CALQUENCE
Clinical safety rating
cautionComprehensive clinical and safety monograph for CALQUENCE (CALQUENCE).
Comprehensive clinical and safety monograph for CALQUENCE (CALQUENCE).
FDA-approved: Treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapyFDA-approved: Treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)Off-label: Treatment of Waldenström macroglobulinemiaOff-label: Treatment of marginal zone lymphoma
Anemia (low number of red blood cells), Decreased white blood cell count (neutrophils), Upper respiratory tract infection, Low blood platelets, Headache, Diarrhea, Musculoskeletal (bone, muscle or joint) pain
Acalabrutinib is a selective, irreversible inhibitor of Bruton tyrosine kinase (BTK). BTK is a key signaling molecule in the B-cell antigen receptor (BCR) and cytokine receptor pathways. In B cells, BTK activation results in pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion. Acalabrutinib and its active metabolite, acalabrutinib M27, form a covalent bond with the cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity and downstream signaling, thereby reducing malignant B-cell survival and proliferation.
| Metabolism | Primarily metabolized by CYP3A4 to form acalabrutinib M27 (active metabolite). Minor routes include glutathione conjugation and hydrolysis. Acalabrutinib is also a substrate of CYP3A5 and to a lesser extent CYP2C8. |
| Excretion | Fecal (77%), renal (15% as unchanged drug and metabolites). |
| Half-life | Terminal elimination half-life is 8 hours at steady state, supporting twice-daily dosing. |
| Protein binding | 97% bound to plasma proteins (albumin and alpha-1 acid glycoprotein). |
| Volume of Distribution | Approximately 10 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 70%; absorption is unaffected by food. |
| Onset of Action | Peak plasma concentration achieved 0.5–1.5 hours after oral administration; clinical response (e.g., reduction in lymphadenopathy) observed within weeks. |
| Duration of Action | Duration of action is 12 hours, consistent with dosing every 12 hours. Continuous BTK inhibition requires sustained plasma levels. |
| Molecular Weight | 506.55 |
100 mg orally twice daily.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for CrCl >=30 mL/min. For CrCl <30 mL/min, reduce dose to 100 mg once daily. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose to 100 mg once daily. Child-Pugh C: avoid use. |
| Pediatric use | Not established for pediatric patients. |
| Geriatric use | No specific dose adjustment beyond standard monitoring for toxicity. |
| 1st trimester | Avoid; based on animal data, may cause fetal harm. No adequate human studies. |
| 2nd trimester | Avoid; based on animal data, may cause fetal harm. No adequate human studies. |
| 3rd trimester | Avoid; based on animal data, may cause fetal harm. No adequate human studies. |
Clinical note
Comprehensive clinical and safety monograph for CALQUENCE (CALQUENCE).
| Placental transfer | Likely transferred due to low molecular weight and animal studies showing embryotoxicity. |
| Breastfeeding | No data on presence in human milk or effects on infant. Consider developmental risks. |
| Lactation Rating | L5 |
| Teratogenic Risk | Based on animal studies and its mechanism of action (Bruton's tyrosine kinase inhibitor), CALQUENCE (acalabrutinib) may cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of acalabrutinib to pregnant rats during organogenesis resulted in embryofetal mortality and malformations at exposures below the clinical exposure at the recommended human dose. There are no adequate and well-controlled studies in pregnant women. The drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. First trimester exposure poses highest risk; second and third trimesters also carry risk of fetal toxicity. |
| Fetal Monitoring | Monitor pregnant women receiving CALQUENCE for potential fetal effects. Perform pregnancy testing prior to initiation of therapy in females of reproductive potential. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 week after the last dose. Monitor for maternal hemorrhage (CALQUENCE increases risk of bleeding) and infections due to immunosuppression. |
| Fertility Effects | Based on animal studies, CALQUENCE may impair fertility in females of reproductive potential. In female rats, acalabrutinib administered at doses resulting in exposures approximately 4 times the clinical exposure caused disruption of estrous cycling, reduced numbers of corpora lutea, and decreased fertility indices. Reversibility of these effects was not assessed. No data are available on male fertility. |
■ FDA Black Box Warning
None
| Serious Effects |
Known hypersensitivity to acalabrutinib or any excipients
| Precautions | Hemorrhage: Fatal and serious bleeding events have occurred. Monitor for signs of bleeding, especially in patients on antithrombotic agents or with thrombocytopenia. Consider benefit-risk of holding acalabrutinib for 3-7 days pre- and post-surgery., Infections: Fatal and serious infections, including opportunistic infections, have occurred. Monitor for signs and symptoms of infection and treat promptly., Cytopenias: Grade 3 or 4 cytopenias (neutropenia, anemia, thrombocytopenia) can occur. Monitor complete blood counts regularly., Second primary malignancies: Including skin cancers and other solid tumors. Advise patients to use sun protection., Cardiac arrhythmias: Atrial fibrillation and atrial flutter have been reported. Monitor for cardiac arrhythmias and manage appropriately., Hepatotoxicity: Elevations in liver enzymes have occurred. Monitor liver function tests., Interstitial lung disease (ILD): Cases of ILD/pneumonitis have occurred. Monitor for pulmonary symptoms and manage as indicated. |
| Food/Dietary | Avoid grapefruit, grapefruit juice, Seville oranges, and starfruit (which contain strong CYP3A4 inhibitors) during treatment with CALQUENCE. No other specific food restrictions are required. The drug can be taken with or without food. |
| Clinical Pearls | CALQUENCE (acalabrutinib) is a selective BTK inhibitor used in B-cell malignancies. It has fewer off-target effects than ibrutinib, particularly less atrial fibrillation and bleeding. Monitor for atrial fibrillation, hypertension, infections (especially respiratory), and bleeding events. Drug interactions with CYP3A4 inducers/inhibitors are significant; avoid concurrent use with strong CYP3A4 inhibitors or inducers. May need to hold for 3 days before and after procedures due to bleeding risk. Consider antiviral prophylaxis for herpes zoster in high-risk patients. Do not crush or break capsules; swallow whole with water. Dose adjustment for severe hepatic impairment (Child-Pugh C) is required. |
| Patient Advice | Take CALQUENCE exactly as prescribed, usually twice daily with or without food. Swallow capsules whole; do not open, break, or chew them. · Avoid grapefruit, grapefruit juice, Seville oranges, and starfruit while taking this medication, as they can affect how the drug works. · Tell your healthcare provider about all medications you take, including prescription, over-the-counter, vitamins, and herbal products, especially St. John's wort. · CALQUENCE can increase your risk of serious infections, bleeding problems, and heart rhythm issues. Report any signs of infection (fever, chills), unusual bruising or bleeding, palpitations, or dizziness. · Do not stop taking CALQUENCE without consulting your healthcare provider. If you miss a dose, take it as soon as you remember unless it is less than 6 hours until your next dose; then skip the missed dose. · Women who are pregnant or breastfeeding should not take CALQUENCE. Effective contraception is needed during treatment and for 1 week after the last dose. · Keep CALQUENCE in the original container at room temperature (68°F to 77°F), away from moisture and light. |
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