FARESTON
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FARESTON (FARESTON).
Selective estrogen receptor modulator (SERM) that competitively binds to estrogen receptors, exerting antiestrogenic effects in breast tissue.
| Metabolism | Primarily hepatic via CYP3A4 and CYP1A2; undergoes glucuronidation; active metabolite N-desmethyltoremifene |
| Excretion | FARESTON (toremifene) is extensively metabolized in the liver. Excretion is primarily fecal (approximately 70%) with renal excretion accounting for less than 10% of the dose as unchanged drug and metabolites. |
| Half-life | The terminal elimination half-life of toremifene is approximately 5 days (range 2-10 days). The half-life of its main metabolite, N-desmethyltoremifene, is about 11 days. This long half-life supports once-daily dosing. |
| Protein binding | Toremifene is >99% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | The apparent volume of distribution (Vd) is approximately 580 L (about 8 L/kg for a 70 kg individual), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability of toremifene is not precisely determined but is estimated to be nearly 100% based on absorption and first-pass metabolism studies. |
| Onset of Action | Clinical response (tumor regression) is typically observed after 4-8 weeks of continuous daily oral dosing. |
| Duration of Action | The therapeutic effect lasts as long as treatment continues. The drug's long half-life results in sustained plasma levels, but clinical duration is not defined as treatment is continuous; effects may persist for weeks after discontinuation due to slow elimination. |
| Molecular Weight | 405.96 |
60 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min; insufficient data for GFR <30 mL/min. |
| Liver impairment | Contraindicated in Child-Pugh class C; use with caution in class A or B without specific dose reduction guidelines. |
| Pediatric use | Safety and efficacy not established; no recommended dose. |
| Geriatric use | No specific dose adjustment; monitor renal function and electrolyte balance. |
| 1st trimester | Contraindicated. Fetotoxic in animal studies with skeletal and visceral malformations, and increased resorption rates. Avoid use in first trimester. |
| 2nd trimester | Contraindicated. Risk of fetal harm; may cause delayed ossification, urogenital malformations, and fetal death in animal models. Not recommended. |
| 3rd trimester | Contraindicated. Potential for fetal harm based on animal data, including central nervous system and cardiovascular effects. Should not be used during third trimester. |
Clinical note
Comprehensive clinical and safety monograph for FARESTON (FARESTON).
| Placental transfer | Extensive placental transfer in experimental models; toremifene and active metabolites cross the placenta and accumulate in fetal tissues. Human data limited but confirm crossing based on maternal-fetal concentration gradients. |
| Breastfeeding | No human data on excretion in breast milk. Toremifene and its metabolites are likely secreted in milk based on animal studies. Potential for serious adverse effects in breastfed infant; alternative agents should be considered, especially for high-dose regimens. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to toremifene or any excipientsHistory of thromboembolic eventsSevere liver impairment (Child-Pugh C)PregnancyBreastfeeding
| Precautions | QT interval prolongation, Hypercalcemia in patients with bone metastases, Endometrial hyperplasia/cancer risk, Thromboembolic events, Ocular toxicity (dose-dependent retinopathy), Tumor flare |
| Food/Dietary | Avoid grapefruit and grapefruit juice due to CYP3A4 inhibition, which can increase toremifene levels and risk of adverse effects. No other significant food interactions known. Take with or without food. |
| Clinical Pearls |
Loading safety data…
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | Pregnancy Category D. First trimester: Risk of fetal harm, including spontaneous abortion and congenital malformations (e.g., craniofacial, cardiac). Second and third trimesters: Potential for fetal hypothalamic-pituitary-gonadal axis disruption, ambiguous genitalia in female fetuses, and other adverse effects based on animal studies. |
| Fetal Monitoring | Monitor liver function tests (AST, ALT, bilirubin) monthly; serum calcium, complete blood count, and renal function periodically. Fetal monitoring via ultrasound for growth and anatomy; consider fetal echocardiography if exposure in first trimester. |
| Fertility Effects | May impair fertility in both males and females. In females: potential anovulation, menstrual irregularities, and ovarian failure. In males: altered spermatogenesis and reduced sperm count. Effects may be reversible upon discontinuation. |
| FARESTON (toremifene) is a selective estrogen receptor modulator (SERM) used for metastatic breast cancer in postmenopausal women with estrogen receptor-positive tumors. Unlike tamoxifen, toremifene has a longer half-life (about 5 days) and may have a lower risk of thromboembolic events. Monitor liver function tests regularly due to potential hepatotoxicity. Prolongation of QT interval has been reported; avoid in patients with pre-existing QTc prolongation or with other QT-prolonging drugs. Use with caution in patients with endometrial hyperplasia or history of thromboembolic disease. |
| Patient Advice | Take this medication exactly as prescribed, usually once daily with or without food. · You may experience hot flashes, nausea, or sweating; these are common and usually manageable. · Report any unusual vaginal bleeding, discharge, or pelvic pain to your doctor immediately. · Watch for signs of blood clots such as leg pain/swelling, sudden chest pain, or shortness of breath. · Avoid grapefruit and grapefruit juice while on this medication as they may increase side effects. · Use non-hormonal contraception if you are still able to become pregnant; toremifene can harm a fetus. · Do not stop or change your dose without consulting your healthcare provider. |