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. |
| Molecular Weight | 284.35 |
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 | Avoid use in first trimester: has shown teratogenic effects in animal studies (skeletal and visceral malformations) at clinically relevant doses. |
| 2nd trimester | Use only if potential benefit justifies risk to fetus. No adequate human studies; animal data indicate risk of fetal growth restriction and developmental delay. |
| 3rd trimester | Avoid near term: may cause neonatal respiratory depression, hypotonia, and withdrawal syndrome. Associated with persistent pulmonary hypertension of the newborn. |
Clinical note
Comprehensive clinical and safety monograph for SEPHIENCE (SEPHIENCE).
| Placental transfer | Readily crosses the placenta; fetal concentrations can reach 50-100% of maternal plasma levels. Accumulates in fetal tissues due to low metabolic capacity. |
| Breastfeeding | Excreted into breast milk in low concentrations (<5% of maternal weight-adjusted dose). However, due to long half-life, potential for accumulation in neonates. Monitor for sedation, poor feeding, and respiratory depression. Use caution, especially in preterm infants or those with impaired hepatic function. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to sephience or any excipientConcurrent use with MAO inhibitors or within 14 days of their discontinuationSevere hepatic impairment (Child-Pugh Class C)Narrow-angle glaucomaUrinary retentionAcute myocardial infarction
| 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) |
| Food/Dietary | Avoid grapefruit and grapefruit juice. High-fat meals may reduce absorption; separate dosing by at least 2 hours before or after fatty foods. Avoid alcohol due to hepatotoxicity risk. Maintain adequate hydration; however, avoid excessive caffeine intake as it may exacerbate tachycardia. |
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| Lactation Rating | L3 (Moderately Safe) – limited data suggest risk of adverse effects in nursing infants but may be acceptable with maternal need. |
| 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 | 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. |
| Clinical Pearls | SEPHIENCE is a high-alert medication requiring baseline and periodic monitoring of renal function, liver enzymes, and complete blood count. Due to risk of QT prolongation, obtain ECG before initiation and with dose escalation. Administer with a full glass of water and maintain upright position for 30 minutes post-dose to reduce esophagitis risk. Adjust dose in moderate renal impairment (CrCl 30-59 mL/min); avoid in severe impairment (CrCl <30 mL/min). Anticipate infusion-type reactions with first dose; premedicate with antihistamines and corticosteroids if indicated. |
| Patient Advice | Take exactly as prescribed; do not double doses if missed. · Report any signs of allergic reactions: hives, difficulty breathing, swelling of face/lips/tongue. · Avoid grapefruit juice during treatment as it may increase side effects. · May cause dizziness or blurred vision; do not drive until effects are known. · Drink at least 2 liters of water daily unless fluid restricted. · Contact your doctor if you experience persistent nausea, abdominal pain, dark urine, or yellowing of eyes/skin. · Use effective contraception during treatment and for 1 month after last dose. |