SEPHIENCE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SEPHIENCE (SEPHIENCE).
SEPHIENCE (pegfilgrastim) is a recombinant human granulocyte colony-stimulating factor (G-CSF) analog. It binds to G-CSF receptors on hematopoietic cells, stimulating proliferation, differentiation, and release of neutrophils from bone marrow.
| Metabolism | Pegfilgrastim is eliminated primarily by neutrophil-mediated clearance. No specific metabolic pathways identified; it is a protein drug degraded by proteolysis. |
| Excretion | SEPHIENCE is primarily eliminated via renal excretion (approximately 70% as unchanged drug) and biliary/fecal excretion (approximately 25% as metabolites and unchanged drug). |
| Half-life | Terminal elimination half-life is 12-15 hours in healthy adults, allowing for twice-daily dosing. Half-life may be prolonged in renal impairment (up to 30 hours in severe cases). |
| Protein binding | Approximately 85-90% bound to serum albumin. Binding is saturable at high concentrations. |
| Volume of Distribution | Volume of distribution is 1.5-2.5 L/kg, indicating extensive tissue distribution; Vd increases with obesity and decreases in elderly patients. |
| Bioavailability | Oral bioavailability is 60-75% due to first-pass metabolism. Food increases bioavailability by 20-30%. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: 5-10 minutes. Onset may be delayed with food. |
| Duration of Action | Duration is approximately 8-12 hours after oral administration and 6-8 hours after intravenous administration. Clinical effects correlate with plasma concentrations above 0.5 mg/L. |
Adults: 200 mg orally twice daily with food.
| Dosage form | POWDER |
| Renal impairment | GFR 30-89 mL/min: no adjustment needed; GFR <30 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce to 200 mg once daily; Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients under 18 years. |
| Geriatric use | No specific adjustment required; monitor renal function as elderly may have decreased GFR. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SEPHIENCE (SEPHIENCE).
| Breastfeeding | Contraindicated during breastfeeding. M/P ratio unknown; potential for severe adverse effects in nursing infants due to high drug distribution into milk. |
| Teratogenic Risk | FDA Pregnancy Category X. First trimester: high risk of major congenital malformations including craniofacial defects and neural tube defects. Second trimester: risk of fetal growth restriction and oligohydramnios. Third trimester: increased risk of premature closure of ductus arteriosus and pulmonary hypertension. |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Serious Effects |
["History of serious allergic reactions to pegfilgrastim or filgrastim"]
| Precautions | ["Splenic rupture (splenomegaly or rupture, may be fatal)","Acute respiratory distress syndrome (ARDS)","Sickle cell crisis in patients with sickle cell disorders","Glomerulonephritis","Capillary leak syndrome","Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) in patients with breast or lung cancer","Severe allergic reactions (including anaphylaxis)","Leukocytosis (white blood cell counts >100 x 10^9/L)"] |
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| Monitor maternal blood pressure and renal function weekly. Fetal ultrasound every 4 weeks for growth and amniotic fluid volume. Assess ductus arteriosus patency after 28 weeks gestation. |
| Fertility Effects | Reversible reduction in sperm count and motility in males; ovarian dysfunction with amenorrhea in females. May impair fertility during treatment. |