acalabrutinib

Absorption: 25% bioavailability following oral administration.

Distribution: Widely distributed to tissues.

Protein Binding: 97.5%.

Metabolism/Excretion: Metabolized in the liver primarily by the CYP3A isoenzyme to an active metabolite (ACP-5862) (50% less potent than acalabrutinib with regard to Bruton tyrosine kinase 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)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	0.75 hr	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Severe hepatic impairment;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Surgical procedures (if possible, withhold for 3–7 days pre- and postoperatively);
Cardiac risk factors, hypertension, previous arrhythmias, or acute infection (↑ risk of arrhythmias);
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: atrial fibrillation/flutter, VENTRICULAR ARRHYTHMIAS

Derm: rash

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

GU: ↑serum creatinine

Hemat: anemia, hemorrhage, neutropenia, thrombocytopenia

MS: myalgia

Neuro: headache, PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML)

Misc: fatigue, infection, second malignancy

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 ↓ levels and effectiveness; avoid concurrent use; if concurrent therapy is necessary, ↑ acalabrutinib dose.
Proton pump inhibitors, H2 receptor antagonists, or antacids may ↓ levels and effectiveness; 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. In patients with chronic lymphocytic leukemia or small lymphocytic lymphoma, when given in combination with obinutuzumab, initiate acalabrutinib in Cycle 1 and administer prior to obinutuzumab when given on the same day. 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 ⬆ ⬇

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 PML (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 postsurgery.
Monitor for signs and symptoms of atrial fibrillation, atrial flutter, ventricular arrhythmia (palpitations, light-headedness, dizziness, fainting, shortness of breath, chest discomfort), and hypertension periodically during therapy. Manage as needed.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
- Monitor CBC and platelet count monthly during therapy, especially if patient is receiving antiplatelet or anticoagulant therapy. If 1st or 2nd occurrence of ≥Grade 3 nonhematologic toxicities, Grade 3 thrombocytopenia with bleeding, 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 3rd occurrence of ≥Grade 3 nonhematologic toxicities, Grade 3 thrombocytopenia with bleeding, Grade 4 thrombocytopenia, or Grade 4 neutropenia lasting 7 days or longer occurs: Hold therapy and resume at 100 mg once daily once toxicity resolved to Grade 1 or baseline level. If 4th occurrence of ≥Grade 3 nonhematologic toxicities, Grade 3 thrombocytopenia with bleeding, Grade 4 thrombocytopenia, or Grade 4 neutropenia lasting 7 days or longer occurs: Discontinue therapy.
- Monitor AST, ALT, and total bilirubin at baseline and regularly during treatment. If hepatotoxicity occurs, discontinue therapy.

Implementation ⬆ ⬇

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

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication as directed. If dose is missed by >3 hr, 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 with blood or that looks like coffee grounds; coughing up blood or blood clots; dizziness; weakness; confusion; changes in speech; prolonged headache); infection (fever, chills, flu-like symptoms); heart rhythm problems (fast or irregular heartbeat, feeling light-headed or dizzy, fainting, shortness of breath, chest discomfort); or back, bone, joint, muscle, or neck pain occur.
Rep: May cause fetal harm and dystocia. Advise females of reproductive potential to use effective contraception during and for at least 1 wk after last dose and to avoid breastfeeding for at least 2 wk after last dose. Advise patient to notify health care professional promptly if pregnancy is suspected.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇