Raloxifene (Evista) Adverse Reactions
- abdominal pain
- diaphoresis
- flatulence
- hot flashes
- infertility
- insomnia
- maculopapular rash
- muscle cramps
- myalgia
- peripheral edema
- pulmonary embolism
- retinal thrombosis
- sinusitis
- teratogenesis
- thromboembolism
- thrombosis
- vaginal bleeding
- weight gain
Raloxifene (Evista) Adverse Reactions
During clinical trials, the most common adverse events associated with use of raloxifene were hot flashes (24.6 - 28.7%) and muscle cramps of the legs (5.9%). Hot flashes were usually reported within the first 6 months of treatment. In controlled clinical trials, drug discontinuation due to hot flashes was similar among patients receiving raloxifene (1.7%) and those receiving placebo (2.2%). Other adverse events reported more frequently in raloxifene-treated women were weight gain (8.8%), peripheral edema (3.3%), sinusitis (10.3%), maculopapular rash (5.5%), diaphoresis (3.1%), myalgia (7.7%), insomnia (5.5%), gastrointestinal complaints such as flatulence (3.1%) and other GI disorders (3.3%). Raloxifene has not been associated with a higher incidence of breast enlargement, breast pain or tenderness, breast cancer, or endometrial proliferation versus placebo. Compared with hormone replacement therapy for the prevention of osteoporosis in postmenopausal women, raloxifene was associated with a lower incidence of breast pain (4.4% vs. 29.7 - 37.5%), vaginal bleeding (6.2% vs. 64.2 - 88.5%), flatulence (1.6% vs. 6.4 - 12.5%), and abdominal pain (6.6% vs. 10.4 - 18.7%).
Similar to estrogen therapy, raloxifene decreases total and LDL cholesterol and lipoprotein A concentrations in postmenopausal women. Compared with baseline values, raloxifene decreases concentrations of total cholesterol by roughly 6.6%, LDL cholesterol by 11%, and lipoprotein A by 4.1%. Estrogen replacement therapy increases HDL cholesterol and serum triglycerides, while raloxifene has no significant effect on these lipoproteins. Raloxifene has also been shown to increase apolipoprotein A1 concentrations and reduce fibrinogen as well as apolipoprotein B concentrations.
In placebo-controlled osteoporosis prevention trials, endometrial thickness was evaluated every 6 months in 831 women. Endometrial thickness measurements in raloxifene-treated women were indistinguishable from placebo. In addition, there was no difference in the reported incidence of vaginal bleeding between the raloxifene and placebo groups. In one study using twice the recommended dose of raloxifene, stimulatory effects on the endometrium were not observed.
In placebo-controlled clinical trials, raloxifene was associated with an increased risk of venous thromboembolism (VTE), defined as deep vein thrombosis, pulmonary embolism (PE), and retinal thrombosis. The overall incidence of VTE was 3.08 per 1000 patient-years in patients treated with raloxifene and 1.43 per 1000 patient-years in those given placebo. This increase in risk is similar in magnitude to that reported with hormone replacement therapy. The annual incidence rate for pulmonary embolism was 1.1 per 1000 patient-years in raloxifene-treated patients and 0.72 in placebo-treated patients. For idiopathic DVT or PE, the relative risk of raloxifene versus placebo was similar to the overall relative risk of VTE (2.9 vs. 3.0). The greatest risk occurred within the first four months of treatment (see Contraindications). The mechanisms by which raloxifene increases VTE is unknown. Unlike estrogens, raloxifene does not appear to enhance fibrinolysis.
Raloxifene is associated with teratogenesis in animal studies. Administration of raloxifene to pregnant rabbits or rats was associated with abortion, fetal heart abnormalities (ventricular septal defects), fetal hydrocephaly, retardation of fetal development, delayed and disrupted parturition, and decreased neonatal survival. When large dosages were used in pregnant rats, raloxifene disrupted parturition which resulted in maternal and progeny death and morbidity. Effects in adult offspring also included uterine hypoplasia and reduced fertility; no ovarian or vaginal pathology was observed.
Raloxifene has been associated with carcinogenesis when given to female mice. An increased incidence of ovarian tumors and benign tumors of epithelial cell origin were observed. When given to male mice, there was an increase in testicular interstitial cell tumors, prostatic adenomas and adenocarcinomas, and prostatic leiomyoblastoma. The clinical relevance of these tumor findings is unknown.
Raloxifene is associated with infertility. In female rats, the drug reversibly disrupts estrous cycles and inhibits ovulation. In contrast, raloxifene does not affect sperm production, sperm quality, or reproductive performance of male rats. In one animal study, raloxifene delayed and disrupted embryo implantation, resulting in prolonged gestation and reduced litter size. These reproductive and developmental effects are consistent with the estrogen receptor activity of raloxifene.
[ Last revised: 9/11/2002 6:21:00 PM ]
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