Drugs List

Therapeutic Indications

Uses

Atypical haemolytic uremic syndrome (aHUS): treatment
Myasthenia gravis
Neuromyelitis optica spectrum disorder
Treatment of paroxysmal nocturnal haemoglobinuria (PNH)

Paroxysmal nocturnal haemoglobinuria (PNH)

Haemolytic uremic syndrome (aHUS).

Refractory generalised myasthenia gravis (gMG) in patients who are anti-acetylcholine receptor (AChR) antibody-positive.

Neuromyelitis optica spectrum disorder (NMOSD) in patients who are anti-aquaporin-4 (AQP4) antibody-positive with a relapsing course of the disease.

Not licensed for all indications in all age groups

Administration

For intravenous infusion over 25 to 45 minutes in adults and 1 to 4 hours in children under 18 years of age via gravity feed, a syringe-type pump, or an infusion pump.

Patients should be monitored for 1 hour following infusion. If an adverse reaction occurs during the administration of eculizumab, the infusion may be slowed or stopped at the discretion of the physician. If the infusion is slowed, the total infusion time must not exceed two hours in adults and four hours in children under 18 years of age.

Home infusions performed by a qualified healthcare professional may be considered based on evaluation and recommendation from the treating physician for patients who have tolerated infusions well in the clinic.

Contraindications

Patients not currently vaccinated against Neisseria meningitidis
Uncontrolled Neisseria meningitidis infection
Breastfeeding

Precautions and Warnings

Uncontrolled systemic infection
Hepatic impairment
Pregnancy

Sodium content of formulation may be significant
Children require vaccination against H.influenzae and pneumococcal infec.
Patients must be vaccinated against Neisseria meningitidis
Prophylactic therapy for N.meningitidis may be required - see product data
Treatment to be initiated and supervised by a specialist
Monitor throughout infusion and for 1 hour post first infusion
Suspend treatment or reduce rate until infusion reactions resolve
aHUS: Monitor patients for signs of thrombotic microangiopathy
Monitor patient for signs of meningococcal infection
Monitor patient for signs of serious infection
Monitor patient for some months after discontinuing treatment
PNH: Monitor patients for signs of intravascular haemolysis
Advise patient to report symptoms of infection immediately
Interrupt treatment if severe infusion reaction occurs
Not licensed for all indications in all age groups
Female: Contraception required during & for at least 5 months after therapy
Breastfeeding: Do not breastfeed during & for 5 months after treatment
Advise patient about gonorrhoea prevention

If infusion reactions occur the infusion may be slowed or stopped at the discretion of the physician. If the infusion is slowed, the total infusion time must not exceed two hours in adults and four hours in children under 18 years of age.

Patients should be provided with a patient safety card and be informed of benefits/risks associated with eculizumab therapy.

All patients must be vaccinated against Neisseria meningitidis at least 2 weeks before starting eculizumab treatment and re-vaccinated according to current vaccination guidelines. aHUS patients treated with eculizumab less than 2 weeks after receiving a tetravalent meningococcal injection must receive prophylactic antibiotics until 2 weeks after vaccination. The use of conjugated tetravalent (serotypes A, C, Y and W135) vaccine is recommended.

Patients with paroxysmal nocturnal haemoglobinuria
Monitor for intravascular haemolysis by measuring serum lactate dehydrogenase (LDH) levels. Patients may require dose adjustments within the 12 to 16 day dosing schedule during the maintenance phase.

Following discontinuation of treatment with eculizumab, patients with PNH should be monitored for at least 8 weeks to detect serious intravascular haemolysis and other reactions. Serious haemolysis is identified by serum LDH levels greater than pre-treatment level, accompanied by any of the following: greater than 25% absolute decrease in PNH clone size in one week or less; a haemoglobin level of less than 5 g/dl or a decrease of greater than 4 g/dl in one week or less; angina; change in mental status; a 50% increase in serum creatinine level; or thrombosis.
If serious haemolysis occurs following discontinuation of treatment, then the following procedures/treatments should be considered: blood transfusion (packed RBCs), or exchange transfusion if the PNH RBCs are more than 50% of the total RBCs by flow cytometry; anticoagulation; corticosteroids; or reinstitution of eculizumab.

Patients with atypical haemolytic uremic syndrome (aHUS)
Monitor for thrombotic microangiopathy by measuring platelet counts, serum LDH and serum creatinine. Patients may require dose adjustments within the 12 to 16 day dosing schedule during the maintenance phase.

Discontinuing treatment in patients with aHUS should only be considered if medically justified, severe thrombotic microangiopathy complications were observed as early as 4 weeks after treatment and up to 127 weeks in clinical studies. If patients discontinue treatment they should be monitored closely for severe thrombotic microangiopathy (TMA) complications. Even close monitoring may be insufficient to predict/ prevent TMA.
Severe thrombotic microangiopathy complications post discontinuation can be identified by any one of the following: a change in mental status or seizures; angina or dyspnoea; or thrombosis or by any two, or repeated measurement of any one, of the following: a decrease in platelet count of 25% or more as compared to either baseline or to peak platelet count during eculizumab treatment; an increase in serum creatinine of 25% or more as compared to baseline or to nadir during eculizumab treatment; or, an increase in serum LDH of 25% or more as compared to baseline or to nadir during eculizumab treatment.
Consider restarting treatment with eculizumab and providing adequate supportive medical care if severe thrombotic microangiopathy complications occur after eculizumab discontinuation.

Pregnancy and Lactation

Pregnancy

Eculizumab should not be used in pregnancy unless compellingly indicated.

There are no data on pregnancy in exposed women and no animal reproduction studies are available with eculizumab. However, human immunoglobulins are known to cross the placenta and hence eculizumab may be expected to cause complement inhibition in the foetus.

Lactation

Eculizumab is contraindicated during breastfeeding.

At the time of writing it is not known whether eculizumab is excreted in human breast milk. Due to the potential risks to the nursing infant the manufacturer states breastfeeding should be discontinued during and for 5 months after treatment. However some sources suggest, due to its large molecular weight and high affinity to complement protein C5 it is unlikely that this antibody will be excreted in human breast milk after the colostral period.

Side Effects

Alopecia
Anaemia
Anaphylactic reaction
Anorexia
Anxiety
Arthralgia
Asthenia
Back pain
Blurred vision
Bone pain
Chest discomfort
Chest pain
Chills
Coagulation disorders
Conjunctival irritation
Cough
Decrease in haematocrit
Decreased appetite
Depression
Dermatitis
Dizziness
Dream abnormalities
Dry skin
Dysgeusia
Dysuria
Epistaxis
Erectile disturbance
Erythema
Extremity pain
Fatigue
Gamma glutamyl transferase (GGT) increased
Gastrointestinal disorder
Graves' disease
Haematoma
Haematuria
Haemoglobin decrease
Haemolysis
Headache
Hot flushes
Hyperhidrosis
Hypersensitivity reactions
Hypertension
Hypotension
Increase in serum ALT/AST
Infections
Influenza-like symptoms
Injection site reactions
Insomnia
Jaundice
Joint swelling
Leucopenia
Lymphopaenia
Malignant melanoma
Menstrual disturbances
Mood changes
Muscle spasm
Myalgia
Myelodysplastic syndrome
Nasal congestion
Neck pain
Oedema
Palpitations
Paraesthesia
Petechiae
Pharyngolaryngeal pain
Positive Coombs test
Pruritus
Pyrexia
Rash
Renal impairment
Rhinorrhoea
Sepsis
Skin depigmentation
Sleep disturbances
Syncope
Throat irritation
Thrombocytopenia
Tinnitus
Tremor
Trismus
Urticaria
Vein disorder
Vertigo

Presentation

Solution for infusion of eculizumab.

This product has been produced by recombinant DNA technology using murine NSO cell lines.

Drugs List

Therapeutic Indications

Uses

Atypical haemolytic uremic syndrome (aHUS): treatment
Myasthenia gravis
Neuromyelitis optica spectrum disorder
Treatment of paroxysmal nocturnal haemoglobinuria (PNH)

Paroxysmal nocturnal haemoglobinuria (PNH)

Haemolytic uremic syndrome (aHUS).

Refractory generalised myasthenia gravis (gMG) in patients who are anti-acetylcholine receptor (AChR) antibody-positive.

Neuromyelitis optica spectrum disorder (NMOSD) in patients who are anti-aquaporin-4 (AQP4) antibody-positive with a relapsing course of the disease.

Not licensed for all indications in all age groups

Dosage

Adults

Children

Additional Dosage Information

Administration

For intravenous infusion over 25 to 45 minutes in adults and 1 to 4 hours in children under 18 years of age via gravity feed, a syringe-type pump, or an infusion pump.

Patients should be monitored for 1 hour following infusion. If an adverse reaction occurs during the administration of eculizumab, the infusion may be slowed or stopped at the discretion of the physician. If the infusion is slowed, the total infusion time must not exceed two hours in adults and four hours in children under 18 years of age.

Home infusions performed by a qualified healthcare professional may be considered based on evaluation and recommendation from the treating physician for patients who have tolerated infusions well in the clinic.

Contraindications

Patients not currently vaccinated against Neisseria meningitidis
Uncontrolled Neisseria meningitidis infection
Breastfeeding

Precautions and Warnings

Uncontrolled systemic infection
Hepatic impairment
Pregnancy

Sodium content of formulation may be significant
Children require vaccination against H.influenzae and pneumococcal infec.
Patients must be vaccinated against Neisseria meningitidis
Prophylactic therapy for N.meningitidis may be required - see product data
Treatment to be initiated and supervised by a specialist
Monitor throughout infusion and for 1 hour post first infusion
Suspend treatment or reduce rate until infusion reactions resolve
aHUS: Monitor patients for signs of thrombotic microangiopathy
Monitor patient for signs of meningococcal infection
Monitor patient for signs of serious infection
Monitor patient for some months after discontinuing treatment
PNH: Monitor patients for signs of intravascular haemolysis
Advise patient to report symptoms of infection immediately
Interrupt treatment if severe infusion reaction occurs
Not licensed for all indications in all age groups
Female: Contraception required during & for at least 5 months after therapy
Breastfeeding: Do not breastfeed during & for 5 months after treatment
Advise patient about gonorrhoea prevention

If infusion reactions occur the infusion may be slowed or stopped at the discretion of the physician. If the infusion is slowed, the total infusion time must not exceed two hours in adults and four hours in children under 18 years of age.

Patients should be provided with a patient safety card and be informed of benefits/risks associated with eculizumab therapy.

All patients must be vaccinated against Neisseria meningitidis at least 2 weeks before starting eculizumab treatment and re-vaccinated according to current vaccination guidelines. aHUS patients treated with eculizumab less than 2 weeks after receiving a tetravalent meningococcal injection must receive prophylactic antibiotics until 2 weeks after vaccination. The use of conjugated tetravalent (serotypes A, C, Y and W135) vaccine is recommended.

Patients with paroxysmal nocturnal haemoglobinuria
Monitor for intravascular haemolysis by measuring serum lactate dehydrogenase (LDH) levels. Patients may require dose adjustments within the 12 to 16 day dosing schedule during the maintenance phase.

Following discontinuation of treatment with eculizumab, patients with PNH should be monitored for at least 8 weeks to detect serious intravascular haemolysis and other reactions. Serious haemolysis is identified by serum LDH levels greater than pre-treatment level, accompanied by any of the following: greater than 25% absolute decrease in PNH clone size in one week or less; a haemoglobin level of less than 5 g/dl or a decrease of greater than 4 g/dl in one week or less; angina; change in mental status; a 50% increase in serum creatinine level; or thrombosis.
If serious haemolysis occurs following discontinuation of treatment, then the following procedures/treatments should be considered: blood transfusion (packed RBCs), or exchange transfusion if the PNH RBCs are more than 50% of the total RBCs by flow cytometry; anticoagulation; corticosteroids; or reinstitution of eculizumab.

Patients with atypical haemolytic uremic syndrome (aHUS)
Monitor for thrombotic microangiopathy by measuring platelet counts, serum LDH and serum creatinine. Patients may require dose adjustments within the 12 to 16 day dosing schedule during the maintenance phase.

Discontinuing treatment in patients with aHUS should only be considered if medically justified, severe thrombotic microangiopathy complications were observed as early as 4 weeks after treatment and up to 127 weeks in clinical studies. If patients discontinue treatment they should be monitored closely for severe thrombotic microangiopathy (TMA) complications. Even close monitoring may be insufficient to predict/ prevent TMA.
Severe thrombotic microangiopathy complications post discontinuation can be identified by any one of the following: a change in mental status or seizures; angina or dyspnoea; or thrombosis or by any two, or repeated measurement of any one, of the following: a decrease in platelet count of 25% or more as compared to either baseline or to peak platelet count during eculizumab treatment; an increase in serum creatinine of 25% or more as compared to baseline or to nadir during eculizumab treatment; or, an increase in serum LDH of 25% or more as compared to baseline or to nadir during eculizumab treatment.
Consider restarting treatment with eculizumab and providing adequate supportive medical care if severe thrombotic microangiopathy complications occur after eculizumab discontinuation.

Pregnancy and Lactation

Pregnancy

Eculizumab should not be used in pregnancy unless compellingly indicated.

There are no data on pregnancy in exposed women and no animal reproduction studies are available with eculizumab. However, human immunoglobulins are known to cross the placenta and hence eculizumab may be expected to cause complement inhibition in the foetus.

Lactation

Eculizumab is contraindicated during breastfeeding.

At the time of writing it is not known whether eculizumab is excreted in human breast milk. Due to the potential risks to the nursing infant the manufacturer states breastfeeding should be discontinued during and for 5 months after treatment. However some sources suggest, due to its large molecular weight and high affinity to complement protein C5 it is unlikely that this antibody will be excreted in human breast milk after the colostral period.

Counselling

Patients should be provided with a patient safety card and be informed of benefits/risks associated with eculizumab therapy.

Advise patient to report symptoms of infections immediately.

Advise patients about gonorrhoea prevention. Treatment may increase susceptibility to infections, particularly with Neisseria and encapsulated bacteria.

Females should use adequate contraception during treatment and for up to 5 months afterwards.

Side Effects

Alopecia
Anaemia
Anaphylactic reaction
Anorexia
Anxiety
Arthralgia
Asthenia
Back pain
Blurred vision
Bone pain
Chest discomfort
Chest pain
Chills
Coagulation disorders
Conjunctival irritation
Cough
Decrease in haematocrit
Decreased appetite
Depression
Dermatitis
Dizziness
Dream abnormalities
Dry skin
Dysgeusia
Dysuria
Epistaxis
Erectile disturbance
Erythema
Extremity pain
Fatigue
Gamma glutamyl transferase (GGT) increased
Gastrointestinal disorder
Graves' disease
Haematoma
Haematuria
Haemoglobin decrease
Haemolysis
Headache
Hot flushes
Hyperhidrosis
Hypersensitivity reactions
Hypertension
Hypotension
Increase in serum ALT/AST
Infections
Influenza-like symptoms
Injection site reactions
Insomnia
Jaundice
Joint swelling
Leucopenia
Lymphopaenia
Malignant melanoma
Menstrual disturbances
Mood changes
Muscle spasm
Myalgia
Myelodysplastic syndrome
Nasal congestion
Neck pain
Oedema
Palpitations
Paraesthesia
Petechiae
Pharyngolaryngeal pain
Positive Coombs test
Pruritus
Pyrexia
Rash
Renal impairment
Rhinorrhoea
Sepsis
Skin depigmentation
Sleep disturbances
Syncope
Throat irritation
Thrombocytopenia
Tinnitus
Tremor
Trismus
Urticaria
Vein disorder
Vertigo

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: April 2015

Reference Sources

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Soliris 300mg concentrate for solution for infusion. Alexion Pharma UK Ltd. Revised October 2022.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 06 December 2022.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Eculizumab. Last revised: 3 October 2015.
Last accessed: 23 April 2015.