acalabrutinib

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.

Availability ⬆ ⬇

Route/Dosage ⬆ ⬇

Mantle Cell Lymphoma

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.

Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia

PO (Adults ): 100 mg twice daily until disease progression or unacceptable toxicity. 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.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

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

Therapeutic effects:

Decreased progression of and improved progression-free survival of mantle cell lymphoma.
Improved progression-free survival in chronic lymphocytic leukemia/small lymphocytic lymphoma.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

Pharmacokinetics ⬆ ⬇

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

Patient/Family Teaching ⬆ ⬇

Explain the purpose and side effects of acalabrutinib. Instruct patient to take medication as directed, about 12 hr apart. If dose is missed by >3 hr, omit dose and take next dose at regularly scheduled time; do not double doses. Do not stop receiving drug without consulting health care professional. Advise patient to read Patient Information before starting and with each Rx refill in case of changes.
Tell patient to take drug ≥2 hr before or after antacids, ≥2 hr before taking a H₂ receptor antagonist and to avoid the use of proton pump inhibitors during therapy.
Advise patient to use protective clothing and sunscreen and to 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.
Advise patient to report any signs or symptoms of hepatotoxicity (abdominal pain, fever, dark urine, nausea, vomiting, weakness, fatigue, yellowing of the skin or eyes).
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, light-headedness or dizziness, fainting, shortness of breath, chest discomfort); or back, bone, joint, muscle, or neck pain occur.
Rep: May cause fetal harm and dystocia. Advise women of reproductive potential to use effective contraception during and for ≥1 wk after last dose and to avoid breastfeeding for ≥2 wk after last dose. Advise patient to notify health care professional promptly if pregnancy is suspected.

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Indications ⬇

Contraind./Precautions ⬆ ⬇