Ralista 60 Tablets
Each film-coated tablet contains Raloxifene hydrochloride 60 mg
Description
Ralista (Raloxifene hydrochloride) is a selective estrogen receptor modulator (SERM) that belongs to the benzothiophene class of compounds. Raloxifene's biological actions are largely mediated through binding to estrogen receptors. This binding results in activation of certain estrogenic pathways and blockade of others. Thus, raloxifene is a selective estrogen receptor modulator (SERM).
Raloxifene decreases resorption of bone and reduces biochemical markers of bone turnover to the premenopausal range. These effects on bone are manifested as reductions in the serum and urine levels of bone turnover markers, decreases in bone resorption based on radiocalcium kinetics studies, increases in bone mineral density (BMD) and decreases in incidence of fractures. Raloxifene also has effects on lipid metabolism. Raloxifene decreases total and LDL cholesterol levels but does not increase triglyceride levels. It does not change total HDL cholesterol levels. Preclinical data demonstrate that raloxifene is an estrogen antagonist in uterine and breast tissues. Clinical trial data (through a median of 42 months) suggest that raloxifene lacks estrogen-like effects on the uterus and breast tissue.
Indications
Ralista is indicated for the treatment and prevention of osteoporosis in postmenopausal women. For either osteoporosis treatment or prevention, supplemental calcium and/or vitamin D should be added to the diet if daily intake is inadequate.
Dosage and administration
The recommended dosage is one 60-mg Ralista tablet daily, which may be administered any time of day without regard to meals.
Contraindications
Ralista is contraindicated in lactating women or women who are or may become pregnant. It may cause fetal harm when administered to a pregnant woman. Ralista is also contraindicated in women with active or past history of venous thromboembolic events, including deep vein thrombosis, pulmonary embolism, retinal vein thrombosis and in women known to be hypersensitive to raloxifene or other constituents of the tablets.
Drug Interactions
Cholestyramine - Cholestyramine, an anion exchange resin, causes a 60% reduction in the absorption and enterohepatic cycling of raloxifene after a single dose. Co-administration of cholestyramine with Ralista is not recommended. Although not specifically studied, it is anticipated that other anion exchange resins would have a similar effect.
Warfarin - In vitro, raloxifene did not interact with the binding of warfarin. The co-administration of Ralista and warfarin, a coumarin derivative, has been assessed in a single dose study. In this study, raloxifene had no effect on the pharmacokinetics of warfarin. However, a 10% decrease in prothrombin time was observed in the single-dose study. If Ralista is given concurrently with warfarin or other coumarin derivatives, prothrombin time should be monitored more closely when starting or stopping therapy with Ralista. In the osteoporosis treatment trial, there were no clinically relevant effects of warfarin co-administration on plasma concentrations of raloxifene.
Other Highly Protein-Bound Drugs - Raloxifene is more than 95% bound to plasma proteins. Other highly protein-bound drugs should not cause clinically relevant changes in Ralista plasma concentrations. Furthermore, in the osteoporosis treatment trial, there were no clinically relevant effects of co-administration of other highly protein-bound drugs (e.g., gemfibrozil) on plasma concentrations of raloxifene. In vitro, raloxifene did not interact with the binding of phenytoin, tamoxifen, or warfarin (see above). Although not examined, Ralista might affect the protein binding of other drugs and should be used with caution with certain other highly protein-bound drugs such as diazepam, diazoxide and lidocaine.
Warnings
Venous Thromboembolism: 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 appears to be similar to the reported risk associated with use of hormone replacement therapy. Because immobilization increases the risk for venous thromboembolic events independent of therapy, Ralista should be discontinued at least 72 hours prior to and during prolonged immobilization (e.g., post-surgical recovery, prolonged bed rest), and Ralista therapy should be resumed only after the patient is fully ambulatory. In addition, women taking Ralista 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.
Concurrent Estrogen Therapy: The concurrent use of Ralista and systemic estrogen or hormone replacement therapy (ERT or HRT) has not been studied in prospective clinical trials and therefore concomitant use of Ralista with systemic estrogens is not recommended.
Lipid Metabolism: Ralista lowers serum total and LDL cholesterol by 6% to 11%, but does not affect serum concentrations of total HDL cholesterol or triglycerides. These effects should be taken into account in therapeutic decisions for patients who may require therapy for hyperlipidemia. Concurrent use of Ralista and lipid-lowering agents has not been studied.
Endometrium: Ralista has not been associated with endometrial proliferation. Unexplained uterine bleeding should be investigated as clinically indicated.
Breast: Ralista has not been associated with breast enlargement, breast pain, or an increased risk of breast cancer. Any unexplained breast abnormality occurring during Ralista therapy should be investigated.
History of Breast Cancer: Ralista has not been adequately studied in women with a prior history of breast cancer.
Renal Insufficiency: Since negligible amounts of raloxifene and eliminated in urine, a study in patients with renal insufficiency was not conducted. In the osteoporosis treatment and prevention trials, raloxifene and metabolite concentrations in women with estimated creatinine clearance as low as 21 mL/min are similar to women with normal creatinine clearance.
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 2.0 mg/dL. 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).
Pregnancy: Pregnancy Category X -- Ralista should not be used in women who are or may become pregnant.
Lactation: Ralista should not be used by lactating women . It is not known whether raloxifene is excreted in human milk.
Pediatric use: Ralista should not be used in pediatric patients.
Use in elderly: 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 appeared to be comparable.
Use in Men: Safety and efficacy have not been evaluated in men.
Side Effects
The safety of raloxifene in the treatment of osteoporosis was assessed in a large (7705 patients) multinational placebo-controlled trial. Common adverse events considered to be related to raloxifene therapy were hot flashes and leg cramps. The majority of adverse events occurring during the study were mild and generally did not require discontinuation of therapy. These included infection, migraine, nausea, myalgia, insomnia, rash, conjunctivitis, vaginitis.
Overdosage
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 (810 times the human dose for rats and 405 times the human dose for mice based on surface area, mg/m 2) or in monkeys at 1000 mg/kg (80 times the AUC in humans). There is no specific antidote for raloxifene.
