SOLIRIS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SOLIRIS (SOLIRIS).

How it works

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

What the body does with it

Metabolism	Eculizumab is a monoclonal antibody; it is degraded into small peptides and amino acids via general protein catabolism. No specific metabolic pathways or enzymes are involved.
Excretion	Eculizumab is not metabolized by cytochrome P450 enzymes; it is degraded via general protein catabolism. Clearance is primarily through the reticuloendothelial system; renal excretion of intact drug is negligible (<1%). No biliary or fecal excretion data are available in humans.
Half-life	Terminal elimination half-life: approximately 11.3 ± 3.4 days (range 8–18 days) following biweekly dosing. This supports a dosing interval of every 2 weeks for paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome.
Protein binding	Eculizumab is a recombinant humanized monoclonal antibody; it does not bind to serum proteins significantly. Protein binding is negligible (approximately 0%), as it is a large protein molecule.
Volume of Distribution	Volume of distribution at steady state: approximately 7.5 L (0.11 L/kg in a 70 kg adult), indicating distribution primarily within the vascular and interstitial spaces, consistent with limited extravascular distribution of a large monoclonal antibody.
Bioavailability	Intravenous administration only; bioavailability is 100% by the intravenous route. No oral or other routes are available.
Onset of Action	Inhibition of terminal complement activity (CH50) occurs within 1 hour of the first intravenous dose, reaching maximum suppression within 2 hours.
Duration of Action	CH50 activity returns to normal within 2–4 weeks after the last dose. Sustained complement inhibition requires maintenance dosing every 2 weeks. In atypical hemolytic uremic syndrome, complement blockade persists for at least 2 weeks post-dose.

Classification & Brands

Dosing & administration

600 mg intravenous over 35 minutes weekly for 4 weeks, then 900 mg 1 week later, followed by 900 mg every 2 weeks for paroxysmal nocturnal hemoglobinuria (PNH). For atypical hemolytic uremic syndrome (aHUS): 900 mg intravenous over 35 minutes weekly for 4 weeks, then 1200 mg 1 week later, followed by 1200 mg every 2 weeks.

Dosage form	INJECTABLE
Renal impairment	No dose adjustment required based on GFR. Eculizumab is not renally cleared.
Liver impairment	No specific guidelines for hepatic impairment; likely no adjustment needed as metabolism is not hepatic.
Pediatric use	For aHUS: weight-based: 5 to <10 kg: 300 mg; 10 to <20 kg: 600 mg; 20 to <30 kg: 600 mg; 30 to <40 kg: 900 mg; >=40 kg: 900 mg. Induction: weekly x4, then dose 1 week later, then maintenance every 2 weeks. For PNH: not approved in children <18 years.
Geriatric use	No specific dose adjustment. Monitor for infections, especially meningococcal, as elderly may have increased susceptibility.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for SOLIRIS (SOLIRIS).

Breastfeeding	No human data; eculizumab is a large monoclonal antibody likely to be present in minimal amounts in breast milk due to molecular size; M/P ratio unknown. Caution advised.
Teratogenic Risk	First trimester: No adequate human data; animal studies show no evidence of teratogenicity. Second and third trimesters: Both mother and fetus may have increased risk of infections due to complement inhibition; monitor for meningococcal and other infections. No known structural teratogenicity.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

SOLIRIS increases the risk of meningococcal infections. Patients must receive meningococcal vaccination at least 2 weeks prior to administration, unless the risks of delaying therapy outweigh the risks of developing a meningococcal infection. Patients should be monitored for early signs of meningococcal infection and evaluated immediately if infection is suspected.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Unresolved serious Neisseria meningitidis infection","Patients not currently vaccinated against Neisseria meningitidis (unless delays in therapy outweigh risks)","Known hypersensitivity to eculizumab or any of its excipients"]

Clinical Precautions

Precautions

["Increased susceptibility to meningococcal infections due to complement inhibition; vaccinate and monitor","Other Neisseria species and encapsulated bacteria infections (e.g., Streptococcus pneumoniae, Haemophilus influenzae type b); consider vaccination","Infusion reactions: including anaphylaxis and hypersensitivity; discontinue if severe","Monitoring for hemolysis in PNH patients: discontinue if evidence of severe hemolysis","Monitoring for thrombotic microangiopathy (TMA) in aHUS patients: discontinue if TMA complications occur"]

Clinical Tips & Counseling

Drug interactions

Loading safety data…

SOLIRIS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SOLIRIS (SOLIRIS).

How it works

What the body does with it

Metabolism	Eculizumab is a monoclonal antibody; it is degraded into small peptides and amino acids via general protein catabolism. No specific metabolic pathways or enzymes are involved.
Excretion	Eculizumab is not metabolized by cytochrome P450 enzymes; it is degraded via general protein catabolism. Clearance is primarily through the reticuloendothelial system; renal excretion of intact drug is negligible (<1%). No biliary or fecal excretion data are available in humans.
Half-life	Terminal elimination half-life: approximately 11.3 ± 3.4 days (range 8–18 days) following biweekly dosing. This supports a dosing interval of every 2 weeks for paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome.
Protein binding	Eculizumab is a recombinant humanized monoclonal antibody; it does not bind to serum proteins significantly. Protein binding is negligible (approximately 0%), as it is a large protein molecule.
Volume of Distribution	Volume of distribution at steady state: approximately 7.5 L (0.11 L/kg in a 70 kg adult), indicating distribution primarily within the vascular and interstitial spaces, consistent with limited extravascular distribution of a large monoclonal antibody.
Bioavailability	Intravenous administration only; bioavailability is 100% by the intravenous route. No oral or other routes are available.
Onset of Action	Inhibition of terminal complement activity (CH50) occurs within 1 hour of the first intravenous dose, reaching maximum suppression within 2 hours.
Duration of Action	CH50 activity returns to normal within 2–4 weeks after the last dose. Sustained complement inhibition requires maintenance dosing every 2 weeks. In atypical hemolytic uremic syndrome, complement blockade persists for at least 2 weeks post-dose.

Classification & Brands

Dosing & administration

Dosage form	INJECTABLE
Renal impairment	No dose adjustment required based on GFR. Eculizumab is not renally cleared.
Liver impairment	No specific guidelines for hepatic impairment; likely no adjustment needed as metabolism is not hepatic.
Pediatric use	For aHUS: weight-based: 5 to <10 kg: 300 mg; 10 to <20 kg: 600 mg; 20 to <30 kg: 600 mg; 30 to <40 kg: 900 mg; >=40 kg: 900 mg. Induction: weekly x4, then dose 1 week later, then maintenance every 2 weeks. For PNH: not approved in children <18 years.
Geriatric use	No specific dose adjustment. Monitor for infections, especially meningococcal, as elderly may have increased susceptibility.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for SOLIRIS (SOLIRIS).

Breastfeeding	No human data; eculizumab is a large monoclonal antibody likely to be present in minimal amounts in breast milk due to molecular size; M/P ratio unknown. Caution advised.
Teratogenic Risk	First trimester: No adequate human data; animal studies show no evidence of teratogenicity. Second and third trimesters: Both mother and fetus may have increased risk of infections due to complement inhibition; monitor for meningococcal and other infections. No known structural teratogenicity.
Fetal Monitoring