Eculizumab


Thông tin thuốc gốc
Chỉ định và Liều dùng
Intravenous
Paroxysmal nocturnal haemoglobinuria
Adult: Initially, 600 mg once wkly for 4 wk, then increased to 900 mg once wkly for 1 wk and every 12-16 days thereafter, given via infusion over 25-45 min.
Child: 5-<10 kg: Initially, 300 mg once wkly for 2 wk, then every 3 wk thereafter; 10-<20 kg: Initially, 600 mg once wkly for 1 wk, then 300 mg once wkly for 1 wk, then every 2 wk thereafter; 20-<30 kg: Initially, 600 mg once wkly for 3 wk, then every 2 wk thereafter; 30-<40 kg: Initially, 600 mg once wkly for 2 wk, then increased to 900 mg once wkly for 1 wk, then every 2 wk thereafter; ≥40 kg: Same as adult dose. Doses are given via infusion over 1-4 hr.

Intravenous
Haemolytic uraemic syndrome, atypical
Adult: Initially, 900 mg once wkly for 4 wk, then increased to 1,200 mg once wkly for 1 wk and every 12-16 days thereafter, given via infusion over 25-45 min. Combination therapy w/ plasmapheresis/plasma exchange (PE/PI) or w/ fresh frozen plasma infusion: Give supplemental doses per session based on the most recent dose (PE/PI: 300 mg if recent dose was 300 mg or 600 mg if recent dose was ≥600 mg; fresh frozen plasma: 300 mg if recent dose was ≥300 mg), w/in 1 hr after PE/PI or 1 hr before fresh frozen plasma infusion.
Child: 5-<10 kg: Initially, 300 mg once wkly for 2 wk, then every 3 wk thereafter; 10-<20 kg: Initially, 600 mg once wkly for 1 wk, then 300 mg once wkly for 1 wk, then every 2 wk thereafter; 20-<30 kg: Initially, 600 mg once wkly for 3 wk, then every 2 wk thereafter; 30-<40 kg: Initially, 600 mg once wkly for 2 wk, then increased to 900 mg once wkly for 1 wk, then every 2 wk thereafter; ≥40 kg: Same as adult dose. Doses are given via infusion over 1-4 hr. Combination therapy w/ plasmapheresis/plasma exchange (PE/PI) or w/ fresh frozen plasma infusion: Give supplemental doses per each session based on the most recent dose (PE/PI: 300 mg if recent dose was 300 mg or 600 mg if recent dose was ≥600 mg; fresh frozen plasma: 300 mg if recent dose was ≥300 mg), w/in 1 hr after PE/PI or 1 hr before fresh frozen plasma infusion.
Hướng dẫn pha thuốc
Dilute w/ appropriate volume of NaCl 0.9% or dextrose 5% in water or Ringer’s soln to prepare a soln containing 5 mg/mL.
Chống chỉ định
Hypersensitivity. Unvaccinated against or unresolved N. meningitidis infection.
Thận trọng
Patient w/ active systemic infections. Not indicated for haemolytic uraemic syndrome associated w/ Shiga toxin producing E. coli. Ensure vaccination against N. meningitidis infections at least 2 wk prior to initiation of therapy. Childn. Pregnancy and lactation.
Tác dụng không mong muốn
Significant: Susceptibility to infections (e.g. pneumonia), infusion reactions/immunogenicity (e.g. hypersensitivity reactions, anaphylaxis).
Nervous: Headache, dizziness, dysgeusia, tremor, insomnia, fatigue, influenza-like illness, asthenia.
CV: HTN, peripheral oedema, tachycardia, hypotension.
GI: Diarrhoea, vomiting, nausea, abdominal pain, gastroenteritis, dyspepsia, constipation.
Resp: Cough, oropharyngeal pain, pneumonia, nasopharyngitis, upper resp tract infection, nasal congestion, bronchitis, sinusitis.
Genitourinary: UTI, uropathy, proteinuria, renal insufficiency.
Haematologic: Leucopenia, anaemia.
Musculoskeletal: Arthralgia, myalgia, pain in extremity, back pain, muscle spasm, limb pain.
Ophthalmologic: Eye disorder.
Dermatologic: Rash, pruritus, alopecia.
Immunologic: Herpes simplex infection, neoplasms.
Others: Pyrexia, chills, hypokalaemia.
Potentially Fatal: Meningococcal infection.
Chỉ số theo dõi
Monitor CBC w/ differential, serum lactate dehydrogenase (LDH), serum creatinine, AST, urinalysis. Monitor for signs and symptoms of infections (e.g. meningococcal, influenza), and infusion reactions during and 1 hr after infusion. Monitor for haemolysis in paroxysmal nocturnal haemoglobinuria (PNH) cases for at least 8 wk and for thrombotic microangiopathy in atypical haemolytic uraemic syndrome (aHUS) cases for at least 12 wk after discontinuation of therapy.
Tương tác
Concurrent admin of live vaccines may increase the risk of secondary transmission of infection.
Tác dụng
Description:
Mechanism of Action: Eculizumab is a recombinant monoclonal antibody which binds w/ high affinity to complement protein C5, preventing cleavage into C5a and C5b which subsequently inhibits the formation of terminal complex C5b-9, thereby inhibiting terminal complement-mediated intravascular haemolysis and thrombotic microangiopathy.
Onset: Reduction of haemolysis: ≤1 wk.
Pharmacokinetics:
Distribution: Crosses the placenta. Volume of distribution: 7.7 L (PNH); 6.14 L (aHUS).
Metabolism: Mainly catabolised by lysosomal enzymes into small peptides and amino acids.
Excretion: Elimination half-life: Approx 11-12 days.
Bảo quản
Store between 2-8°C. Do not shake or freeze. Protect from light.
Phân loại MIMS
Thuốc ức chế miễn dịch
Phân loại ATC
L04AJ01 - eculizumab ; Belongs to the class of complement inhibitors. Used as immunosuppressants.
Tài liệu tham khảo
Anon. Eculizumab. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 07/09/2017.

Buckingham R (ed). Eculizumab. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/09/2017.

Joint Formulary Committee. Eculizumab. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/09/2017.

McEvoy GK, Snow EK, Miller J et al (eds). Eculizumab. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 04/09/2017.

Soliris (Alexion Pharmaceuticals Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 04/09/2017.

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