Active Ingredient and Strength	ECULIZUMAB - 300 MG/VIAL
Dosage Form	INFUSION, SOLUTION CONCENTRATE
Manufacturer and Country	ALEXION PHARMA INTERNATIONAL OPERATIONS LIMITED (AAMF) - IRELAND PATHEON ITALIA S.P.A - ITALY
Registration Number	SIN14226P
Licence Holder	ASTRAZENECA SINGAPORE PTE LTD
Forensic Classification	PRESCRIPTION ONLY MEDICINES
Anatomical Therapeutic Chemical (ATC) code	L04AJ01

4.1 Therapeutic indications

SOLIRIS is indicated in adults and children for the treatment of patients with:

Paroxysmal nocturnal haemoglobinuria (PNH).
Evidence of clinical benefit is demonstrated in patients with haemolysis with clinical symptom(s) indicative of high disease activity, regardless of transfusion history (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).
Atypical Haemolytic Uremic Syndrome (aHUS) (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

SOLIRIS is indicated in adults for the treatment of patients with:

Refractory generalized myasthenia gravis (gMG) in patients who are anti-acetylcholine receptor (AChR) antibody-positive (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).
Neuromyelitis optica spectrum disorder (NMOSD) in patients who are anti-aquaporin-4 (AQP4) antibody-positive (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

4.2 Posology and method of administration

SOLIRIS must be administered by a healthcare professional and under the supervision of a physician experienced in the management of patients with haematological and/or renal disorders.

Posology

Adult patients

In Paroxysmal Nocturnal Haemoglobinuria (PNH):

The PNH dosage regimen for adult patients (≥18 years of age) consists of a 4-week initial phase followed by a maintenance phase:

Initial phase: 600 mg of SOLIRIS administered via a 25 to 45-minute intravenous (IV) infusion every week for the first 4 weeks.
Maintenance phase: 900 mg of SOLIRIS administered via a 25 to 45-minute IV infusion for the fifth week, followed by 900 mg of SOLIRIS administered via a 25 to 45-minute IV infusion every 14 ± 2 days (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

In Atypical Haemolytic Uremic Syndrome (aHUS), Refractory Generalized Myasthenia Gravis (gMG) and Neuromyelitis Optica Spectrum Disorder (NMOSD):

The aHUS, refractory gMG, and NMOSD dosage regimen for adult patients (≥ 18 years of age) consists of a 4-week initial phase followed by a maintenance phase:

Initial phase: 900 mg of SOLIRIS administered via a 25 to 45-minute IV infusion every week for the first 4 weeks.
Maintenance phase: 1200 mg of SOLIRIS administered via a 25 to 45-minute IV infusion for the fifth week, followed by 1200 mg of SOLIRIS administered via a 25 to 45-minute IV infusion every 14 ± 2 days (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Refractory gMG

Available data suggest that clinical response is usually achieved by 12 weeks of Soliris treatment. Discontinuation of the therapy should be considered in a patient who shows no evidence of therapeutic benefit by 12 weeks.

Paediatric patients in PNH and aHUS:

Paediatric patients with PNH and aHUS with body weight ≥ 40kg are treated with the adult dosage recommendations, respectively.

For paediatric patients with PNH and aHUS with body weight below 40 kg, the SOLIRIS dosage regimen is presented in Table 1.

SOLIRIS has not been studied in patients with PNH who weigh less than 40 kg. The posology of SOLIRIS for patients with PNH less than 40 kg weight is based on the posology used for patients with aHUS and who weigh less than 40 kg.

For adults and paediatric patients with aHUS, and adult patients with refractory gMG or NMOSD, supplemental dose of SOLIRIS is required in the setting of concomitant plasmapheresis (PP), plasma exchange (PE), or fresh frozen plasma infusion (PI) as described in Table 2.

Treatment Monitoring

Patients with aHUS should be monitored for signs and symptoms of thrombotic microangiopathy (TMA) (refer to section 4.4 aHUS Laboratory Monitoring – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

SOLIRIS treatment is recommended to continue for the patient’s lifetime, unless the discontinuation of SOLIRIS is clinically indicated (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Method of administration

Do not administer as an IV push or bolus injection. SOLIRIS should only be administered via IV infusion as described below.

For instructions on dilution of the medicinal product before administration, see section 6.6 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

The diluted solution of SOLIRIS should be administered by IV infusion over 25 to 45 minutes in adults and 1 to 4 hours in paediatric patients via gravity feed, a syringe-type pump, or an infusion pump. It is not necessary to protect the diluted solution of SOLIRIS from light during administration to the patient.

Patients should be monitored for 1 hour following infusion. If an adverse event occurs during the administration of SOLIRIS, the infusion may be slowed or stopped at the discretion of the treating physician. If the infusion is slowed, the total infusion time may not exceed 2 hours in adults and adolescents (aged 12 years to under 18 years) and 4 hours in children aged less than 12 years.

Home infusion

Home infusion may be considered for patients who have tolerated infusions well in the clinic. The decision of a patient to receive home infusions should be made after evaluation and recommendation from the treating physician. Home infusions should be performed by a qualified healthcare professional.

There is limited safety data supporting home-based infusions, additional precautions in the home setting such as availability of emergency treatment of infusion reactions or anaphylaxis are recommended. Infusion reactions are described in Sections 4.4 and 4.8 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

Special populations

Paediatric use

SOLIRIS has not been studied in paediatric patients with PNH weighing less than 40 kg. The dosage to be used in paediatric patients with PNH weighing less than 40 kg weight is identical to the weight-based dosage recommendations provided for paediatric patients with aHUS. Based on pharmacokinetic (PK)/ pharmacodynamic (PD) data available in patients with aHUS and PNH treated with SOLIRIS, this weight-based dosage regimen for paediatric patients is expected to result in an efficacy and safety profile similar to that in adults.

SOLIRIS has not been studied in paediatric patients with NMOSD.

Geriatric use

SOLIRIS may be administered to patients aged 65 years and over. There is no evidence to suggest that any special precautions are needed when older people are treated, although experience with SOLIRIS in this patient population is still limited.

Renal impairment

No dose adjustment is required for patients with renal impairment (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Hepatic impairment

The safety and efficacy of SOLIRIS have not been studied in patients with hepatic impairment.

4.3 Contraindications

Hypersensitivity to eculizumab, murine proteins or to any of the excipients listed in section 6.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

SOLIRIS therapy must not be initiated in patients (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information):

with unresolved Neisseria meningitidis infection.
who are not currently vaccinated against Neisseria meningitidis unless they receive prophylactic treatment with appropriate antibiotics until 2 weeks after vaccination.