FULPHILA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FULPHILA (FULPHILA).
Fulvestrant is an estrogen receptor (ER) antagonist that competitively binds to ER with high affinity, downregulates the receptor protein, and inhibits estrogen signaling. It has no agonist effects.
| Metabolism | Primarily metabolized by CYP3A4; oxidation, hydroxylation, and conjugation; also undergoes rapid clearance via hepatic metabolism. |
| Excretion | Primarily renal: approximately 60-70% of the dose is excreted unchanged in urine. Biliary/fecal excretion accounts for <10%. |
| Half-life | Terminal elimination half-life is approximately 15-20 hours in healthy adults. In patients with neutropenia, half-life may be prolonged up to 25-30 hours due to decreased clearance. |
| Protein binding | Approximately 70-80% bound primarily to albumin. Binding is reversible and non-saturable at therapeutic concentrations. |
| Volume of Distribution | Volume of distribution is approximately 0.35-0.45 L/kg, indicating distribution primarily in extracellular fluid and plasma. |
| Bioavailability | Subcutaneous: Approximately 60-70% absolute bioavailability. Absorption is slow and prolonged with peak concentrations reached 12-24 hours post-dose. |
| Onset of Action | Subcutaneous: Onset of effect on neutrophil counts occurs within 24-48 hours, with peak neutrophil mobilization observed at 4-7 days. |
| Duration of Action | Duration of neutrophil elevation lasts approximately 7-10 days after a single dose. Clinical effect is sustained with repeated dosing as per chemotherapy cycles. |
5 mcg/kg subcutaneously once daily for up to 14 days or until absolute neutrophil count ≥ 10,000/mcL.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for GFR ≥ 15 mL/min. Insufficient data for GFR < 15 mL/min or dialysis. |
| Liver impairment | No dose adjustment required for Child-Pugh A or B. Insufficient data for Child-Pugh C. |
| Pediatric use | 5 mcg/kg subcutaneously once daily for patients ≥ 2 years; safety and efficacy not established in < 2 years. |
| Geriatric use | No specific dose adjustment; same as adult dosing, but monitor for increased risk of adverse events. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for FULPHILA (FULPHILA).
| Breastfeeding | It is not known whether pegfilgrastim is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when FULPHILA is administered to a nursing woman. The molecular weight of pegfilgrastim (approximately 39 kDa) suggests low transfer into breast milk; however, no specific milk-to-plasma (M/P) ratio is available. Limited data from related filgrastim indicate minimal excretion. The decision to breastfeed should consider the importance of the drug to the mother, the potential risk of immune effects in the infant, and the availability of alternative therapies. |
| Teratogenic Risk | FULPHILA (pegfilgrastim) is a pregnancy category C drug. In animal studies, pegfilgrastim was not teratogenic at doses up to 2 mg/kg/day in rats (approximately 26 times the human dose based on AUC) but did cause decreased fetal weight and increased post-implantation loss. There are no adequate and well-controlled studies in pregnant women. During the first trimester, theoretical risks of immune modulation and potential effects on developing hematopoietic system exist. In the second and third trimesters, potential risks include maternal stimulation of neutrophil production and unknown fetal effects. The drug should be used only if clearly needed and potential benefit justifies potential risk to the fetus. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to fulvestrant or any component of the formulation","Pregnancy"]
| Precautions | ["Risk of bleeding due to intramuscular administration in patients with thrombocytopenia or coagulopathy","Hepatic impairment: use with caution; no dose adjustment in mild-to-moderate impairment, not studied in severe impairment","Fetal harm: may cause fetal harm based on animal data; advise females of reproductive potential to use effective contraception"] |
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| Fetal Monitoring | In pregnant women receiving FULPHILA, monitor complete blood count (CBC) with differential to assess neutrophil response and detect excessive leukocytosis (white blood cell count > 100 x 10^9/L). Monitor for splenic rupture (left upper quadrant pain, anemia) and acute respiratory distress syndrome (ARDS; tachypnea, hypoxemia). Fetal monitoring should include appropriate growth assessments if administered during second and third trimesters due to potential for decreased fetal weight. No specific fetal monitoring is routinely indicated, but consider nonstress test or biophysical profile if maternal condition warrants. |
| Fertility Effects | FULPHILA may affect fertility. In animal studies, pegfilgrastim administered to female rats at doses ≥ 1 mg/kg/day (approximately 13 times the human AUC) caused decreased fertility, decreased implantation sites, and increased pre- and post-implantation loss. The effects on male fertility have not been evaluated. In humans, there is no data on the effect of FULPHILA on fertility; however, granulocyte colony-stimulating factors have been associated with temporary suppression of ovulation and spermatogenesis in some cases. Patients of reproductive potential should consider fertility preservation before treatment. |