Dosing and uses of Soliris (eculizumab)
Adult dosage forms and strengths
injectable solution
- 10mg/mL
Paroxysmal Nocturnal Hemoglobinuria
600 mg IV infusion over 35 minutes q7days for the first 4 weeks, THEn
900 mg (fifth dose) after 7 days, THEn
900 mg q14days thereafater
Hemolytic Uremic Syndrome
Indicated for treatment of atypical hemolytic uremic syndrome to inhibit complement-mediated thrombotic microangiopathy; effectiveness based on the effects on thrombotic microangiopathy and renal function
Not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS)
900 mg IV infusion over 35 minutes q7days for 4 weeks, THEn
1200 mg (5th dose) after 7 days, THEn
1200 mg q14days THEREAFTEr
Supplemental Doses After PE/PI
Supplemental dosing required in the setting of concomitant support with PE/PI (plasmapheresis or plasma exchange; or fresh frozen plasma infusion)
Plasmapheresis or plasma exchange
- 300 mg most recent dose: Give 300 mg per each session within 60 minutes following completion
- 600 mg or more most recent dose: Give 600 mg per each session within 60 minutes following completion
Fresh frozen plasma infusion
- 300 mg or more most recent dose: Give 300 mg per each unit of FFP; administer 60 minutes prior to each 1 unit of FFP
Degos Disease (Off-label)
Doses 1-4: 600 mg IV q7days for 4 wk
Dose 5 and thereafter: Wait 7 days following 4th dose, then administer 900 mg IV for 5th dose, then 900 mg IV q14days thereafter
This dosage regimen is for PNH, in cases of Degos disease the dosing can reach 1200 mg/dose
Orphan Designations
Dermatomyositis
Myasthenia gravis
Idiopathic membranous glomerular nephropathy
Neuromyelitis optica
Renal transplantation: prevention of delayed graft function
Shiga-Toxin producing Escherichia coli hemolytic uremic syndrome
Orphan sponsor
- Alexion Pharmaceuticals, Inc; 352 Knotter Drive; Cheshire, CT 06410
Pediatric dosage forms and strengths
injectable solution
- 10mg/mL
Hemolytic Uremic Syndrome
Indicated for treatment of atypical hemolytic uremic syndrome to inhibit complement-mediated thrombotic microangiopathy; effectiveness based on the effects on thrombotic microangiopathy and renal function
Not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS)
5 to <10 kg
- 300 mg IV infusion once then, THEN
- 300 mg (second dose) after 7 days, THE
- 300 mg every 21 days THEREAFTER
10 to <20 kg
- 600 mg IV infusion once, THEN
- 300 mg (second dose) after 7 days, THEN
- 300 mg every 14 days THEREAFTER
20 to <30 kg
- 600 mg IV infusion q7days for 2 weeks, THEN
- 600 mg (third dose) after 7 days, THEN
- 600 mg q14days THEREAFTER
30 to <40 kg
- 600 mg IV infusion q7days for 2 weeks, THEN
- 900 mg (third dose) after 7 days, THEN
- 900 mg every 14 days THEREAFTER
>40 kg
- 900 mg IV infusion q7days for 4 weeks, THEN
- 1200 mg (fifth dose) after 7 days, THEN
- 1200 mg q14days THEREAFTER
Supplemental Doses After PE/PI
Supplemental dosing required in the setting of concomitant support with PE/PI (plasmapheresis or plasma exchange; or fresh frozen plasma infusion)
Plasmapheresis or plasma exchange
- 300 mg most recent dose: Give 300 mg per each session within 60 minutes following completion
- 600 mg or more most recent dose: Give 600 mg per each session within 60 minutes following completion
Fresh frozen plasma infusion
- 300 mg or more most recent dose: Give 300 mg per each unit of FFP; administer 60 minutes prior to each 1 unit of FFP
Soliris (eculizumab) adverse (side) effects
>10%
Paroxysmal Nocturnal Hemoglobinuria
- Headache (44%)
- Nasopharyngitis (23%)
- Back pain (19%)
- Nausea (16%)
- Cough (12%)
- Fatigue (12%)
Hemolytic Uremic Syndrome
- Hypertension (47%)
- Headache (41%)
- Diarrhea (35%)
- Anemia (35%)
- Vomiting (29%)
- Upper respiratory infection (29%)
- UTI (24%)
- Leukopenia (24%), Fatigue (18%),Peripheral edema (18%), Pyrexia (18%), Cough (12%)
1-10%
Paroxysmal nocturnal hemoglobinuria
- Constipation
- Flu-like illness
- Myalgia
- Pain
- Various infections (eg, HSV)
- Serious or fatal meningococcal infections
Hemolytic uremic syndrome
- Pharyngolaryngeal pain
- Vertigo
- Pain in extremity
Frequency not defined
As with all proteins, there is a potential for immunogenicity
Warnings
Black box warnings
Increases the risk of meningococcal infections
Vaccinate with a meningococcal vaccine at least 2 weeks prior to receiving the first dose; revaccinate according to current medical guidelines for vaccine use
Monitor for early signs of meningococcal infections, evaluate immediately if infection is suspected, and treat with antibiotics if necessary
Contraindications
Documented hypersensitivity
Unresolved serious Neisseria meningitidis infection or patients who are unvaccinated against N. meningitidis (unless risk of delaying treatment outwiegh the risk for meningococcal infection)
Cautions
Discontinue if being treated for serious meningococcal infection
Caution with any systemic infection
Increased risk of susceptibility to infections
Meningococcal infection may occur and become rapidly life-threatening or fatal if not recognized and treated early
Supplement dose with plasma infusion or exchange
Only administer as an IV infusion, do not give IVP or bolus
Pregnancy and lactation
Pregnancy category: C; based on animal data, may cause fetal harm
Lactation: excretion in milk unknown; use with caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Soliris (eculizumab)
Mechanism of action
Monoclonal blocking antibody to complement protein C5; inhibits cleavage to C5a and C5b, thus preventing terminal complement complex C5b-9, thereby preventing RBC hemolysis
Inhibits terminal complement mediated intravascular hemolysis in PNH patients and complement-mediated thrombotic microangiopathy (TMA) in patients with aHUs
Pharmacokinetics
Peak serum concentration (at week 26): 194 mcg/mL
Trough concentration (at week 26): 97 mcg/mL
Vd: 7.7 L
Half-Life: 8-15 days
Half-Life following plasma exchange: 1.26 hours
Clearance: 22 mL/hr/70 kg
Clearance following plasma exhange: 3660 mL/hr
Administration
IV Administration
Dilute to 5 mg/mL by first adding dose to infusion bag, and then add appropriate amount of D5W, NS, ½NS, or Ringers
Adults: Infuse IV over at least 35 min; may slow/stop infusion if adverse effect occurs, but total infusion time should not exceed 2 hr
Children: Infuse IV over 1-4 hr
Administer by IV infusion, do NOT give IV push or bolus
