FASLODEX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FASLODEX (FASLODEX).
FASLODEX (fulvestrant) is an estrogen receptor (ER) antagonist that binds to ERs with high affinity, downregulates ER protein levels, and inhibits estrogen signaling via both AF-1 and AF-2 domains, thereby blocking cell proliferation in ER-positive breast cancer cells.
| Metabolism | Primarily hepatic via CYP3A4; metabolism involves biotransformation to active metabolites (fulvestrant sulfone, fulvestrant sulfoxide, and others). |
| Excretion | Primarily hepatic metabolism followed by biliary excretion; less than 1% excreted unchanged in urine; fecal elimination accounts for approximately 90% of the administered dose. |
| Half-life | Terminal elimination half-life is approximately 50 days (range 40–60 days) following intramuscular administration, reflecting slow release from the depot and enterohepatic recirculation. |
| Protein binding | 99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 10–20 L/kg, indicating extensive tissue binding and distribution into extravascular compartments, including breast and uterine tissues. |
| Bioavailability | Intramuscular: 100% (not applicable for other routes as it is only administered intramuscularly). |
| Onset of Action | Intramuscular: Clinical effects (e.g., estrogen receptor downregulation) detectable within 1–2 weeks; maximal suppression of estradiol-mediated effects achieved after 3–6 months. |
| Duration of Action | Intramuscular: Duration of action persists for at least 1 month after a single 500 mg dose, with sustained estrogen receptor antagonism for up to 6 months; repeated dosing at 2-week intervals maintains continuous blockade. |
| Molecular Weight | 606.77 Da |
| Action Class | Estrogen receptor antagonist |
| Brand Substitutes | Fulveser Injection, Celvestrant PFS Injection, Fulvira 250mg Injection, Fulviglen 250mg Injection, Faslomax 250mg Injection |
500 mg intramuscularly on days 1, 15, 29, and then once monthly.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl >= 30 mL/min). Not studied in severe impairment (CrCl < 30 mL/min). |
| Liver impairment | No dose adjustment for mild hepatic impairment (Child-Pugh A). Not recommended in moderate to severe impairment (Child-Pugh B or C) due to limited data. |
| Pediatric use | Safety and effectiveness not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended. Clinical studies included patients aged 65 and older with no differences in safety or efficacy observed. |
| 1st trimester | Based on animal studies and mechanism of action, FASLODEX (fulvestrant) may cause fetal harm when administered to a pregnant woman. It is an estrogen receptor antagonist and has been shown to cause pregnancy loss and fetal abnormalities in animals. Adequate contraception should be used during treatment and for at least 1 year after last dose. |
| 2nd trimester | Same as first trimester: FASLODEX may cause fetal harm. Use is contraindicated in pregnancy. There are no adequate human studies. |
| 3rd trimester | Same as first and second trimesters: FASLODEX may cause fetal harm. Use is contraindicated in pregnancy. |
Clinical note
Comprehensive clinical and safety monograph for FASLODEX (FASLODEX).
| Placental transfer | Fulvestrant is extensively protein bound (>99%) and has a high molecular weight, which may limit placental transfer. However, animal studies have demonstrated embryofetal toxicity and abortion, indicating placental exposure. The exact degree of human placental transfer is unknown. |
| Breastfeeding |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to fulvestrant or any excipientsPregnancy
| Precautions | Increased risk of thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism), Hepatic impairment (use with caution; dose adjustment not required for mild-to-moderate impairment), Injection site reactions (e.g., pain, inflammation, hematoma), Bone marrow suppression (when used in combination with CDK4/6 inhibitors; monitor blood counts), Fetal harm (if used during pregnancy; confirm pregnancy status before initiation), Hypersensitivity reactions (including angioedema and urticaria) |
| Food/Dietary | No significant food interactions. Grapefruit may not interact, but to be cautious, avoid excessive grapefruit intake. Maintain adequate hydration. |
Loading safety data…
| It is not known whether fulvestrant is excreted in human milk. However, due to the potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during treatment and for at least 1 year after the last dose. Animal studies have shown detection of fulvestrant in milk. |
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | Category X. FASLODEX is contraindicated in pregnancy and can cause fetal harm when administered to a pregnant woman. Based on its mechanism of action (estrogen receptor antagonist), there is a risk of pregnancy loss and fetal malformations. No adequate studies in pregnant women; animal studies show reproductive toxicity including embryo-fetal lethality and skeletal anomalies. |
| Fetal Monitoring | Pregnancy testing should be performed prior to initiation in women of reproductive potential. Contraception must be used during treatment and for 1 year after last dose. Monitor for signs of fetal distress if inadvertent exposure occurs (though contraindicated). No specific fetal monitoring recommended if not pregnant; liver function tests and INR should be monitored in patients on anticoagulants. |
| Fertility Effects | Based on animal studies and mechanism, FASLODEX may impair fertility in females and males. In female rats, decreased fertility and increased preimplantation loss were observed. In humans, potential for reversible or irreversible impairment of spermatogenesis and ovulation due to estrogen receptor blockade. |
| Clinical Pearls | Faslodex (fulvestrant) is an estrogen receptor antagonist with no agonist effects, used in hormone receptor-positive metastatic breast cancer. Administer as two 5 mL intramuscular injections slowly (1-2 min each) into the buttocks (gluteal area) on days 1, 15, 29, and monthly thereafter. Monitor for injection site reactions, including sciatica if given near the sciatic nerve. Not effective in estrogen receptor-negative disease. May cause mild antiestrogenic effects like hot flashes and vaginal dryness. Avoid use in severe hepatic impairment (Child-Pugh class C). No dose adjustment for mild-to-moderate hepatic impairment. Concomitant use with CYP3A4 inducers or inhibitors is unlikely to require dose adjustment due to minimal CYP involvement. |
| Patient Advice | Faslodex is given as two shots into the buttocks on specific days; you will need to visit the clinic for administration. · Common side effects include nausea, fatigue, hot flashes, and pain at the injection site. · Report any severe injection site pain, swelling, or difficulty walking to your doctor. · Do not take hormone replacement therapy or other estrogen-containing medications while on Faslodex. · Faslodex may cause a low risk of blood clots; seek immediate medical help for leg swelling, chest pain, or shortness of breath. · You may experience bone pain or tumor flare initially; this does not mean the drug is not working. · Inform your doctor if you have liver problems or are taking blood thinners. |