Acalabrutinib – Uses, Dosage, Side Effects, Interactions

Acalabrutinib is an oral inhibitor of Bruton’s tyrosine kinase that is used in the therapy of B cell malignancies including refractory mantle cell lymphoma and chronic lymphocytic leukemia. Acalabrutinib has been associated with mild-to-moderate serum enzyme elevations during therapy but has not been linked to instances of idiosyncratic acute liver injury, although it has been associated with cases of reactivation of hepatitis B which can be severe and even fatal.

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

This 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

The following conditions are contraindicated with this drug. Check with your physician if you have any of the following:

• 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

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 disease progresses or unacceptable toxicity.

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

Most Common

• 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
• headache
• nausea
• vomiting
• constipation
• diarrhea
• abdominal pain
• rash
• light bruising or small red or purple spots on the skin
• joint or muscle pain
• extreme tiredness

More Common

• dizziness, weakness, confusion, headache,
• speech problems,
• black or bloody stools,
• pink or brown urine, or
• coughing up blood or vomit that looks like coffee grounds.
• bruising;
• headache;
• muscle pain;
• diarrhea;
• feeling tired.
• an active or chronic infection;
• a heart rhythm disorder
• bleeding problems; or

Rare

• unusual bleeding (nose, mouth, vagina, or rectum), or any bleeding that will not stop;
• signs of bleeding inside your body–dizziness, weakness, confusion, problems with speech, prolonged headache, black or bloody stools, pink or brown urine, or coughing up blood or vomit that looks like coffee grounds;
• heart rhythm problems–chest pain, shortness of breath, pounding heartbeats or fluttering in your chest, feeling light-headed;
• low red blood cells (anemia)–pale skin, unusual tiredness, feeling light-headed or short of breath, cold hands and feet;
• signs of infection–fever, chills, tiredness, flu-like symptoms, cough with mucus, chest pain, trouble breathing; or
• 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).

Drug Interactions

Drug-Food Interactions

Pregnancy and Lactation

Pregnancy

TGA pregnancy category C

You should not become pregnant while you are taking acalabrutinib. You should not start taking acalabrutinib until a pregnancy test has shown that you are not pregnant and you should use birth control to prevent pregnancy during your treatment and for at least 1 week after your final dose.

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