Use in Cancer

Acalabrutinib is approved to treat:

• Chronic lymphocytic leukemia or small lymphocytic lymphoma in adults.
• Mantle cell lymphoma in adults who have received at least one other type of treatment.¹

¹This use is approved under FDA’s Accelerated Approval Program. As a condition of approval, a confirmatory trial(s) must show that acalabrutinib provides a clinical benefit in these patients.

Acalabrutinib is also being studied in the treatment of other types of cancer.

Contraindications

• Safety and efficacy have not been established in patients younger than 18 years.
• a bad infection
• an increased risk of bleeding
• decreased blood platelets
• low levels of a type of white blood cell called neutrophils
• atrial fibrillation
• pregnancy
• a patient who is producing milk and breastfeeding
• Anticoagulant therapy, bleeding, dental work, intracranial bleeding, surgery.
• Anemia, neutropenia, thrombocytopenia.
• Fungal infection, hepatitis B exacerbation, infection, progressive multifocal leukoencephalopathy, viral infection.
• New primary malignancy, sunlight (UV) exposure.

Dosage

Strengths: 100 mg

Lymphoma

• 100 mg orally every 12 hours
• Start treatment at cycle 1 (each cycle is 28 days) when use concomitantly with obinutuzumab.
• Start obinutuzumab at Cycle 2 for a total of 6 cycles and refer to the obinutuzumab prescribing information for recommended dosing; administer this drug prior to obinutuzumab when given on the same day.
• Treatment should be continued until the disease progresses or has unacceptable toxicity.
• As monotherapy for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy
• As monotherapy or in combination with obinutuzumab for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)

Dose Adjustments

RECOMMENDED DOSE ADJUSTMENTS FOR ADVERSE REACTIONS:
Grade 3 or greater nonhematologic toxicities, Grade 3 thrombocytopenia with bleeding, Grade 4 thrombocytopenia, or Grade 4 neutropenia lasting longer than 7 days:

• First and second occurrence: Temporarily interrupt this drug; when toxicity has resolved to Grade 1 or baseline, this drug may be resumed at 100 mg orally 2 times a day
• Third occurrence: Temporarily interrupt this drug; when toxicity has resolved to Grade 1 or baseline, this drug may be resumed at 100 mg orally once daily
• Fourth occurrence: Discontinue this drug

CONCOMITANT USE WITH CYP450 3A INDUCERS OR INHIBITORS:

• Strong CYP450 3A inhibitor: Avoid concomitant use; if the inhibitor will be used short-term (e.g., anti-infectives for up to 7 days), interrupt this drug
• Moderate CYP450 3A inhibitor: 100 mg orally once daily
• Strong CYP450 3A inducer: Avoid concomitant use. If these inducers cannot be avoided, increase the dose to 200 mg approximately every 12 hours

CONCOMITANT USE WITH GASTRIC ACID-REDUCING AGENTS:

• Proton pump inhibitors: Avoid concomitant use
• H2 receptor antagonist: Administer this drug 2 hours before or 10 hours after taking an H2-receptor antagonist
• Antacid: Separate dosing by at least 2 hours

Side Effects

The Most Common

• headache
• nausea
• vomiting
• constipation
• diarrhea
• abdominal pain
• rash
• light bruising or small red or purple spots on skin
• joint or muscle pain
• extreme tiredness
• fever, sore throat, chills, or other signs of infection
• cough, shortness of breath, chest pain when you breathe or cough, fever
• fast or irregular heartbeat, palpitations, feeling lightheaded or dizzy, fainting, shortness of breath, chest pain
• unusual or severe bleeding or bruising
• blood in your stools or black, tarry stools; pink or brown urine; vomiting blood or coffee-ground vomit; coughing up blood
• feeling dizzy, weak, or confused; changes in speech; a headache that lasts a long time

More Common

• arm, leg, and back pain
• constipation
• decreased appetite
• diarrhea
• dizziness
• headache
• mouth sores
• nausea
• skin rash or redness
• stomach pain or cramps
• tingling, pain, or numbness in the hands, legs, or feet
• tiredness
• trouble sleeping
• unsteadiness, causing falls
• vomiting
• watery eyes
• unusual bleeding (nose, mouth, vagina, or rectum), or any bleeding that will not stop;
• heart rhythm problems–chest pain, shortness of breath, pounding heartbeats or fluttering in your chest, feeling light-headed;
• signs of a serious brain infection–any change in your mental state, decreased vision, weakness on one side of your body, or problems with walking (may start gradually and get worse quickly).

Rare

• memory loss
• new cancers (skin or other)
• rapid, pounding heartbeat
• signs of anemia (low red blood cells; e.g., dizziness, pale skin, unusual tiredness or weakness, shortness of breath)
• signs of clotting problems (e.g., unusual nosebleeds, bruising, blood in urine, coughing blood, bleeding gums, cuts that don’t stop bleeding)
• signs of infection (symptoms may include fever or chills, severe diarrhea, shortness of breath, prolonged dizziness, headache, stiff neck, weight loss, or listlessness)
• symptoms of irregular heartbeat (e.g., chest pain, dizziness, confusion, rapid, pounding heartbeat, shortness of breath)
• symptoms of low blood pressure (e.g., fainting, dizziness, lightheadedness, blurred vision, nausea)
• symptoms of pneumonia (e.g., cough with or without mucus, fever, chills, difficult and painful breathing, shortness of breath when climbing stairs)
• signs of bleeding in the stomach (e.g., bloody, black, or tarry stools, spitting up of blood, vomiting blood or material that looks like coffee grounds)

Drug Interaction

There may be an interaction between acalabrutinib and any of the following:

• antacids (e.g., aluminum hydroxide, calcium carbonate, magnesium hydroxide)
• anticancer medications (e.g., cladribine, irinotecan)
• anticoagulants (e.g. apixaban, dabigatran, edoxaban, rivaroxaban, warfarin)
• apalutamide
• aripiprazole
• “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
• baricitinib
• BCG
• bosentan
• calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
• carbamazepine
• clozapine
• cobicistat
• conivaptan
• deferasirox
• denosumab
• dronedarone
• echinacea
• enzalutamide
• fingolimod
• grapefruit juice
• H2 antagonists (e.g., famotidine, ranitidine)
• HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs; e.g., efavirenz, etravirine, nevirapine)
• HIV protease inhibitors (e.g., atazanavir, indinavir, ritonavir, saquinavir)
• leflunomide
• macrolide antibiotics (e.g., clarithromycin, erythromycin)
• mesalamine
• mifepristone
• mitotane
• modafinil
• natalizumab
• ocrelizumab
• phenobarbital
• phenytoin
• pimecrolimus
• primidone
• protein kinase inhibitors (e.g., crizotinib, dabrafenib, idelalisib, imatinib, palbociclib,)
• proton pump inhibitors (e.g., lansoprazole, omeprazole)
• rifabutin
• rifampin
• roflumilast
• St. John’s wort
• sarilumab
• sertraline
• stiripentol
• tocilizumab
• tofacitinib
• vaccines

Pregnancy And Lactation

US FDA pregnancy category Not Assigned

Pregnancy

This medication should not be used during pregnancy. If you become pregnant while taking this medication, contact your doctor immediately.

Lactation

No information is available on the clinical use of acalabrutinib during breastfeeding. Because acalabrutinib is over 97% bound to plasma proteins, and the half-life of the drug and metabolite are less than 7 hours, the amount in milk is likely to be low. However, the protein binding of the active metabolite is not known and the manufacturer recommends that breastfeeding be discontinued during acalabrutinib therapy and for at least 2 weeks after the final dose.

References