Drugs List

Therapeutic Indications

Uses

Neuroblastoma

High-risk neuroblastoma in patients aged 12 months and above, who have previously received induction chemotherapy and achieved at least a partial response, followed by myeloablative therapy and stem cell transplantation, as well as patients with a history of relapsed or refractory neuroblastoma, with or without residual disease. Prior to the treatment of relapsed neuroblastoma, any actively progressing disease should be stabilised by other measures.

Administration

For administration by intravenous infusion, peripherally or centrally. Dinutuximab beta may also be combined with interleukin-2 (IL-2) which is administered as a subcutaneous injection.

For the typical 10-day dosing schedule, administer the continuous infusion at a rate of 2ml per hour, totalling 48ml per day.

For the alternative 5-day dosing schedule, administer the infusion at a rate of approximately 13ml per hour for 8 hours.

Contraindications

Absolute neutrophil count below 0.5 x 10 to the power of 9 / L
Children under 1 year
Haemoglobin concentration below 8g / dL
Platelet count below 20 x 10 to the power of 9 / L
Systemic infection
Abnormal liver function test
Acute grade 3 or 4, or extensive chronic graft-versus-host disease
Breastfeeding
Pregnancy
Renal impairment - creatinine clearance below 60ml/minute

Precautions and Warnings

Females of childbearing potential

Avoid vaccines during and for 10 weeks after treatment
Advise patient not to drive or operate machinery until assessed
Avoid corticosteroids 2 weeks prior to, during and 1 week after treatment
Premedication with analgesic recommended
Premedication with antihistamine recommended
Treat and control infections prior to commencing therapy
Consult local policy on the safe use of anti-cancer drugs
Must be diluted before use
Reduce infusion rate by 50% if grade 1 or 2 infusion reaction
Resuscitation facilities must be immediately available
Staff: Not to be handled by pregnant staff
Treatment to be administered under the supervision of a specialist
Monitor cardio-respiratory function
Monitor for hypersensitivity reactions-particularly 1st and 2nd infusions
Monitor for symptoms of Capillary Leak Syndrome
Monitor hepatic function regularly
Monitor patient for infusion-associated reactions (IARs)
Monitor pulse oximetry
Monitor serum electrolytes
Advise patient to report any blurred vision or any other eye symptoms
Risk of peripheral neuropathy
Discontinue if grade 3 or greater adverse reaction that recurs/persists
Discontinue if grade 3 or higher neuropathy occurs
Discontinue if grade 3 vision toxicity occurs
Discontinue if grade 4 hyponatremia occurs despite fluid management
Discontinue if recurrent or grade 4 capillary leak syndrome
Discontinue if serious allergic or anaphylactic reaction occurs
Interrupt treatment and/or reduce dose for any grade 3 toxicity
Interrupt treatment if mild hypersensitivity reactions occur
Interrupt treatment if severe infusion reaction occurs
Suspend treatment if grade 2 or 3 neuropathy
Female: Contraception required during and for 6 months after treatment
Breastfeeding: Do not breastfeed during & for 6 months after treatment

Nonopioid analgesics should be used permanently throughout treatment.

Clinical parameters
Prior to starting each treatment course, the following clinical parameters must be evaluated. Delay treatment until these values are reached.
Pulse oximetry above 94% on room air.
Adequate bone marrow function, defined as platelet count equal to or above 20,000 per microlitre, absolute neutrophil count equal to or above 500 per microlitre and haemoglobin above 8g per decilitre.
Adequate liver function, defined as alanine aminotransferase and aspartate aminotransferase less than 5 times the upper limit of normal.
Adequate renal function, defined as creatinine clearance or glomerular filtration rate above 60ml per minute per 1.73 metre squared.

Pregnancy and Lactation

Pregnancy

Dinutuximab beta is contraindicated during pregnancy.

The manufacturer contraindicates the use of dinutuximab beta in pregnancy. At the time of writing there is limited published information regarding the use of dinutuximab beta during pregnancy. Dinutuximab beta may theoretically have an effect on neuronal tissue during embryofoetal development.

Lactation

Dinutuximab beta is contraindicated during breastfeeding.

The manufacturer states that breastfeeding should be discontinued during treatment, and for 6 months afterwards. At the time of writing it is not known if dinutuximab beta is excreted in human breast milk. LactMed suggests that the high molecular weight may limit the amount present in breast milk, and absorption by the infant may also be limited as dinutuximab beta is thought to be destroyed in the infant's gastrointestinal tract.

Side Effects

Abdominal distension
Agitation
Altered liver function tests
Anaemia
Anaphylactic reaction
Anxiety
Ascites
Blurred vision
Bronchospasm
Capillary leak syndrome
Cardiac failure
Chills
Constipation
Cough
Cytokine release syndrome
Decrease in glomerular filtration rate
Decreased appetite
Dehydration
Dermatitis
Diarrhoea
Dizziness
Dry lips
Dry skin
Dyspnoea
Electrolyte disturbances
Encephalomyelitis
Enterocolitis
Eosinophilia
Erythema
Eyelid oedema
Facial oedema
Fluid retention
Haematuria
Headache
Hepatocellular damage
Herpes infections
Hyperhidrosis
Hyperphosphaturia
Hypersensitivity reactions
Hypertension
Hypertriglyceridaemia
Hypoalbuminaemia
Hypotension
Hypovolaemia
Hypoxia
Ileus
Increased partial thromboplastin time
Infections
Injection site reactions
Intravascular coagulation (disseminated)
Laryngospasm
Left ventricular failure
Leukopenia
Lymphopenia
Muscle spasm
Mydriasis
Myelitis
Nausea
Neutropenia
Oliguria
Ophthalmoplegia
Pain
Papilloedema
Paraesthesia
Pericardial effusion
Peripheral neuropathy
Peripheral oedema
Petechiae
Photophobia
Photosensitivity
Pleural effusion
Pneumonia
Posterior reversible encephalopathy syndrome (PRES)
Proteinuria
Prothrombin time increased
Pruritus
Pulmonary infiltration
Pulmonary oedema
Pyrexia
Raised intracranial pressure
Rash
Renal failure
Respiratory failure
Seizures
Sepsis
Serum bilirubin increased
Serum creatinine increased
Serum sickness
Skin infection
Stomatitis
Tachycardia
Tachypnoea
Thrombocytopenia
Tremor
Urinary retention
Urticaria
Veno-occlusive disease
Vomiting
Weight changes

Presentation

Infusions containing dinutuximab beta.

Drugs List

Therapeutic Indications

Uses

Neuroblastoma

High-risk neuroblastoma in patients aged 12 months and above, who have previously received induction chemotherapy and achieved at least a partial response, followed by myeloablative therapy and stem cell transplantation, as well as patients with a history of relapsed or refractory neuroblastoma, with or without residual disease. Prior to the treatment of relapsed neuroblastoma, any actively progressing disease should be stabilised by other measures.

Dosage

Each treatment course of dinutuximab beta consists of 5 consecutive courses, each comprising of 35 days.

The total dose for a single course should be 100mg per metre squared.

Adults

Additional Dosage Information

Administration

For administration by intravenous infusion, peripherally or centrally. Dinutuximab beta may also be combined with interleukin-2 (IL-2) which is administered as a subcutaneous injection.

For the typical 10-day dosing schedule, administer the continuous infusion at a rate of 2ml per hour, totalling 48ml per day.

For the alternative 5-day dosing schedule, administer the infusion at a rate of approximately 13ml per hour for 8 hours.

Contraindications

Absolute neutrophil count below 0.5 x 10 to the power of 9 / L
Children under 1 year
Haemoglobin concentration below 8g / dL
Platelet count below 20 x 10 to the power of 9 / L
Systemic infection
Abnormal liver function test
Acute grade 3 or 4, or extensive chronic graft-versus-host disease
Breastfeeding
Pregnancy
Renal impairment - creatinine clearance below 60ml/minute

Precautions and Warnings

Females of childbearing potential

Avoid vaccines during and for 10 weeks after treatment
Advise patient not to drive or operate machinery until assessed
Avoid corticosteroids 2 weeks prior to, during and 1 week after treatment
Premedication with analgesic recommended
Premedication with antihistamine recommended
Treat and control infections prior to commencing therapy
Consult local policy on the safe use of anti-cancer drugs
Must be diluted before use
Reduce infusion rate by 50% if grade 1 or 2 infusion reaction
Resuscitation facilities must be immediately available
Staff: Not to be handled by pregnant staff
Treatment to be administered under the supervision of a specialist
Monitor cardio-respiratory function
Monitor for hypersensitivity reactions-particularly 1st and 2nd infusions
Monitor for symptoms of Capillary Leak Syndrome
Monitor hepatic function regularly
Monitor patient for infusion-associated reactions (IARs)
Monitor pulse oximetry
Monitor serum electrolytes
Advise patient to report any blurred vision or any other eye symptoms
Risk of peripheral neuropathy
Discontinue if grade 3 or greater adverse reaction that recurs/persists
Discontinue if grade 3 or higher neuropathy occurs
Discontinue if grade 3 vision toxicity occurs
Discontinue if grade 4 hyponatremia occurs despite fluid management
Discontinue if recurrent or grade 4 capillary leak syndrome
Discontinue if serious allergic or anaphylactic reaction occurs
Interrupt treatment and/or reduce dose for any grade 3 toxicity
Interrupt treatment if mild hypersensitivity reactions occur
Interrupt treatment if severe infusion reaction occurs
Suspend treatment if grade 2 or 3 neuropathy
Female: Contraception required during and for 6 months after treatment
Breastfeeding: Do not breastfeed during & for 6 months after treatment

Nonopioid analgesics should be used permanently throughout treatment.

Clinical parameters
Prior to starting each treatment course, the following clinical parameters must be evaluated. Delay treatment until these values are reached.
Pulse oximetry above 94% on room air.
Adequate bone marrow function, defined as platelet count equal to or above 20,000 per microlitre, absolute neutrophil count equal to or above 500 per microlitre and haemoglobin above 8g per decilitre.
Adequate liver function, defined as alanine aminotransferase and aspartate aminotransferase less than 5 times the upper limit of normal.
Adequate renal function, defined as creatinine clearance or glomerular filtration rate above 60ml per minute per 1.73 metre squared.

Pregnancy and Lactation

Pregnancy

Dinutuximab beta is contraindicated during pregnancy.

The manufacturer contraindicates the use of dinutuximab beta in pregnancy. At the time of writing there is limited published information regarding the use of dinutuximab beta during pregnancy. Dinutuximab beta may theoretically have an effect on neuronal tissue during embryofoetal development.

Lactation

Dinutuximab beta is contraindicated during breastfeeding.

The manufacturer states that breastfeeding should be discontinued during treatment, and for 6 months afterwards. At the time of writing it is not known if dinutuximab beta is excreted in human breast milk. LactMed suggests that the high molecular weight may limit the amount present in breast milk, and absorption by the infant may also be limited as dinutuximab beta is thought to be destroyed in the infant's gastrointestinal tract.

Side Effects

Abdominal distension
Agitation
Altered liver function tests
Anaemia
Anaphylactic reaction
Anxiety
Ascites
Blurred vision
Bronchospasm
Capillary leak syndrome
Cardiac failure
Chills
Constipation
Cough
Cytokine release syndrome
Decrease in glomerular filtration rate
Decreased appetite
Dehydration
Dermatitis
Diarrhoea
Dizziness
Dry lips
Dry skin
Dyspnoea
Electrolyte disturbances
Encephalomyelitis
Enterocolitis
Eosinophilia
Erythema
Eyelid oedema
Facial oedema
Fluid retention
Haematuria
Headache
Hepatocellular damage
Herpes infections
Hyperhidrosis
Hyperphosphaturia
Hypersensitivity reactions
Hypertension
Hypertriglyceridaemia
Hypoalbuminaemia
Hypotension
Hypovolaemia
Hypoxia
Ileus
Increased partial thromboplastin time
Infections
Injection site reactions
Intravascular coagulation (disseminated)
Laryngospasm
Left ventricular failure
Leukopenia
Lymphopenia
Muscle spasm
Mydriasis
Myelitis
Nausea
Neutropenia
Oliguria
Ophthalmoplegia
Pain
Papilloedema
Paraesthesia
Pericardial effusion
Peripheral neuropathy
Peripheral oedema
Petechiae
Photophobia
Photosensitivity
Pleural effusion
Pneumonia
Posterior reversible encephalopathy syndrome (PRES)
Proteinuria
Prothrombin time increased
Pruritus
Pulmonary infiltration
Pulmonary oedema
Pyrexia
Raised intracranial pressure
Rash
Renal failure
Respiratory failure
Seizures
Sepsis
Serum bilirubin increased
Serum creatinine increased
Serum sickness
Skin infection
Stomatitis
Tachycardia
Tachypnoea
Thrombocytopenia
Tremor
Urinary retention
Urticaria
Veno-occlusive disease
Vomiting
Weight changes

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: October 2019

Reference Sources

Summary of Product Characteristics: Qarziba 20mg per 4.5ml concentrate for solution for infusion. EUSA Pharma UK Ltd. Revised March 2019.

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
Dinutuximab. Last revised: 03 December 2018.
Last accessed: 15 October 2019