acalabrutinib (Rx)

Brand and Other Names:Calquence
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 100mg

Mantle Cell Lymphoma (MCL)

Patients who have received at least 1 prior therapy

100 mg PO q12hr

Also see Administration

Dosage Modifications

Management of Grade ≥3 adverse reactions

  • Grade 3 or greater nonhematologic toxicities,
  • Grade 3 thrombocytopenia with bleeding,
  • Grade 4 thrombocytopenia, OR
  • Grade 4 neutropenia lasting >7 days
  • First to third occurrence
    • Interrupt drug
    • Once toxicity resolves to Grade ≤1, resume therapy at 100 mg PO BID
  • Fourth occurrence
    • Discontinue drug

Coadministration with CYP3A4 inhibitors or inducers

  • Strong CYP3A4 inhibitors: Avoid concomitant use; if CYP3A4 inhibitors will be used short-term (eg, anti-infectives for ≤7 days), interrupt treatment
  • Moderate CYP3A4 inhibitor: 100 mg PO qDay
  • Strong CYP3A4 inducers: Avoid concomitant use; if these inducers cannot be avoided, increase dose to 200 mg PO BID

Coadministration with gastric acid reducing agents

  • Proton pump inhibitors: Avoid concomitant use
  • H2-receptor antagonists: Take dose 2 hr before taking a H2-receptor antagonist
  • Antacids: Separate dosing by at least 2 hr

Dosing Considerations

Indication is approved under accelerated approval based on overall response; continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials

Safety and efficacy not established

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Interactions

Interaction Checker

and acalabrutinib

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            All grades

            • Decreased hemoglobin (46%)
            • Decreased platelets (44%)
            • Headache (39%)
            • Decreased neutrophils (36%)
            • Diarrhea (31%)
            • Fatigue (28%)
            • Myalgia (21%)
            • Bruising (21%)
            • Nausea (19%)
            • Rash (18%)
            • Abdominal pain (15%)
            • Constipation (15%)
            • Vomiting (13%)

            Grade ≥3

            • Decreased neutrophils (15%)
            • Decreased platelets (12%)

            1-10%

            Increased creatinine, 1.5-3X ULN (4.8%)

            All grades

            • Hemorrhage/hematoma (8%)
            • Epistaxis (6%)

            Grade ≥3

            • Decreased hemoglobin (10%)
            • Diarrhea (3.2%)
            • Abdominal pain (1.6%)
            • Headache (1.6%)
            • Vomiting (1.6%)

            <1%

            Grade ≥3

            • Nausea (0.8%)
            • Fatigue (0.8%)
            • Myalgia (0.8%)
            • Rash (0.8%)
            • Hemorrhage/hematoma (0.8%)
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            Warnings

            Contraindications

            None

            Cautions

            Serious hemorrhagic events, including fatal events, reported; the mechanism for the bleeding events is not well understood; acalabrutinib may further increase hemorrhage risk in patients receiving antiplatelet or anticoagulant therapies, and patients should be monitored for signs of bleeding; consider the benefit-risk of withholding acalabrutinib for 3-7 days presurgery and postsurgery depending on the type of surgery and the risk of bleeding

            Serious infections (bacterial, viral, or fungal), including fatal events and opportunistic infections, reported; monitor for infection and consider prophylaxis in patients who are at increased risk for opportunistic infections

            Cytopenias reported, including neutropenia, anemia, and thrombocytopenia; assess complete blood cell counts monthly during treatment

            Second primary malignancies, including nonskin carcinomas, have occurred in patients with hematologic malignancies treated with acalabrutinib; the most frequent was skin cancer; advise patients regarding need for protection from sun exposure

            Atrial fibrillation and flutter occurred (rare) during clinical trials; monitor patients and manage as appropriate

            Drug interaction overview

            • Coadministration with CYP3A inhibitors or inducers
              • Acalabrutinib is predominantly metabolized by CYP3A enzymes
              • CYP3A inhibitors are expected to increase acalabrutinib systemic exposure
              • CYP3A inducers are expected to decrease acalabrutinib systemic exposure
              • See Dosage Modifications
            • Coadministration with gastric acid-reducing agents
              • Coadministration with PPIs, H2-antagonists, or antacids may decrease acalabrutinib plasma concentrations
              • See Dosage Modifications
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            Pregnancy & Lactation

            Pregnancy

            Based on findings in animals, may cause fetal harm when administered to pregnant women

            There are no available data in pregnant women to inform the drug-associated risk

            In animal reproduction studies, administration of acalabrutinib to pregnant rabbits during organogenesis resulted in reduced fetal growth; rabbit maternal exposures (AUC) were ~4 times that of humans given a dose of 100 mg twice daily

            Advise pregnant women of the potential risk to a fetus

            Lactation

            No data are available regarding the presence of acalabrutinib or its active metabolite in human milk, its effects on the breastfed child, or on milk production

            Acalabrutinib and its active metabolite were present in the milk of lactating rats

            Owing to the potential for adverse reactions in a breastfed child, advise lactating women not to breastfeed while taking acalabrutinib and for at least 2 weeks after the final dose

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Bruton tyrosine kinase (BTK) inhibitor; acalabrutinib and its active metabolite, ACP-5862, form a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity

            BTK is a signaling molecule of the B-cell antigen receptor (BCR) and cytokine receptor pathways; in B cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion

            Absorption

            Absolute bioavailability: 25%

            Peak plasma time: 0.75 hr; administered under fasting conditions delayed Tmax by 1-2 hr

            Peak plasma concentration: 323 ng/mL; administered under fasting conditions decreased Cmax by 73%

            AUC: 1111 ng·h/mL

            High-fat, high-calorie meal did not affect AUC

            Distribution

            Protein bound: 97.5%

            Vd: 34 L

            Metabolism

            Predominantly metabolized by CYP3A enzymes, and to a minor extent, by glutathione conjugation and amide hydrolysis, based on in vitro studies

            Active metabolite: ACP-5862 with mean exposure (AUC) ~2- to 3-fold higher than the exposure of acalabrutinib; ACP-5862 is ~50% less potent than acalabrutinib with regard to BTK inhibition

            Elimination

            Half-life: 0.9 hr; 6.9 hr (active metabolite)

            Clearance: 159 L/hr

            Excretion: 84% feces; 12% urine

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            Administration

            Oral Administration

            Take with or without food

            Swallow capsule whole with water

            Do not open, break, or chew the capsules

            Missed dose

            • If a dose is missed by >3 hr, skip dose; take next dose at its regularly scheduled time
            • Extra capsules should not be taken to make up for a missed dose

            Storage

            Store at room temperature, 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F)

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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.