Acalabrutinib oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of acalabrutinib.
Drugs List
Therapeutic Indications
Uses
Leukaemia - chronic lymphocytic
As monotherapy or in combination with obinutuzumab for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL).
As monotherapy for the treatment of adult patients with chronic lymphocytic leukaemia (CLL) who have received at least one prior therapy.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Adults
100mg twice a day.
Additional Dosage Information
Dose adjustments for adverse reactions
Grade 3 thrombocytopenia with bleeding
First and second occurrence: Interrupt acalabrutinib. Resume acalabrutinib at 100mg every 12 hours once toxicity has resolved to Grade 1 or baseline.
Third occurrence: Interrupt acalabrutinib. Resume acalabrutinib at 100mg once daily once toxicity has resolved to Grade 1 or baseline.
Fourth occurrence: Discontinue acalabrutinib.
Grade 4 thrombocytopenia
First and second occurrence: Interrupt acalabrutinib. Resume acalabrutinib at 100mg every 12 hours once toxicity has resolved to Grade 1 or baseline.
Third occurrence: Interrupt acalabrutinib. Resume acalabrutinib at 100mg once daily once toxicity has resolved to Grade 1 or baseline.
Fourth occurrence: Discontinue acalabrutinib.
Grade 4 neutropenia lasting longer than 7 days
First and second occurrence: Interrupt acalabrutinib. Resume acalabrutinib at 100mg every 12 hours once toxicity has resolved to Grade 1 or baseline.
Third occurrence: Interrupt acalabrutinib. Resume acalabrutinib at 100mg once daily once toxicity has resolved to Grade 1 or baseline.
Fourth occurrence: Discontinue acalabrutinib.
Grade 3 or greater non-haematological toxicities
First and second occurrence: Interrupt acalabrutinib. Resume acalabrutinib at 100mg every 12 hours once toxicity has resolved to Grade 1 or baseline.
Third occurrence: Interrupt acalabrutinib. Resume acalabrutinib at 100mg once daily once toxicity has resolved to Grade 1 or baseline.
Fourth occurrence: Discontinue acalabrutinib.
Missed dose
If a dose of acalabrutinib is missed by more than 3 hours, the patient should take the next dose at its regularly scheduled time.
Contraindications
Children under 18 years
Breastfeeding
Pregnancy
Severe hepatic impairment
Precautions and Warnings
Predisposition to haemorrhage
Hepatitis B
History of hepatitis B
Moderate hepatic impairment
Severe cardiovascular disorder
Severe renal impairment
Consider anti-infective prophylaxis in immunocompromised patients
Consider withholding for 3 days pre and post surgery
Advise ability to drive/operate machinery may be affected by side effects
Avoid H2 antagonists 10 hours before or 2 hours after dose
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
Treatment to be initiated and supervised by a specialist
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Consider PTLD or PML if new or worsening neurological symptoms occur
If atrial fibrillation occurs, assess risk for thromboembolic disease
Monitor for atrial fibrillation
Monitor for bleeding during treatment
Monitor full blood count regularly
Monitor patient for skin cancer during and after treatment
Monitor patients for development of second primary malignancies
Monitor patients with hepatic impairment for toxic effects
Monitor serum creatine periodically
Perform ECG if arrhythmic symptoms develop
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patient to report symptoms of infection immediately
Reactivation of herpes zoster may occur
Risk of developing opportunistic infections
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Suspend treatment and reduce dose if grade 4 neutropenia occurs
Suspend treatment and/or reduce dose if grade 4 thrombocytopenia
Suspend treatment and/or reduce dose in grade 3 non-haematological toxicity
Suspend treatment/reduce dose for grade 3 thrombocytopenia with bleeding
Advise patient not to take St John's wort concurrently
Avoid antacids within 2 hours of dose
Advise patient grapefruit products may increase plasma level
Advise patient to avoid grapefruit products
Breastfeeding: Do not breastfeed & discard milk for 48 hours after therapy
Advise patient on appropriate sun protection methods
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.
Atrial Fibrillation
In patients who develop atrial fibrillation, a thorough assessment of risk for thromboembolic disease should be undertaken. In patients at high risk for thromboembolic disease, tightly controlled treatment with anticoagulants and alternative treatment options to acalabrutinib should be considered.
Pregnancy and Lactation
Pregnancy
Acalabrutinib is contraindicated during pregnancy.
The manufacturer states that acalabrutinib should not be used during pregnancy unless the clinical condition of the woman requires treatment with acalabrutinib. Animal studies have shown there may be a risk to the foetus from the exposure to acalabrutinib. There are no or limited human data and as such a potential risk cannot be ruled out.
Lactation
Acalabrutinib is contraindicated during breastfeeding.
The manufacturer does not recommend breastfeeding during treatment with acalabrutinib and for 2 days after the last dose. Animal data shows that acalabrutinib and its active metabolite is present in breast milk, however the presence in human breast milk is unknown. Effects on exposed infants are unknown and therefore a risk to the breast fed infant cannot be excluded.
Side Effects
Abdominal pain
Anaemia
Arthralgia
Aspergillosis
Asthenia
Atrial fibrillation
Atrial flutter
Bronchitis
Bruising
Constipation
Contusion
Cough
Decrease in haemoglobin
Diarrhoea
Dizziness
Ecchymosis
Epistaxis
Fatigue
Gastro-intestinal haemorrhage
Haematoma
Haemorrhage
Headache
Herpes infections
Infections
Intracranial bleeding
Leucopenia
Lymphocytosis
Musculoskeletal pain
Nasopharyngitis
Nausea
Neutropenia
Non melanoma skin cancer
Petechiae
Pneumonia
Progressive multifocal leukoencephalopathy (PML)
Rash
Reactivation of hepatitis B
Reduced neutrophil count
Reduced platelet count
Second primary malignancies
Sepsis
Sinusitis
Thrombocytopenia
Tumour lysis syndrome
Upper respiratory tract infection
Urinary tract infections
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: April 2021
Reference Sources
Summary of Product Characteristics: Calquence 100 mg hard capsules. AstraZeneca UK Ltd. Revised January 2021.
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.