Toremifene Citrate

1 INDICATIONS AND USAGE Toremifene citrate tablets are estrogen agonist/antagonist indicated for the treatment of metastatic breast cancer in postmenopausal women with estrogen-receptor positive or unknown tumors. Toremifene citrate tablets are estrogen agonist/antagonist indicated for the treatment of metastatic breast cancer in postmenopausal women with estrogen-receptor positive or unknown tumors.

6 ADVERSE REACTIONS Because clinical trials 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 clinical practice. Most common adverse reactions are hot flashes, sweating, nausea and vaginal discharge. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Novadoz Pharmaceuticals LLC at 1-855-668-2369 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Adverse drug reactions are principally due to the antiestrogenic actions of toremifene citrate and typically occur at the beginning of treatment.

8.1 Pregnancy Pregnancy Category D [ see Warnings and Precautions (5.6).] Based on its mechanism of action in humans and findings of increased pregnancy loss and fetal malformation in animal studies, toremifene citrate can cause fetal harm when administered to a pregnant woman. Toremifene caused embryo-fetal toxicities at maternal doses that were lower than the 60 mg daily recommended human dose on a mg/m 2 basis. There are no adequate and well-controlled studies in pregnant women using toremifene citrate.

WARNING: QT PROLONGATION Toremifene citrate has been shown to prolong the QTc interval in a dose- and concentration-related manner [see Clinical Pharmacology (12.2)]. Prolongation of the QT interval can result in a type of ventricular tachycardia called Torsade de pointes, which may result in syncope, seizure, and/or death. Toremifene should not be prescribed to patients with congenital/acquired QT prolongation, uncorrected hypokalemia or uncorrected hypomagnesemia. 5 WARNINGS AND PRECAUTIONS Prolongation of the QT Interval (5.1) Heptatotoxicty (5.2) Hypercalcemia and Tumor Flare (5.3) Risk of Uterine Malignancy (5.4) General (5.5) Laboratory Tests ( 5.6) Pregnancy: Fetal harm may occur when administered to a pregnant woman. Women should be advised not to become pregnant when taking toremifene citrate. ( 5.7 , 8.1 ) Women of Childbearing Potential: Use effective nonhormonal contraception during toremifene citrate therapy. (5.8) 5.1 Prolongation of the QT Interval Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner [see Clinical Pharmacology (12.2)] . 4 CONTRAINDICATIONS Hypersensitivity to the drug (4.1) QT Prolongation, Hypokalemia, Hypomagnesemia (4.2) 4.1 Hypersensitivity to the Drug Toremifene citrate is contraindicated in patients with known hypersensitivity to the drug.