Acalabrutinib: Drug information

(For additional information see "Acalabrutinib: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)

Brand Names: US

Calquence

Brand Names: Canada

Calquence

Pharmacologic Category

Antineoplastic Agent;
Antineoplastic Agent, Bruton Tyrosine Kinase Inhibitor;
Antineoplastic Agent, Tyrosine Kinase Inhibitor

Dosing: Adult

Note: Consider prophylaxis in patients who are at increased risk for opportunistic infections. Due to the potential bleeding risk, consider benefit-risk of interrupting acalabrutinib treatment for 3 to 7 days prior to and after surgery (depending on the type of surgery and the risk of bleeding).

Chronic lymphocytic leukemia/small lymphocytic lymphoma

Chronic lymphocytic leukemia/small lymphocytic lymphoma:

Single-agent therapy: Oral: 100 mg approximately every 12 hours; continue until disease progression or unacceptable toxicity (Ref).

Combination therapy with obinutuzumab (previously untreated patients): Oral: 100 mg approximately every 12 hours; continue until disease progression or unacceptable toxicity; begin acalabrutinib at cycle 1 (each cycle is 28 days); obinutuzumab is administered for 6 cycles beginning at cycle 2 (Ref).

Mantle cell lymphoma, previously treated

Mantle cell lymphoma, previously treated: Oral: 100 mg approximately every 12 hours; continue until disease progression or unacceptable toxicity (Ref).

Waldenström macroglobulinemia

Waldenström macroglobulinemia (off-label use): Oral: 100 mg twice daily; continue until disease progression or unacceptable toxicity (Ref).

Missed doses: If a dose is missed by >3 hours, omit that dose and administer the next dose at the regularly scheduled time; do not administer extra doses to make up for a missed dose.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Note: Kidney function estimated using the MDRD (modification of diet in renal disease) equation.

eGFR ≥30 to <89 mL/minute/1.73 m²: There are no dosage adjustments provided in the manufacturer's labeling; however, there are no clinically significant differences in acalabrutinib (or the active metabolite) pharmacokinetics.

eGFR <30 mL/minute/1.73 m²: There are no dosage adjustments provided in the manufacturer's labeling (effect on pharmacokinetics is unknown).

eGFR <30 mL/minute/1.73 m² requiring dialysis: There are no dosage adjustments provided in the manufacturer's labeling (effect on pharmacokinetics is unknown).

Dosing: Hepatic Impairment: Adult

Mild to moderate impairment (Child-Pugh classes A and B): No dosage adjustment necessary.

Severe impairment (Child-Pugh class C): Avoid the use of acalabrutinib.

Dosing: Adjustment for Toxicity: Adult

**Acalabrutinib Recommended Dosage Modifications for Adverse Reactions^a**
Adverse reaction	Occurrence	Acalabrutinib^b dosage modification
^a Obinutuzumab may also require dosage modification (refer to Obinutuzumab monograph).
^b Acalabrutinib usual initial dose is 100 mg approximately every 12 hours.
Hematologic toxicities: Grade 3 thrombocytopenia with bleeding, grade 4 thrombocytopenia, or grade 4 neutropenia lasting >7 days	First and second occurrence	Interrupt acalabrutinib treatment; after toxicity has resolved to grade 1 or baseline, may resume at 100 mg approximately every 12 hours.
	Third occurrence	Interrupt acalabrutinib treatment; after toxicity has resolved to grade 1 or baseline, may resume with the dose reduced to 100 mg once daily.
	Fourth occurrence	Discontinue acalabrutinib.
Grade 3 or higher nonhematologic toxicities	First and second occurrence	Interrupt acalabrutinib treatment; after toxicity has resolved to grade 1 or baseline, may resume at 100 mg approximately every 12 hours.
	Third occurrence	Interrupt acalabrutinib treatment; after toxicity has resolved to grade 1 or baseline, may resume with the dose reduced to 100 mg once daily.
	Fourth occurrence	Discontinue acalabrutinib.
Arrhythmia	Any	Manage as appropriate.
Infection	Any	Manage promptly.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.

>10%:

Dermatologic: Skin rash (9% to 25%)

Endocrine & metabolic: Increased uric acid (15% to 22%)

Gastrointestinal: Abdominal pain (15%), constipation (15%), diarrhea (18% to 35%; grade ≥3: ≤3%), nausea (19% to 22%; grade ≥3: <1%), vomiting (13%; grade ≥3: 2%)

Genitourinary: Urinary tract infection (15%)

Hematologic & oncologic: Anemia (47% to 53%; grade ≥3: 10% to 15%), bruise (10% to 21%), hemorrhage (8% to 20%; grade ≥3: ≤2%; major hemorrhage: ≤3%), lymphocytosis (16% to 26%; grades ≥3: 15% to 19%), neutropenia (23% to 48%; grade ≥3: 13% to 23%), second primary malignant neoplasm (12%), thrombocytopenia (32% to 33%; grade ≥3 : 3% to 6%)

Hepatic: Increased serum alanine aminotransferase (15% to 20%), increased serum aspartate aminotransferase (13% to 17%), increased serum bilirubin (13% to 15%)

Infection: Infection (56% to 65%; serious infection [including bacterial, fungal, or viral infection: ≤19%])

Nervous system: Dizziness (12%), fatigue (15% to 28%), headache (22% to 39%)

Neuromuscular & skeletal: Arthralgia (8% to 16%), musculoskeletal pain (15% to 32%), myalgia (21%)

Respiratory: Lower respiratory tract infection (18% to 23%), upper respiratory tract infection (29% to 35%)

1% to 10%:

Cardiovascular: Atrial fibrillation (≤5%), atrial flutter (≤5%), hypertension (3%)

Hematologic & oncologic: Lymphocytopenia (grades 3/4: ≤7%), skin carcinoma (6%)

Infection: Herpes virus infection (5%), neutropenic infection (≤2%)

Renal: Increased serum creatinine (1% to 5%)

Respiratory: Epistaxis (6%)

Frequency not defined:

Infection: Cytomegalovirus disease, opportunistic infection, reactivation of HBV, reactivation of latent Epstein-Barr virus

Nervous system: Progressive multifocal leukoencephalopathy

Respiratory: Pneumonia, pneumonia due to Pneumocystis jirovecii

Contraindications

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Hypersensitivity to acalabrutinib or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Grade 3 or 4 cytopenias including neutropenia, anemia, thrombocytopenia, and lymphopenia have occurred in patients with hematologic malignancies treated with acalabrutinib.

• Cardiovascular adverse effects: Atrial fibrillation and atrial flutter (any grade) occurred in a small percentage of patients with hematologic malignancies treated with acalabrutinib; grade 3 events were reported. The risk may be increased in patients with cardiac risk factors, hypertension, prior arrhythmia, and acute infection.

• Hemorrhage: Serious hemorrhagic events (some fatal) have been reported in patients with hematologic malignancies who received acalabrutinib. Major hemorrhages (serious or ≥ grade 3 bleeding or any CNS bleeding) have been reported in a small percentage of patients. Bleeding events of any grade (excluding bruising and petechiae) occurred in almost one-fourth of patients. Acalabrutinib may further increase the risk of hemorrhage in patients receiving antithrombotic agents (assess risks versus benefits of concomitant therapy). Depending upon the type of surgery and the risk of bleeding, consider the benefit-risk of withholding acalabrutinib treatment for 3 to 7 days before and after surgery.

• Infection: Serious and fatal infections (including opportunistic infections) have occurred in patients with hematologic malignancies treated with acalabrutinib. Serious or ≥ grade 3 infections (bacterial, viral, or fungal) occurred in about one-fifth of these patients, most often due to respiratory infections. Infections usually occurred in the absence of grade 3 or 4 neutropenia (neutropenic infection occurred in a small percentage of patients). Opportunistic infections have included (although were not limited to) hepatitis B virus reactivation, fungal pneumonia, pneumocystis jirovecii pneumonia, Epstein-Barr virus reactivation, cytomegalovirus, and progressive multifocal leukoencephalopathy.

• Secondary malignancies: Second primary malignancies, including skin cancers and other solid tumors, have occurred in patients treated with acalabrutinib; the most frequent second primary malignancy was skin cancer (protection from sun exposure is recommended).

Special populations:

• Older adults: Patients ≥65 years of age experienced a higher incidence of serious or ≥ grade 3 adverse reactions.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral:

Calquence: 100 mg [DSC] [contains fd&c blue #2 (indigotine,indigo carmine)]

Tablet, Oral, as maleate:

Calquence: 100 mg

Generic Equivalent Available: US

Pricing: US

Tablets (Calquence Oral)

100 mg (per each): $307.36

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Calquence: 100 mg [contains corn starch, fd&c blue #2 (indigotine,indigo carmine)]

Tablet, Oral, as maleate:

Calquence: 100 mg

Prescribing and Access Restrictions

Available through specialty pharmacy distributors. Information regarding distribution is available from the manufacturer at www.calquence.com.

Administration: Adult

Oral: Administer doses ~12 hours apart. May administer with or without food. Swallow whole with water. Do not chew, crush, dissolve, or cut tablets; do not open, break, or chew capsules.

When administered on the same day as obinutuzumab (in previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma), administer acalabrutinib prior to obinutuzumab.

Use: Labeled Indications

Chronic lymphocytic leukemia or small lymphocytic lymphoma: Treatment of chronic lymphocytic leukemia or small lymphocytic lymphoma in adults.

Mantle cell lymphoma, previously treated: Treatment of mantle cell lymphoma in adults who have received at least 1 prior therapy.

Use: Off-Label: Adult

Waldenström macroglobulinemia

Medication Safety Issues

Sound-alike/look-alike issues:

Acalabrutinib may be confused with abemaciclib, afatinib, alectinib, alpelisib, avapritinib, axitinib, ibrutinib, zanubrutinib

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

Substrate of BCRP/ABCG2, CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): Acalabrutinib may enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Antacids: May decrease the serum concentration of Acalabrutinib. Management: Separate administration of acalabrutinib capsules from the administration of any antacid by at least 2 hours in order to minimize the potential for a significant interaction. Acalabrutinib tablets are not expected to interact with antacids. Risk D: Consider therapy modification

Anticoagulants: Acalabrutinib may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy

Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination

Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy

Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification

COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy

COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification

COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy

COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Acalabrutinib. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Acalabrutinib. Management: Avoid co-administration of strong CYP3A inducers in patients taking acalabrutinib. If strong CYP3A inducers cannot be avoided, increase the dose of acalabrutinib to 200 mg twice daily. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Acalabrutinib. Management: Reduce acalabrutinib dose to 100 mg once daily with concurrent use of a moderate CYP3A4 inhibitor. Monitor patient closely for both acalabrutinib response and evidence of adverse effects with any concurrent use. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Acalabrutinib. Risk X: Avoid combination

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination

Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification

Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Histamine H2 Receptor Antagonists: May decrease the serum concentration of Acalabrutinib. Management: Give acalabrutinib capsules 2 hours before a histamine H2 receptor antagonist (H2RA). No action is required if acalabrutinib tablets are coadministered with H2RAs. Risk D: Consider therapy modification

Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy

Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification

Inhibitors of the Proton Pump (PPIs and PCABs): May decrease the serum concentration of Acalabrutinib. This interaction is only applicable to acalabrutinib capsules. Risk X: Avoid combination

Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification

Mumps- Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination

Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy

Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy

Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy

Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination

Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification

Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification

Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification

Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy

Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination

Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination

Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination

Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination

Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination

Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy

Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification

Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination

Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination

Food Interactions

Administration with a high-fat, high-calorie meal (~918 calories; 59 g carbohydrate; 59 g fat; 39 g protein) results in C_max decreased by 54% (tablets) or 73% (capsules) and T_max delayed 1 to 2 hours.

Reproductive Considerations

Evaluate pregnancy status prior to use in patients who could become pregnant. Patients who could become pregnant should use effective contraception during therapy and for 1 week after the last acalabrutinib dose.

Pregnancy Considerations

Based on data from animal reproduction studies, in utero exposure to acalabrutinib may cause fetal harm.

Breastfeeding Considerations

It is not known if acalabrutinib is present in breast milk.

Due to the potential for adverse events in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy or for 2 weeks after the final acalabrutinib dose.

Monitoring Parameters

CBC regularly during treatment (was monitored monthly in studies). Evaluate pregnancy status prior to use in patients who could become pregnant. Monitor for signs/symptoms of atrial fibrillation and atrial flutter (eg, palpitations, dizziness, syncope, dyspnea); monitor for signs/symptoms of bleeding (in patients receiving antiplatelet or anticoagulant therapies), infection, and/or secondary malignancies. Monitor adherence.

The American Society of Clinical Oncology hepatitis B screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends hepatitis B virus (HBV) screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017]). Assess BP at baseline and each clinical visit (as well as weekly home monitoring for initial 3 months), obtain ECG at each clinical visit, obtain a baseline echocardiography (transthoracic preferred) in high-risk patients; echocardiography is also recommended in all patients who develop atrial fibrillation (ESC [Lyon 2022]).

Mechanism of Action

Acalabrutinib is a selective and irreversible second-generation Bruton's tyrosine kinase (BTK) inhibitor (Byrd 2016). Acalabrutinib and the active metabolite (ACP-5862) form a bond (covalent) with a cysteine residue in the active BTK site to inhibit BTK enzyme activity. BTK is an integral component of the B-cell receptor (BCR) and cytokine receptor pathways. BTK signals activation of the pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion. BTK inhibition results in decreased malignant B-cell proliferation and tumor growth.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: V_dss: Acalabrutinib: ~101 L; ACP-5862: ~67 L.

Protein binding: Acalabrutinib: 97.5%; ACP-5862: 98.6%; to human plasma protein.

Metabolism: Hepatic, primarily via CYP3A enzymes, and to a lesser degree by glutathione conjugation and amide hydrolysis; major (active) metabolite: ACP-5862 (geometric mean exposure 2- to 3-fold higher than acalabrutinib, but Bruton's tyrosine kinase inhibition by ACP-5862 is ~50% less potent than that of acalabrutinib).

Bioavailability: 25%; administration with a high-fat, high-calorie meal results in C_max decreased by 73% and T_max delayed 1 to 2 hours.

Half-life elimination: Tablets: Acalabrutinib: 1.4 hours; ACP-5862 (active metabolite): 6.4 hours; Capsules: Acalabrutinib: 1 hour; ACP-5862: 3.5 hours.

Time to peak: Tablets: Acalabrutinib: 0.5 hours; ACP-5862: 0.75 hours; Capsules: Acalabrutinib: 0.9 hours; ACP-5862: 1.6 hours.

Excretion: Feces (84%; <2% as unchanged drug); Urine (12%; <2% as unchanged drug).

Clearance: Acalabrutinib: 71 L/hour; ACP-5862 13 L/hour.

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Hepatic function impairment: Acalabrutinib exposure (AUC) was increased 1.9-fold in subjects with mild impairment (Child-Pugh class A), 1.5-fold in subjects with moderate impairment (Child-Pugh class B), and 5.3-fold in subjects with severe impairment (Child-Pugh class C), compared to subjects with normal hepatic function.

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AE) United Arab Emirates: Calquence;
(AR) Argentina: Calquence;
(AT) Austria: Calquence;
(AU) Australia: Calquence;
(BD) Bangladesh: Acalanib;
(BE) Belgium: Calquence;
(BG) Bulgaria: Calquence;
(BR) Brazil: Calquence;
(CH) Switzerland: Calquence;
(CO) Colombia: Calquence;
(CZ) Czech Republic: Calquence;
(DE) Germany: Calquence;
(EC) Ecuador: Calquence;
(EE) Estonia: Calquence;
(EG) Egypt: Calquence;
(ES) Spain: Calquence;
(FI) Finland: Calquence;
(FR) France: Calquence;
(GB) United Kingdom: Calquence;
(HK) Hong Kong: Calquence;
(HU) Hungary: Calquence;
(ID) Indonesia: Calquence;
(IE) Ireland: Calquence;
(IN) India: Acabrunat | Acaone;
(IT) Italy: Calquence;
(KR) Korea, Republic of: Calquence;
(KW) Kuwait: Calquence;
(LT) Lithuania: Calquence;
(LU) Luxembourg: Calquence;
(LV) Latvia: Calquence;
(MX) Mexico: Calquence;
(MY) Malaysia: Calquence;
(NL) Netherlands: Calquence;
(NO) Norway: Calquence;
(PE) Peru: Calquence;
(PL) Poland: Calquence;
(PR) Puerto Rico: Calquence;
(PT) Portugal: Calquence;
(QA) Qatar: Calquence;
(RO) Romania: Calquence;
(RU) Russian Federation: Calquence;
(SE) Sweden: Calquence;
(SG) Singapore: Calquence;
(SI) Slovenia: Calquence;
(SK) Slovakia: Calquence;
(UY) Uruguay: Calquence;
(ZA) South Africa: Calquence

Armenian SH, Lacchetti C, Barac A, et al. Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2017;35(8):893-911. doi:10.1200/JCO.2016.70.5400 [PubMed 27918725]
Byrd JC, Harrington B, O'Brien S, et al. Acalabrutinib (ACP-196) in relapsed chronic lymphocytic leukemia. N Engl J Med. 2016;374(4):323-332. [PubMed 26641137]
Calquence (acalabrutinib capsules) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; March 2022.
Calquence (acalabrutinib tablets) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; August 2022.
Calquence (acalabrutinib) [product monograph]. Mississauga, Ontario, Canada: AstraZeneca Canada Inc; November 2019.
Castillo JJ, Advani RH, Branagan AR, et al. Consensus treatment recommendations from the tenth International Workshop for Waldenström Macroglobulinaemia. Lancet Haematol. 2020;7(11):e827-e837. doi:10.1016/S2352-3026(20)30224-6 [PubMed 33091356]
Ghia P, Pluta A, Wach M, et al. ASCEND: phase III, randomized trial of acalabrutinib versus idelalisib plus rituximab or bendamustine plus rituximab in relapsed or refractory chronic lymphocytic leukemia. J Clin Oncol. 2020;38(25):2849-2861. doi:10.1200/JCO.19.03355 [PubMed 32459600]
Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
Lyon AR, López-Fernández T, Couch LS, et al; ESC Scientific Document Group. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022;43(41):4229-4361. doi:10.1093/eurheartj/ehac244 [PubMed 36017568]
Owen RG, McCarthy H, Rule S, et al. Acalabrutinib monotherapy in patients with Waldenström macroglobulinemia: a single-arm, multicentre, phase 2 study. Lancet Haematol. 2020;7(2):e112-e121. doi:10.1016/S2352-3026(19)30210-8 [PubMed 31866281]
Sharman JP, Egyed M, Jurczak W, et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzumab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. Lancet. 2020;395(10232):1278-1291. doi:10.1016/S0140-6736(20)30262-2 [PubMed 32305093]
Wang M, Rule S, Zinzani PL, et al. Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. Lancet. 2018;391(10121):659-667. doi:10.1016/S0140-6736(17)33108-2 [PubMed 29241979]

Topic 115440 Version 156.0

خرید پکیج

Acalabrutinib: Drug information