Drugs List

Therapeutic Indications

Uses

Amyloid light-chain amyloidosis
Myeloma - multiple

For the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant, as a combination therapy with lenalidomide and dexamethasone, or bortezomib, melphalan and prednisone.

For the treatment of adult patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant, in combination with bortezomib, thalidomide and dexamethasone.

For the treatment of adult patients with multiple myeloma who have received at least one prior therapy, in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone.

As monotherapy for adult patients with relapsed and refractory multiple myeloma, who have demonstrated disease progression in prior therapy which included a proteasome inhibitor and an immunomodulatory agent.

For the treatment of adult patients with newly diagnosed systemic light-chain amyloidosis, in combination with cyclophosphamide, bortezomib and dexamethasone.

Administration

Daratumumab 20mg/ml concentrate for solution for infusion is for intravenous infusion only.

Daratumumab 1.8g/15ml solution for injection is for subcutaneous injection only. Rotate injection site.

Contraindications

Children under 18 years
Breastfeeding
Pregnancy

Precautions and Warnings

Females of childbearing potential
Restricted sodium intake
Chronic obstructive pulmonary disease
Hepatitis B
Hereditary fructose intolerance

Sodium content of formulation may be significant
Advise ability to drive/operate machinery may be affected by side effects
Before initiating screen all patients for hepatitis B infection
Herpes zoster reactivation possible - consider antiviral prophylaxis
Not all available brands are licensed for all routes of administration
Not all formulations are licensed for all uses
Premedicate with intravenous corticosteroids and antihistamines
Premedication with antipyretic recommended
Treatment to be initiated and supervised by a specialist
Contains polysorbate
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Avoid injection into broken or bruised skin
Avoid injection into rash covered skin
Avoid injection into scar tissue
Consult local policy on the safe use of anti-cancer drugs
COPD: Consider bronchodilators & inhaled corticosteroids after treatment
Corticosteroid should be administered for 2 days following treatment
Do not use if solution is discoloured or particulates are apparent
Record name and batch number of administered product
Resuscitation facilities must be immediately available
Staff: Not to be handled by pregnant staff
Monitor for hepatitis B reactivation during treatment and 6 months after
Monitor full blood count regularly
Monitor patient for infusion-associated reactions (IARs)
Advise patients at risk of neutropenia to report any signs of infection
Interrupt therapy/reduce infusion rate if infusion-related reactions occur
Test interference: May cause false positive Coombs test
May affect results of some laboratory tests
Discontinue permanently if life threatening infusion reactions occur
Hepatitis B reactivation: Suspend treatment and refer to liver specialist
Female: Contraception required during and for 3 months after treatment

Patients should be monitored and counselled regarding IRRs, especially during the first and second treatments.

Pre and Post treatment medicinal products should be administered to minimise IRRs, it is recommended to pre-medicate the patient with antihistamines, anti-pyretics and corticosteroids. Corticosteroids are recommended following treatment to reduce the risk of delayed IRRs.

For IRRs of any severity immediately interrupt treatment and manage symptoms.

If after three treatments the patient experiences no major IRRs post-treatment corticosteroids may be discontinued.

Pregnancy and Lactation

Pregnancy

Daratumumab is contraindicated during pregnancy.

The manufacturer recommends that daratumumab should not be used during pregnancy unless the expected benefit of treatment clearly outweighs the potential risk to the foetus.

No human or animal data exists for the use of daratumumab in pregnancy.

IgG1 monoclonal antibodies are known to cross the placenta after the first trimester of pregnancy.

The effect of concurrent therapies must also be considered.

Lactation

Daratumumab is contraindicated during breastfeeding.

The manufacturer advises that the decision to discontinue breastfeeding or to discontinue daratumumab must take into account the benefit of breastfeeding for the child and the benefit of treatment for the patient.

It is not known if daratumumab is excreted into human or animal milk. Maternal IgG is excreted in human milk, but does not enter the neonatal and infant circulation in substantial amounts as they are degraded in the gastrointestinal tract, and not absorbed.

LactMed (2022) suggests that due to the large molecular weight of daratumumab (148,000 Da) the amount in breastmilk is expected to be low.

The effect of daratumumab on newborns or infants is unknown.

The effect of concurrent therapies must also be considered.

Side Effects

Anaemia
Anaphylactic reaction
Arthralgia
Asthenia
Atrial fibrillation
Back pain
Bronchitis
Bronchospasm
Chest discomfort
Chills
Constipation
Cough
Cytomegalovirus infection
Decreased appetite
Dehydration
Diarrhoea
Dizziness
Dyspnoea
Erythema at injection site
Fatigue
Haemolysis
Headache
Hyperglycaemia
Hypertension
Hypocalcaemia
Hypogammaglobulinaemia
Hypotension
Hypoxia
Infections
Influenza
Infusion related reaction
Injection site reactions
Insomnia
Laryngeal oedema
Leukopenia
Lymphopenia
Muscle spasm
Musculoskeletal chest pain
Nasal congestion
Nausea
Neutropenia
Pancreatitis
Paraesthesia
Peripheral oedema
Peripheral sensory neuropathy
Pneumonia
Pruritus
Pulmonary oedema
Pyrexia
Rash
Reactivation of hepatitis B
Rhinitis
Sepsis
Syncope
Tachycardia
Throat irritation
Thrombocytopenia
Upper respiratory tract infection
Urinary tract infections
Vomiting
Wheezing

Presentation

Parenteral formulations of daratumumab.

Drugs List

Therapeutic Indications

Uses

Amyloid light-chain amyloidosis
Myeloma - multiple

For the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant, as a combination therapy with lenalidomide and dexamethasone, or bortezomib, melphalan and prednisone.

For the treatment of adult patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant, in combination with bortezomib, thalidomide and dexamethasone.

For the treatment of adult patients with multiple myeloma who have received at least one prior therapy, in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone.

As monotherapy for adult patients with relapsed and refractory multiple myeloma, who have demonstrated disease progression in prior therapy which included a proteasome inhibitor and an immunomodulatory agent.

For the treatment of adult patients with newly diagnosed systemic light-chain amyloidosis, in combination with cyclophosphamide, bortezomib and dexamethasone.

Dosage

Due to the complexity and specialist nature of dosage regimens for the treatment of malignant disease, specific dosing information on this agent is not included.
Doses may vary significantly if this agent is used as monotherapy or different combinations.

Patients receiving the intravenous formulation may be given the subcutaneous injection formulation as an alternative at their next scheduled treatment.
When using this agent, specialist literature, national guidelines, cancer network protocols and Trust chemotherapy protocols should be consulted.

Additional Dosage Information

Administration

Daratumumab 20mg/ml concentrate for solution for infusion is for intravenous infusion only.

Daratumumab 1.8g/15ml solution for injection is for subcutaneous injection only. Rotate injection site.

Contraindications

Children under 18 years
Breastfeeding
Pregnancy

Precautions and Warnings

Females of childbearing potential
Restricted sodium intake
Chronic obstructive pulmonary disease
Hepatitis B
Hereditary fructose intolerance

Sodium content of formulation may be significant
Advise ability to drive/operate machinery may be affected by side effects
Before initiating screen all patients for hepatitis B infection
Herpes zoster reactivation possible - consider antiviral prophylaxis
Not all available brands are licensed for all routes of administration
Not all formulations are licensed for all uses
Premedicate with intravenous corticosteroids and antihistamines
Premedication with antipyretic recommended
Treatment to be initiated and supervised by a specialist
Contains polysorbate
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Avoid injection into broken or bruised skin
Avoid injection into rash covered skin
Avoid injection into scar tissue
Consult local policy on the safe use of anti-cancer drugs
COPD: Consider bronchodilators & inhaled corticosteroids after treatment
Corticosteroid should be administered for 2 days following treatment
Do not use if solution is discoloured or particulates are apparent
Record name and batch number of administered product
Resuscitation facilities must be immediately available
Staff: Not to be handled by pregnant staff
Monitor for hepatitis B reactivation during treatment and 6 months after
Monitor full blood count regularly
Monitor patient for infusion-associated reactions (IARs)
Advise patients at risk of neutropenia to report any signs of infection
Interrupt therapy/reduce infusion rate if infusion-related reactions occur
Test interference: May cause false positive Coombs test
May affect results of some laboratory tests
Discontinue permanently if life threatening infusion reactions occur
Hepatitis B reactivation: Suspend treatment and refer to liver specialist
Female: Contraception required during and for 3 months after treatment

Patients should be monitored and counselled regarding IRRs, especially during the first and second treatments.

Pre and Post treatment medicinal products should be administered to minimise IRRs, it is recommended to pre-medicate the patient with antihistamines, anti-pyretics and corticosteroids. Corticosteroids are recommended following treatment to reduce the risk of delayed IRRs.

For IRRs of any severity immediately interrupt treatment and manage symptoms.

If after three treatments the patient experiences no major IRRs post-treatment corticosteroids may be discontinued.

Pregnancy and Lactation

Pregnancy

Daratumumab is contraindicated during pregnancy.

The manufacturer recommends that daratumumab should not be used during pregnancy unless the expected benefit of treatment clearly outweighs the potential risk to the foetus.

No human or animal data exists for the use of daratumumab in pregnancy.

IgG1 monoclonal antibodies are known to cross the placenta after the first trimester of pregnancy.

The effect of concurrent therapies must also be considered.

Lactation

Daratumumab is contraindicated during breastfeeding.

The manufacturer advises that the decision to discontinue breastfeeding or to discontinue daratumumab must take into account the benefit of breastfeeding for the child and the benefit of treatment for the patient.

It is not known if daratumumab is excreted into human or animal milk. Maternal IgG is excreted in human milk, but does not enter the neonatal and infant circulation in substantial amounts as they are degraded in the gastrointestinal tract, and not absorbed.

LactMed (2022) suggests that due to the large molecular weight of daratumumab (148,000 Da) the amount in breastmilk is expected to be low.

The effect of daratumumab on newborns or infants is unknown.

The effect of concurrent therapies must also be considered.

Side Effects

Anaemia
Anaphylactic reaction
Arthralgia
Asthenia
Atrial fibrillation
Back pain
Bronchitis
Bronchospasm
Chest discomfort
Chills
Constipation
Cough
Cytomegalovirus infection
Decreased appetite
Dehydration
Diarrhoea
Dizziness
Dyspnoea
Erythema at injection site
Fatigue
Haemolysis
Headache
Hyperglycaemia
Hypertension
Hypocalcaemia
Hypogammaglobulinaemia
Hypotension
Hypoxia
Infections
Influenza
Infusion related reaction
Injection site reactions
Insomnia
Laryngeal oedema
Leukopenia
Lymphopenia
Muscle spasm
Musculoskeletal chest pain
Nasal congestion
Nausea
Neutropenia
Pancreatitis
Paraesthesia
Peripheral oedema
Peripheral sensory neuropathy
Pneumonia
Pruritus
Pulmonary oedema
Pyrexia
Rash
Reactivation of hepatitis B
Rhinitis
Sepsis
Syncope
Tachycardia
Throat irritation
Thrombocytopenia
Upper respiratory tract infection
Urinary tract infections
Vomiting
Wheezing

Effects on Laboratory Tests

Daratumumab treatment may result in a positive indirect Coombs test during and for up to 6 months following the last infusion. Detection of antibodies to minor antigens in patient's serum may be masked by daratumumab bound to red blood cells. In the event of planned blood transfusion, the transfusion centre should be notified of this interference with indirect antiglobulin tests. Non-cross-matched ABO/RhD-compatible blood may be given in an emergency as per local blood bank practices.

Daratumumab may interfere with serum protein electrophoresis and immunofixation assays, leading to false positives for these tests in patients with IgG kappa myeloma protein. A validated daratumumab-specific immunofixation assay should be used in patients with persistent very good partial response, where daratumumab interference is suspected.

Daratumumab may interfere with the determination of complete response tests, and disease progression in some patients with IgG kappa myeloma protein. This is because daratumumab is a human IgG kappa monoclonal antibody, therefore it can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays, used for endogenous M-protein clinical monitoring.

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 2022

Reference Sources

Summary of Product Characteristics: Darzalex 20mg/ml concentrate for solution for infusion. Janssen-Cilag Ltd. Revised April 2022.
Summary of Product Characteristics: Darzalex 1800mg solution for injection. Janssen-Cilag Ltd. Revised April 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
Daratumumab. Last revised: 18th April 2022.
Last accessed: 6th July 2022.