SOLIRIS
Clinical safety rating
cautionComprehensive clinical and safety monograph for SOLIRIS (SOLIRIS).
Comprehensive clinical and safety monograph for SOLIRIS (SOLIRIS).
Paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysisAtypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathyGeneralized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor antibody-positiveNeuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 antibody-positive
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.
| 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. |
| Molecular Weight | 147800 Da |
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. |
| 1st trimester | Soliris should be used during the first trimester only if the potential benefit justifies the potential risk to the fetus. There are no adequate and well-controlled studies in pregnant women. However, case reports suggest no increased risk of major birth defects. |
| 2nd trimester | Use during the second trimester if clearly needed. Monitor for potential effects on fetal complement system and growth. Limited data available. |
| 3rd trimester | Use during the third trimester if clearly needed. May cross placenta and theoretically affect fetal complement activity. Monitor neonate for complement deficiency and infections. |
Clinical note
Comprehensive clinical and safety monograph for SOLIRIS (SOLIRIS).
| Placental transfer | Eculizumab is a humanized monoclonal antibody (IgG2/IgG4) and is expected to cross the placenta. IgG antibodies are transferred across the placenta, especially during the third trimester. Limited studies confirm placental transfer with measurable levels in cord blood. |
| Breastfeeding | It is unknown whether eculizumab is excreted in human milk. However, given its large molecular weight and high molecular weight, transfer into breast milk is expected to be low. Caution should be exercised when administering to a breastfeeding woman. Consider the benefits of breastfeeding, the risk of potential infant exposure, and the mother's need for treatment. |
| Lactation Rating | L3 - Probably Compatible (limited data, but likely low transfer) |
| 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 | Maternal: Monitor for signs of infection, especially meningococcal infection (vaccination required). Fetal: Ultrasound for growth and anatomy due to underlying maternal disease; no specific drug-related monitoring. |
| Fertility Effects | No known effects on human fertility; animal studies show no impairment of fertility. |
■ 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.
| Serious Effects |
Unresolved Neisseria meningitidis infectionPatients not vaccinated against Neisseria meningitidis (unless receiving prophylactic antibiotics)
| 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 |
| Food/Dietary | No clinically significant food interactions reported; administer intravenously over 35 minutes. |
| Clinical Pearls | Administer meningococcal vaccines at least 2 weeks prior to first dose; vaccinate against Neisseria meningitidis serogroups A, C, Y, W-135 and serogroup B. Monitor for hemolysis in patients with paroxysmal nocturnal hemoglobinuria (PNH) after discontinuation. Do not administer live vaccines. Infusion reactions may occur; premedicate with antihistamines and corticosteroids if needed. Eculizumab increases risk of serious infections, especially encapsulated bacteria. Prescribe prophylactic antibiotics if vaccination cannot be given 2 weeks prior. Monitor LDH, hemoglobin, and reticulocyte count in PNH. |
| Patient Advice | You must receive meningococcal vaccines at least 2 weeks before starting treatment. · This medication increases your risk of serious infections, especially meningitis. · Report any signs of infection such as fever, headache with stiff neck, or rash immediately. · Do not receive live vaccines while on this medication. · If you stop treatment, your healthcare provider will monitor you for red blood cell breakdown. · Promptly report any bruises, bleeding, or signs of injection site reaction. |
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