Calquence (Acalabrutinib)
Bruton's Tyrosine Kinase (BTK) Inhibitor for CLL and Mantle Cell Lymphoma
Calquence (acalabrutinib) is a targeted cancer therapy that belongs to a class of drugs called Bruton's tyrosine kinase (BTK) inhibitors. It is prescribed for adults with chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL). Calquence works by blocking BTK, a protein that helps cancer cells grow and survive, thereby reducing the number of malignant cells and slowing disease progression.
Quick Facts
Key Takeaways
- Calquence is a second-generation BTK inhibitor approved for treating chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) in adults.
- The standard dosage is one 100 mg tablet taken orally twice daily, approximately 12 hours apart, with or without food.
- Common side effects include headache, diarrhea, fatigue, muscle/joint pain, and reduced blood cell counts; serious risks include bleeding, infections, and heart rhythm problems.
- Calquence has significant drug interactions with strong CYP3A inhibitors and inducers, anticoagulants, and several other medications that must be carefully managed.
- Regular blood monitoring is required during treatment to track blood cell counts, liver function, and other parameters.
What Is Calquence and What Is It Used For?
Calquence contains the active substance acalabrutinib and belongs to a class of medications known as Bruton's tyrosine kinase (BTK) inhibitors. BTK is a critical signaling molecule in the B-cell antigen receptor pathway, which plays a central role in the growth, survival, and migration of malignant B lymphocytes. By selectively and irreversibly binding to BTK, acalabrutinib disrupts the signaling cascades that cancer cells depend on for proliferation.
Chronic Lymphocytic Leukemia (CLL)
Chronic lymphocytic leukemia is the most common form of leukemia in adults in Western countries. It is a type of blood cancer that originates in the white blood cells called B lymphocytes (B cells), which are a key part of the immune system. In CLL, these B cells become cancerous and accumulate in the blood, bone marrow, lymph nodes, and spleen, eventually crowding out healthy blood cells and impairing immune function.
Calquence is approved for the treatment of adult patients with CLL, either as a single agent (monotherapy) or in combination with other anti-cancer medicines such as obinutuzumab. Clinical trials, including the ELEVATE-TN and ASCEND studies, have demonstrated that acalabrutinib significantly improves progression-free survival compared to standard chemoimmunotherapy regimens. The drug can be used in both previously untreated (first-line) and relapsed or refractory CLL patients.
Mantle Cell Lymphoma (MCL)
Mantle cell lymphoma is a relatively rare but aggressive form of non-Hodgkin lymphoma that arises from B cells in the mantle zone of lymph nodes. MCL accounts for approximately 3–10% of all non-Hodgkin lymphomas and tends to be diagnosed at an advanced stage. It is generally more difficult to treat than many other lymphoma subtypes.
Calquence has received approval for the treatment of adult patients with MCL who have received at least one prior therapy. The ACE-LY-004 trial demonstrated an overall response rate of approximately 81% in patients with relapsed or refractory MCL, with a complete response rate of around 40%. These results established acalabrutinib as an important therapeutic option for patients who have not responded to or have relapsed after initial treatment.
How Does Calquence Work?
Calquence works by selectively blocking Bruton's tyrosine kinase, a protein that is essential for the activation and survival of malignant B cells. When BTK is active, it sends signals through multiple downstream pathways — including NF-kB, MAPK, and PI3K — that promote cancer cell proliferation, adhesion, and migration. By covalently binding to a cysteine residue (Cys481) in the active site of BTK, acalabrutinib permanently inactivates the enzyme.
As a second-generation BTK inhibitor, acalabrutinib was specifically designed to be more selective for BTK compared to the first-generation inhibitor ibrutinib. This improved selectivity means it has less off-target kinase inhibition, which may translate to a more favorable side effect profile, particularly with regard to cardiovascular effects such as atrial fibrillation and bleeding. However, regular monitoring remains essential during treatment.
The net effect of BTK inhibition is that cancer cells can no longer receive the survival signals they need. This leads to apoptosis (programmed cell death) of the malignant B cells, a reduction in tumor burden, and slowing of disease progression. Patients may also experience lymphocytosis (a temporary increase in circulating lymphocytes) in the early weeks of treatment, which is a known pharmacodynamic effect and does not indicate treatment failure.
What Should You Know Before Taking Calquence?
Before starting treatment with Calquence, it is essential to have a thorough discussion with your healthcare provider about your complete medical history, current medications, and any planned procedures. Several conditions and circumstances require special consideration or may contraindicate the use of this medication.
Contraindications
Do not take Calquence if you have a known hypersensitivity (severe allergic reaction) to acalabrutinib or any of the other ingredients in the formulation. If you have previously experienced an allergic reaction to a BTK inhibitor, discuss this with your doctor before starting Calquence, as cross-reactivity may occur. Symptoms of hypersensitivity may include rash, hives, swelling, difficulty breathing, or anaphylaxis.
Warnings and Precautions
Talk to your doctor, pharmacist, or nurse before taking Calquence if any of the following apply to you:
- Bleeding history or anticoagulant use: Calquence may increase the risk of bleeding. If you have ever had unusual bruising or bleeding, or if you take medications that increase the risk of bleeding (such as anticoagulants or antiplatelet agents), your healthcare team should be informed. Serious bleeding events, including intracranial hemorrhage, have been reported.
- Active infections: Calquence can increase susceptibility to infections, including serious opportunistic infections. If you currently have an infection or are prone to infections, this should be carefully evaluated before starting treatment. Infections such as pneumonia, urinary tract infections, and upper respiratory tract infections are common during treatment.
- Planned surgery or dental procedures: Your doctor may recommend pausing Calquence for 3–7 days before and after any surgical, medical, or dental procedure due to the increased risk of bleeding.
- Hepatitis B history: Calquence may cause reactivation of hepatitis B virus (HBV) in patients who are carriers or have had past infection. Your doctor will test for HBV before starting treatment and monitor for signs of reactivation throughout therapy. HBV reactivation can lead to serious liver damage.
- Heart rhythm disorders: If you have or have had an irregular heartbeat (arrhythmia), particularly atrial fibrillation or atrial flutter, inform your doctor. Calquence has been associated with new-onset or worsening cardiac arrhythmias, and patients with pre-existing cardiac conditions may require additional monitoring.
- Skin cancer risk: Patients treated with Calquence have an increased risk of developing secondary malignancies, including skin cancers. Use sun protection (sunscreen SPF 30+, protective clothing) and perform regular skin self-examinations. Report any new or changing skin lesions to your doctor promptly.
Your doctor will monitor your blood counts regularly during treatment. This includes complete blood counts to check for anemia, neutropenia (low white blood cells), and thrombocytopenia (low platelet counts), as these are common during treatment with Calquence.
Calquence is not approved for use in children and adolescents under 18 years of age, as safety and efficacy have not been established in this age group. If you experience sudden severe headache, confusion, vision changes, or weakness on one side of the body, seek emergency medical attention immediately, as these may be signs of a serious brain infection (progressive multifocal leukoencephalopathy, PML).
Pregnancy and Breastfeeding
Calquence is not recommended during pregnancy. Based on findings from animal studies and its mechanism of action, acalabrutinib may cause harm to the developing fetus. Women of childbearing potential should use effective contraception during treatment and for at least one week after the last dose. If you become pregnant while taking Calquence, contact your healthcare provider immediately.
Breastfeeding should be avoided during treatment with Calquence and for 2 days after the last dose. It is not known whether acalabrutinib or its metabolites pass into human breast milk. Because of the potential for serious adverse reactions in the nursing infant, a decision should be made to either discontinue breastfeeding or discontinue the drug, taking into account the importance of the medication to the mother.
Driving and Operating Machinery
Calquence is not expected to affect your ability to drive or operate machinery under normal circumstances. However, some patients may experience dizziness, fatigue, or weakness during treatment. If you experience any of these symptoms, do not drive or use machinery until you feel well enough to do so safely.
Calquence tablets contain less than 1 mmol (23 mg) sodium per dose, meaning they are essentially sodium-free. This is relevant for patients on a sodium-restricted diet.
How Does Calquence Interact with Other Drugs?
Acalabrutinib is primarily metabolized by the cytochrome P450 enzyme CYP3A and, to a lesser extent, by glutathione conjugation. Because of this metabolic pathway, medications that inhibit or induce CYP3A can significantly alter the blood levels of acalabrutinib, potentially leading to increased toxicity or reduced effectiveness. It is critically important that you inform your doctor, pharmacist, or nurse about all medications you are taking, including prescription drugs, over-the-counter medicines, vitamins, and herbal supplements.
Major Interactions
The following drug classes and specific medications have clinically significant interactions with Calquence and should generally be avoided or require dose adjustments:
| Drug / Class | Examples | Interaction Type | Clinical Effect |
|---|---|---|---|
| Strong CYP3A inhibitors | Ketoconazole, posaconazole, itraconazole, voriconazole, clarithromycin | Increased acalabrutinib levels | Avoid concomitant use; significantly increases toxicity risk |
| Strong CYP3A inducers | Rifampicin, carbamazepine, phenytoin, St. John's Wort | Decreased acalabrutinib levels | Avoid concomitant use; may reduce therapeutic effectiveness |
| HIV protease inhibitors | Indinavir, ritonavir | Strong CYP3A inhibition | Avoid concomitant use due to increased acalabrutinib exposure |
| Hepatitis C antivirals | Telaprevir | CYP3A inhibition | Potential increase in acalabrutinib levels |
| Anticoagulants | Warfarin, enoxaparin | Additive bleeding risk | Increased risk of hemorrhage; use with caution and monitor closely |
| Antiplatelet agents | Acetylsalicylic acid (aspirin), clopidogrel | Additive bleeding risk | Increased risk of hemorrhage; use with caution |
Minor Interactions and Special Considerations
The following medications have interactions with Calquence that may require monitoring, timing adjustments, or clinical awareness:
| Drug / Class | Examples | Recommendation |
|---|---|---|
| Ergot alkaloids | Ergotamine (migraine medications) | Avoid concomitant use |
| Immunosuppressants | Ciclosporin | Use with caution; monitor drug levels |
| Pimozide | Antipsychotic for Tourette syndrome | Avoid concomitant use |
| Conivaptan | Treatment for low blood sodium | Avoid concomitant use (strong CYP3A inhibitor) |
| Theophylline | Bronchodilator | Monitor theophylline levels |
| Metformin | Diabetes medication | Monitor glucose levels; generally safe |
| Methotrexate | Immunosuppressant/chemotherapy | Take at least 6 hours before or after Calquence |
| Acid-reducing agents | Omeprazole, ranitidine, calcium carbonate | Can be taken with Calquence tablets |
Unlike some other formulations of acalabrutinib (such as capsules), Calquence film-coated tablets can be taken with proton pump inhibitors, H2-receptor antagonists, and antacids without affecting drug absorption. This is an important practical advantage for patients who require acid-reducing therapy.
If you are taking methotrexate, it should be taken at least 6 hours before or after your Calquence dose. This timing separation helps minimize the potential for interaction between these two medications.
What Is the Correct Dosage of Calquence?
Calquence should only be prescribed by a physician experienced in the use of anticancer medicines. It is essential to follow your doctor's dosing instructions exactly. The dosage may be adjusted or treatment temporarily paused based on side effects or other clinical considerations. Do not change your dose or stop taking Calquence without consulting your healthcare provider.
Adults
Standard Adult Dosage
Dose: 100 mg (one tablet) taken orally twice daily
Schedule: Approximately 12 hours apart (e.g., morning and evening)
Administration: Swallow whole with water. Do not chew, crush, dissolve, or split tablets.
Food: May be taken with food or on an empty stomach.
Duration: Continue until disease progression or unacceptable side effects.
Depending on your type of cancer and treatment plan, Calquence may be given as monotherapy or in combination with other anticancer drugs. For CLL, common combinations include Calquence with obinutuzumab. Your oncologist will determine the most appropriate regimen based on your individual clinical situation.
The Calquence blister pack features sun and moon symbols to help you track your doses — the sun symbol indicates the morning dose and the moon symbol indicates the evening dose. Both blisters contain the same medication at the same strength.
Children and Adolescents
Calquence is not approved for use in children and adolescents under 18 years of age. The safety and efficacy of acalabrutinib have not been established in pediatric patients. Do not give this medicine to anyone under 18.
Elderly Patients
No specific dose adjustment is required for elderly patients. Clinical trials have included substantial numbers of patients aged 65 years and older, and no overall differences in safety or efficacy were observed between older and younger patients. However, elderly patients may be more susceptible to certain side effects, particularly infections and cardiac arrhythmias, and may require closer monitoring.
Missed Dose
- Less than 3 hours since the scheduled time: Take the missed dose immediately. Then take the next dose at the usual time.
- More than 3 hours since the scheduled time: Skip the missed dose. Take the next dose at the usual time.
- Never take a double dose to make up for a missed dose.
Overdose
If you take more Calquence than prescribed, contact your doctor or go to the nearest emergency department immediately. Take the tablets and this medication guide with you. There is no specific antidote for acalabrutinib overdose. Treatment is supportive and symptomatic. In clinical experience, overdoses with up to 12 times the recommended daily dose have been reported. Common symptoms of overdose may include an exaggeration of the known side effects, particularly gastrointestinal symptoms and bleeding.
What Are the Side Effects of Calquence?
Like all medications, Calquence can cause side effects, although not everyone will experience them. Some side effects can be serious and require immediate medical attention, while others are mild and manageable. It is important to understand the potential risks and know which symptoms to report to your healthcare team. Your doctor will monitor you regularly to detect and manage side effects early.
Stop taking Calquence and contact your doctor or go to the nearest emergency department immediately if you experience any of the following: signs of serious bleeding (black stools, blood in urine, unexpected bruising, coughing or vomiting blood, severe dizziness), signs of serious infection (high fever, chills, severe weakness, shortness of breath), or signs of heart problems (rapid or irregular heartbeat, dizziness, fainting, chest discomfort).
Side Effect Frequency Overview
Very Common
May affect more than 1 in 10 people
- Bleeding (various sites including skin, gastrointestinal tract, and brain)
- Infections (including pneumonia and upper respiratory tract infections)
- Muscle or joint pain (musculoskeletal pain)
- Headache
- Skin rash
- Fatigue, weakness, or lack of energy
- Nausea, vomiting, abdominal pain, constipation, diarrhea
- Decreased red blood cell count (anemia)
- Decreased neutrophil count (neutropenia)
- Decreased platelet count (thrombocytopenia)
- High blood pressure (hypertension)
- Dizziness
- Sinusitis (sinus inflammation)
- Nasopharyngitis (sore throat and runny nose)
- Urinary tract infection
- Herpes infections
- New cancers including skin cancer
Common
May affect up to 1 in 10 people
- Atrial fibrillation or atrial flutter (heart rhythm problems)
- Tumor lysis syndrome (rapid breakdown of cancer cells)
- Elevated liver enzymes (AST and ALT) — particularly when used in combination therapy for MCL
- Bronchitis
- Hepatitis B reactivation
- Pneumonia
Uncommon
May affect up to 1 in 100 people
- Progressive multifocal leukoencephalopathy (PML) — a serious brain infection with symptoms including memory loss, difficulty thinking, walking, or vision loss
- Aspergillus infection (fungal infection)
- Lymphocytosis (elevated lymphocyte count in the blood)
Bleeding Events
Bleeding is one of the most clinically significant side effects of Calquence. Because acalabrutinib inhibits BTK, which is involved in platelet function, patients may experience an increased tendency to bleed. Bleeding events can range from minor bruising and nosebleeds to serious and potentially life-threatening hemorrhages. In clinical trials, serious bleeding events (grade 3 or higher) occurred in approximately 3–4% of patients. Signs to watch for include:
- Black or tarry stools, or blood in the stool
- Pink or brown-colored urine
- Nosebleeds that are difficult to stop
- Unusual or easy bruising
- Coughing or vomiting blood
- Severe dizziness, weakness, or confusion
Cardiac Arrhythmias
Atrial fibrillation and atrial flutter have been reported in patients receiving Calquence. In clinical trials, the incidence of atrial fibrillation was approximately 4–5%, which is lower than reported rates with first-generation BTK inhibitors. Symptoms may include a rapid or irregular heartbeat, dizziness, lightheadedness, chest discomfort, or shortness of breath. Patients with pre-existing cardiac conditions or risk factors for arrhythmias should be monitored more closely. If you develop any cardiac symptoms, report them to your healthcare provider immediately.
Infections
Because Calquence affects the immune system by targeting B cells, patients are at an increased risk of infections during treatment. These range from common viral infections like upper respiratory tract infections and herpes virus reactivation to more serious bacterial and fungal infections including pneumonia and aspergillosis. Your doctor may prescribe prophylactic antimicrobial medications in some cases and will monitor you for signs of infection throughout treatment.
Tumor Lysis Syndrome
Tumor lysis syndrome (TLS) is a potentially serious complication that can occur when cancer cells break down rapidly, releasing their contents into the bloodstream. This can lead to kidney damage, heart rhythm disturbances, seizures, and other serious metabolic complications. TLS is more common in patients with a high tumor burden. Symptoms may include fever, chills, nausea, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark or cloudy urine, and unusual fatigue. Your doctor will take precautions to minimize this risk, which may include hydration and blood monitoring.
How Should You Store Calquence?
Proper storage of medications is important to maintain their effectiveness and safety. Calquence film-coated tablets do not require any special storage conditions. Keep the medicine at room temperature, protected from extreme heat and moisture. Store the tablets in their original blister packaging until you are ready to take them.
Keep Calquence out of the sight and reach of children. Young children may mistake the tablets for sweets, and accidental ingestion of a cancer medicine can be very dangerous. Always store your medication in a secure location.
Do not use Calquence after the expiry date printed on the blister foil and the outer carton after “EXP.” The expiry date refers to the last day of the stated month. Once expired, the tablet may no longer be effective or safe.
Do not dispose of unused or expired Calquence in household waste or down the drain. Return unused medicine to your pharmacy for proper disposal. This protects the environment and prevents accidental exposure to potent cancer medications. Many pharmacies and hospitals have medication take-back programs for safe disposal of cytotoxic medicines.
What Does Calquence Contain?
Active Ingredient
The active substance is acalabrutinib. Each film-coated tablet contains 100 mg of acalabrutinib (as acalabrutinib maleate). Acalabrutinib maleate is the salt form used in the formulation, which provides optimal bioavailability and stability. The molecular target of acalabrutinib is the cysteine residue Cys481 in the ATP-binding pocket of Bruton's tyrosine kinase.
Inactive Ingredients (Excipients)
The inactive ingredients serve important functions in the formulation, including ensuring tablet integrity, controlled disintegration, and adequate shelf stability:
- Tablet core: Mannitol (E421), microcrystalline cellulose (E460), low-substituted hydroxypropylcellulose (E463), and sodium stearyl fumarate
- Film coating: Hypromellose (E464), copovidone, titanium dioxide (E171), macrogol, medium-chain triglycerides, yellow iron oxide (E172), and red iron oxide (E172)
Appearance and Pack Sizes
Calquence is an orange, 7.5 × 13 mm, oval, biconvex film-coated tablet engraved with “ACA 100” on one side and plain on the other. The tablets are supplied in aluminum blisters containing either 8 or 10 tablets per blister strip. Each blister features sun and moon symbols to help you identify morning and evening doses. Both the sun blister and moon blister contain the same medicine at the same strength.
Calquence is available in cartons containing either 56 or 60 film-coated tablets. Not all pack sizes may be marketed in every country. Consult your pharmacist for information on available pack sizes in your region.
Frequently Asked Questions About Calquence
Medical References and Sources
This article is based on current medical research, regulatory submissions, and international guidelines. All claims are supported by scientific evidence from peer-reviewed sources.
- European Medicines Agency (EMA). “Calquence (acalabrutinib) – Summary of Product Characteristics.” EMA Product Information Official European regulatory documentation for Calquence.
- U.S. Food and Drug Administration (FDA). “CALQUENCE (acalabrutinib) – Prescribing Information.” FDA Label FDA-approved prescribing information for the United States.
- Sharman JP, et al. (2020). “Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzumab for treatment-naive chronic lymphocytic leukaemia (ELEVATE-TN): a randomised, controlled, phase 3 trial.” The Lancet. 395(10232):1278–1291. Pivotal phase 3 trial demonstrating efficacy in treatment-naive CLL. Evidence level: 1A.
- Ghia P, et al. (2020). “ASCEND: Phase III, randomized trial of acalabrutinib versus idelalisib plus rituximab or bendamustine plus rituximab in relapsed or refractory chronic lymphocytic leukemia.” Journal of Clinical Oncology. 38(25):2849–2861. Phase 3 trial in relapsed/refractory CLL. Evidence level: 1A.
- Wang M, et al. (2018). “Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial.” The Lancet. 391(10121):659–667. Pivotal trial establishing efficacy in relapsed/refractory MCL.
- Byrd JC, et al. (2021). “Acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia: results of the first randomized phase III trial (ELEVATE-RR).” Journal of Clinical Oncology. 39(31):3441–3452. Head-to-head comparison of acalabrutinib vs. ibrutinib in CLL. Evidence level: 1A.
- National Comprehensive Cancer Network (NCCN). “NCCN Clinical Practice Guidelines in Oncology: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.” Version 1.2025. Current treatment guidelines for CLL including BTK inhibitor recommendations.
- Eichhorst B, et al. (2021). “Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.” Annals of Oncology. 32(1):23–33. European Society for Medical Oncology guidelines for CLL management.
Evidence grading: This article uses the GRADE framework (Grading of Recommendations Assessment, Development and Evaluation) for evidence-based medicine. Evidence level 1A represents the highest quality of evidence, based on systematic reviews of randomized controlled trials.
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