1. Pregnancy Related Haemolytic Uraemic Syndrome (P-aHUS)

2. aHUS: A Chronic, Complement-Mediated TMA with Life-Threatening Consequences1,2
aHUS is a chronic, rare, genetic disorder that causes complement-mediated thrombotic microangiopathy (TMA)1,2
aHUS may result in death and progressive organ damage1,2
79% of aHUS patients die, require dialysis or have permanent renal damage within 3 years1
33 to 40% of patients die or progress to end-stage renal disease with the first clinical manifestation1,2
Pregnancy related aHUS (P-aHUS) has similar presenting signs and symptoms to pregnancy related TTP and HELLP syndrome3-5
TTP = thrombotic thrombocytopenic purpura
HELLP = haemolytic anaemia, elevated liver enzymes and low platelets
References: 1. Noris M, Caprioli J, Bresin E, et al. Clin J Am Soc Nephrol. 2010;5: Caprioli J, Noris M, Brioschi S, et al; for the International Registry of Recurrent and Familial HUS/TTP. Blood. 2006;108: Fakhouri F, et al. J Am Soc Nephrol 2010; 21: Machado S, et al. J Nephrol. 2012; 25(01):19-30.

3. Natural Complement Regulators are Required for Control of the Complement System1-3
The complement system is part of the natural (innate) protective immune system1
Activity is continuously occurring by a spontaneous process called “tick-over” which enables rapid immune responses1
Natural inhibitors of complement keep amplification in check and prevent uncontrolled complement activity2
When unregulated, complement activity can lead to destructive consequences, including TMA lesions and progressive organ damage3
aHUS can be unmasked by pregnancy-associated complement amplification4-7
References: 1. Holers VM et al. Immunol Rev. 2008;223: Zipfel PF et al. Curr Opin Nephrol Hypertens. 2010;4: Legendre CM, Licht C, Muus P, et al. N Engl J Med. 2013;368: Noris M, Caprioli J, Bresin E, et al. Clin J Am Soc Nephrol. 2010;5: Richani K, Soto E, Romero R, et al. J Matern Fetal Neonatal Med. 2005;17: Denny KJ, Woodruff TM, Taylor SM, et al. Am J Reprod Immunol. 2013;69: Fakhouri F, Roumenina L, Provot F, et al. J Am Soc Nephrol. 2010;21:

4. Immune Complex Clearance Microbial Opsonisation
Natural Inhibitors are Required for Control of the Complement System1-17
Lectin Pathway
Classical Pathway
Alternative Pathway
iC3b
C3-Convertase
C3b
Immune Complex Clearance
Microbial Opsonisation
Weak Anaphylatoxin C3a
C3 + H2O: always active (chronic) C3
Amplification
Natural Inhibitors: Factor I, Factor H, MCP
Proximal
Thrombomodulin
C5b-9 (Membrane Attack Complex)
Cell lysis
Proinflammatory
Platelet activation
Leukocyte activation
Endothelial activation
Prothrombotic
C5a
Potent anaphylatoxin
Chemotaxis C5
C5-Convertase
Terminal
C5b C6 C7 C8 C9
References: 1. Zipfel PF et al. Vaccine 2008;26(Suppl 8):I67-I74. 2.Figueroa JE, Densen P. Clin Microbiol Rev. 1991;4: Walport MJ. N Engl J Med. 2001;344: Rother RP et al. Nat Biotechnol. 2007;25:

5. Immune Complex Clearance Microbial Opsonisation
In aHUS, Chronic Uncontrolled Complement Activity Leads to Devastating Consequences1-8
Lectin Pathway
Classical Pathway
Alternative Pathway
Immune Complex Clearance
Microbial Opsonisation C3
C3 + H2O: always active (chronic)
Amplification
Natural Inhibitors: Factor H, Factor I, MCP −
Proximal
Weak Anaphylatoxin C3a
C3b
Thrombomodulin −
iC3b
C3-Convertase
Gain of Function
Mutations:
C3, CFB +
C5-Convertase C5
Terminal
C5b C6 C7 C8 C9
C5a
Potent anaphylatoxin
Chemotaxis
Proinflammatory
Leukocyte activation
Endothelial activation
Prothrombotic
C5b-9 (Membrane Attack Complex)
Cell lysis
Proinflammatory
Platelet activation
Leukocyte activation
Endothelial activation
Prothrombotic
Consequences
Consequences
Anaphylaxis
Inflammation
Thrombosis
Haemolysis
Inflammation
Thrombosis
Tissue Damage
References: 1. Zipfel PF et al. Vaccine 2008;26(Suppl 8):I67-I74. 2.Figueroa JE, Densen P. Clin Microbiol Rev. 1991;4: Walport MJ. N Engl J Med. 2001;344: Rother RP et al. Nat Biotechnol. 2007;25: Caprioli J et al. Blood. 2006;108: Noris M et al. Clin J Am Soc Nephrol. 2010;5: Loirat C et al. Pediatr Nephrol. 2008;23:

6. Elevated Baseline Complement Activity Chronic Complement Activity
Chronic, Uncontrolled Complement Activity Results in Continuous Endothelial Damage and Ongoing Risk of TMA1
Elevated Baseline Complement Activity
Chronic Complement Activity
The assembly of multiple C5b-9 complexes on the surface of endothelial cells causes endothelial injury and platelet activation2-5
Binding of C5a to the C5a receptor, results in a decrease in the endothelium’s anti-complement and anti-thrombotic properties2,4,6,7
red blood cell
leukocyte
platelet
activated leukocyte
activated platelet
vWF
prothrombotic factors
schistocyte
Footnotes: vWF = Von Willebrand Factor; Image for illustrative purposes only, objects are not to scale. References: 1. Noris M and Remuzzi G Nat Rev Nephrol. 2014;10(3): Noris M, Mescia F, Remuzzi G. Nat Rev Nephrol. 2012;8: Barbour T, Johnson S, Cohney S, et al. Nephrol Dial Transplant. 2012;27: Fang CJ, Richards A, Liszewski MK, et al. Br J Haematol. 2008;143: Loirat C, Frémeaux-Bacchi V. Orphanet J Rare Dis. 2011;6: Gastoldi S, Noris M, Macor P, et al. Immunobiology. 2012;217: Salant DJ. J Am Soc Nephrol. 2011;22:7-9.

7. Chronic, Uncontrolled Complement Activity Results in Continuous Endothelial Damage and Ongoing Risk of TMA1
Elevated Baseline Complement Activity
Chronic Complement Activity
Complement-Mediated TMA
Disrupted endothelial cells:
Release complement- activating microparticles, resulting in a vicious cycle of endothelial activation, complement amplification, and ongoing endothelial injury2,3
Release pro-thrombotic coagulation proteins, activate platelets, and recruit leukocytes, resulting in the formation of thrombi in small blood vessels throughout the body2
red blood cell
leukocyte
platelet
activated leukocyte
activated platelet
vWF
prothrombotic factors
schistocyte
Footnotes: vWF = Von Willebrand Factor; Image for illustrative purposes only, objects are not to scale. References: 1. Noris M and Remuzzi G Nat Rev Nephrol. 2014;10(3): Noris M, Mescia F, Remuzzi G. Nat Rev Nephrol. 2012;8: Renner B, Klawitter J, Goldberg R, et al. J Am Soc Nephrol. 2013;24:

8. Chronic, Uncontrolled Complement Activity Results in Continuous Endothelial Damage and Ongoing Risk of TMA1
Elevated Baseline Complement Activity
Chronic Complement Activity
Complement-Mediated TMA
Ischemia
Progressive Organ Damage
red blood cell
leukocyte
platelet
activated leukocyte
activated platelet
vWF
prothrombotic factors
schistocyte
Uncontrolled complement activity causes ongoing vascular endothelial injury2-5
Resulting TMA lesions may progress toward irreversible multi-organ damage2-5
Footnotes: vWF = Von Willebrand Factor; Image for illustrative purposes only, objects are not to scale. References: 1. Noris M and Remuzzi G Nat Rev Nephrol. 2014;10(3): Laurence J. Clin Adv Hematol Oncol. 2012;10(suppl 17): Legendre CM, Licht C, Muus P, et al. N Engl J Med. 2013;368: Sellier-Leclerc A-L, Frémeaux-Bacchi V, Dragon-Durey MA, et al;French Society of Pediatric Nephrology. J Am Soc Nephrol. 2007;18: Nester CM, Thomas CP. Hematology Am Soc Hematol Educ Program. 2012;2012:

9. Systemic, Complement-Mediated TMA Affects Multiple Vital Organs and Tissues1-16
Renal: More than 50% of patients progress to ESRD1
Elevated creatinine2,3
Proteinuria4
Oedema,3 malignant hypertension5
Decreased eGFR6
CNS: Up to 48% of patients experience neurological symptoms4
Confusion7
Stroke7
Encephalopathy5
Seizure4
Blood:
Thrombocytopenia1
Decreased haptoglobin1
Elevated LDH1
Decreased haemoglobin1
Schistocytes1
Visual:
Ocular occlusion8
Cardiovascular: Up to 43% of patients experience cardiovascular symptoms4
Myocardial infarction9,16
Hypertension10
Diffuse vasculopathy6
Peripheral gangrene11,16
Gastrointestinal: 37% of patients experience GI symptoms12
Diarrhoea12,13
Colitis7
Nausea/Vomiting12
Pancreatitis14
Abdominal pain7
Gastroenteritis5
Liver necrosis6
Pulmonary:
Dyspnea9
Pulmonary haemorrhage15
Pulmonary oedema9
A full clinical assessment should evaluate multiple organ systems
References: 1. Caprioli J, Noris M, Brioschi S,et al; for the International Registry of Recurrent and Familial HUS/TTP. Blood. 2006;108: Ariceta G, Besbas N, Johnson S, et al; for the European Paediatric Study Group for HUS. Pediatr Nephrol. 2009;24: Ståhl A-L, Vaziri-Sani F, Heinen S, et al.. Blood. 2008;111: Neuhaus TJ et al. Arch Dis Child. 1997;76: Noris M et al. Clin J Am Soc Nephrol. 2010; 5: Loirat C et al. Pediatr Nephrol. 2008;23: Ohanian M et al. Clin Pharmacol. 2011;3: Larakeb A et al. Pediatr Nephrol. 2007;22: Sallée M et al. Nephrol Dial Transplant. 2010;25: Kavanagh D et al. Med Bull. 2006;77-78: Malina M et al. Pediatr Nephrol. 2011;26: Langman C. Haematologica. 2012;97(s1): Zuber J et al. Nat Rev Nephrol. 2011;7: Dragon-Durey M-A et al. J Am Soc Nephrol. 2010;21: Sellier-Leclerc A-L al; French Society of Pediatric Nephrology. J Am Soc Nephrol. 2007;18: Noris M and Remuzzi G Nat Rev Nephrol. 2014;10(3):

10. aHUS can be Unmasked by Complement-Amplifying Conditions1
Complement-amplifying conditions present a situation where aHUS can be identified in patients who may otherwise go undiagnosed1
Patients with aHUS are particularly susceptible to TMA when experiencing a complement-amplifying condition such as pregnancy and childbirth 2-6
Amplification of complement in patients with aHUS can upregulate the complement cascade beyond the patient’s ability to regulate
References: 1. Noris M, Caprioli J, Bresin E, et al. Clin J Am Soc Nephrol. 2010;5: Noris M, Mescia F, Remuzzi G. Nat Rev Nephrol. 2012;8: Frémeaux-Bacchi V, Fakhouri F, Garnier A, et al. Clin J Am Soc Nephrol. 2013;8: Liszewski MK, Atkinson JP. Hematology Am Soc Hematol Educ Program. 2011;2011: Fang CJ, Richards A, Liszewski MK, et al. Br J Haematol. 2008;143: Campistol JM, Arias M, Ariceta G, et al. Nefrologia. 2013;33:27-45.

11. 69% of Patients with aHUS Showed their First Clinical Manifestation While Experiencing One of the Following Complement-Amplifying Conditions (N=191*)1
Study description: Analysis of 273 patients with aHUS, registered consecutively from 1996 to 2007 within the International Registry of Recurrent and Familial HUS/TTP.
Footnotes: *Patients with non-familial aHUS **E.g., Systemic Lupus Erythematosus and Scleroderma.
Reference: 1. Noris M, Caprioli J, Bresin E, et al. Clin J Am Soc Nephrol. 2010;5:

12. Thrombotic Microangiopathy in Pregnancy and Post-Partum1
Microangiopathic haemolytic anaemia +
Thrombocytopenia
Pre-eclampsia or
HELLP
TTP
aHUS
STEC-HUS
Sepsis
Placenta ablation
Haemorrhage
TTP = thrombotic thrombocytopenic purpura
HELLP = haemolytic anaemia, elevated liver enzymes and low platelets
aHUS = atypical Haemolytic Uraemic Syndrome
STEC-HUS = shiga-toxin-producing E coli Haemolytic Uraemic Syndrome
1. George Am Soc Hematol Educ Program Dec 5;2015(1):644-8.

13. Pregnancy-Associated aHUS1
Complement dysregulation associated aHUS occurs mainly post-partum1
ADAMTS-13 deficiency associated TTP occurs mainly during pregnancy1
Adapted from Fakhouri et al, 2010
Study design: A retrospective analysis of 100 adult women with aHUS referred between 2000 and 2008 to the laboratory of immunology at Hôpital Européen Georges – Pompidou (Paris, France), a reference center for the evaluation of complement disorders. A diagnosis of aHUS was defined by the presence of haemolytic anaemia, thrombocytopaenia, and acute renal failure.
*Defined as complement dysregulation TMA.
1.Fakhouri F, et al. J Am Soc Nephrol 2010; 21:

14. In Up to 1 in 5 Women With aHUS the First Manifestation is Pregnancy-Related1
P-aHUS is a subgroup of aHUS1
21%
aHUS
aHUS unmasked by pregnancy1
57% (12/21) of patients with aHUS were diagnosed during a second or subsequent pregnancy1
1. Fakhouri F, et al. J Am Soc Nephrol 2010; 21:

15. P-aHUS Can Lead to Significant and Rapid Onset of Renal Damage1
76% of patients with P-aHUS progressed to ESRD, 62% within one month1
aHUS-patients developing a TMA during pregnancy are at high risk of TMA manifestations post pregnancy2,3
Patients with ESRD by last follow up
Patient with ESRD within 1 month
62%
76%
81% (17/20) of patients required haemodialysis
1. Fakhouri F, et al. J Am Soc Nephrol 2010; 21: Carr R, et al. Ann Hematol 2013; 92: Zuber J et al. Nat Rev Nephrol. 2012;8:

16. A Clinical Diagnosis of aHUS Should be Considered in all Patients With Pregnancy-Associated TMA1-4
aHUS shared common clinical features with other pregnancy- associated complications2-4
aHUS complement mutations have been identified in 5-15% of preeclampsia cases and in a higher percentage of HELLP cases1
aHUS is commonly unmasked post-partum, while TMA due to severe ADAMTS13 deficiency occurs more often during pregnancy2
79% of the aHUS diagnoses presented in the post-partum period2
A normal first pregnancy does not exclude a diagnosis of aHUS2
57% (12/21) of patients first presented with aHUS unmasked during a second or subsequent pregnancy2
Reference: 1. Liszewski MK, Atkinson JP. Hematology Am Soc Hematol Educ Program. 2011;2011: Fakhouri, et al. Pregnancy-Associated haemolytic uraemic Syndrome Revisited in the Era of Complement Gene Mutations. J Am Soc Nephrol Machado S, et al. J Nephrol. 2012; 25(01): Sanchez-Luceros A, et al. Thromb Haemost. 2004;92(6):

17. Differential Diagnosis of TMAs in Pregnancy1
Parameter
Pre-eclampsia
HELLP
TTP
aHUS
Hypertension
+++ + ++
Proteinuria
+/-
Epigastralgia
Neurological symptoms
Thrombocytopenia
Haemolysis
Renal failure
AST/ALT
Disseminated intravascular coagulation
Peak incidence
3rd trimester
3rd trimester / post-partum
2nd / 3rd trimester
post-partum
+/- sometimes (0-20%); + moderately frequent (20-50%); ++ frequent (50-80%); +++ very frequent (80-100%)
1. Bergmann F. Dtsch Arztebl Int Nov 20;112(47):

18. Likelihood of TTP, HELLP and aHUS in Pregnancy by Trimester1-3
TTP aHUS HELLP
1st Trimester
2nd Trimester
3rd Trimester
Post-partum +/ /-
- Does not present
+ Less frequent
++ Frequent
+++ Typical timepoint
1. Martin et al. Am J Obstet Gynecol Fakhouri F, et al. J Am Soc Nephrol 2010; 21: George, Current Opinion in Hematology 2003, 10:339–344

19. Other Indicators May Also Support the Differential Diagnosis of P-aHUS1-5
History of previous TMA3,4
Family history of renal impairment5
History of previous pregnancy –related complications, particularly preeclampsia or HELLP1
No recovery of thrombocytopenia or haemolysis despite delivery of the infant2
1. Tsai H-M. J Hematol Thrombo Dis. 2014, 2:5. 2. Machado S, et al. J Nephrol. 2012; 25(01): Legendre CM, et al. N Engl J Med. 2013;368: Sellier-Leclerc A-L, et al; French Society of Pediatric Nephrology. J Am Soc Nephrol. 2007;18: Kaur A, et al. Am J Respir Crit Care Med. 2014;189:Abstract 6421.

20. Prompt Diagnosis and Treatment of aHUS in a Patient With Pregnancy Related TMA is Critical1
Any patient suspected of having P-aHUS should be referred to a nephrologist2
In aHUS, early initiation of treatment with Soliris® (eculizumab, rmc) results in rapid normalisation of haematological parameters and time dependent improvement in renal function3,4
Use in Pregnancy – Category B2: Soliris should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus. Women of childbearing potential should use adequate contraception during treatment with Soliris, and for up to 5 months after treatment.5
Use in Lactation: It is unknown whether eculizumab, rmc is excreted into human milk. Since many medicinal products and immunoglobulins are secreted into human milk, and because of the potential for serious adverse reactions in nursing infants, breastfeeding should be discontinued during treatment and up to 5 months after treatment5
1. Fakhouri F, et al. J Am Soc Nephrol. 2010;21: Salvadori M, Bertoni E. World J Nephrol. 2013;2(3): Legendre CM, et al. N Engl J Med. 2013;368: Licht C, et al. Kidney International 2015;87:1061– Approved Product Information for Soliris® (eculizumab, rmc)

21. Differential Diagnosis for TMAs: aHUS, TTP and STEC-HUS
Thrombocytopenia
Platelet count <150 x 109/L OR >25% Decrease from baseline
Microangiopathic Hemolysis
Schistocytes and/or Elevated LDH and/or Decreased haptoglobin and/or Decreased haemoglobin
AND
AND
Plus 1 or more of the following:
Neurological Symptoms
Confusion and/or Seizures and/or Other cerebral abnormalities
Renal Impairment
Elevated creatinine and/or Decreased eGFR and/or Elevated blood pressure2 and/or Abnormal urinalysis
Gastrointestinal Symptoms
Diarrhea +/– blood and/or Nausea/vomiting and/or Abdominal pain and/or Gastroenteritis
Evaluate ADAMTS13 activity and Shiga-toxin/EHEC* test
While waiting for ADAMTS13 results, a platelet count >30 x109/L or serum creatinine >150–200 µmol/L (>1.7–2.3 mg/dL) almost eliminates a diagnosis of severe ADAMTS13 deficiency (TTP)3,4
≤5% ADAMTS13 Activity
>5% ADAMTS13 Activity
Shiga-toxin/EHEC Positive
TTP
aHUS
STEC-HUS
This pathway is intended as educational information for healthcare providers. It does not replace a healthcare professional’s judgment or clinical diagnosis.
Footnotes: *Shiga-toxin/EHEC test is warranted with history/presence of GI symptoms.
References: 1. Laurence J. Clin Adv Hematol Oncol. 2012;10(suppl 17): Kavanagh D et al. Med Bull. 2006;77-78: Coppo P, et al. PLOS ONE 2010;5:e Zuber J et al. Nat Rev Nephrol. 2012;8:

22. Summary
In aHUS, 79% of patients die, require dialysis, or have permanent renal damage within three years1
33 to 40% of patients die or progress to end-stage renal disease with the first clinical manifestation1,2
Chronic, uncontrolled complement activity results in continuous endothelial and tissue injury1,2
Complement amplification is common, unpredictable and puts patients at constant risk of sudden death and multi-organ damage1,2
aHUS should be suspected in patients presenting with pregnancy related TMA3
Advancements in treatment options warrant early diagnosis and intervention4,5
Any patient suspected of having P-aHUS should be referred to a nephrologist6
References: 1. Noris M, Caprioli J, Bresin E, et al. Clin J Am Soc Nephrol. 2010;5: Caprioli J, Noris M, Brioschi S, et al; for the International Registry of Recurrent and Familial HUS/TTP. Blood. 2006;108: Fakhouri F, et al. J Am Soc Nephrol. 2010;21: Legendre CM, et al. N Engl J Med. 2013;368: Licht C, et al. Kidney International 2015;87:1061– Salvadori M, Bertoni E. World J Nephrol. 2013;2(3):56-76.

24. Minimum Product Information
WARNING: SERIOUS MENINGOCOCCAL INFECTION. SOLIRIS® increases the risk of meningococcal infections
Vaccinate patients with a meningococcal vaccine prior to, or at the time of initiating SOLIRIS; revaccinate according to current medical guidelines for vaccine use.
Patients who initiate SOLIRIS treatment less than 2 weeks after receiving a meningococcal vaccine must receive treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination. Monitor patients for early signs of meningococcal infections, evaluate immediately if infection is suspected, and treat with antibiotics if necessary.
Soliris (eculizumab, rmc) Minimum Product Information INDICATIONS: Treatment of paroxysmal nocturnal haemoglobinuria (PNH) to reduce haemolysis; treatment of atypical haemolytic uraemic syndrome (aHUS). CONTRAINDICATIONS: murine protein hypersensitivity; unresolved Neisseria meningitidis infection; unvaccinated against Neisseria meningitidis (including patients who have not received prophylactic treatment with appropriate antibiotics until 2 wks after vaccination). PRECAUTIONS: Meningococcal Infection/Immunisation: meningococcal infection susceptibility, vaccinate all patients prior to, or at the time of initiating SOLIRIS; if treated < 2 wks after meningococcal vaccination, admin prophylactic antibiotics for 2 wks after vaccination; maintain immunisation currency (esp < 18 yrs of age against Haemophilus influenza, pneumococcal); vaccination may further activate complement, consideration should be given to the timing of vaccination relative to administration of SOLIRIS (see full PI); admin with caution with active systemic infections; monitor for early signs of infection, including fever, headache +/- stiff neck, light sensitivity. Laboratory Monitoring: (PNH) monitor serum LDH for intravascular haemolysis; (aHUS) monitor serum LDH, serum creatinine and platelet count for TMA. Discontinuation: (PNH) closely monitor patients who discontinue treatment for at least 8 wks. (aHUS) discontinuation of treatment is not recommended unless medically justified; closely monitor patients who discontinue treatment for severe TMA complications immediately; monitoring may be insufficient to predict or prevent severe TMA complications. Other: classic aHUS; Na restricted diet. Use in Pregnancy-Category B2: women of childbearing potential should use adequate contraception during treatment with SOLIRIS, and for up to 5 months after treatment. Use in Lactation: discontinue breastfeeding during treatment, and up to 5 months after treatment. Paediatric Use: SOLIRIS has not been studied in PNH paediatric pts weighing < 40 kg. Educational Materials: All prescribing physicians must be familiar with the physician’s guide to prescribing, discuss the benefits and risks of treatment with patients and provide them with Patient Safety Card and Patient Information Brochure. ADVERSE EFFECTS: Headache, infections (including meningococcal, sepsis, Aspergillus), blood dyscrasia, hypersensitivity (including anaphylaxis), decreased appetite, dizziness, nausea, dysgeusia, vertigo, hypotension, dyspnoea, cough, nasal congestion, pharyngolaryngeal pain, rhinorrhoea, GI upset, alopecia, pruritis, rash, arthralgia, back/neck/muscle/extremity pain, muscle spasms, bone pain, chest discomfort, chills, fatigue, asthenia, oedema, pyrexia, influenza-like illness, Coombs test +ve and others, see full PI. DOSAGE: (Adult PNH) initial phase: 600 mg/wk for 4 wks, followed by maintenance phase: 900 mg in wk 5, then every 14 +/- 2 days thereafter; (Adult aHUS) initial phase: 900 mg/wk for 4 wks, followed by maintenance phase: 1200 mg in wk 5, then every 14 days +/- 2 days thereafter; (children < 18 yrs of age) initial phase: 600 mg/wk for 2 wks (20 to < 40 kg), 600 mg in wk 1 (10 to < 20 kg), 300 mg in wk 1 (5 to < 10 kg), then followed by maintenance phase: 900 mg in wk 3 and every 2 wks after (30 to < 40 kg), 600 mg in wk 3 and every 2 wks after (20 to < 30 kg), 300 mg in wk 2 and every 2 wks thereafter (10 to < 20 kg), 300 mg in wk 2 and every 3 wks after (5 to < 10 kg), children with body weight > 40 kg are treated with the adult dosing recommendations. Dose modification: administer recommended dosage regimen +/- 2 days; if dose missed, monitor for TMA complication and resume regular schedule ASAP; if multiple doses missed, consider re-induction; supplemental dosing required with concomitant PE/PI (see full PI). ADMINISTRATION: reconstitute to 5 mg/mL with 0.9%, 0.45% Sodium Chloride Injection, 5% Dextrose in Water for Injection, or Ringer’s Injection; admin as IV infusion over min (max 2 hrs in adults and adolescents, 4 hrs in children < 12 yrs of age). Monitor for at least 1 hr for signs of an infusion reaction. Date of most recent amendment: 22 June 2016.
Please refer to the full Product Information before prescribing, including Black Box Warning regarding meningococcal infection and vaccination. Please contact Alexion Pharmaceuticals Australasia Pty Ltd on to request the Full Product Information.
All rights reserved. Alexion Pharmaceutical Australasia Pty Limited. ACN Suite 401, Level 4, Building A, 20 Rodborough Rd, Frenchs Forest, NSW 2086 Australia. Date of preparation August 2016 AU/SOL-aHUS/16/0042