Ibrutinib

• Imbruvica^®

Percentages are for all grades of toxicity unless otherwise noted

>10% (MCL)

Increased serum creatinine, 1.5 x ULN (67%)

Platelets decreased, all grades (57%)

Diarrhea (51%)

Hemorrhage (48%)

Neutrophils decreased, all grades (47%)

Hemoglobin decreased, all grades (41%)

Fatigue (41%)

Musculoskeletal pain (37%)

Peripheral edema (35%)

URI infection (34%)

Nausea (31%)

Bruising (30%)

Neutropenia, grades 3 or 4 (29%)

Dyspnea (27%)

Constipation (25%)

Rash (25%)

Abdominal pain (24%)

Vomiting (23%)

Decreased appetite (221%)

Cough (19%)

Pyrexia (18%)

Stomatitis (17%)

Thrombocytopenia, grades 3 or 4 (17%)

UTI infection (14%)

Pneumonia (14%)

Skin infections (14%)

Asthenia (14%)

Muscle spasms (14%)

Dizziness (14%)

Sinusitis (13%)

Headache (13%)

Dehydration (12%)

Dyspepsia (11%)

Petechiae (11%)

Arthralgia (11%)

Epistaxis (11%)

>10% (CLL)

Platelets decreased, all grades (71%)

Diarrhea (63%)

Bruising (54%)

Neutrophils decreased, all grades (54%)

URT infection (48%)

Hemoglobin decreased, all grades (44%)

Fatigue (31%)

Rash (27%)

Musculoskeletal pain (27%)

Neutropenia, grades 3 or 4 (27%)

Pyrexia (25%)

Peripheral edema (23%)

Constipation (23%)

Arthralgia (23%)

Nausea (21%)

Stomatitis (21%)

Sinusitis (21%)

Dizziness (21%)

Vomiting (19%)

Cough (19%)

Muscle spasms (19%)

Headache (19%)

Skin infection (17%)

Petechiae (17%)

Decreased appetite (17%)

Hypertension (17%

Abdominal pain (15%)

Oropharyngeal pain (15%)

Dyspepsia (13%)

Asthenia (13%)

Chills (13%)

1-10% (MCL)

Anemia, grades 3 or 4 (9%)

Increased serum creatinine, 1.5-3 x ULN (9%)

Hemorrhage, grades 3 or 4 (5%)

Secondary primary malignancies (5%)

1-10% (CLL)

Pneumonia (10%)

UTI (10%)

Dyspnea (10%)

Peripheral neuropathy (10%)

Second malignancies (10%)

Anxiety (10%)

Insomnia (10%)

Thrombocytopenia, grades 3 or 4 (10%)

Postmarketing reports

Fatal bleeding events have occurred

Tumor lysis syndrome reported; use caution

Interstitial lung disease

Hepatitis B reactivation

Ibrutinib is a prescription medication used to treat patients with mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) patients who have received at least one prior therapy. This medication is approved to treat Waldenström’s macroglobulinemia (WM), a rare form of cancer that begins in the body’s immune system. Ibrutinib is also approved to treat Marginal zone lymphoma (MZL) and chronic graft versus host disease (cGVHD). 

Ibrutinib belongs to a group of drugs called kinase inhibitors. It works by blocking the enzyme that allows cancer cells to grow and divide.

This medication comes in capsule form and is taken once a day with a full glass of water. Do not open, break, or chew the capsules.

Common side effects include diarrhea, fatigue, and muscle and joint pain.

Ibrutinib may be found in some form under the following brand names:

• Imbruvica

Ibrutinib is part of the drug class:

• Protein kinase inhibitors

Serious side effects have been reported with ibrutinib including the following:

• Bleeding problems can happen during treatment with ibrutinib that can be serious. Tell your healthcare provider if you have any signs of bleeding, including: blood in your stools or black stools (looks like tar), pink or brown urine, unexpected bleeding or bleeding that is severe or that you can not control, vomit blood or vomit looks like coffee grounds, cough up blood or blood clots, increased bruising, feel dizzy or weak, confusion, change in your speech, or a headache that lasts a long time.
• Infections can happen during treatment with ibrutinib. Infections can be serious and may lead to death. Tell your healthcare provider if you have fever, chills, or any other signs or symptoms of an infection while taking ibrutinib.
• a decrease in blood cell counts. Your healthcare provider should do monthly blood tests to check your blood counts.
• High Blood pressure. Your doctor will monitor your blood pressure. New or worsening high blood pressure has happened in people treated with this medication. Your healthcare provider may start you on blood pressure medicine or change current medicines to treat your blood pressure.
• Heart rhythm problems (atrial fibrillation and atrial flutter). Heart rhythm problems have happened in people treated with ibrutinib, especially in people who have an increased risk for heart disease, have an infection, or who have had heart rhythm problems in the past. Tell your healthcare provider if you get any symptoms of heart rhythm problems, such as feeling as if your heart is beating fast and irregular, lightheadedness, dizziness, shortness of breath, chest discomfort, or you faint 
• Second primary cancers. New cancers have happened in people who have been treated with ibrutinib, including cancers of the skin or other organs.
• Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure and the need for dialysis treatment, abnormal heart rhythm, seizure, and sometimes death. Your healthcare provider may do blood tests to check you for TLS.

This medication can cause harm to your unborn baby. Pregnancy should be avoided during treatment and for 1 month after the last dose of this medication.

Ibrutinib is not recommended in those with liver dysfunction (h moderate or severe baseline liver impairment). 

Diarrhea is a common side effect in people who take ibrutinib. Drink plenty of fluids during treatment to help lower your risk of losing too much fluid (dehydration) due to diarrhea. Tell your healthcare provider if you have diarrhea that does not go away.

Do not take ibrutinib if you are allergic to ibrutinib or to any of its ingredients.

Take ibrutinib exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The recommended dose of ibrutinib for mantle cell lymphoma (MCL) and Marginal zone lymphoma (MZL) is 560 mg (four 140 mg capsules) by mouth once daily.

The recommended dose of ibrutinib for chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma and Waldenström’s macroglobulinemia (WM), and chronic graft versus host disease is 420 mg taken orally once daily (three 140 mg capsules once daily).

For those patients with mild liver impairment, the dose of Imbruvica needs to be lowered. 

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Take this medicine with a full glass of water. Drink plenty of liquids while you are taking ibrutinib.

Ibrutinib is usually taken once per day until your body no longer responds to the medication. Take the medicine at the same time each day.

Do not crush, chew, break, or open an ibrutinib capsule. Swallow it whole.

If you need surgery or dental work, tell the surgeon or dentist ahead of time that you are using ibrutinib. You may need to stop using the medicine for a short time.

Call your doctor if you have severe or ongoing diarrhea. You can easily become dehydrated while taking ibrutinib.

You may need frequent medical tests to be sure this medicine is not causing harmful effects. Your cancer treatments may be delayed based on the results of these tests.

Store at room temperature away from moisture and heat. Keep the bottle tightly closed when not in use.

In the U.S.

• Imbruvica

Available Dosage Forms:

• Capsule

Therapeutic Class: Antineoplastic Agent

Pharmacologic Class: Tyrosine Kinase Inhibitor

• It is used to treat a type of lymphoma.
• It is used to treat a type of leukemia.
• It is used to treat Waldenstroms' macroglobulinemia (WM).
• It is used to treat graft versus host effects after a bone marrow transplant.
• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache.
• Feeling tired or weak.
• Not hungry.
• Upset stomach or throwing up.
• Belly pain.
• Loose stools (diarrhea).
• Hard stools (constipation).
• Muscle or joint pain.
• Muscle spasm.
• Anxiety.
• Signs of a common cold.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Chronic graft-versus-host disease (cGVHD; refractory): Oral: 420 mg once daily; continue until cGVHD disease progression, recurrence of underlying malignancy, or unacceptable toxicity (Miklos 2016). When cGVHD treatment is no longer required, discontinue ibrutinib based on medical assessment of patient.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): Oral: 420 mg once daily (either as monotherapy or in combination with bendamustine and rituximab); continue until disease progression or unacceptable toxicity (Byrd 2014; Chanan-Khan 2016).

CLL/SLL with 17p deletion: Oral: 420 mg once daily; continue until disease progression or unacceptable toxicity (Byrd 2014).

Mantle cell lymphoma (MCL), previously treated: Oral: 560 mg once daily; continue until disease progression or unacceptable toxicity (Wang 2013; Wang 2015).

Marginal zone lymphoma (MZL), relapsed/refractory: Oral: 560 mg once daily; continue until disease progression or unacceptable toxicity (Noy 2017).

Waldenström macroglobulinemia (WM): Oral: 420 mg once daily; continue until disease progression or unacceptable toxicity (Treon 2015).

Missed doses: Administer as soon as the missed dose is remembered on the same day; return to normal scheduling the following day. Do not take extra capsules to make up for the missed dose.

Dosage adjustment for concomitant therapy:

B-cell malignancies:

Moderate CYP3A inhibitors, posaconazole at doses ≤200 mg twice daily, and voriconazole (any dose): Reduce ibrutinib dose to 140 mg once daily. Monitor closely and interrupt ibrutinib treatment as recommended for toxicities.

Other strong CYP3A inhibitors and posaconazole at doses >200 mg twice daily: Avoid concurrent use. If these inhibitors will be used short-term (eg, anti-infectives for ≤7 days), interrupt ibrutinib treatment.

cGVHD:

Moderate CYP3A inhibitors: Administer ibrutinib at 420 mg once daily. Monitor closely and interrupt ibrutinib treatment as recommended for toxicities.

Posaconazole immediate release 200 mg twice daily or delayed release 300 mg once daily or voriconazole (any dose): Reduce ibrutinib dose to 280 mg once daily. Monitor closely and interrupt ibrutinib treatment as recommended for toxicities.

Other strong CYP3A inhibitors and posaconazole at doses >200 mg immediate release twice daily or >300 mg delayed release once daily: Avoid concurrent use. If these inhibitors will be used short-term (eg, anti-infectives for ≤7 days), interrupt ibrutinib treatment.

CrCl ≥25 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, renal excretion is minimal and drug exposure is not altered in patients with mild to moderate impairment.

CrCl <25 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

End-stage renal disease (ESRD) requiring dialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Initial dose: 560 mg orally once a day

Comment: Dose modifications may be necessary for adverse reactions.

Use: For the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.

-Mild liver impairment (Child-Pugh class A): 140 mg orally once a day
-Moderate liver impairment (Child-Pugh class B): Use not recommended
-Severe liver impairment (Child-Pugh class C): Use not recommended