Ibrutinib oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of ibrutinib.
Drugs List
Therapeutic Indications
Uses
Leukaemia - chronic lymphocytic
Mantle cell lymphoma (MCL)
Waldenstrom's macroglobulinaemia
Treatment of relapsed or refractory mantle cell lymphoma (MCL) as a single agent.
Treatment of chronic lymphocytic leukaemia (CLL) in adult patients as a single agent or in combination with rituximab or obinutuzumab.
Treatment of CLL in patients who have received at least one prior treatment, as a single agent or in combination with bendamustine and rituximab.
Treatment of Waldenstrom's macroglobulinaemia (WM) as a single agent in patients who have received one prior therapy, or first line treatment in patients unsuitable for chemo-immunotherapy, or in combination with rituximab.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Adults
Mantle cell lymphoma
560mg once daily.
Chronic lymphocytic leukaemia
420mg once daily either as a single agent or in combination therapy.
Waldenstrom's macroglobulinaemia
420mg once daily either as a single agent or in combination therapy.
Patients with Hepatic Impairment
Child-Pugh Class A: 280mg once daily.
Child-Pugh Class B: 140mg once daily.
Child-Pugh Class C: Not recommended.
Additional Dosage Information
Concurrent use of CYP3A4 inhibitors
Moderate inhibitor: Reduce dose of ibrutinib to 280mg once daily.
Strong inhibitor: Concomitant use of strong CYP3A4 inhibitors with ibrutinib should be avoided where possible. If treatment is deemed necessary after thorough risk/benefit analysis, reduce ibrutinib dose to 140mg once daily and monitor patient for signs of toxicity.
Suspend treatment in the following conditions:
New onset or worsening grade 3 or greater non-haematological toxicity.
Grade 3 or greater neutropenia with infection or fever.
Grade 4 or greater haematological toxicity.
Once symptoms have resolved to grade 1 or baseline (recovery), therapy may be reinitiated at the starting dose. If toxicity reoccurs reduce dose as follows.
Mantle cell lymphoma
First toxicity occurrence: 560mg once daily.
Second toxicity occurrence: 420mg once daily.
Third toxicity occurrence: 280mg once daily.
Forth toxicity occurrence: Discontinue treatment.
Chronic lymphocytic leukaemia or Waldenstrom's macroglobulinaemia
First toxicity occurrence: 420mg once daily.
Second toxicity occurrence: 280mg once daily.
Third toxicity occurrence: 140mg once daily.
Forth toxicity occurrence: Discontinue treatment.
Combination with anti-CD20 therapies
Administer ibrutinib prior to rituximab or obinutuzumab when given on the same day.
Missed doses
Advise patients to take missed dose as soon as remembered if on the same day and return to the normal dose schedule the following day. Patients should not take extra tablets to make up for the missed dose.
Contraindications
Children under 18 years
Breastfeeding
Pregnancy
Severe hepatic impairment
Precautions and Warnings
Acute infection
Predisposition to haemorrhage
Risk factors for cardiovascular disorder
Atrial fibrillation
Dehydration
Galactosaemia
Glucose-galactose malabsorption syndrome
Lactose intolerance
Mild hepatic impairment
Renal impairment
Consider anti-infective prophylaxis in immunocompromised patients
Consider withholding for 3 to 7 days pre and post surgery
Reduce dose in patients with hepatic impairment
Advise ability to drive/operate machinery may be affected by side effects
Before initiating screen all patients for hepatitis B infection
Hepatitis B: Refer prior to initiation to liver disease specialist
Maintain adequate hydration of patient prior / during treatment
Monitor patients for non-melanoma skin cancer prior to and during treatment
Treatment to be initiated and supervised by a specialist
Some formulations contain lactose
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Perform blood counts before and at monthly intervals during treatment
Perform liver function tests before commencing therapy and during therapy
Consider immunosuppressant adjustment in the event of PML
Consider splenic rupture if patient has abdominal or shoulder pain
If atrial fibrillation occurs, assess risk for thromboembolic disease
Monitor blood pressure
Monitor for signs and symptoms of interstitial lung disease
Monitor patients for arrhythmias
Monitor patients for signs and symptoms of cardiac failure
Monitor patients for signs of tumour lysis syndrome
Monitor patients receiving concurrent anticoagulants
Monitor serum creatinine in patients with renal impairment
Monitor spleen size
Perform ECG for new onset dyspnoea
Perform ECG if arrhythmic symptoms develop
Risk of developing hyperleukocytosis
Advise patient to report any signs of cardiac arrhythmias
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patient to report signs of haemophagocytic lymphohistiocytosis (HLH)
Advise patient to report symptoms of infection immediately
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Potential for increased risk of bleeding
Suspend treatment if ventricular tachyarrhythmia is suspected
Consider suspending therapy if lymphocyte count > 400 x 10 to the power 9/L
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Suspend and/or reduce dose in grade 3 neutropenia with fever/infection
Suspend treatment and/or reduce dose in grade 3 non-haematological toxicity
Suspend treatment and/or reduce dose in grade 4 haematological toxicity
Suspend treatment if interstitial lung disease is suspected
Advise patient not to take St John's wort concurrently
Advise patient to avoid supplements containing fish oil
Advise patient to avoid supplements containing vitamin E
Advise patient grapefruit products may increase plasma level
Advise patient Seville (sour) orange products may increase plasma level
Female:Barrier contraception required during & for 3 months after treatment
Patients who develop atrial fibrillation during treatment should be assessed for the risk of thromboembolic disease. Other treatment options should be considered in high risk patients. If the use of ibrutinib is necessary, consider treatment with anticoagulants.
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.
Pregnancy and Lactation
Pregnancy
Ibrutinib is contraindicated during pregnancy.
The manufacturer states that ibrutinib should not be used during pregnancy.
There is no data available on the use of ibrutinib in pregnant women. Animal studies have shown reproductive toxicity.
Lactation
Ibrutinib is contraindicated during breastfeeding.
The manufacturer states that breastfeeding should be discontinued during treatment with ibrutinib.
It is not known whether ibrutinib is excreted into human breast milk. A risk to neonates cannot be excluded.
Side Effects
Anaemia
Angioedema
Arthralgia
Asthenia
Atrial fibrillation
Atrial flutter
Basal cell carcinoma
Blurred vision
Bruising
Constipation
Diarrhoea
Dizziness
Dyspnoea
Epistaxis
Erythema
Fatigue
Febrile neutropenia
Gastro-intestinal haemorrhage
Haematuria
Haemophagocytic lymphohistiocytosis
Haemorrhage
Headache
Hepatic failure
Hepatitis
Hyperleukocytosis
Hypertension
Hyperuricaemia
Infections
Interstitial lung disease
Intracranial bleeding
Leukocytosis
Lymphocytosis
Muscle spasm
Musculoskeletal pain
Nausea
Neutropenia
Non melanoma skin cancer
Onycholysis
Panniculitis
Peripheral neuropathy
Peripheral oedema
Petechiae
Pneumonia
Progressive multifocal leukoencephalopathy (PML)
Pyrexia
Rash
Reactivation of hepatitis B
Sepsis
Serum creatinine increased
Sinusitis
Skin infection
Splenic rupture
Squamous cell carcinoma
Stevens-Johnson syndrome
Stomatitis
Subdural haematoma
Thrombocytopenia
Tumour lysis syndrome
Upper respiratory tract infection
Urinary tract infections
Urticaria
Ventricular tachycardia
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: August 2019
Reference Sources
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 01 August 2019
Summary of Product Characteristics: Imbruvica 140mg hard capsules. Janssen-Cilag Ltd. Revised August 2019.
Summary of Product Characteristics: Imbruvica 140mg, 280mg, 420mg, 560mg film-coated tablets. Janssen-Cilag Ltd. Revised January 2021.
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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