-treated women. The incidence per year of all-cause mortality was similar between the raloxifene (2.07%) and placebo (2.25%) groups.

Adverse reactions reported more frequently in EVISTA-treated women than in placebo-treated women included peripheral edema (14.1% raloxifene versus 11.7% placebo), muscle spasms/leg cramps (12.1% raloxifene versus 8.3% placebo), hot flashes (7.8% raloxifene versus 4.7% placebo), venous thromboembolic events (2.0% raloxifene versus 1.4% placebo), and cholelithiasis (3.3% raloxifene versus 2.6% placebo) .

Tamoxifen-Controlled Trial of Postmenopausal Women at Increased Risk for Invasive Breast Cancer (STAR) - The safety of Raloxifene 60 mg/day versus tamoxifen 20 mg/day over 5 years was assessed in 19,747 postmenopausal women (age range 35-83 years) in a randomized, double-blind trial. As of 31 December 2005, the median follow-up was 4.3 years. The safety profile of raloxifene was similar to that in the placebo-controlled raloxifene trials .

6.2 Postmarketing Experience

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Adverse reactions reported very rarely since market introduction include retinal vein occlusion, stroke, and death associated with venous thromboembolism (VTE).

7 DRUG INTERACTIONS

  • Cholestyramine: Use with Raloxifene is not recommended. Reduces the absorption and enterohepatic cycling of raloxifene.
  • Warfarin: Monitor prothrombin time when starting or stopping Raloxifene. (7.2, 12.3)
  • Highly Protein-Bound Drugs: Use with Raloxifene with caution. Highly protein-bound drugs include diazepam, diazoxide, and lidocaine. Raloxifene is more than 95% bound to plasma proteins. (7.3, 12.3)

7.1 Cholestyramine

Concomitant administration of cholestyramine with Raloxifene is not recommended. Although not specifically studied, it is anticipated that other anion exchange resins would have a similar effect. Raloxifene should not be co-administered with other anion exchange resins .

7.2 Warfarin

If Raloxifene is given concomitantly with warfarin or other warfarin derivatives, prothrombin time should be monitored more closely when starting or stopping therapy with Raloxifene .

7.3 Other Highly Protein-Bound Drugs

Raloxifene should be used with caution with certain other highly protein-bound drugs such as diazepam, diazoxide, and lidocaine. Although not examined, Raloxifene might affect the protein binding of other drugs. Raloxifene is more than 95% bound to plasma proteins .

7.4 Systemic Estrogens

The safety of concomitant use of Raloxifene with systemic estrogens has not been established and its use is not recommended.

7.5 Other Concomitant Medications

Raloxifene can be concomitantly administered with ampicillin, amoxicillin, antacids, corticosteroids, and digoxin .

The concomitant use of Raloxifene and lipid-lowering agents has not been studied.

8 USE IN SPECIFIC POPULATIONS

  • Pediatric Use: Safety and effectiveness not established.

8.1 Pregnancy

Pregnancy Category X. Raloxifene should not be used in women who are or may become pregnant .

8.3 Nursing Mothers

Raloxifene should not be used by lactating women . It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when raloxifene is administered to a nursing woman.

8.4 Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

8.5 Geriatric Use

Of the total number of patients in placebo-controlled clinical studies of Raloxifene, 61% were 65 and over, while 15.5% were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Based on clinical trials, there is no need for dose adjustment for geriatric patients .

8.6 Renal Impairment

Raloxifene should be used with caution in patients with moderate or severe renal impairment .

8.7 Hepatic Impairment

Raloxifene should be used with caution in patients with hepatic impairment .

10 OVERDOSAGE

In an 8-week study of 63 postmenopausal women, a dose of Raloxifene (HCl) 600 mg/day was safely tolerated. In clinical trials, no raloxifene overdose has been reported.

In postmarketing spontaneous reports, raloxifene overdose has been reported very rarely (less than 1 out of 10,000 [<0.01%] patients treated). The highest overdose has been approximately 1.5 grams. No fatalities associated with raloxifene overdose have been reported. Adverse reactions were reported in approximately half of the adults who took ≥180 mg raloxifene HCl and included leg cramps and dizziness.

Two 18-month-old children each ingested raloxifene HCl 180 mg. In these two children, symptoms reported included ataxia, dizziness, vomiting, rash, diarrhea, tremor, and flushing, as well as elevation in alkaline phosphatase.

There is no specific antidote for raloxifene.

No mortality was seen after a single oral dose in rats or mice at 5000 mg/kg (810 times the human dose for rats and 405 times the human dose for mice based on surface area, mg/m2) or in monkeys at 1000 mg/kg (80 times the AUC in humans).

11 DESCRIPTION

Raloxifene is an estrogen agonist/antagonist, commonly referred to as a selective estrogen receptor modulator (SERM) that belongs to the benzothiophene class of compounds. The chemical structure is:

Figure 1

Effect on Endometrium

In placebo-controlled osteoporosis prevention trials, endometrial thickness was evaluated every 6 months (for 24 months) by transvaginal ultrasonography (TVU). A total of 2978 TVU measurements were collected from 831 women in all dose groups. Placebo-treated women had a 0.04 mm mean increase from baseline in endometrial thickness over 2 years, whereas the EVISTA-treated women had a 0.09 mm mean increase. Endometrial thickness measurements in raloxifene-treated women were indistinguishable from placebo. There were no differences between the raloxifene and placebo groups with respect to the incidence of reported vaginal bleeding.

14.3 Reduction in Risk of Invasive Breast Cancer in Postmenopausal Women with Osteoporosis

MORE Trial

The effect of Raloxifene on the incidence of breast cancer was assessed as a secondary safety endpoint in a randomized, placebo-controlled, double-blind, multinational osteoporosis treatment trial in postmenopausal women . After 4 years, Raloxifene, 60 mg administered once daily, reduced the incidence of all breast cancers by 62%, compared with placebo (HR 0.38, 95% CI 0.22-0.67). Raloxifene reduced the incidence of invasive breast cancer by 71%, compared with placebo (ARR 3.1 per 1000 women-years); this was primarily due to an 80% reduction in the incidence of ER-positive invasive breast cancer in the Raloxifene group compared with placebo. Table 7 presents efficacy and selected safety outcomes.

CORE Trial

The effect of Raloxifene on the incidence of invasive breast cancer was evaluated for 4 additional years in a follow-up study conducted in a subset of postmenopausal women originally enrolled in the MORE osteoporosis treatment trial. Women were not re-randomized; the treatment assignment from the osteoporosis treatment trial was carried forward to this study. Raloxifene, 60 mg administered once daily, reduced the incidence of invasive breast cancer by 56%, compared with placebo (ARR 3.0 per 1000 women-years); this was primarily due to a 63% reduction in the incidence of ER-positive invasive breast cancer in the Raloxifene group compared with placebo. There was no reduction in the incidence of ER-negative breast cancer. In the osteoporosis treatment trial and the follow-up study, there was no difference in incidence of noninvasive breast cancer between the Raloxifene and placebo groups. Table 7 presents efficacy and selected safety outcomes.

In a subset of postmenopausal women followed for up to 8 years from randomization in MORE to the end of CORE, Raloxifene, 60 mg administered once daily, reduced the incidence of invasive breast cancer by 60% in women assigned Raloxifene (N=1355) compared with placebo (N=1286) (HR 0.40, 95% CI 0.21, 0.77; ARR 1.95 per 1000 women-years); this was primarily due to a 65% reduction in the incidence of ER-positive invasive breast cancer in the Raloxifene group compared with placebo.

Outcomes MORE

4 years

COREa

4 years

Placebo

(N=2576)

Raloxifene

(N=2557)

HR

(95% CI)b

Placebo

(N=1286)

Raloxifene

(N=2725)

HR

(95% CI)b

n IRb n IRb n IRb n IRb
a CORE was a follow-up study conducted in a subset of 4011 postmenopausal women who originally enrolled in MORE. Women were not re-randomized; the treatment assignment from MORE was carried forward to this study. At CORE enrollment, the Raloxifene group included 2725 total patients with 1355 patients who were originally assigned to raloxifene HCl 60 mg once daily and 1370 patients who were originally assigned to raloxifene HCl 120 mg at MORE randomization.

b Abbreviations: CI = confidence interval; ER = estrogen receptor; HR = hazard ratio; IR = annual incidence rate per 1000 women; N/A = not applicable.

c Included 1274 patients in placebo and 2716 patients in Raloxifene who were not diagnosed with breast cancer prior to CORE enrollment.

d p<0.05, obtained from the log-rank test, and not adjusted for multiple comparisons in MORE.

e All cases were ductal carcinoma in situ.

f Only patients with an intact uterus were included (MORE: placebo = 1999, Raloxifene = 1950; CORE: placebo = 1008, Raloxifene = 2138).

Invasivec breast cancer 38 4.36 11 1.26 0.29

(0.15, 0.56)d

20 5.41 19 2.43 0.44

(0.24, 0.83)d

    ERb, c positive 29 3.33 6 0.69 0.20

(0.08, 0.49)

15 4.05 12 1.54 0.37

(0.17, 0.79)

    ERb, c negative 4 0.46 5 0.57 1.23

(0.33, 4.60)

3 0.81 6 0.77 0.95

(0.24, 3.79)

    ERb, c unknown 5 0.57 0 0.00 N/Ab 2 0.54 1 0.13 N/Ab
Noninvasivec, e breast cancer 5 0.57 3 0.34 0.59

(0.14, 2.47)

2 0.54 5 0.64 1.18

(0.23, 6.07)

Clinical vertebral fractures 107 12.27 62 7.08 0.57

(0.42, 0.78)

N/Ab N/Ab N/Ab N/Ab N/Ab
Death 36 4.13 23 2.63 0.63

(0.38, 1.07)

29 7.76 47 5.99 0.77

(0.49, 1.23)

Death due to stroke 6 0.69 3 0.34 0.49

(0.12, 1.98)

1 0.27 6 0.76 2.87

(0.35, 23.80)

Stroke 56 6.42 43 4.91 0.76

(0.51, 1.14)

14 3.75 49 6.24 1.67

(0.92, 3.03)

Deep vein thrombosis 8 0.92 20 2.28 2.50

(1.10, 5.68)

4 1.07 17 2.17 2.03

(0.68, 6.03)

Pulmonary embolism 4 0.46 11 1.26 2.76

(0.88, 8.67)

0 0.00 9 1.15 N/Ab
Endometrial and uterine cancerf 5 0.74 5 0.74 1.01

(0.29, 3.49)

3 1.02 4 0.65 0.64

(0.14, 2.85)

Ovarian cancer 6 0.69 3 0.34 0.49

(0.12, 1.95)

2 0.54 2 0.25 0.47

(0.07, 3.36)

Hot flashes 151 17.31 237 27.06 1.61

(1.31, 1.97)

11 2.94 26 3.31 1.12

(0.55, 2.27)

Peripheral edema 134 15.36 164 18.73 1.23

(0.98, 1.54)

30 8.03 61 7.77 0.96

(0.62, 1.49)

Cholelithiasis 45 5.16 53 6.05 1.18

(0.79, 1.75)

12 3.21 35 4.46 1.39

(0.72, 2.67)


RUTH Trial

The effect of Raloxifene on the incidence of invasive breast cancer was assessed in a randomized, placebo-controlled, double-blind, multinational study in 10,101 postmenopausal women at increased risk of coronary events. Women in this study had a median age of 67.6 years (range 55-92) and were followed for a median of 5.6 years (range 0.01-7.1). Eighty-four percent were White, 9.8% of women reported a first-degree relative with a history of breast cancer, and 41.4% of the women had a 5-year predicted risk of invasive breast cancer ≥1.66%, based on the modified Gail model.

Raloxifene, 60 mg administered once daily, reduced the incidence of invasive breast cancer by 44% compared with placebo [absolute risk reduction (ARR) 1.2 per 1000 women-years]; this was primarily due to a 55% reduction in estrogen receptor (ER)-positive invasive breast cancer in the Raloxifene group compared with placebo (ARR 1.2 per 1000 women-years). There was no reduction in ER-negative invasive breast cancer. Table 8 presents efficacy and selected safety outcomes.

Outcomes Placeboa

(N=5057)

Raloxifenea

(N=5044)

HR

(95% CI)b

n IRb n IRb
a Note: There were a total of 76 breast cancer cases in the placebo group and 52 in the Raloxifene group. For two cases, one in each treatment group, invasive status was unknown.

b Abbreviations: CI = confidence interval; ER = estrogen receptor; HR = hazard ratio; IR = annual incidence rate per 1000 women.

c p<0.05, obtained from the log-rank test, after adjusting for the co-primary endpoint of major coronary events.

d All cases were ductal carcinoma in situ.

e Only patients with an intact uterus were included (placebo = 3882, Raloxifene = 3900).

f Only patients with at least one ovary were included (placebo = 4606, Raloxifene = 4559).

g Only patients with an intact gallbladder at baseline were included (placebo = 4111, Raloxifene = 4144).

Invasive breast cancer 70 2.66 40 1.50 0.56 (0.38, 0.83)c
    ERb positive 55 2.09 25 0.94 0.45 (0.28, 0.72)
    ERb negative 9 0.34 13 0.49 1.44 (0.61, 3.36)
    ERb unknown 6 0.23 2 0.07 0.33 (0.07, 1.63)
Noninvasived breast cancer 5 0.19 11 0.41 2.17 (0.75, 6.24)
Clinical vertebral fractures 97 3.70 64 2.40 0.65 (0.47, 0.89)
Death 595 22.45 554 20.68 0.92 (0.82, 1.03)
Death due to stroke 39 1.47 59 2.20 1.49 (1.00, 2.24)
Stroke 224 8.60 249 9.46 1.10 (0.92, 1.32)
Deep vein thrombosis 47 1.78 65 2.44 1.37 (0.94, 1.99)
Pulmonary embolism 24 0.91 36 1.35 1.49 (0.89, 2.49)
Endometrial and uterine cancere 17 0.83 21 1.01 1.21 (0.64 - 2.30)
Ovarian cancerf 10 0.41 17 0.70 1.69 (0.78, 3.70)
Hot flashes 241 9.09 397 14.82 1.68 (1.43, 1.97)
Peripheral edema 583 22.00 706 26.36 1.22 (1.09, 1.36)
Cholelithiasisg 131 6.20 168 7.83 1.26 (1.01, 1.59)

The effect of Raloxifene in reducing the incidence of invasive breast cancer was consistent among women above or below age 65 or with a 5-year predicted invasive breast cancer risk, based on the modified Gail model, <1.66%, or ≥1.66%.

14.4 Reduction in Risk of Invasive Breast Cancer in Postmenopausal Women at High Risk of Invasive Breast Cancer

STAR Trial

The effects of Raloxifene 60 mg/day versus tamoxifen 20 mg/day over 5 years on reducing the incidence of invasive breast cancer were assessed in 19,747 postmenopausal women in a randomized, double-blind trial conducted in North America by the National Surgical Adjuvant Breast and Bowel Project and sponsored by the National Cancer Institute. Women in this study had a mean age of 58.5 years, a mean 5-year predicted invasive breast cancer risk of 4.03% (range 1.66-23.61%), and 9.1% had a history of lobular carcinoma in situ (LCIS). More than 93% of participants were White. As of 31 December 2005, the median time of follow-up was 4.3 years (range 0.07-6.50 years).

Raloxifene was not superior to tamoxifen in reducing the incidence of invasive breast cancer. The observed incidence rates of invasive breast cancer were Raloxifene 4.4 and tamoxifen 4.3 per 1000 women per year. The results from a noninferiority analysis are consistent with Raloxifene potentially losing up to 35% of the tamoxifen effect on reduction of invasive breast cancer. The effect of each treatment on invasive breast cancer was consistent when women were compared by baseline age, history of LCIS, history of atypical hyperplasia, 5-year predicted risk of breast cancer by the modified Gail model, or the number of relatives with a history of breast cancer. Fewer noninvasive breast cancers occurred in the tamoxifen group compared to the Raloxifene group. Table 9 presents efficacy and selected safety outcomes.

a Abbreviations: CI = confidence interval; DCIS = ductal carcinoma in situ; ER = estrogen receptor; IR = annual incidence rate per 1000 women; LCIS = lobular carcinoma in situ; RR = risk ratio for women in the Raloxifene group compared with those in the tamoxifen group.

b Of the 60 noninvasive breast cases in the tamoxifen group, 5 were mixed types. Of the 83 noninvasive breast cancers in the raloxifene group, 7 were mixed types.

c Only patients with an intact uterus at baseline were included (tamoxifen = 4739, Raloxifene = 4715).

d Only patients with at least one intact ovary at baseline were included (tamoxifen = 6813, Raloxifene = 6787).

e Defined as myocardial infarction, severe angina, or acute ischemic syndromes.

f Only patients who were free of cataracts at baseline were included (tamoxifen = 8342, Raloxifene = 8333).

g Peripheral edema events are included in the term edema.

Outcomes Raloxifene

(N=9751)

Tamoxifen

(N=9736)

RR

(95% CI)a

n IRa n IRa
Invasive breast cancer 173 4.40 168 4.30 1.02 (0.82, 1.27)
    ERa positive 115 2.93 120 3.07 0.95 (0.73, 1.24)
    ERa negative 52 1.32 46 1.18 1.12 (0.74, 1.71)
    ERa unknown 6 0.15 2 0.05 2.98 (0.53, 30.21)
Noninvasive breast cancerb 83 2.12 60 1.54 1.38 (0.98, 1.95)
    DCISa 47 1.20 32 0.82 1.46 (0.91, 2.37)
    LCISa 29 0.74 23 0.59 1.26 (0.70, 2.27)
Uterine cancerc 23 1.21 37 1.99 0.61 (0.34, 1.05)
Endometrial hyperplasiac 17 0.90 100 5.42 0.17 (0.09, 0.28)
Hysterectomyc 92 4.84 246 13.25 0.37 (0.28, 0.47)
Ovarian cancerd 18 0.66 14 0.52 1.27 (0.60, 2.76)
Ischemic heart diseasee 138 3.50 125 3.19 1.10 (0.86, 1.41)
Stroke 54 1.36 56 1.42 0.96 (0.65, 1.42)
Deep vein thrombosis 67 1.69 92 2.35 0.72 (0.52, 1.00)
Pulmonary embolism 38 0.96 58 1.47 0.65 (0.42, 1.00)
Clinical vertebral fractures 58 1.46 58 1.47 0.99 (0.68, 1.46)
Cataractsf 343 10.34 435 13.19 0.78 (0.68, 0.91)
    Cataract surgeryf 240 7.17 295 8.85 0.81 (0.68, 0.96)
Death 104 2.62 109 2.76 0.95 (0.72, 1.25)
Edemag 741 18.66 664 16.83 1.11 (1.00, 1.23)
Hot flashes 6748 169.91 7170 181.71 0.94 (0.90, 0.97)

14.5 Effects on Cardiovascular Disease

In a randomized, placebo-controlled, double-blind, multinational clinical trial (RUTH) of 10,101 postmenopausal women with documented coronary heart disease or at increased risk for coronary events, no cardiovascular benefit was demonstrated after treatment with Raloxifene 60 mg once daily for a median follow-up of 5.6 years. No significant increase or decrease was observed for coronary events (death from coronary causes, nonfatal myocardial infarction, or hospitalization for an acute coronary syndrome). An increased risk of death due to stroke after treatment with Raloxifene was observed: 59 (1.2%) EVISTA-treated women died due to a stroke compared to 39 (0.8%) placebo-treated women (2.2 versus 1.5 per 1000 women-years; hazard ratio 1.49; 95% confidence interval, 1.00-2.24; p=0.0499). The incidence of stroke did not differ significantly between treatment groups (249 with Raloxifene [4.9%] versus 224 with placebo [4.4%]; hazard ratio 1.10; 95% confidence interval 0.92-1.32; p=0.30; 9.5 versus 8.6 per 1000 women-years) .

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Raloxifene 60 mg tablets are white, elliptical, and film coated. They are imprinted on one side with LILLY and the tablet code 4165 in edible blue ink. They are available as follows:

Bottles of 30 NDC 0002-4165-30
Bottles of 100 (unit of use) NDC 0002-4165-02
Bottles of 2000 NDC 0002-4165-07

16.2 Storage and Handling

Store at controlled room temperature, 20° to 25°C (68° to 77°F) [see USP]. The USP defines controlled room temperature as a temperature maintained thermostatically that encompasses the usual and customary working environment of 20° to 25°C (68° to 77°F); that results in a mean kinetic temperature calculated to be not more than 25°C; and that allows for excursions between 15° and 30°C (59° and 86°F) that are experienced in pharmacies, hospitals, and warehouses.

17 PATIENT COUNSELING INFORMATION

See FDA-approved Medication Guide.

Physicians should instruct their patients to read the Medication Guide before starting therapy with Raloxifene and to reread it each time the prescription is renewed.

17.1 Osteoporosis Recommendations, Including Calcium and Vitamin D Supplementation

For osteoporosis treatment or prevention, patients should be instructed to take supplemental calcium and/or vitamin D if intake is inadequate. Patients at increased risk for vitamin D insufficiency should be instructed to take additional vitamin D if needed. Weight-bearing exercises should be considered along with the modification of certain behavioral factors, such as cigarette smoking and/or excessive alcohol consumption, if these factors exist.

17.2 Patient Immobilization

Raloxifene should be discontinued at least 72 hours prior to and during prolonged immobilization (e.g., post-surgical recovery, prolonged bed rest), and patients should be advised to avoid prolonged restrictions of movement during travel because of the increased risk of venous thromboembolic events .

17.3 Hot Flashes or Flushes

Raloxifene may increase the incidence of hot flashes and is not effective in reducing hot flashes or flushes associated with estrogen deficiency. In some asymptomatic patients, hot flashes may occur upon beginning Raloxifene therapy.

17.4 Reduction in Risk of Invasive Breast Cancer in Postmenopausal Women with Osteoporosis or at High Risk of Invasive Breast Cancer

Use of Raloxifene is associated with the reduction of the risk of invasive breast cancer in postmenopausal women. Raloxifene has not been shown to reduce the risk of noninvasive breast cancer. When considering treatment, physicians need to discuss the potential benefits and risks of Raloxifene treatment with the patient.

Raloxifene is not indicated for the treatment of invasive breast cancer or reduction of the risk of recurrence.

Patients should have breast exams and mammograms before starting Raloxifene and should continue regular breast exams and mammograms in keeping with good medical practice after beginning treatment with Raloxifene.

Literature revised January 7, 2011

Marketed by: Lilly USA, LLC

Indianapolis, IN 46285, USA

Copyright © 1997, 2011, Eli Lilly and Company. All rights reserved.

PV 6771 AMP

Medication Guide

Raloxifene® (Ē-VISS-tah)

(raloxifene hydrochloride tablets)

Tablets for Oral Use

Read the Medication Guide that comes with Raloxifene before you start taking it and each time you refill your prescription. The information may have changed. This Medication Guide does not take the place of talking with your doctor about your medical condition or treatment. Talk with your doctor about Raloxifene when you start taking it and at regular checkups.

What is the most important information I should know about Raloxifene?

Serious and life-threatening side effects can occur while taking Raloxifene. These include blood clots and dying from stroke:

  • Increased risk of blood clots in the legs (deep vein thrombosis) and lungs (pulmonary embolism) have been reported with Raloxifene. Women who have or have had blood clots in the legs, lungs, or eyes should not take Raloxifene.
  • Women who have had a heart attack or are at risk for a heart attack may have an increased risk of dying from stroke when taking Raloxifene.
  • Before starting Raloxifene, tell your doctor if you have had blood clots in your legs, lungs, or eyes, a stroke, mini-stroke (transient ischemic attack), or have an irregular heartbeat.
  • Stop taking Raloxifene and call your doctor if you have:
    • leg pain or a feeling of warmth in the lower leg (calf).
    • swelling of the legs, hands, or feet.
    • sudden chest pain, shortness of breath, or coughing up blood.
    • sudden change in your vision, such as loss of vision or blurred vision.
  • Being still for a long time (such as sitting still during a long car or airplane trip or being in bed after surgery) can increase your risk of blood clots. (See “What should I avoid if I am taking Raloxifene?”)

What is Raloxifene?

Raloxifene is a type of prescription medicine called a Selective Estrogen Receptor Modulator (SERM). Raloxifene is for women after menopause, and has more than one use:

  • Osteoporosis: Raloxifene treats and prevents osteoporosis by helping make your bones stronger and less likely to break.
  • Invasive Breast Cancer: If you have osteoporosis or are at high risk for breast cancer, Raloxifene can be used to lower your chance of getting invasive breast cancer. Raloxifene will not totally get rid of your chance of getting breast cancer. Your doctor can estimate your risk of breast cancer by asking you about risk factors, including:
    • your age (getting older).
    • family history of breast cancer in your mother, sister, or daughter.
    • a history of any breast biopsy, especially an abnormal biopsy.

    You and your doctor should talk about whether the possible benefit of Raloxifene in lowering your chance of getting invasive breast cancer is greater than its possible risks.


Raloxifene is not for use in premenopausal women (women who have not passed menopause).

Who should not take Raloxifene?

Do not take Raloxifene if you:

  • have or have had blood clots in your legs, lungs, or eyes. Taking Raloxifene may increase the risk of getting blood clots.
  • are pregnant or could become pregnant. Raloxifene could harm your unborn child.
  • are nursing a baby. It is not known if Raloxifene passes into breast milk or what effect it might have on the baby.
What should I tell my doctor before taking Raloxifene?

Raloxifene may not be right for you. Before taking Raloxifene, tell your doctor about all your medical conditions, including if you:

  • have had blood clots in your legs, lungs, or eyes, a stroke, mini-stroke (TIA/transient ischemic attack), or a type of irregular heartbeat (atrial fibrillation).
  • have had breast cancer. Raloxifene has not been fully studied in women who have a history of breast cancer.
  • have liver or kidney problems.
  • have taken estrogen in the past and had a high increase of triglycerides (a kind of fat in the blood).
  • are pregnant, planning to become pregnant, or breast-feeding (see “Who should not take Raloxifene?”).

Tell your doctor about all medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist each time you get a new medicine. Especially tell your doctor if you take*:

  • warfarin (Coumadin®, Jantoven®)

    If you are taking warfarin or other coumarin blood thinners, your doctor may need to do a blood test when you first start or if you need to stop taking Raloxifene. Names for this test include “prothrombin time,” “pro-time,” or “INR.” Your doctor may need to adjust the dose of your warfarin or other coumarin blood thinner.

  • cholestyramine
  • estrogens

Raloxifene should not be taken with cholestyramine or estrogens.

How should I take Raloxifene?

  • Take Raloxifene exactly how your doctor tells you to.
  • Keep taking Raloxifene for as long as your doctor prescribes it for you. It is not known how long you should keep taking Raloxifene to lower your chance of getting invasive breast cancers.
  • It is important to get your refills on time so you do not run out of the medicine.
  • Take one Raloxifene tablet each day.
  • Take Raloxifene at any time of the day, with or without food.
  • To help you remember to take Raloxifene, it may be best to take it at about the same time each day.
  • Calcium and vitamin D may be taken at the same time as Raloxifene. It is important to take calcium and vitamin D, as directed by your physician, to prevent or treat osteoporosis.
  • If you miss a dose, take it as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and take only your next regularly scheduled dose. Do not take two doses at the same time.
What should I avoid while taking Raloxifene?

  • Being still for a long time (such as during long trips or being in bed after surgery) can increase the risk of blood clots. Raloxifene may add to this risk. If you will need to be still for a long time, talk with your doctor about ways to reduce the risk of blood clots. On long trips, move around periodically. Stop taking Raloxifene at least 3 days before a planned surgery or before you plan on being still for a long time. You should start taking Raloxifene again when you return to your normal activities.
  • Some medicines should not be taken with Raloxifene (see “What should I tell my doctor before taking Raloxifene?”).
What are the possible side effects of Raloxifene?

Serious and life-threatening side effects can occur while taking Raloxifene. These include blood clots and dying from stroke:

  • Increased risk of blood clots in the legs (deep vein thrombosis) and lungs (pulmonary embolism) have been reported with Raloxifene. Women who have or have had blood clots in the legs, lungs, or eyes should not take Raloxifene.
  • Women who have had a heart attack or are at risk for a heart attack may have an increased risk of dying from stroke when taking Raloxifene.

See “What is the most important information I should know about Raloxifene?”

The most common side effects of Raloxifene are hot flashes, leg cramps, swelling of the feet, ankles, and legs, flu syndrome, joint pain, and sweating. Hot flashes are more common during the first 6 months after starting treatment.

These are not all the side effects of Raloxifene. Tell your doctor about any side effect that bothers you or that does not go away. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What else should I know about Raloxifene?

  • Do not use Raloxifene to prevent heart disease, heart attack, or strokes.
  • To get the calcium and vitamin D you need, your doctor may advise you to change your diet and/or take supplemental calcium and vitamin D. Your doctor may suggest other ways to help treat or prevent osteoporosis, in addition to taking Raloxifene and getting the calcium and vitamin D you need. These may include regular exercise, stopping smoking, and drinking less alcohol.
  • Women who have hot flashes can take Raloxifene. Raloxifene does not treat hot flashes, and it may cause hot flashes in some women. (See “What are the possible side effects of Raloxifene?”)
  • Raloxifene has not been found to cause breast tenderness or enlargement. If you notice any changes in your breasts, call your doctor to find out the cause. Before starting and while taking Raloxifene you should have breast exams and mammograms, as directed by your doctor. Because Raloxifene does not eliminate the chance of developing breast cancers, you need these examinations to find any breast cancers as early as possible.
  • Raloxifene should not cause spotting or menstrual-type bleeding. If you have any vaginal bleeding, call your doctor to find out the cause. Raloxifene has not been found to increase the risk for cancer of the lining of the uterus.
  • Women in clinical trials have taken Raloxifene for up to eight years.

How should I store Raloxifene?

  • Store Raloxifene at 68°F to 77°F (20°C-25°C).
  • Keep Raloxifene and all medicines out of the reach of children.

General Information about the safe and effective use of Raloxifene

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Raloxifene for a condition for which it was not prescribed. Do not give your Raloxifene to other people, even if they have the same symptoms you have. It may harm them.

This Medication Guide is a summary of the most important information about Raloxifene. If you would like more information about Raloxifene, talk with your doctor. You can ask your doctor or pharmacist for information about Raloxifene that is written for health professionals. For more information, call 1-800-545-5979 (toll-free) or go to the following website: www.evista.com.

What are the ingredients in Raloxifene?

Active Ingredient: Raloxifene

Inactive Ingredients: anhydrous lactose, carnauba wax, crospovidone, FD&C Blue No. 2 aluminum lake, hypromellose, lactose monohydrate, magnesium stearate, modified pharmaceutical glaze, polyethylene glycol, polysorbate 80, povidone, propylene glycol, and titanium dioxide.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

*The brands listed are trademarks of their respective owners and are not trademarks of Eli Lilly and Company. The makers of these brands are not affiliated with and do not endorse Eli Lilly and Company or its products.

Medication Guide revised January 7, 2011

Marketed by: Lilly USA, LLC, Indianapolis, IN 46285, USA

Copyright © 1997, 2011, Eli Lilly and Company. All rights reserved.

PV 3126 AMP

Raloxifene pharmaceutical active ingredients containing related brand and generic drugs:

infoActive ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Raloxifene available forms, composition, doses:

infoForm of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.

Price
Evista 60 mg tablet4.37 USD
Tablets; Oral; Raloxifene Hydrochloride 60 mg

Raloxifene destination | category:

infoDestination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Raloxifene Anatomical Therapeutic Chemical codes:

infoA medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Raloxifene pharmaceutical companies:

infoPharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."EVISTA (RALOXIFENE HYDROCHLORIDE) TABLET [LAKE ERIE MEDICAL & SURGICAL SUPPLY DBA QUALITY CARE PRODUCTS LLC]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. "raloxifene". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).
  3. "raloxifene". http://www.drugbank.ca/drugs/DB0048... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Raloxifene?

Depending on the reaction of the Raloxifene after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Raloxifene not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Raloxifene addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sDrugs.com conducted a study on Raloxifene, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Raloxifene consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Arunabha Ray, MD Pharmacology

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