Drugs List

Therapeutic Indications

Uses

Atypical haemolytic uremic syndrome (aHUS): treatment
Treatment of paroxysmal nocturnal haemoglobinuria (PNH)

Treatment of adults and paediatrics with body weight 10kg or above with paroxysmal nocturnal haemoglobinuria (PNH) in patients:
With haemolysis with clinical symptom(s) indicative of high disease activity.
Who are clinically stable after been treated with eculizumab for at least the past 6 months.

Treatment of patients with body weight 10kg or above with atypical haemolytic uraemic syndrome (aHUS) untreated with complement inhibitor or who have received eculizumab for at least 3 months and have evidence of response to eculizumab.

Contraindications

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

Precautions and Warnings

Restricted sodium intake
Systemic infection
Pregnancy

Sodium content of formulation may be significant
Before starting therapy ensure immunisations are up to date
Children require vaccination against H.influenzae and pneumococcal infec.
Patients must be vaccinated against Neisseria meningitidis
Contains polysorbate
Record name and batch number of administered product
Treatment to be administered under the supervision of a specialist
Monitor patient for signs of meningococcal infection
Monitor patient for some months after discontinuing treatment
Advise patient on signs/symptoms of meningococcal infection/sepsis
Advise patient to report symptoms of infection immediately
Interrupt treatment if severe infusion reaction occurs
Female: contraception required during and for 8 months after treatment
Breastfeeding: Do not breastfeed during & for 8 months after treatment
Advise patient about gonorrhoea prevention
Give patient package leaflet and patient reminder card

Serious meningococcal infection
Patients who start ravulizumab treatment less than 2 weeks after receiving a meningococcal vaccine, must receive appropriate prophylactic antibiotics until 2 weeks after vaccination. Patients must be vaccinated or revaccinated according to current national guidelines for vaccination use. Patients switching from eculizumab, the prescriber should verify that the patients meningococcal vaccination is current according to national guidelines for vaccination use.

Immunisation
Vaccination may activate complement. Patients with complement-mediated diseases, including PNH and aHUS, may experience increased signs and symptoms of their underlying disease (e.g. haemolysis). Patients should be closely monitored for disease symptoms after vaccinations.

Thrombotic microangiopathy (TMA)
Treatment to resolve TMA in aHUS should be for a minimum of 6 months. After this time, the treatment length should be considered for each patient individually. Patients at higher risk of TMA recurrence may require long term therapy.

Treatment discontinuation for PNH
Patients should be monitored for at least 16 weeks after discontinuing ravulizumab for PNH, to detect haemolysis and other reactions. If signs and symptoms of haemolysis occur after discontinuation, including raised lactate dehydrogenase (LDH), consider restarting treatment with ravulizumab.

Treatment discontinuation for aHUS
Monitor patients closely for signs and symptoms of thrombotic microangiopathy on an on-going basis after discontinuing treatment with ravulizumab for aHUS. If complications occur after discontinuation for aHUS, consider restarting treatment with ravulizumab, beginning with the loading dose and maintenance dose.

Concomitant plasmapheresis, plasma exchange or fresh frozen plasma infusion
Although there is no experience of concomitant plasmapheresis, plasma exchange or fresh frozen plasma infusion use with ravulizumab, administration may reduce the serum levels of ravulizumab.

Pregnancy and Lactation

Pregnancy

Use ravulizumab with caution during pregnancy.

The manufacturer states the use of ravulizumab in pregnancy may be considered following an assessment of the risks and benefits. There is no data from the use of ravulizumab in pregnancy. Animal studies on reproductive toxicity were insufficient. Human IgG is known to cross the human placental barrier, therefore, ravulizumab may potentially cause terminal complement inhibition in foetal circulation.

Lactation

Ravulizumab is contraindicated during breastfeeding.

The manufacturer does not indicate for the use of ravulizumab during breastfeeding. There is no data available on the excretion of ravulizumab in human milk. It is known that human IgGs are excreted in breast, therefore, a risk to the breast-fed infant cannot be excluded. Breastfeeding should be discontinued during treatment and up to 8 months after treatment.

Side Effects

Abdominal pain
Anaphylactic reaction
Antibody formation (transient)
Arthralgia
Asthenia
Back pain
Chills
Diarrhoea
Dizziness
Dyspepsia
Fatigue
Headache
Hypersensitivity reactions
Influenza-like symptoms
Infusion related reaction
Meningococcal infection
Meningococcal sepsis
Muscle spasm
Myalgia
Nasopharyngitis
Nausea
Pruritus
Pyrexia
Rash
Upper respiratory tract infection
Vomiting

Presentation

Infusion of ravulizumab.

Ravulizumab is a humanised monoclonal antibody produced using recombinant DNA technology in Chinese hamster ovary cells.

Drugs List

Therapeutic Indications

Uses

Atypical haemolytic uremic syndrome (aHUS): treatment
Treatment of paroxysmal nocturnal haemoglobinuria (PNH)

Treatment of adults and paediatrics with body weight 10kg or above with paroxysmal nocturnal haemoglobinuria (PNH) in patients:
With haemolysis with clinical symptom(s) indicative of high disease activity.
Who are clinically stable after been treated with eculizumab for at least the past 6 months.

Treatment of patients with body weight 10kg or above with atypical haemolytic uraemic syndrome (aHUS) untreated with complement inhibitor or who have received eculizumab for at least 3 months and have evidence of response to eculizumab.

Dosage

Adults

Children

Additional Dosage Information

Contraindications

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

Precautions and Warnings

Restricted sodium intake
Systemic infection
Pregnancy

Sodium content of formulation may be significant
Before starting therapy ensure immunisations are up to date
Children require vaccination against H.influenzae and pneumococcal infec.
Patients must be vaccinated against Neisseria meningitidis
Contains polysorbate
Record name and batch number of administered product
Treatment to be administered under the supervision of a specialist
Monitor patient for signs of meningococcal infection
Monitor patient for some months after discontinuing treatment
Advise patient on signs/symptoms of meningococcal infection/sepsis
Advise patient to report symptoms of infection immediately
Interrupt treatment if severe infusion reaction occurs
Female: contraception required during and for 8 months after treatment
Breastfeeding: Do not breastfeed during & for 8 months after treatment
Advise patient about gonorrhoea prevention
Give patient package leaflet and patient reminder card

Serious meningococcal infection
Patients who start ravulizumab treatment less than 2 weeks after receiving a meningococcal vaccine, must receive appropriate prophylactic antibiotics until 2 weeks after vaccination. Patients must be vaccinated or revaccinated according to current national guidelines for vaccination use. Patients switching from eculizumab, the prescriber should verify that the patients meningococcal vaccination is current according to national guidelines for vaccination use.

Immunisation
Vaccination may activate complement. Patients with complement-mediated diseases, including PNH and aHUS, may experience increased signs and symptoms of their underlying disease (e.g. haemolysis). Patients should be closely monitored for disease symptoms after vaccinations.

Thrombotic microangiopathy (TMA)
Treatment to resolve TMA in aHUS should be for a minimum of 6 months. After this time, the treatment length should be considered for each patient individually. Patients at higher risk of TMA recurrence may require long term therapy.

Treatment discontinuation for PNH
Patients should be monitored for at least 16 weeks after discontinuing ravulizumab for PNH, to detect haemolysis and other reactions. If signs and symptoms of haemolysis occur after discontinuation, including raised lactate dehydrogenase (LDH), consider restarting treatment with ravulizumab.

Treatment discontinuation for aHUS
Monitor patients closely for signs and symptoms of thrombotic microangiopathy on an on-going basis after discontinuing treatment with ravulizumab for aHUS. If complications occur after discontinuation for aHUS, consider restarting treatment with ravulizumab, beginning with the loading dose and maintenance dose.

Concomitant plasmapheresis, plasma exchange or fresh frozen plasma infusion
Although there is no experience of concomitant plasmapheresis, plasma exchange or fresh frozen plasma infusion use with ravulizumab, administration may reduce the serum levels of ravulizumab.

Pregnancy and Lactation

Pregnancy

Use ravulizumab with caution during pregnancy.

The manufacturer states the use of ravulizumab in pregnancy may be considered following an assessment of the risks and benefits. There is no data from the use of ravulizumab in pregnancy. Animal studies on reproductive toxicity were insufficient. Human IgG is known to cross the human placental barrier, therefore, ravulizumab may potentially cause terminal complement inhibition in foetal circulation.

Lactation

Ravulizumab is contraindicated during breastfeeding.

The manufacturer does not indicate for the use of ravulizumab during breastfeeding. There is no data available on the excretion of ravulizumab in human milk. It is known that human IgGs are excreted in breast, therefore, a risk to the breast-fed infant cannot be excluded. Breastfeeding should be discontinued during treatment and up to 8 months after treatment.

Side Effects

Abdominal pain
Anaphylactic reaction
Antibody formation (transient)
Arthralgia
Asthenia
Back pain
Chills
Diarrhoea
Dizziness
Dyspepsia
Fatigue
Headache
Hypersensitivity reactions
Influenza-like symptoms
Infusion related reaction
Meningococcal infection
Meningococcal sepsis
Muscle spasm
Myalgia
Nasopharyngitis
Nausea
Pruritus
Pyrexia
Rash
Upper respiratory tract infection
Vomiting

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: July 2021

Reference Sources

Summary of Product Characteristics: Ultomiris 300mg/3ml concentrate for solution for infusion. Alexion Pharma UK Ltd. Revised November 2021.

Summary of Product Characteristics: Ultomiris 300mg/30ml concentrate for solution for infusion. Alexion Pharma UK Ltd. Revised November 2021.

Summary of Product Characteristics: Ultomiris 1100mg/11ml concentrate for solution for infusion. Alexion Pharma UK Ltd. Revised November 2021.