PracticeUpdate Oncology Best of 2018

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 THERAPEUTIC INDICATION(S): paroxysmal nocturnal haemoglobinuria (PNH) to reduce haemolysis; atypical haemolytic uraemic syndrome (aHUS). DOSE: (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 PNH or aHUS) 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 modifications: administer recommended dosage regimen +/- 2 days; if dose missed, monitor aHUS patients for TMA complications and resume regular schedule ASAP; if multiple doses missed, consider re- induction; supplemental dosing required with concomitant plasma interventions (see full PI). Administration: dilute to final concentration of 5 mg/mL with 0.9% or 0.45% Sodium Chloride, 5% Dextrose, or Ringer’s Solution; administer as IV infusion over 25-45 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. CONTRAINDICATIONS: hypersensitivity to eculizumab, excipients or murine proteins; unresolved Neisseria meningitidis infection; unvaccinated against Neisseria meningitidis (including patients who have not received prophylactic antibiotics until 2 wks after vaccination). SPECIAL WARNINGS AND PRECAUTIONS FOR USE: Meningococcal Infection/ Immunisation: meningococcal (N. meningitidis) infection susceptibility, vaccinate all patients prior to, or at the time of initiating Soliris; if treated < 2 wks after meningococcal vaccination, administer prophylactic antibiotics for 2 wks after vaccination; ensure revaccination according to current guidelines; vaccination may further activate complement, consider timing of vaccination relative to administration of Soliris (see full PI); vaccination may not be sufficient to prevent meningococcal infection, monitor for signs of infection, including fever, headache +/- stiff neck, light sensitivity; children < 18 yrs must also be vaccinated against H. influenza and pneumococcus and adhere to national vaccination guidelines. Other Systemic Infections: administer with caution in patients with active systemic infections; increased susceptibility to infections especially with Neisseria and encapsulated bacteria. Serious infections with Neisseria species (other than N. meningitidis) including disseminated gonococcal infections have been reported. Monitoring after treatment discontinuation: (PNH) closely monitor patients for intravascular haemolysis and other reactions 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; monitoring may be insufficient to predict or prevent severe TMA complications. Educational Materials: All prescribers must be familiar with the Physician’s Guide, discuss the benefits and risks of treatment, and provide patients with a Patient Safety Information Card and Patient/Parent Guide. Use in Pregnancy- Category B2: women of childbearing potential should use adequate contraception during, and for 5 months after Soliris treatment. Use in Lactation: discontinue breastfeeding during, and for up to 5 months after Soliris treatment. ADVERSE EFFECTS (UNDESIRABLE EFFECTS): Headache, serious infections (including meningococcal sepsis and Aspergillus infection), pneumownia, bronchitis, nasopharyngitis, oral herpes, URTI, UTI, viral infection, arthritis bacterial, thrombocytopenia, leukopenia, anaemia, haemolysis, immunogenicity, hypersensitivity (including anaphylaxis), decreased appetite, insomnia, dizziness, dysgeusia, tremor, vertigo, hypertension, hypotension, dyspnoea, cough, nasal congestion, pharyngolaryngeal pain, rhinorrhoea, abdominal pain, constipation, diarrhea, dyspepsia, nausea, vomiting, alopecia, pruritus, 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. Date Revised: 03 August 2018. REF: SOL/PI/09JUL2018 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 1800 788 189 to request the Full Product Information. Product Information is also available at https://www.ebs.tga.gov.au.

PBS Information: Soliris (eculizumab rmc ) is listed on the PBS as a Section 100 item for the treatment of aHUS. Refer to PBS Schedule for full authority information. Soliris is funded on the Life Saving Drug Program for the treatment of PNH. Application and consent forms for Soliris treatment are available from the LSDP website: http://www.health.gov.au/lsdp#Eculizumab