Browse by Alaphabet

Call 1-866-335-8064 for pricing

Evista - Evista Side Effects - Evista - Canada Pharmacy

Evista
Raloxifene HCl

Pharmacology: Raloxifene is a selective estrogen receptor modulator (SERM) that belongs to the benzothiophene class of compounds. The SERM profile of raloxifene includes estrogen agonist effects on bone and lipid metabolism but not in uterine or breast tissues. rx canada pharmacy

Pharmacokinetics: The disposition of raloxifene has been evaluated in more than 3000 postmenopausal women in selected raloxifene osteoporosis treatment and prevention clinical trials using a population approach. Pharmacokinetic data were also obtained in conventional clinical pharmacology studies in 292 postmenopausal women. Raloxifene exhibits high within-subject variability (approximately 30%) of most pharmacokinetic parameters. Table I summarizes the pharmacokinetic parameters of raloxifene. rx canada pharmacy

Absorption: Raloxifene is absorbed rapidly after oral administration. Approximately 60% of an oral dose is absorbed, but presystemic glucuronide conjugation is extensive. Absolute bioavailability of raloxifene is 2%. The time to reach average maximum plasma concentration and bioavailability are functions of systemic interconversion and enterohepatic cycling of raloxifene and its glucuronide metabolites. rx canada pharmacy

Administration of raloxifene with a standardized, high-fat meal increases the absorption of raloxifene slightly, but does not lead to clinically meaningful changes in systemic exposure. Raloxifene can be administered without regard to meals. rx canada pharmacy

Distribution: Following oral administration of single doses ranging from 30 to 150 mg of raloxifene, the apparent volume of distribution is 2348 L/kg and is not dose dependent. rx canada pharmacy

Raloxifene and the monoglucuronide conjugates are highly bound to plasma proteins. Raloxifene binds to both albumin and a1-acid glycoprotein, but not to sex steroid binding globulin. rx canada pharmacy

Metabolism: Biotransformation and disposition of raloxifene in humans have been determined following oral administration of ¹⁴C-labeled raloxifene. 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. Unconjugated raloxifene comprises less than 1% of the total radiolabeled material in plasma. The terminal log-linear portion of the plasma concentration curve for raloxifene and the glucuronides are generally parallel. This is consistent with interconversion of raloxifene and the glucuronide metabolites. rx canada pharmacy

Following i.v. administration, raloxifene is cleared at a rate approximating hepatic blood flow. Apparent oral clearance is 44.1 L/kg.h. Raloxifene and its glucuronide conjugates are interconverted by reversible systemic metabolism and enterohepatic cycling, thereby prolonging its plasma elimination half-life to 27.7 hours after oral dosing. rx canada pharmacy

Results from single oral doses of raloxifene predict multiple-dose pharmacokinetics. Following chronic dosing, clearance ranges from 40 to 60 L/kg.h. Increasing doses of raloxifene (ranging from 30 to 150 mg) result in slightly less than a proportional increase in the area under the plasma time concentration curve (AUC). rx canada pharmacy

Excretion: Raloxifene is primarily excreted in feces, and negligible amounts are excreted unchanged in urine. Less than 6% of the raloxifene dose is eliminated in urine as glucuronide conjugates. rx canada pharmacy

Special Populations: Geriatrics: The pharmacokinetics of raloxifene are independent of age (42 to 84 years). rx canada pharmacy

Children: The pharmacokinetics of raloxifene have not been evaluated in a pediatric population. rx canada pharmacy

Gender: Total extent of exposure and oral clearance, normalized for lean body weight, are not significantly different between age-matched male and female volunteers. rx canada pharmacy

Race: Pharmacokinetic differences due to race have been studied in 1712 women including 97.5% Caucasian, 1.0% Asian, 0.7% Hispanic, and 0.5% Black in the osteoporosis treatment trial and in 1053 women including 93.5% Caucasian, 4.3% Hispanic, 1.2% Asian, and 0.5% Black in the osteoporosis prevention trials. There were no discernible differences in raloxifene plasma concentrations among these groups. The influence of race can not be conclusively determined because of the small numbers of non-Caucasians. rx canada pharmacy

Renal Insufficiency: Since negligible amounts of raloxifene are eliminated in urine, a study in patients with renal insufficiency was not conducted. In the osteoporosis treatment and prevention trials, raloxifene and metabolite concentrations were not affected by renal function in women having estimated creatinine clearance as low as 21 mL/min (0.35 mL/s). rx canada pharmacy

Hepatic Dysfunction: Raloxifene was studied, as a single dose, in Child-Pugh Class A patients with cirrhosis and total serum bilirubin ranging from 0.6 to 2 mg/dL (10.3 to 34.2 µmol/L). Plasma raloxifene concentrations were approximately 2.5 times higher than in controls and correlated with bilirubin concentrations. Safety and efficacy have not been evaluated further in patients with hepatic insufficiency (see Warnings). rx canada pharmacy

Drug-Drug Interactions : Clinically significant drug-drug interactions are discussed in Precautions. rx canada pharmacy

Ampicillin and Other Oral Antimicrobials: Peak concentrations of raloxifene are reduced with coadministration of ampicillin. The reduction in peak concentrations is consistent with reduced enterohepatic cycling associated with antibiotic reduction of enteric bacteria. Since the overall extent of absorption and the elimination rate of raloxifene are not affected, raloxifene can be concurrently administered with ampicillin. In the osteoporosis treatment trial, coadministered oral antimicrobial agents (including amoxicillin, cephalexin, ciprofloxacin, macrolide antibiotics, sulfamethoxazole/trimethoprim and tetracycline) had no effect on plasma raloxifene concentrations. rx canada pharmacy

Corticosteroids: The chronic administration of raloxifene in postmenopausal women has no effect on the pharmacokinetics of methylprednisolone given as a single oral dose. rx canada pharmacy

Digoxin: Raloxifene has no effect on the pharmacokinetics of digoxin. In the osteoporosis treatment trial, coadministered digoxin had no effect on plasma raloxifene concentration. rx canada pharmacy

Gastrointestinal Medications: Concurrent administration of calcium carbonate or aluminum and magnesium hydroxide-containing antacids does not affect the systemic exposure of raloxifene. In the osteoporosis treatment trial, coadministered gastrointestinal medications (including bisacodyl, cisapride, docusate, H ₂-antagonists, laxatives, loperamide, omeprazole and psyllium) had no effect on plasma raloxifene concentration. rx canada pharmacy

Highly Protein-bound Drugs: Raloxifene is more than 95% bound to plasma proteins. The influence of coadministered highly protein-bound drugs (including diazepam, gemfibrozil, ibuprofen, naproxen and warfarin) on raloxifene plasma concentrations was evaluated in the osteoporosis treatment trial. No clinically significant effects of these agents on raloxifene plasma concentrations were identified. In vitro, raloxifene did not affect the binding of phenytoin, tamoxifen or warfarin. rx canada pharmacy

Highly Glucuronidated Drugs: Raloxifene undergoes extensive first-pass metabolism to glucuronide conjugates. The influence of co-administered highly glucuronidated drugs (including acetaminophen, ketoprofen, morphine and oxazepam) on raloxifene plasma concentrations was evaluated in the osteoporosis treatment trial. No clinically significant effects of these agents on raloxifene plasma concentrations were identified. rx canada pharmacy

Other Medications: The influence of concomitant medications on raloxifene plasma concentrations was evaluated in the osteoporosis treatment clinical trial. The 152 most commonly coadministered medications were grouped by pharmacological class based on their therapeutic use. Frequently coadministered drugs included:inhibitors and angiotensin antagonists, alpha agonists and antagonists, anticholinergics, antidepressants, antimicrobials, antipsychotics, benzodiazepines, beta-blockers and -agonists, bisphosphonates, calcium channel blockers, diuretics, estrogen preparations, glucocorticoids, guaifenesin, H ₁-antagonists, H ₂-antagonists and proton pump inhibitors, hypoglycemics, hypolipidemics, iron preparations, muscle relaxants, nitrates, nonbenzodiazepine hypnotics, NSAIDs, opioid analgesics, theophylline and thyroid hormone. No clinically relevant effects of the coadministration of any of these agents on raloxifene plasma concentrations were observed. rx canada pharmacy

Pharmacodynamics: General: Postmenopausal women have an increased risk of chronic illnesses such as osteoporosis and atherosclerotic cardiovascular disease resulting from estrogen deficiency. Estrogen replacement reduces the risk of osteoporosis and coronary artery disease, but it also increases the risk of endometrial carcinoma and possibly breast cancer. The selective estrogen receptor modulator (SERM) profile of raloxifene includes estrogen agonist effects on bone and lipid metabolism, and estrogen antagonist effects in uterine and breast tissues. Thus, raloxifene is a first line option for the treatment and prevention of postmenopausal osteoporosis. rx canada pharmacy

Raloxifene's biological actions, like those of estrogen, are mediated through high-affinity binding to estrogen receptors and regulation of gene expression. This binding results in differential expression of multiple estrogen-regulated genes in different tissues. Recent data suggest that the estrogen receptor can regulate gene expression by at least 2 distinct pathways which are ligand-, tissue- and/or gene-specific. rx canada pharmacy

Effects on the Skeleton: During early to middle adult life, bone undergoes continuous remodeling. In this process, local areas of bone resorption are refilled completely by ensuing bone formation; that is, resorption and formation are in balance. The result is that bone mass remains relatively constant. Ovarian estrogen is important for maintenance of this balance in bone turnover. Marked decreases in estrogen availability, such as after oophorectomy or menopause, lead to marked increases in bone resorption, accelerated bone loss and increased risk of fracture. After menopause, bone is initially lost rapidly because the compensatory increase in bone formation is inadequate to offset resorptive losses. rx canada pharmacy

This imbalance between resorption and formation may be related to loss of estrogen, or to age-related impairment of osteoblasts or their precursors. Estrogen replacement therapy reduces resorption of bone by inhibiting the formation and action of osteoclasts and decreases overall bone turnover. These effects on bone are manifested as reductions in the serum and urine levels of bone turnover markers, histologic evidence of decreased bone resorption and formation, and increased bone mineral density (BMD). Although raloxifene increases BMD to a lesser extent than estrogen, the effects of raloxifene on bone turnover in postmenopausal women parallel those of estrogen, as shown by studies of bone mineral densitometry, radiocalcium kinetics, bone markers and bone histomorphometry. rx canada pharmacy

Treatment of Osteoporosis: The effects of raloxifene on fracture incidence and BMD in postmenopausal women with osteoporosis were examined at 3 years in a large, randomized, placebo-controlled, double-blind multinational osteoporosis treatment trial. The study population consisted of 7705 postmenopausal women with osteoporosis as defined by: a) low BMD (vertebral or hip bone mineral density at least 2.5 standard deviations below the mean value for healthy young women) without baseline vertebral fractures, or b) one or more baseline vertebral fractures. Women enrolled in this study had a median age of 67 years (range 31 to 80) and a median time since menopause of 19 years. All women received calcium (500 mg/day) and vitamin D (400 to 600 IU/day). Raloxifene, 60 mg administered once daily, decreased the incidence of one or more vertebral fractures by as much as 55% (Table II) and increased BMD compared to an active therapy of calcium plus vitamin D supplemented placebo. Raloxifene reduced the incidence of vertebral fractures whether or not patients had experienced a previous fracture. The decrease in incidence of vertebral fracture was greater than could be accounted for by increase in BMD alone (Figure I). rx canada pharmacy

Figure I. Changes in BMD do not fully account for vertebral fracture risk reduction. This figure shows the correlation between vertebral fracture risk and percent change in femoral neck BMD at 3 years based on a logistic regression analysis of the clinical trial data. For any given change in BMD from baseline, Evista-treated patients had a lower risk for vertebral fracture compared to placebo. rx canada pharmacy

Overall osteoporotic fracture risk was significantly reduced with raloxifene therapy. Although nonvertebral fracture risk reduction was not significant, the risk of individual nonvertebral fractures versus placebo decreased with increasing exposure to raloxifene. rx canada pharmacy

At every time point, the mean percentage change in BMD from baseline for raloxifene was significantly greater than for placebo at each skeletal site measured (Table III). rx canada pharmacy

Discontinuation from the study was required when excessive bone loss or multiple incident vertebral fractures occurred. Such discontinuation was significantly more frequent in the calcium- and vitamin D-supplemented placebo group (3.9%) than in the raloxifene group (1.1%). rx canada pharmacy

Prevention of Osteoporosis: The effects of raloxifene on BMD in postmenopausal women were examined in 3 large randomized, placebo-controlled, double-blind osteoporosis prevention trials: (1) a North American trial enrolled 544 women; (2) a European trial, 601 women; and (3) an international trial, 619 women who had undergone hysterectomy. In these trials, all women received calcium supplementation (400 to 600 mg/day). Raloxifene, 60 mg administered once daily, produced significant increases in bone mass versus calcium supplementation alone, as reflected by dual-energy x-ray absorptiometric (DXA) measurements of hip, spine and total body BMD. The increases in BMD were statistically significant at 12 months and were maintained at 24 months (see Table IV). In contrast, the calcium-supplemented placebo groups lost approximately 1% of BMD over 24 months. rx canada pharmacy

Raloxifene also increased BMD compared with placebo in the total body by 1.3% to 2% and in Ward's Triangle (hip) by 3.1% to 4%. In the international trial, conjugated equine estrogen 0.625 mg/day (ERT) was used as an active comparator. The mean increases in BMD at 24 months for estrogen compared with placebo were: lumbar spine, 5.4%; total hip, 2.9%. rx canada pharmacy

Thus, in postmenopausal women, raloxifene preserves bone mass and increases BMD significantly relative to calcium alone at 24 months. The effect on hip bone mass is similar to that for the spine. rx canada pharmacy

Assessments of Bone Turnover: In a 31-week radiocalcium kinetics study, raloxifene was associated with reduced bone resorption and a positive shift in calcium balance (+60 mg Ca/day), due primarily to decreased urinary calcium losses. These findings were similar to those observed with hormone replacement therapy. rx canada pharmacy

In both the osteoporosis treatment and prevention trials, raloxifene therapy resulted in consistent, statistically significant suppression of bone resorption, bone formation, and overall bone turnover, as reflected by changes in serum and urine markers of bone turnover (e.g., bone-specific alkaline phosphatase, osteocalcin, and collagen breakdown products). The suppression of bone turnover markers was evident by 3 months and persisted throughout the 36-month and 24-month observation periods, respectively. rx canada pharmacy

Bone Histomorphometry: In the treatment study, bone biopsies for qualitative and quantitative histomorphometry were obtained at baseline and after 2 years of treatment. There were 56 paired biopsies evaluable for all indices. In raloxifene-treated patients, there were significant decreases in bone formation rate per tissue volume, consistent with a reduction in bone turnover. Normal bone quality was maintained; specifically, there was no evidence of osteomalacia, marrow fibrosis, cellular toxicity or woven bone after 2 years of treatment. rx canada pharmacy

The tissue- and cellular-level effects of raloxifene were assessed by quantitative measurements (bone histomorphometry) on animal bones and human iliac crest bone biopsies taken after administration of a fluorochrome substance to label areas of mineralizing bone. The effects of raloxifene on bone histomorphometry were determined by pre-and post-treatment biopsies in a 6-month study of postmenopausal women. Bone in raloxifene-treated women was histologically normal, showing no evidence of mineralization defects, woven bone, or marrow fibrosis. The patterns of change were consistent with reduced bone turnover, although most changes were not statistically significant. In another bone histomorphometry study, postmenopausal women were treated for 6 months with raloxifene at a higher dose (150 mg/day). Bone was also histologically normal, with no woven bone, marrow fibrosis, or mineralization defects. rx canada pharmacy

In rats, raloxifene prevented increased bone resorption and bone loss after ovariectomy and preserved bone strength in biomechanical studies. Ovariectomized cynomolgus monkeys were treated with raloxifene for 2 years, equivalent at the bone level to 6 years in humans. The biomechanical properties of bone from the raloxifene-treated monkeys were normal. Histologic examination of bone from rats and monkeys treated with raloxifene showed normal cancellous bone morphology and no evidence of woven bone, marrow fibrosis, or mineralization defects. rx canada pharmacy

The animal and human bone histomorphometric results are consistent with data from studies of radiocalcium kinetics and markers of bone metabolism and demonstrate that raloxifene is a skeletal antiresorptive agent. rx canada pharmacy

Effects on Lipid Metabolism: In animal studies, the effects of raloxifene on cholesterol metabolism were mediated through the estrogen receptor. rx canada pharmacy

The effects of raloxifene on cardiovascular intermediate endpoints were evaluated in a 6-month study of 390 postmenopausal women. Raloxifene was compared with continuous combined estrogen/progestin (0.625 mg conjugated equine estrogen plus 2.5 mg medroxyprogesterone acetate, [HRT]) and placebo (see Table V). Raloxifene decreased serum total and LDL cholesterol without significant effects on serum total HDL cholesterol or triglycerides. Raloxifene significantly increased HDL-2 cholesterol subfraction. In addition, raloxifene significantly decreased serum fibrinogen and lipoprotein (a). rx canada pharmacy

Consistent with results from the 6-month study, in the osteoporosis treatment (36 months) and prevention (24 months) studies raloxifene significantly decreased serum total and LDL cholesterol, but did not increase HDL cholesterol or triglycerides. In the osteoporosis treatment study, significantly fewer raloxifene-treated patients required initiation of hypolipidemic therapy compared to placebo. rx canada pharmacy

Effects on the Uterus: Postmenopausal estrogen deficiency leads to endometrial atrophy. Estrogen replacement therapy is associated with endometrial proliferation and hyperplasia and increased risk of endometrial carcinoma. All forms of hormone replacement therapy are often accompanied by spotting and bleeding. In contrast, raloxifene has no endometrial stimulatory effect and does not induce spotting or bleeding. rx canada pharmacy

In the osteoporosis treatment trial, endometrial thickness was evaluated annually in a subset of the study population (1781 patients) for 3 years. Endometrial thickness measurements in raloxifene-treated women were not different from baseline after 3 years of therapy. Placebo-treated women had a 0.27 mm decrease from baseline in endometrial thickness over 3 years. There was no difference between raloxifene- and placebo-treated women in the incidences of endometrial carcinoma, vaginal bleeding or vaginal discharge. rx canada pharmacy

In placebo-controlled osteoporosis prevention trials, endometrial thickness was evaluated every 6 months (for 24 months) by transvaginal ultrasonography (TVU), a noninvasive method of visualizing the uterus. A total of 2978 TVU measurements were collected from 831 women in all dose groups. Raloxifene-treated women consistently had endometrial thickness measurements indistinguishable from placebo. Furthermore, there were no differences between the raloxifene and placebo groups with respect to the incidence of reported vaginal bleeding. rx canada pharmacy

In a 6-month study comparing raloxifene to conjugated equine estrogens (0.625 mg/day [ERT]), endpoint endometrial biopsies demonstrated stimulatory effects of ERT which were not observed for raloxifene (see Table VI). All samples from raloxifene-treated women showed nonproliferative endometrium. rx canada pharmacy

A 12-month study of uterine effects compared a higher dose of raloxifene (150 mg/day) with HRT. At baseline, 43 raloxifene-treated women and 37 HRT-treated women had a nonproliferative endometrium. At study completion, endometrium in all of the raloxifene-treated women remained nonproliferative whereas 13 HRT-treated women had developed proliferative changes. Also, HRT significantly increased uterine volume; raloxifene did not increase uterine volume. Thus, no stimulatory effect of raloxifene on the endometrium was detected at more than twice the recommended dose. rx canada pharmacy

The postmenopausal endometrium is atrophic due to the lack of endogenous estrogen. Consequently, the estrogen antagonist effects of raloxifene on this tissue could not be demonstrated in the clinical trials. However, raloxifene is a potent estrogen antagonist in the rat uterus where it completely blocks the stimulatory effects of estrogen. In the absence of estrogen stimulation, raloxifene did not have any stimulatory effects on the endometrium in any animal models tested. rx canada pharmacy

Effects on the Breast: Estrogen replacement therapy and hormone replacement therapy stimulate glandular and stromal components of breast tissue, resulting in symptoms of breast pain and tenderness in some postmenopausal women. In contrast, raloxifene does not stimulate breast tissue. Across all placebo-controlled trials, raloxifene was indistinguishable from placebo with regard to frequency and severity of breast symptoms. Raloxifene was associated with significantly fewer breast symptoms than reported by women receiving estrogens with or without added progestin (see Adverse Effects). rx canada pharmacy

The estrogen antagonist aspects of raloxifene's SERM profile were examined in a variety of preclinical breast cancer models. Raloxifene inhibited the growth of MCF-7 human breast cancer cells in vitro and of MCF-7 xenograft tumors in mice. In animal models of carcinogen-induced breast cancer (nitrosomethylurea [NMU] and dimethylbenzanthracene [DMBA]), raloxifene decreased tumor burden. rx canada pharmacy

In clinical trials with raloxifene involving 17 151 patients, at least 10 850 women were exposed to raloxifene for up to 58 months. There was a statistically significant reduction in the frequency of newly diagnosed breast cancers in raloxifene-treated women compared with placebo (see Adverse Effects, Additional Safety Information). These observations are consistent with the preclinical pharmacologic profile of raloxifene (selective estrogen receptor modulator) and support the conclusion that raloxifene has no intrinsic estrogen agonist activity in mammary tissue. The long-term effectiveness of raloxifene in reducing the risk of breast cancer has not been fully established. rx canada pharmacy


Indications: For the treatment and prevention of osteoporosis in postmenopausal women. rx canada pharmacy

For either osteoporosis treatment or prevention, supplemental calcium and/or vitamin D should be added to the diet if daily intake is inadequate. rx canada pharmacy

Postmenopausal osteoporosis may be diagnosed by history or radiographic documentation of osteoporotic fracture, bone mineral densitometry, or physical signs of vertebral crush fractures (e.g., height loss, dorsal kyphosis). Women with diagnosed postmenopausal osteoporosis should be considered for pharmacologic therapy, in conjunction with education and appropriate lifestyle modifications. rx canada pharmacy

No single clinical finding or test result can quantify risk of postmenopausal osteoporosis with certainty. However, clinical assessment can help to identify women at increased risk. Widely accepted risk factors include Caucasian or Asian descent, slender body build, early estrogen deficiency, smoking, alcohol consumption, low calcium diet, sedentary lifestyle, personal history of any fracture after age 40 and family history of osteoporosis. Evidence of increased bone turnover from serum and urine markers and low bone mass (e.g., at least 1 standard deviation below the mean for healthy, young adult women) as determined by densitometric techniques are also predictive. The greater the number of clinical risk factors, the greater the probability of developing postmenopausal osteoporosis. These risk factors may be considered in the decision to use raloxifene for prevention of postmenopausal osteoporosis. rx canada pharmacy

Contraindications: In women of childbearing potential. Raloxifene therapy during pregnancy may be associated with an increased risk of congenital defects in the fetus. rx canada pharmacy

Raloxifene is contraindicated in women with active or past history of venous thromboembolic events, including deep vein thrombosis, pulmonary embolism and retinal vein thrombosis. rx canada pharmacy

Raloxifene is contraindicated in women known to be hypersensitive to raloxifene or other constituents of the tablets. rx canada pharmacy


Warnings: Venous Thromboembolic Events: In clinical trials, raloxifene-treated women had an increased risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism). Other venous thromboembolic events could also occur. A less serious event, superficial thrombophlebitis, also has been reported more frequently with raloxifene. The greatest risk for deep vein thrombosis and pulmonary embolism occurs during the first 4 months of treatment, and the magnitude of risk is similar to that associated with use of hormone replacement therapy. Raloxifene should be discontinued at least 72 hours prior to and during prolonged immobilization (e.g., postsurgical recovery, prolonged bed rest) and raloxifene therapy should be resumed only after the patient is fully ambulatory. The risk-benefit balance should be considered in women at risk of thromboembolic disease for other reasons. rx canada pharmacy

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 (see Contraindications). rx canada pharmacy

Hepatic Dysfunction: Raloxifene was studied, as a single dose, in Child-Pugh Class A patients with cirrhosis and serum total bilirubin ranging from 0.6 to 2 mg/dL (10.3 to 34.2 µmol/L). Plasma raloxifene concentrations were approximately 2.5 times higher than in controls and correlated with total bilirubin concentrations. Safety and efficacy have not been evaluated further in patients with hepatic insufficiency. rx canada pharmacy

Precautions: General: Concurrent Estrogen Therapy: The concurrent use of raloxifene and systemic estrogen or hormone replacement therapy (ERT or HRT) has not been studied in prospective clinical trials. rx canada pharmacy

Lipid Metabolism: Raloxifene lowers serum total and LDL cholesterol by 6 to 11%, but does not affect serum concentrations of total HDL cholesterol or triglycerides. HDL-2 cholesterol subfraction is increased by raloxifene. These effects should be taken into account in therapeutic decisions for patients who may require therapy for hyperlipidemia. Concurrent use of raloxifene and lipid lowering agents has not been studied. rx canada pharmacy

Endometrium: Raloxifene does not cause endometrial proliferation (see Pharmacology and Adverse Effects). Unexplained uterine bleeding should be investigated as clinically indicated. rx canada pharmacy

Breast: Raloxifene is not associated with breast enlargement, breast pain, or increased risk of breast cancer (see Pharmacology and Adverse Effects). Any unexplained breast abnormality occurring during raloxifene therapy should be investigated. rx canada pharmacy

History of Breast Cancer: Raloxifene has not been studied in women with a prior history of breast cancer. rx canada pharmacy

Cognition and Affect: Raloxifene has not been associated with deterioration of cognitive function or a change in affect. Any such change during raloxifene use is unlikely to be related to therapy, and should be investigated as clinically indicated. rx canada pharmacy

Use in Men: There is no indication for use of raloxifene in men. rx canada pharmacy

Children: Raloxifene should not be used in pediatric patients. rx canada pharmacy

Geriatrics: In the osteoporosis treatment trial of 7705 postmenopausal women, 4621 women were considered geriatric (greater than 65 years old). Of these, 845 women were greater than 75 years old. Safety and efficacy in older and younger postmenopausal women in the osteoporosis treatment trial appear to be comparable. rx canada pharmacy

Estrogen-induced Hypertriglyceridemia: In a 12 patient, single-arm, open-label study in patients with a history of oral estrogen-induced marked hypertriglyceridemia (generally 5.6 to 39 mmol/L [500 to 3400 mg/dL]), 3 patients had increases of serum triglycerides to >11.3 mmol/L (1000 mg/dL) within 2 weeks after initiation of raloxifene therapy. In 2 of these 3 patients, serum triglyceride levels decreased while raloxifene was continued. Patients with this medical history should have serum triglycerides monitored when taking raloxifene. rx canada pharmacy

Information to be Provided to the Patient: For safe and effective use of raloxifene, the physician should inform patients about the following: Patient Immobilization: Raloxifene should be discontinued at least 72 hours prior to and during prolonged immobilization (e.g., postsurgical recovery, prolonged bed rest) and raloxifene therapy should be resumed only after the patient is fully ambulatory because of the increased risk of venous thromboembolic events. rx canada pharmacy

Vasodilatation: Raloxifene is not effective in reducing vasodilatation (hot flashes or flushes) associated with estrogen deficiency. In some patients, vasodilatation may occur on beginning raloxifene therapy. rx canada pharmacy

Other Osteoporosis Treatment and Prevention Measures: Patients should be instructed to take supplemental calcium and/or vitamin D if daily dietary intake is inadequate. Weight-bearing exercise should be considered along with the modification of certain behavioral factors, such as cigarette smoking and/or alcohol consumption, if these factors exist. rx canada pharmacy

Drug Interactions : Cholestyramine: Cholestyramine, an anion exchange resin, significantly reduces the absorption and enterohepatic cycling of raloxifene and should not be coadministered with raloxifene. Although not specifically studied, it is anticipated that other anion exchange resins would have a similar effect. rx canada pharmacy

Warfarin: Coadministration of raloxifene and warfarin does not alter the pharmacokinetics of either compound. However, modest decreases in prothrombin time have been observed in single-dose studies. If raloxifene is given concurrently with warfarin or other coumarin derivatives, prothrombin time should be monitored. rx canada pharmacy

Laboratory Test Interactions : Raloxifene is not known to interfere with any common laboratory assays (see Adverse Effects for additional laboratory safety information). rx canada pharmacy

Pregnancy: Raloxifene should not be used in women who are or may become pregnant (see Contraindications). rx canada pharmacy

Labor and Delivery: Raloxifene has no recognized use during labor or delivery. rx canada pharmacy

Lactation: Raloxifene should not be used by lactating women (see Contraindications). It is not known whether raloxifene is excreted in human milk. rx canada pharmacy

Adverse Effects: The safety of raloxifene has been established in Phase 2 and Phase 3 placebo-controlled, estrogen-controlled, and HRT-controlled studies. Twelve studies comprised the primary safety database for the prevention indication, and the safety of raloxifene in the treatment of osteoporosis was assessed in a large (N=7705), multinational, placebo-controlled trial. In the osteoporosis prevention trials, the duration of treatment ranged from 2 to 30 months and 2036 women were exposed to raloxifene. In the osteoporosis treatment trial, 5129 women were exposed to raloxifene (2557 received 60 mg/day and 2572 received 120 mg/day) for 36 months. All events were reported irrespective of causality. rx canada pharmacy

Commonly Observed Adverse Events: The most commonly observed treatment-emergent adverse events associated with the use of raloxifene in double-blind, placebo-controlled, osteoporosis treatment and prevention clinical trials that occurred at an incidence ³2% are shown in Table VII. These events occurred in postmenopausal women who took raloxifene for up to 36 months in the osteoporosis treatment trial and for up to 30 months in the osteoporosis prevention trials. The differences between raloxifene and placebo treatments were significant at p<0.05. rx canada pharmacy

Vasodilatation events (hot flashes or flushes) were common in placebo-treated women and the frequency was modestly increased in raloxifene-treated women. The first occurrence of this event was most commonly reported during the first 6 months of treatment and infrequently was reported de novo after that time. rx canada pharmacy

Adverse Events Associated with Discontinuation of Therapy: The majority of adverse events occurring during clinical trials have been mild and have not required discontinuation of therapy. Discontinuation of therapy due to any clinical adverse experience occurred in 10.9% of 2557 raloxifene-treated women and 8.8% of 2576 placebo-treated women in the osteoporosis treatment trial, and in 11.4% of 581 raloxifene-treated women and 12.2% of 584 placebo-treated women in the osteoporosis prevention trials. rx canada pharmacy

Adverse Events in Placebo-controlled Clinical Trials: Table VIII lists adverse events occurring in either the osteoporosis treatment or prevention placebo-controlled clinical trials with raloxifene at a frequency ³2.0% in either group and at rates in raloxifene-treated women numerically greater than in placebo-treated women. Events previously discussed are not included in this table. Only one of the differences shown in the table (flu syndrome) was statistically significant and no causal inferences can be made for any of these adverse events. rx canada pharmacy

Additional Safety Information: Incidences of estrogen-dependent carcinoma of the endometrium and breast are being evaluated across all completed and ongoing clinical trials involving 17 151 patients. At least 10 850 women have been exposed to raloxifene for up to 58 months. rx canada pharmacy

Endometrium: All cases of endometrial carcinoma are reviewed without knowledge of treatment status (blinded) by an independent Adjudication Review Board. Raloxifene does not increase the risk of endometrial cancer when compared to placebo. rx canada pharmacy

Breast: All cases of breast cancer in women enrolled in clinical trials are reviewed without knowledge of treatment status (blinded) by an independent Adjudication Review Board. A statistically significant 56% reduction (95% confidence interval, 31 to 73% reduction) has been observed in the incidence of newly diagnosed breast cancer in raloxifene-treated women compared with placebo. The incidence rate of breast cancer was 3.97 per 1000 subject-years for the women receiving placebo and 1.65 per 1000 subject-years for those receiving raloxifene. The long-term effectiveness of raloxifene in reducing the risk of breast cancer has not been fully established. rx canada pharmacy

Ovary: Raloxifene does not increase the risk of ovarian carcinoma. rx canada pharmacy

Laboratory Changes: The following changes in analyte concentrations are commonly observed during raloxifene therapy: increased serum HDL-2 cholesterol subfraction and apolipoprotein A1; and reduced serum total cholesterol, LDL cholesterol, fibrinogen, apolipoprotein B and lipoprotein (a). Raloxifene modestly increases hormone-binding globulin concentrations, including sex steroid binding globulin, thyroxine binding globulin, and corticosteroid binding globulin with corresponding increases in measured total hormone concentrations. There is no evidence that these changes in hormone binding globulin concentrations affect concentrations of the corresponding free hormones. rx canada pharmacy

Glycemic Control: Diabetes mellitus was reported more frequently as an adverse event among raloxifene-treated patients (1.2%) compared with placebo-treated patients (0.5%) in the osteoporosis treatment trial. However, there were no differences between the raloxifene and placebo groups in either fasting glucose or hemoglobin A _1c (objective measures of glycemic control) in the osteoporosis treatment trial. The diabetes mellitus adverse event finding may have been due to the lower prevalence of diabetes among patients assigned to placebo. rx canada pharmacy

Overdose: Symptoms and Treatment: Incidents of overdose in humans have not been reported. In an 8-week study of 63 postmenopausal women, a dose of raloxifene HCl 600 mg/day was safely tolerated. No mortality was seen after a single oral dose in rats or mice at 5000 mg/kg or in monkeys at 1000 mg/kg. There is no specific antidote for raloxifene. rx canada pharmacy


Dosage: The recommended dosage is one 60 mg tablet daily which may be administered any time of day without regard to meals. rx canada pharmacy

Information for the Patient: See Blue Section--Information for the Patient Evista£. rx canada pharmacy

Supplied: Each white, elliptical, film-coated tablet, imprinted on one side with the tablet code 4165 in blue ink, contains: raloxifene HCl 60 mg. Nonmedicinal ingredients: anhydrous lactose, crospovidone, FD&C Blue No. 2 aluminum lake, hydroxypropyl methylcellulose, lactose monohydrate, macrogol 400, magnesium stearate, polysorbate 80, povidone and titanium dioxide E171. Blister packages of 28. Store at room temperature, 15 to 30°C.

Canada Pharmacy - Evista - Evista Side Effects - Evista