Drugs List

Therapeutic Indications

Uses

Follicular non-Hodgkin's lymphoma
Leukaemia - chronic lymphocytic

Treatment of previously untreated chronic lymphocytic leukaemia (CLL) in combination with chlorambucil in patients unsuitable for full-dose fludarabine based therapy.

Treatment of follicular lymphoma (FL) in combination with bendamustine in patients who did not respond or who progressed during or up to 6 months after treatment with rituximab or a rituximab containing regimen.

Treatment of FL in combination with chemotherapy followed by maintenance therapy, in patients with previously untreated advanced FL.

Administration

To be administered after dilution as an intravenous infusion.

Contraindications

Acute infection
Children under 18 years
Breastfeeding
Hepatitis B
Pregnancy

Precautions and Warnings

History of recurrent infection
Lymphocyte count above 25 x 10 to the power of 9/L
Cardiac disorder
Dehydration
Hepatic impairment
History of hepatitis B
Pulmonary disease
Renal impairment - creatinine clearance below 70ml/min

Administration of live vaccines is not recommended
Consider withholding antihypertensives 12 hours prior to treatment
Advise ability to drive/operate machinery may be affected by side effects
Before initiating screen all patients for hepatitis B infection
Consider premedication with hypouricaemic agent
Hepatitis B: Refer prior to initiation to liver disease specialist
Maintain adequate hydration of patient prior / during treatment
Premedicate with intravenous corticosteroids and antihistamines
Premedication with analgesic recommended
Premedication with antipyretic recommended
Treatment to be initiated and supervised by a specialist
Concentrate must be diluted and used as an infusion
Consult local policy on the safe use of anti-cancer drugs
Record name and batch number of administered product
Reduce infusion rate if mild to moderate infusion reaction occurs
Resuscitation facilities must be immediately available
Staff: Not to be handled by pregnant staff
Consider immunosuppressant adjustment in the event of PML
Monitor closely patients who develop neutropenia
Monitor patient for infusion-associated reactions (IARs)
Monitor patients for signs of tumour lysis syndrome
Monitor patients with cardiac disorders
Monitor patients with high tumour burden closely during therapy
Monitor platelets
Advise patient to report headaches, seizures, confusion, visual disturbance
Antimicrobial prophylaxis recommended if severe neutropenia occurs
Discontinue if hypersensitivity reactions occur
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Discontinue permanently if life threatening infusion reactions occur
Interrupt treatment if severe infusion reaction occurs
Permanently discontinue treatment if severe respiratory symptoms occur
Female: Contraception required during and for 18 months after treatment
Breastfeeding: Do not breastfeed during & for 18 months after treatment

Progressive Multifocal Leukoencephalopathy Syndrome (PML)
Progressive multifocal leukoencephalopathy syndrome (PML) has been reported in some patients treated with this agent. If patients present with symptoms indicating PML such as worsening neurological, cognitive or behavioural signs or symptoms, an MRI should be performed. If PML is diagnosed, treatment should be permanently discontinued.
Patients at risk of tumour lysis syndrome including patients with a high tumour burden, lymphocyte count greater than 25 x 10 to the power of 9/L and/or creatinine clearance less than 70 ml/minute should receive prophylaxis. These patients should be carefully monitored during the initial days of treatment with special focus on renal function, potassium and uric acid values.
Chronic Lymphocytic Leukaemia (CLL)
Patients with CLL and a creatinine clearance less than 50 ml/minute are at a greater risk of serious adverse events including events leading to death.

Pregnancy and Lactation

Pregnancy

Obinutuzumab is contraindicated during pregnancy.

The manufacturer advises obinutuzumab is not used in pregnancy unless the potential benefit to the mother outweighs the potential risk to the foetus. In case of exposure during pregnancy, depletion of B cells may be expected in newborns. Newborns should be monitored for B cell depletion and vaccinations should be postponed until the infant's B cell count has recovered.

There is no experience of the use of obinutuzuamb in humans. However studies in monkeys showed no embryofoetal toxicity or teratogenic effects but did result in the complete depletion of B lymphocytes in offspring. Serum concentrations in offspring (similar to the mother at 28 days) also suggest that obinutuzumab crosses the placenta.

Lactation

Obinutuzumab is contraindicated during breastfeeding.

The manufacturer advises breastfeeding should be discontinued during and for 18 months after obinutuzumab treatment.

It is unknown if obinutuzumab is excreted in human breast milk. Obinutuzuamb is unlikely to be absorbed due to its molecular weight (around 150,000). Animal studies have shown excretion of obinutuzumab into breast milk, therefore the risk to the breastfed child cannot be excluded.

Side Effects

Alopecia
Anaemia
Angina pectoris
Arrhythmias
Arthralgia
Asthenia
Atrial fibrillation
Back pain
Bone pain
Bronchospasm
Cardiac failure
Cardiac symptoms
Chest pain
Chills
Colitis
Constipation
Cough
Cytokine release syndrome
Depression
Diarrhoea
Dyspepsia
Dyspnoea
Dysuria
Eczema
Extremity pain
Flushing
Gastro-intestinal perforation
Haemorrhoids
Headache
Herpes simplex
Hypertension
Hyperuricaemia
Hypotension
Increase in alkaline phosphatase
Increase in serum ALT/AST
Influenza
Infusion-related symptoms
Laryngeal oedema
Leukopenia
Lung infection
Lymph node pain
Musculoskeletal pain
Myocardial infarction
Nasal congestion
Nasopharyngitis
Nausea
Neutropenia
Night sweats
Ocular hyperaemia
Pharyngitis
Progressive multifocal leukoencephalopathy (PML)
Pruritus
Pyrexia
Reactivation of hepatitis B
Reduced neutrophil count
Respiratory symptoms
Rhinitis
Rhinorrhoea
Sinusitis
Squamous cell carcinoma
Tachycardia
Throat irritation
Thrombocytopenia
Tumour lysis syndrome
Upper respiratory tract infection
Urinary incontinence
Urinary tract infections
Vomiting
Weight gain
Wheezing
White blood cell count decreased

Presentation

Infusions of obinutuzumab.

Drugs List

Therapeutic Indications

Uses

Follicular non-Hodgkin's lymphoma
Leukaemia - chronic lymphocytic

Treatment of previously untreated chronic lymphocytic leukaemia (CLL) in combination with chlorambucil in patients unsuitable for full-dose fludarabine based therapy.

Treatment of follicular lymphoma (FL) in combination with bendamustine in patients who did not respond or who progressed during or up to 6 months after treatment with rituximab or a rituximab containing regimen.

Treatment of FL in combination with chemotherapy followed by maintenance therapy, in patients with previously untreated advanced FL.

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.
When using this agent, specialist literature, national guidelines, cancer network protocols and Trust chemotherapy protocols should be consulted.

Additional Dosage Information

Administration

To be administered after dilution as an intravenous infusion.

Contraindications

Acute infection
Children under 18 years
Breastfeeding
Hepatitis B
Pregnancy

Precautions and Warnings

History of recurrent infection
Lymphocyte count above 25 x 10 to the power of 9/L
Cardiac disorder
Dehydration
Hepatic impairment
History of hepatitis B
Pulmonary disease
Renal impairment - creatinine clearance below 70ml/min

Administration of live vaccines is not recommended
Consider withholding antihypertensives 12 hours prior to treatment
Advise ability to drive/operate machinery may be affected by side effects
Before initiating screen all patients for hepatitis B infection
Consider premedication with hypouricaemic agent
Hepatitis B: Refer prior to initiation to liver disease specialist
Maintain adequate hydration of patient prior / during treatment
Premedicate with intravenous corticosteroids and antihistamines
Premedication with analgesic recommended
Premedication with antipyretic recommended
Treatment to be initiated and supervised by a specialist
Concentrate must be diluted and used as an infusion
Consult local policy on the safe use of anti-cancer drugs
Record name and batch number of administered product
Reduce infusion rate if mild to moderate infusion reaction occurs
Resuscitation facilities must be immediately available
Staff: Not to be handled by pregnant staff
Consider immunosuppressant adjustment in the event of PML
Monitor closely patients who develop neutropenia
Monitor patient for infusion-associated reactions (IARs)
Monitor patients for signs of tumour lysis syndrome
Monitor patients with cardiac disorders
Monitor patients with high tumour burden closely during therapy
Monitor platelets
Advise patient to report headaches, seizures, confusion, visual disturbance
Antimicrobial prophylaxis recommended if severe neutropenia occurs
Discontinue if hypersensitivity reactions occur
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Discontinue permanently if life threatening infusion reactions occur
Interrupt treatment if severe infusion reaction occurs
Permanently discontinue treatment if severe respiratory symptoms occur
Female: Contraception required during and for 18 months after treatment
Breastfeeding: Do not breastfeed during & for 18 months after treatment

Progressive Multifocal Leukoencephalopathy Syndrome (PML)
Progressive multifocal leukoencephalopathy syndrome (PML) has been reported in some patients treated with this agent. If patients present with symptoms indicating PML such as worsening neurological, cognitive or behavioural signs or symptoms, an MRI should be performed. If PML is diagnosed, treatment should be permanently discontinued.
Patients at risk of tumour lysis syndrome including patients with a high tumour burden, lymphocyte count greater than 25 x 10 to the power of 9/L and/or creatinine clearance less than 70 ml/minute should receive prophylaxis. These patients should be carefully monitored during the initial days of treatment with special focus on renal function, potassium and uric acid values.
Chronic Lymphocytic Leukaemia (CLL)
Patients with CLL and a creatinine clearance less than 50 ml/minute are at a greater risk of serious adverse events including events leading to death.

Pregnancy and Lactation

Pregnancy

Obinutuzumab is contraindicated during pregnancy.

The manufacturer advises obinutuzumab is not used in pregnancy unless the potential benefit to the mother outweighs the potential risk to the foetus. In case of exposure during pregnancy, depletion of B cells may be expected in newborns. Newborns should be monitored for B cell depletion and vaccinations should be postponed until the infant's B cell count has recovered.

There is no experience of the use of obinutuzuamb in humans. However studies in monkeys showed no embryofoetal toxicity or teratogenic effects but did result in the complete depletion of B lymphocytes in offspring. Serum concentrations in offspring (similar to the mother at 28 days) also suggest that obinutuzumab crosses the placenta.

Lactation

Obinutuzumab is contraindicated during breastfeeding.

The manufacturer advises breastfeeding should be discontinued during and for 18 months after obinutuzumab treatment.

It is unknown if obinutuzumab is excreted in human breast milk. Obinutuzuamb is unlikely to be absorbed due to its molecular weight (around 150,000). Animal studies have shown excretion of obinutuzumab into breast milk, therefore the risk to the breastfed child cannot be excluded.

Side Effects

Alopecia
Anaemia
Angina pectoris
Arrhythmias
Arthralgia
Asthenia
Atrial fibrillation
Back pain
Bone pain
Bronchospasm
Cardiac failure
Cardiac symptoms
Chest pain
Chills
Colitis
Constipation
Cough
Cytokine release syndrome
Depression
Diarrhoea
Dyspepsia
Dyspnoea
Dysuria
Eczema
Extremity pain
Flushing
Gastro-intestinal perforation
Haemorrhoids
Headache
Herpes simplex
Hypertension
Hyperuricaemia
Hypotension
Increase in alkaline phosphatase
Increase in serum ALT/AST
Influenza
Infusion-related symptoms
Laryngeal oedema
Leukopenia
Lung infection
Lymph node pain
Musculoskeletal pain
Myocardial infarction
Nasal congestion
Nasopharyngitis
Nausea
Neutropenia
Night sweats
Ocular hyperaemia
Pharyngitis
Progressive multifocal leukoencephalopathy (PML)
Pruritus
Pyrexia
Reactivation of hepatitis B
Reduced neutrophil count
Respiratory symptoms
Rhinitis
Rhinorrhoea
Sinusitis
Squamous cell carcinoma
Tachycardia
Throat irritation
Thrombocytopenia
Tumour lysis syndrome
Upper respiratory tract infection
Urinary incontinence
Urinary tract infections
Vomiting
Weight gain
Wheezing
White blood cell count decreased

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: August 2019

Reference Sources

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 24 July 2019

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Summary of Product Characteristics: Gazyvaro 1000 mg concentrate for solution for infusion. Roche Products Ltd. Revised April 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
Obinutuzumab Last revised: 03 December 2018
Last accessed: 08 August 2019