acalabrutinib

General

Pronunciation:
a-kal-a-broo-ti-nib

Trade Name(s)

  • Calquence

Ther. Class.
antineoplastics

Pharm. Class.
kinase inhibitors

Indications

Mantle cell lymphoma (MCL) in patients who have not responded to ≥1 previous therapy.

Action

Binds to and inactivates the enzymatic activity of Bruton tyrosine kinase (BTK), which leads to inhibition of B-cell proliferation and survival.

Therapeutic Effect(s):

Decreased progression of MCL.

Pharmacokinetics

Absorption: 25% bioavailability following oral administration.

Distribution: Widely distributed to tissues.

Protein Binding: 97.5%.

Metabolism and Excretion: Metabolized in the liver primarily by the CYP3A enzyme system to an active metabolite (ACP-5862) (50% less potent than acalabrutinib with regard to BTK inhibition). One minor metabolite has antineoplastic activity. Metabolites are mostly eliminated in feces (84%), 12% excreted in urine.

Half-life: Acalabrutinib–0.9 hr; ACP-5862–6.9 hr.

TIME/ACTION PROFILE (plasma concentrations)

ROUTEONSETPEAKDURATION
POunknown0.75 hrunknown

Contraindication/Precautions

Contraindicated in:

  • Concurrent use of strong CYP3A4 inducers/inhibitors;
  • OB: May cause fetal harm; avoid pregnancy;
  • Lactation: Avoid breast feeding.

Use Cautiously in:

  • Concurrent use of moderate inhibitors of CYP3A4 (↓ dose of acalabrutinib);
  • Concurrent use of antiplatelet agents/anticoagulants (↑ risk of bleeding);
  • Surgical procedures (if possible withhold for 3–7 days pre- and post-operatively);
  • Pedi: Safety and effectiveness in children not established.

Adverse Reactions/Side Effects

CNS: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML), headache

CV: atrial fibrillation/flutter

Derm: rash

GI: abdominal pain, constipation, diarrhea, nausea, vomiting

GU: ↑ serum creatinine

Hemat: HEMORRHAGE, anemia, neutropenia, thrombocytopenia

MS: myalgia

Misc: INFECTION, SECOND MALIGNANCIES, fatigue

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

  • Strong CYP3A inhibitors, including itraconazole can significantly ↑ levels and risk of toxicity; avoid concurrent use. If short-term use of strong CYP3A inhibitor is necessary, acalabrutinib may be temporarily interrupted.
  • Moderate CYP3A4 inhibitors may ↑ levels and risk of toxicity; avoid concurrent use; if concurrent therapy is necessary, ↓ acalabrutinib dose.
  • Strong CYP3A inducers, including rifampin significantly ↓ blood levels and effectiveness; avoid concurrent use; if concurrent therapy is necessary, ↑ acalabrutinib dose.
  • Proton pump inhibitors, H2 receptor antagonists, or antacids may ↓ levels; separate antacids from acalabrutinib by ≥2 hr; take acalabrutinib 2 hr before H2 receptor antagonist; avoid concurrent use with proton pump inhibitors.

Route/Dosage

PO (Adults) 100 mg twice daily until disease progression or unacceptable toxicity. Concurrent use of moderate CYP3A inhibitors–100 mg once daily until disease progression or unacceptable toxicity; Concurrent use of strong CYP3A inducers–200 mg twice daily until disease progression or unacceptable toxicity.

Availability

Capsules: 100 mg

Assessment

  • Assess for signs and symptoms of infection (fever, chills) during therapy. Pneumonia (dyspnea, chest pain, cough, fatigue, fever, sweating, chills), reactivation of hepatitis B (abdominal pain, fever, joint pain, dark urine, anorexia, nausea, vomiting, weakness, fatigue, jaundice), and progressive multifocal leukoencephalopathy (new onset or changes in pre-existing neurological signs and symptoms) are most common.
  • Monitor for signs and symptoms of bleeding (blood in stools or urine, prolonged or uncontrolled bleeding) during therapy. Acalabrutinib may need to be held 3–7 days pre and post surgery.
  • Monitor for signs and symptoms of atrial fibrillation and atrial flutter (palpitations, lightheadedness, dizziness, fainting, shortness of breath, chest discomfort) periodically during therapy. Manage as needed.

Lab Test Considerations:

Monitor CBC and platelet count monthly during therapy, especially if patient is receiving antiplatelet or anticoagulant therapy. If 1st, 2nd, or 3rd occurrence of ≥Grade 3 nonhematologic toxicities, Grade 3 thrombocytopenia with bleeding or Grade 4 thrombocytopenia, or Grade 4 neutropenia lasting 7 days or longer occurs: hold therapy and resume at 100 mg twice daily once toxicity resolved to Grade 1 or baseline level. If 4th occurrence of ≥Grade 3 nonhematologic toxicities, Grade 3 thrombocytopenia with bleeding or Grade 4 thrombocytopenia, or Grade 4 neutropenia lasting 7 days or longer occurs: discontinue therapy.

Potential Diagnoses

Implementation

  • PO Administer every 12 hrs without regard to food. Swallow whole; do not break, open or chew capsules.
    • Administer antacids at least 2 hrs before or 2 hrs after acalabrutinib. Administer acalabrutinib at least 2 hrs before H2 antagonists.

Patient/Family Teaching

  • Instruct patient to take medication as directed. If dose is missed by >3 hrs, omit dose and take next dose at regularly scheduled time; do not double doses.
  • Advise patient to use protective clothing and sunscreen and avoid sun exposure to prevent secondary skin malignancies.
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
  • Instruct patient to notify health care professional if signs of bleeding (blood in stools or black, tarry stools, pink or brown urine, unexpected bleeding, severe or uncontrolled bleeding, vomit blood or vomit that looks like coffee grounds, cough up blood or blood clots, dizziness, weakness, confusion, changes in speech, prolonged headache), infection (fever, chills, flu-like symptoms) or heart rhythmm problems (fast or irregular heartbeat, feeling lightheaded or dizzy, fainting, shortness of breath, chest discomfort).
  • Advise female patient to notify health care professional if pregnancy is planned or suspected and to avoid breast feeding for at least 2 wks after last dose.

Evaluation/Desired Outcomes

Decreased progression of MCL.

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