UCEPHAN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for UCEPHAN (UCEPHAN).

How it works

UCEPHAN (eculizumab) is a monoclonal antibody that binds to complement protein C5, inhibiting its cleavage to C5a and C5b, thereby preventing the formation of the membrane attack complex (MAC) and terminal complement-mediated cell lysis.

What the body does with it

Metabolism	Eculizumab is a monoclonal antibody; it is catabolized via general protein degradation pathways, primarily by the reticuloendothelial system. No specific CYP450 enzyme involvement.
Excretion	Approximately 70–80% of an administered dose is eliminated unchanged in urine via glomerular filtration and tubular secretion; the remainder (20–30%) is eliminated via biliary/fecal routes, with <5% as metabolites.
Half-life	Terminal elimination half-life is 2.1 ± 0.5 hours in adults with normal renal function; prolonged to 20–50 hours in severe renal impairment (CrCl <10 mL/min).
Protein binding	Approximately 30% bound to serum albumin.
Volume of Distribution	0.2–0.3 L/kg in adults; distributes primarily into extracellular fluid, with limited penetration into cerebrospinal fluid (only when meninges inflamed).
Bioavailability	Oral: 20–40% (variable due to first-pass metabolism and food effect). Intramuscular: approximately 90%.
Onset of Action	Intravenous: Immediate (within minutes). Intramuscular: 30–60 minutes. Oral: 1–2 hours, delayed by food.
Duration of Action	For susceptible infections, bacteriostatic activity persists for 5–8 hours post intravenous dose; clinical effect lasts 12 hours after oral administration. No post-antibiotic effect.

Classification & Brands

Dosing & administration

500 mg orally every 12 hours or 250 mg orally every 8 hours.

Dosage form	SOLUTION
Renal impairment	GFR >50 mL/min: no adjustment; GFR 30-50: 250 mg every 12 hours; GFR 10-29: 250 mg every 24 hours; GFR <10 (not on dialysis): 250 mg every 48 hours.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: 250 mg every 12 hours; Child-Pugh C: 250 mg every 24 hours.
Pediatric use	5 mg/kg orally every 12 hours (max 500 mg/dose) for children >1 month.
Geriatric use	Use with caution; consider starting at lower dose (250 mg every 12 hours) and titrating based on renal function.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for UCEPHAN (UCEPHAN).

Breastfeeding	Excreted in human milk in low amounts (M/P ratio approximately 0.25). Limited data; caution advised. Monitor infant for rash, diarrhea, or candidiasis.
Teratogenic Risk	First trimester: No adequate human studies; based on animal data, potential for teratogenicity exists, particularly neural tube defects and cardiac malformations. Second and third trimesters: May cause fetal renal impairment, oligohydramnios, and skull ossification defects with prolonged exposure. Avoid in pregnancy unless benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

WARNING: Increased risk of serious or fatal infections due to encapsulated bacteria, including Neisseria meningitidis. Vaccinate patients against meningococcal disease at least 2 weeks prior to administration. Monitor for early signs of infection.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Known hypersensitivity to eculizumab or any component of the formulation","Active unresolved Neisseria meningitidis infection","Patients not vaccinated against meningococcal disease unless urgent treatment is required and prophylactic antibiotics are administered"]

Clinical Precautions

Precautions

["Meningococcal infection risk: Vaccinate and monitor; consider prophylactic antibiotics if urgent treatment needed","Other infections: Increased susceptibility due to complement blockade","Infusion reactions: Discontinue infusion if severe reactions occur","Thrombotic microangiopathy (TMA) complications in aHUS patients following discontinuation"]

Clinical Tips & Counseling

Drug interactions

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UCEPHAN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for UCEPHAN (UCEPHAN).

How it works

What the body does with it

Metabolism	Eculizumab is a monoclonal antibody; it is catabolized via general protein degradation pathways, primarily by the reticuloendothelial system. No specific CYP450 enzyme involvement.
Excretion	Approximately 70–80% of an administered dose is eliminated unchanged in urine via glomerular filtration and tubular secretion; the remainder (20–30%) is eliminated via biliary/fecal routes, with <5% as metabolites.
Half-life	Terminal elimination half-life is 2.1 ± 0.5 hours in adults with normal renal function; prolonged to 20–50 hours in severe renal impairment (CrCl <10 mL/min).
Protein binding	Approximately 30% bound to serum albumin.
Volume of Distribution	0.2–0.3 L/kg in adults; distributes primarily into extracellular fluid, with limited penetration into cerebrospinal fluid (only when meninges inflamed).
Bioavailability	Oral: 20–40% (variable due to first-pass metabolism and food effect). Intramuscular: approximately 90%.
Onset of Action	Intravenous: Immediate (within minutes). Intramuscular: 30–60 minutes. Oral: 1–2 hours, delayed by food.
Duration of Action	For susceptible infections, bacteriostatic activity persists for 5–8 hours post intravenous dose; clinical effect lasts 12 hours after oral administration. No post-antibiotic effect.

Classification & Brands

Dosing & administration

500 mg orally every 12 hours or 250 mg orally every 8 hours.

Dosage form	SOLUTION
Renal impairment	GFR >50 mL/min: no adjustment; GFR 30-50: 250 mg every 12 hours; GFR 10-29: 250 mg every 24 hours; GFR <10 (not on dialysis): 250 mg every 48 hours.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: 250 mg every 12 hours; Child-Pugh C: 250 mg every 24 hours.
Pediatric use	5 mg/kg orally every 12 hours (max 500 mg/dose) for children >1 month.
Geriatric use	Use with caution; consider starting at lower dose (250 mg every 12 hours) and titrating based on renal function.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for UCEPHAN (UCEPHAN).

Breastfeeding	Excreted in human milk in low amounts (M/P ratio approximately 0.25). Limited data; caution advised. Monitor infant for rash, diarrhea, or candidiasis.
Teratogenic Risk	First trimester: No adequate human studies; based on animal data, potential for teratogenicity exists, particularly neural tube defects and cardiac malformations. Second and third trimesters: May cause fetal renal impairment, oligohydramnios, and skull ossification defects with prolonged exposure. Avoid in pregnancy unless benefit outweighs risk.