Calquence is the brand name of Acalabrutinib. It is a Tyrosine Kinase inhibitor, a BTK or Bruton Tyrosine Kinase inhibitor that targets cells positive for CD86 and CD69.

Calquence (Acalabrutinib) Indications:

Mantle Cell Lymphoma

• Mantle cell lymphoma (MCL) in adults who have had at least one previous therapy.

Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL):

• Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in Adults.

Calquence (Acalabrutinib) Dosage:

CALQUENCE as Monotherapy

• 100 mg orally every 12 hours.
• The treatment is continued until either the drug is no more tolerated because of side effects or there is disease progression.

CALQUENCE in Combination with Obinutuzumab

• 100 mg of CALQUENCE orally twice daily.
• Begin CALQUENCE in Cycle 1, where each cycle is 28 days long.
• Obinutuzumab should begin in Cycle 2, with a total of 6 cycles.
• Administer CALQUENCE before administering Obinutuzumab if both drugs are to be administered on the same day.

How to take Calquence (Acalabrutinib)?

• Swallow the tablet whole with water. Avoid crushing, chewing, cutting, or dissolving the tablets.
• You can take the tablet with food or even on an empty stomach.
• Skip the dose if you miss it and 3 hours or more have passed since the last scheduled dose. Do not take a double dose. Follow the dosing schedule from the next scheduled dose.

Recommended Dosage for Drug Interactions

When CALQUENCE is co-administered with CYP3A inhibitors or inducers, the recommended dosage modifications are as follows:

CYP3A Co-administered Drug Recommendations:

• Inhibition:
  • Strong CYP3A inhibitor:
    • Avoid taking it with a strong CYP3A inhibitor.
    • If these inhibitors must be taken for a short time (up to seven days), temporarily stop taking CALQUENCE. Once you have discontinued a strong CYP3A inhibitor for at least 24 hours, you can resume taking CALQUENCE at the previous dosage.
  • Moderate CYP3A inhibitor:
    • Reduce the dose to 100 mg once daily.
• Induction:
  • Strong CYP3A inducer:
    • Avoid taking it with a strong CYP3A inducer.
    • However, if co-administration is unavoidable, the dosage of CALQUENCE should be increased to 200 mg approximately every 12 hours.

Adverse Event Management and Dosage Modifications

Adverse events can occur during CALQUENCE treatment, and dosage modifications may be necessary to manage these reactions. The following section outlines the appropriate dosage modifications for managing adverse events.

The recommended starting dose is 100 mg taken orally twice daily.

Dosage modifications are required in the following cases:

• Grade 3 or greater non-hematologic toxicities and thrombocytopenia with bleeding
• Grade 4 thrombocytopenia and neutropenia lasting longer than 7 days

Dosage Modifications for Adverse Events:

First and Second Occurrences:

• Discontinue CALQUENCE.
• Once the toxicity has resolved to Grade 1 or baseline level, resume at 100 mg twice daily.

Third Occurrence:

• Discontinue CALQUENCE.
• Once the toxicity has resolved to Grade 1 or baseline level, CALQUENCE may be resumed at a reduced frequency of 100 mg once daily.

Fourth Occurrence:

• Discontinue CALQUENCE.

Contraindication to Calquence (Acalabrutinib):

No contraindications have been mentioned in the FDA prescribing information.

Warning & Precaution:

• Serious and Opportunistic Infections:

CALQUENCE may cause serious and opportunistic infections in patients with hematologic malignancies. Grade 3 or higher infections (bacterial, viral, or fungal) were reported in up to 19% of the patients in clinical trials. These primarily were respiratory tract infections and affected those with severe neutropenia.

Hepatitis B virus reactivation, fungal pneumonia, Pneumocystis jirovecii pneumonia, Epstein-Barr virus reactivation, cytomegalovirus, and progressive multifocal leukoencephalopathy (PML) were also seen.

Patients should be monitored and treated promptly for infections and prophylaxis should be considered.

• Hemorrhage Risks with CALQUENCE

Bleeding can occur which can be serious and life-threatening. Minor bleeding episodes are more common, especially in patients taking antiplatelet drugs.

Physicians must decide whether to continue or discontinue antiplatelets and anticoagulants and weigh the risks and benefits. Most experts recommend stopping Calquence drugs 3 to 7 days before and after surgery.

• Cytopenias and CALQUENCE

There is an increased risk of low blood counts with the treatment. Severe cytopenias were reported in clinical trials of Grade 3 or 4 severity.

• Neutropenia (23%) (severe neutropenia of Grade 4 severity developed in 12%)
• Anemia (8%)
• Thrombocytopenia (7%)
• Lymphopenia (7%)

Monitor complete blood counts during treatment. The treatment may need interruption, dose reduction, or discontinuation of depending on the severity of the cytopenia.

• Second Primary Malignancies

Secondary malignancies such as skin cancers and other solid tumors may develop. In clinical trials, 12% of the patients developed secondary malignancies with most developing blood cancers followed by skin cancers.

Monitoring for skin cancer is recommended. All patients should also avoid sun exposure and apply sunscreens during the treatment.

• Atrial Fibrillation and Flutter

Atrial fibrillation or flutter was reported in 4.1% of the patients receiving the treatment including atrial fibrillation of Grade 3 severity in 1.1% of the patients.

Patients with cardiac risk factors, hypertension, previous arrhythmias, and acute infection may be at an increased risk. Monitoring is recommended for arrhythmia (e.g., palpitations, dizziness, syncope, dyspnea).

Side Effects of Calquence (Acalabrutinib):

Systems	Adverse Reaction
Infections and infestations	Upper and lower respiratory tract infections including pneumonia, herpesvirus infection, bronchitis, bronchiolitis, and tracheitis
Neoplasms	Second primary malignancy, non-melanoma skin cancer
Cardiac	Atrial fibrillation or flutter, hypertension
Hepatobiliary	ALT/AST/Bilirubin increase
Metabolic	Uric acid increase
CNS	Headache
Respiratory	Shortness of breath
Gastrointestinal	Diarrhea, nausea, vomiting
General	Lethargy, Fever
Skin	Rash
Musculoskeletal	Joint and muscle pains
Blood and lymphatics	Neutropenia, anemia, thrombocytopenia

 

Drug Interactions (Effect of Other Drugs on CALQUENCE):

Strong CYP3A Inhibitors
Clinical Effect	Taking Acalabrutinib with a strong CYP3A inhibitor can increase its levels in the blood, which can be harmful.
Prevention or Management	Do not take Acalabrutinib with strong CYP3A inhibitors. If you need to take the inhibitor for a short period of time, stop taking it during that time.
Moderate CYP3A Inhibitors
Clinical Effect	When Acalabrutinib is taken with a moderate CYP3A inhibitor, its levels may increase in the blood, which could lead to harmful effects.
Prevention or Management	If it is co-administered with a moderate CYP3A inhibitor, the dose should be reduced.
Strong CYP3A Inducers
Clinical Effect	When Acalabrutinib is taken with a strong CYP3A inducer, its levels in the blood may decrease, which can reduce its effectiveness.
Prevention or Management	Avoid using strong CYP3A inducers with Acalabrutinib. If it cannot be avoided, increase its dose.

 

Pregnancy Risk Summary:

Acalabrutinib may cause fetal harm and dystocia in pregnant women based on animal studies. No data is available on human pregnancy risk. Animal studies show potential adverse effects on fetal growth and labor.

Lactating women should not breastfeed while taking CALQUENCE. Pregnancy testing and effective contraception are recommended for females of reproductive potential, and patients should be informed of potential harm to the fetus if pregnant while taking Acalabrutinib.

Use in Children and Older people:

Acalabrutinib has not been tested in pediatric patients. Adverse reactions were more common in patients aged 65 years or older in clinical trials, but treatment effectiveness was similar between age groups. Further studies are needed to determine safety and efficacy in geriatric populations.

Hepatic Impairment

CALQUENCE should not be used in patients with severe hepatic impairment. No dosage adjustment is required in mild or moderate hepatic impairment, but safety has not been established in these populations. Consult with a healthcare provider before using CALQUENCE in patients with hepatic impairment

Mechanism of action of Acalabrutinib:

• Acalabrutinib inhibits BTK enzymes involved in BCR and cytokine receptor pathways.
• Inhibition leads to inactivation of downstream signaling proteins CD86 and CD69, resulting in reduced malignant B-cell proliferation and tumor growth.
• BTK occupancy of ≥ 95% is maintained for 12 hours when given at a dose of 100mg every 12 hours.
• It has minimal effect on cardiac electrophysiology at four times the recommended dosage.

Pharmacokinetic Properties	Acalabrutinib
Dose Proportionality	Exposure of Acalabrutinib and ACP-5862 increases proportionally with the dose
Absorption	The absolute bioavailability of Acalabrutinib is 25%, median Tmax is 0.5 hours. Median Tmax for ACP-5862 is 0.75 hours.
Effect of Food	A single 100mg dose with a high-fat, high-calorie meal did not affect mean AUC. Cmax decreased by 54% and Tmax was delayed by 1-2 hours.
Distribution	The plasma protein binding of Acalabrutinib and ACP-5862 is 97.5% and 98.6%, respectively.
Elimination	The terminal elimination half-life of Acalabrutinib and ACP-5862 is 1.4 hours and 6.4 hours, respectively.
Metabolism	Acalabrutinib is primarily metabolized by CYP3A enzymes and to a minor extent by glutathione conjugation and amide hydrolysis. ACP-5862 is the major active metabolite in plasma, with approximately 2-3 times more exposure than Acalabrutinib.
Excretion	Feces: 84% Urine: 12%

 

Patient Counselling Information

Before taking CALQUENCE, it is important for patients to understand the potential risks and benefits of this medication. Below are some important counseling points:

FDA-Approved Patient Labelling

• Advise patients to read and understand the FDA-approved patient labeling (Patient Information).

Serious and Opportunistic Infections

• Patients should be informed about the possibility of developing serious infections and report any signs or symptoms of infections.

Bleeding:

• Patients should be advised to report any signs or symptoms of bleeding, such as easy bruising or bleeding.
• In addition, the treatment may need to be stopped before major surgeries.

Blood counts:

• Periodic blood tests are recommended to monitor counts during the treatment.

Second Primary Malignancies

• Patients should be informed that Acalabrutinib has been associated with other malignancies, including skin cancer and other solid tumors.
• Patients should be advised to use sun protection when outdoors.

Atrial Fibrillation and Flutter

• Patients should be asked to report any signs or symptoms of palpitations, dizziness, fainting, chest discomfort, or shortness of breath.

Pregnancy Complication

• Effective contraception during treatment and for one week after the last dose is recommended as the drug is toxic to the fetus.

Lactation

• Breastfeeding should be avoided during the treatment and for two weeks after the last dose.

Dosing Instructions

• The drug is taken orally two times a day (12 hours apart) with or without food.
• The tablets should be swallowed whole with a glass of water and should not be chewed, crushed, dissolved, or cut.

Missed Dose

• Patients should be informed that if they miss a dose of CALQUENCE, they may still take it up to 3 hours after the time they would normally take it.
• If more than 3 hours have passed, patients should skip that missed dose and take their next dose at the usual time.
• Patients should not take extra tablets to make up for a missed dose.

Drug Interactions

• Patients should be advised to inform their healthcare providers of all medications they are taking, including over-the-counter medications, vitamins, and herbal products.
• Some medications may interact with CALQUENCE and could affect its effectiveness or increase the risk of side effects.