Active Ingredient and Strength	ACALABRUTINIB MALEATE EQV ACALABRUTINIB - 100 MG
Dosage Form	TABLET, FILM COATED
Manufacturer and Country	ASTRAZENECA AB - SWEDEN
Registration Number	SIN16875P
Licence Holder	ASTRAZENECA SINGAPORE PTE LTD
Forensic Classification	PRESCRIPTION ONLY MEDICINES
Anatomical Therapeutic Chemical (ATC) code	L01EL02

4.1 Therapeutic indications

CALQUENCE is indicated:

in combination with obinutuzumab or as monotherapy for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).
as monotherapy for the treatment of patients with CLL/SLL who have received at least one prior therapy.
for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.

4.2 Posology and method of administration

Treatment with CALQUENCE should be initiated and supervised by a physician experienced in the use of anticancer therapies.

Posology

MCL

The recommended dose of CALQUENCE for the treatment of MCL is 100 mg (1 tablet) twice daily.

CLL/SLL

The recommended dose of CALQUENCE for the treatment of CLL/SLL is 100 mg (1 tablet) twice daily, either as monotherapy or in combination with obinutuzumab. Refer to the obinutuzumab prescribing information for recommended obinutuzumab dosing information. (For details of the combination regimen, see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Doses should be separated by approximately 12 hours.

Treatment with CALQUENCE should continue until disease progression or unacceptable toxicity.

Missed Dose

If a patient misses a dose of CALQUENCE by more than 3 hours, instruct the patient to take the next dose at its regularly scheduled time. Extra tablets of CALQUENCE should not be taken to make up for a missed dose.

Dose Adjustments

Adverse Reactions

Recommended dose modifications of CALQUENCE for Grade ≥ 3 adverse reactions are provided in Table 1.

Temporarily interrupt CALQUENCE to manage a Grade ≥ 3 non-haematological treatment-related adverse reaction, Grade 3 thrombocytopenia with significant bleeding, Grade 4 thrombocytopenia, or Grade 4 neutropenia lasting longer than 7 days. Upon resolution of the adverse reaction to Grade 1 or baseline (recovery), restart CALQUENCE as recommended in Table 1.

Acalabrutinib tablets can be co-administered with gastric acid reducing agents (proton pump inhibitors, H2-receptor antagonists, antacids), unlike acalabrutinib capsules which show impaired uptake when given with acid reducing agents (see section 4.5 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Method of Administration

CALQUENCE should be swallowed whole with water at approximately the same time each day. CALQUENCE can be taken with or without food. The tablet should not be chewed, crushed, dissolved, or divided.

Special patient populations

Elderly (≥ 65 years)

No dose adjustment is necessary based on age (see section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Renal Impairment

No dose adjustment is recommended in patients with mild to moderate renal impairment (eGFR greater than or equal to 30 mL/min/1.73m² as estimated by MDRD (modification of diet in renal disease equation)). The pharmacokinetics and safety of CALQUENCE in patients with severe renal impairment (eGFR less than 29 mL/min/1.73m² ) or end-stage renal disease have not been studied (see section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Hepatic Impairment

No dose adjustment is recommended in patients with mild or moderate hepatic impairment (Child-Pugh A, Child-Pugh B, or total bilirubin between 1.5-3 times the upper limit of normal [ULN] and any AST). Avoid administration of CALQUENCE in patients with severe hepatic impairment (Child-Pugh C or total bilirubin > 3 times ULN and any AST) (see section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Severe Cardiac Disease

Patients with severe cardiovascular disease were excluded from CALQUENCE clinical studies.

Paediatric and adolescents

The safety and efficacy of CALQUENCE in children and adolescents aged less than 18 years have not been established.

4.3 Contraindications

Hypersensitivity to acalabrutinib or to any of the excipients in the formulation.