Raloxifene Hcl (raloxifene HCl)

Dosage of raloxifene hydrochloride is expressed in terms of the hydrochloride. Raloxifene hydrochloride 60 mg contains 55.71 mg of raloxifene.

Patients receiving raloxifene for prevention or treatment of osteoporosis should receive supplemental calcium and/or vitamin D if their daily dietary intake is inadequate.

Plasma concentrations are higher in individuals with moderate to severe renal impairment compared with individuals with normal renal function. The manufacturer makes no specific recommendations for raloxifene dosage adjustment in patients with renal impairment.

Limited evidence from patients with cirrhosis (Child-Pugh class A) and total serum bilirubin concentrations of 0.6-2 mg/dL indicate that plasma concentrations of raloxifene are 150% higher in such patients relative to plasma concentrations in patients with normal hepatic function. Raloxifene has not been evaluated in patients with hepatic impairment other than Child-Pugh class A. The manufacturer currently makes no specific recommendation for adjustment of raloxifene dosage in patients with hepatic impairment. However, the drug is extensively metabolized in the liver and excreted principally in feces.

Raloxifene is administered orally as a single daily dose. The manufacturer states that the drug may be taken without regard to meals or time of day. Raloxifene may be administered concomitantly with calcium carbonate or aluminum and magnesium hydroxide-containing antacids.

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Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Estrogen Receptor Blockers (Erbs)/Fluoroestradiol F-18

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Drugs that bind to the estrogen receptor (ER) may compete with the binding of radioactive diagnostic agent fluoroestradiol F-18.(1)

CLINICAL EFFECTS: Concurrent use of estrogen receptor blockers such as selective estrogen receptor modulators (SERMs) and selective estrogen receptor down-regulators (SERDs) may reduce the detection of ER-positive lesions with fluoroestradiol F-18.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Before administering fluoroestradiol F-18, discontinue drugs that bind to the ER, such as SERMs and SERDs, for at least 5 biological half-lives.(1) The following washout periods apply when discontinuing ERBs, prior to fluoroestradiol F-18 administration: - Bazedoxifene = 7 days - Clomiphene = 25 days - Elacestrant = 11 days - Enclomiphene = 25 days - Fulvestrant = 28 weeks - Imlunestrant = 7 days - Ospemifene = 5 days - Raloxifene = 7 days - Tamoxifen = 8 weeks - Toremifene = 5 weeks

DISCUSSION: The following ERBs are linked to this monograph: SERDs: elacestrant, imlunestrant, and fulvestrant. SERMs: bazedoxifene, clomiphene, enclomiphene, ospemifene, raloxifene, tamoxifen and toremifene.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Raloxifene/Bile Acid Sequestrants

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Bile acid sequestrants may reduce the absorption and enterohepatic recycling of raloxifene.(1)

CLINICAL EFFECTS: Concurrent use may result in decreased levels and clinical effects of raloxifene.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of raloxifene states that concurrent use with cholestyramine is not recommended, and raloxifene should not be coadministered with other anion exchange resins.(1)

DISCUSSION: Cholestyramine was found to decrease the absorption and enterohepatic circulation of raloxifene by 60% after only one dose. Other anion exchange resins, such as colestipol and colesevelam, are thought to produce similar effects.(1) In a study, cholestyramine given at 4 hours and 10 hours after raloxifene administration decreased raloxifene AUC by 40%.(2)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Raloxifene/Estrogen

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Raloxifene binds to estrogen receptors and activates certain estrogenic pathways while blocking others.(1)

CLINICAL EFFECTS: The concurrent use of raloxifene and estrogen may increase the risk of estrogen-related toxicities (bloating, vaginal bleeding, mood changes, cardiovascular events, thromboembolism, and breast cancer) and antagonize the anti-estrogenic effects of raloxifene.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of raloxifene does not recommend the use of systemic estrogen or hormone replacement therapy with raloxifene.(1)

DISCUSSION: Information on the interaction between raloxifene and estrogen is lacking and the manufacturer of raloxifene states that the concurrent use of these medications has not been studied in prospective clinical trials.(1)

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• Deep venous thrombosis
• History of deep vein thrombosis
• History of pulmonary embolism
• History of retinal vein thrombosis
• History of venous thromboembolism
• Pregnancy
• Pulmonary thromboembolism
• Retinal thrombosis
• Venous thrombosis

• Cerebrovascular accident
• Coronary artery disease
• Hypertension
• Lupus anticoagulant disorder
• Thrombophilia
• Thrombophlebitis
• Tobacco smoker
• Transient cerebral ischemia

• Atrial fibrillation
• Chronic heart failure
• Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
• Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
• Disease of liver
• Hypertriglyceridemia
• Kidney disease with likely reduction in glomerular filtration rate (GFr)

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More Frequent

• Chest pain
• Infection
• Urinary tract infection

Less Frequent

• Biliary calculus
• Gastroenteritis
• Migraine
• Pneumonia

Rare or Very Rare

• Cerebrovascular accident
• Deep venous thrombosis
• Pulmonary thromboembolism
• Retinal thrombosis
• Thromboembolic disorder
• Thrombotic disorder

More Frequent

• Cramps in legs
• Cystitis
• Drug-induced hot flash
• Fever
• Flu-like symptoms
• Peripheral edema
• Pharyngitis
• Sinusitis
• Skin rash
• Vaginitis

Less Frequent

• Arthralgia
• Arthritis
• Depression
• Gastrointestinal irritation
• Hyperhidrosis
• Insomnia
• Laryngitis
• Myalgia
• Vaginal discharge
• Weight gain

Rare or Very Rare

• Phlebitis

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No enhanced messaging available.

Raloxifene may cause fetal toxicity when administered to pregnant women. Effects on reproductive function are expected because raloxifene is an estrogen agonist-antagonist. Since the risks clearly outweigh any possible benefits in women who are pregnant, raloxifene is contraindicated in such women; the drug also is not indicated for use in women of childbearing potential. If raloxifene is inadvertently administered during pregnancy or if the patient becomes pregnant while receiving the drug, raloxifene should be discontinued and the patient informed of the potential hazard to the fetus.

In reproductive studies in rabbits using raloxifene hydrochloride doses of 0.1 mg/kg or more (at least 0.04 times the recommended dose in humans on a mg/m2 basis), abortion and a low rate of fetal heart anomalies (i.e., ventricular septal defects) were observed, and in rabbits using raloxifene doses of 10 mg/kg or more (at least 4 times the recommended dose in humans on a mg/m2 basis), hydrocephaly was observed in the fetuses. In reproductive studies in rats using raloxifene hydrochloride doses of 1 mg/kg or more (at least 0.2 times the recommended dose in humans on a mg/m2 basis), retardation of fetal development and developmental abnormalities (i.e., wavy ribs, kidney cavitation) were observed.

In studies in rats using raloxifene hydrochloride doses of 0.1-10 mg/kg (0.02-1.6 times the recommended dose in humans on a mg/m2 basis) during gestation and lactation, 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 were observed. Disruption of parturition, which resulted in maternal and progeny morbidity and/or death, was observed in rats given raloxifene hydrochloride 10 mg/kg. While ovarian or vaginal pathology was not observed in adult offspring (4 months of age), uterine hypoplasia and reduced fertility were noted.

It is not known whether raloxifene distributes into human milk or if the drug affects milk production or the nursing infant; however, because raloxifene is an estrogen agonist-antagonist, estrogenic effects on mammary tissue during lactation may be affected.

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