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Imbruvica

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Imbruvica

Imbruvica Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

Imbruvica (ibrutinib) is an inhibitor of Bruton's tyrosine kinase (BTK) used to treat patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Common side effects include low platelet count, diarrhea, neutropenia, anemia, fatigue, musculoskeletal pain, swelling of the extremities, upper respiratory tract infection, nausea, bruising, indigestion, constipation, rash, abdominal pain, vomiting and decreased appetite.

The recommended dose of Imbruvica for MCL is 560 mg (four 140 mg capsules) orally once daily. Imbruvica may interact with ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, grapefruit and oranges, carbamazepine, rifampin, phenytoin and St. John's Wort. Tell your doctor all medications and supplements you use.

Imbruvica is not recommended for use during pregnancy. It can harm a fetus. It is unknown if this drug passes into breast milk. Consult your doctor before breastfeeding.

Our Imbruvica (ibrutinib) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is Prescribing information?

The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.

Imbruvica FDA Prescribing Information: Side Effects
(Adverse Reactions)

SIDE EFFECTS

The following adverse reactions are discussed in more detail in other sections of the labeling:

Because clinical trials are conducted under widely variable conditions, adverse event rates observed in clinical trials of a drug cannot be directly compared with rates of clinical trials of another drug and may not reflect the rates observed in practice.

Mantle Cell Lymphoma

The data described below reflect exposure to IMBRUVICA in a clinical trial that included 111 patients with previously treated MCL treated with 560 mg daily with a median treatment duration of 8.3 months.

The most commonly occurring adverse reactions ( ≥ 20%) were thrombocytopenia, diarrhea, neutropenia, anemia, fatigue, musculoskeletal pain, peripheral edema, upper respiratory tract infection, nausea, bruising, dyspnea, constipation, rash, abdominal pain, vomiting and decreased appetite (See Tables 1 and 2).

The most common Grade 3 or 4 non-hematological adverse reactions ( ≥ 5%) were pneumonia, abdominal pain, atrial fibrillation, diarrhea, fatigue, and skin infections.

Fatal and serious cases of renal failure have occurred with IMBRUVICA therapy. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 9% of patients.

Adverse reactions from the MCL trial (N=111) using single agent IMBRUVICA 560 mg daily occurring at a rate of ≥ 10% are presented in Table 1.

Table 1: Non-Hematologic Adverse Reactions in ≥ 10% of Patients with MCL (N=111)

System Organ Class Preferred Term All Grades (%) Grade 3 or 4 (%)
Gastrointestinal disorders Diarrhea 51 5
Nausea 31 0
Constipation 25 0
Abdominal pain 24 5
Vomiting 23 0
Stomatitis 17 1
Dyspepsia 11 0
Infections and infestations Upper respiratory tract
infection 34 0
Urinary tract infection 14 3
Pneumonia 14 7
Skin infections 14 5
Sinusitis 13 1
General disorders and administrative site conditions Fatigue 41 5
Peripheral edema 35 3
Pyrexia 18 1
Asthenia 14 3
Skin and subcutaneous tissue disorders Bruising 30 0
Rash 25 3
Petechiae 11 0
Musculoskeletal and connective tissue disorders Musculoskeletal pain 37 1
Muscle spasms 14 0
Arthralgia 11 0
Respiratory, thoracic and mediastinal disorders Dyspnea 27 4
Cough 19 0
Epistaxis 11 0
Metabolism and nutrition disorders Decreased appetite 21 2
Dehydration 12 4
Nervous system disorders Dizziness 14 0
Headache 13 0

Table 2: Treatment-Emergent* Decrease of Hemoglobin, Platelets, or Neutrophils in Patients with MCL (N=111)

  Percent of Patients
(N=111)
All Grades (%) Grade 3 or 4 (%)
Platelets Decreased 57 17
Neutrophils Decreased 47 29
Hemoglobin Decreased 41 9
* Based on laboratory measurements and adverse reactions

Ten patients (9%) discontinued treatment due to adverse reactions in the trial (N=111). The most frequent adverse reaction leading to treatment discontinuation was subdural hematoma (1.8%). Adverse reactions leading to dose reduction occurred in 14% of patients.

Patients with MCL who develop lymphocytosis greater than 400,000/mcL have developed intracranial hemorrhage, lethargy, gait instability, and headache. However, some of these cases were in the setting of disease progression.

Forty percent of patients had elevated uric acid levels on study including 13% with values above 10 mg/dL. Adverse reaction of hyperuricemia was reported for 15% of patients.

Chronic Lymphocytic Leukemia

The data described below reflect exposure to IMBRUVICA in an open label clinical trial (Study 1) that included 48 patients with previously treated CLL and a randomized clinical trial (Study 2) that included 391 randomized patients with previously treated CLL or SLL.

The most commonly occurring adverse reactions in Study 1 and Study 2 ( ≥ 20%) were thrombocytopenia, neutropenia, diarrhea, anemia, fatigue, musculoskeletal pain, upper respiratory tract infection, rash, nausea, and pyrexia.

Approximately five percent of patients receiving IMBRUVICA in Study 1 and 2 discontinued treatment due to adverse events. These included infections, subdural hematomas and diarrhea. Adverse events leading to dose reduction occurred in approximately 6% of patients.

Study 1

Adverse reactions and laboratory abnormalities from the CLL trial (N=48) using single agent IMBRUVICA 420 mg daily occurring at a rate of ≥ 10% are presented in Tables 3 and 4.

Table 3: Non-Hematologic Adverse Reactions in ≥ 10% of Patients with CLL (N=48) in Study 1

System Organ Class Preferred Term All Grades (%) Grade 3 or 4 (%)
Gastrointestinal disorders Diarrhea 63 4
Constipation 23 2
Nausea 21 2
Stomatitis 21 0
Vomiting 19 2
Abdominal pain 15 0
Dyspepsia 13 0
Infections and infestations Upper respiratory tract infection 48 2
Sinusitis 21 6
Skin infection 17 6
Pneumonia 10 8
Urinary tract infection 10 0
General disorders and administrative site conditions Fatigue 31 4
Pyrexia 25 2
Peripheral edema 23 0
Asthenia 13 4
Chills 13 0
Skin and subcutaneous tissue disorders Bruising 54 2
Rash 27 0
Petechiae 17 0
Respiratory, thoracic and mediastinal disorders Cough 19 0
Oropharyngeal pain 15 0
Dyspnea 10 0
Musculoskeletal and connective tissue disorders Musculoskeletal pain 27 6
Arthralgia 23 0
Muscle spasms 19 2
Nervous system disorders Dizziness 21 0
Headache 19 2
Peripheral neuropathy 10 0
Metabolism and nutrition disorders Decreased appetite 17 2
Neoplasms benign, malignant, unspecified Second malignancies* 10* 0
Injury, poisoning and procedural complications Laceration 10 2
Psychiatric disorders Anxiety 10 0
Insomnia 10 0
Vascular disorders Hypertension 17 8
*One patient death due to histiocytic sarcoma.

Table 4: Treatment-Emergent* Decrease of Hemoglobin, Platelets, or Neutrophils in Patients with CLL (N=48) in Study 1

  Percent of Patients (N=48)
All Grades (%) Grade 3 or 4 (%)
Platelets Decreased 71 10
Neutrophils Decreased 54 27
Hemoglobin Decreased 44 0
* Based on laboratory measurements per IWCLL criteria and adverse reactions

Study 2

Adverse reactions and laboratory abnormalities described below in Tables 5 and 6 reflect exposure to IMBRUVICA with a median duration of 8.6 months and exposure to ofatumumab with a median of 5.3 months in Study 2.

Table 5: Non-Hematologic Adverse Reactions ≥ 10% Reported in Study 2

System Organ Class
ADR Term
IMBRUVICA
(N=195)
Ofatumumab
(N=191)
All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%)
Gastrointestinal disorders
  Diarrhea 48 4 18 2
  Nausea 26 2 18 0
  Stomatitis* 17 1 6 1
  Constipation 15 0 9 0
  Vomiting 14 0 6 1
General disorders and administration site conditions
  Fatigue 28 2 30 2
  Pyrexia 24 2 15 1
Infections and infestations
  Upper respiratory tract infection 16 1 11 2
  Pneumonia* 15 10 13 9
  Sinusitis* 11 1 6 0
  Urinary tract infection 10 4 5 1
Skin and subcutaneous tissue disorders
  Rash* 24 3 13 0
  Petechiae 14 0 1 0
  Bruising* 12 0 1 0
Musculoskeletal and connective tissue disorders
  Musculoskeletal Pain* 28 2 18 1
  Arthralgia 17 1 7 0
Nervous system disorders
  Headache 14 1 6 0
  Dizziness 11 0 5 0
Injury, poisoning and procedural complications
  Contusion 11 0 3 0
Eye disorders
  Vision blurred 10 0 3 0
Subjects with multiple events for a given ADR term are counted once only for each ADR term.
The system organ class and individual ADR terms are sorted in descending frequency order in the IMBRUVICA arm.
* Includes multiple ADR terms

Table 6: Treatment-Emergent* Decrease of Hemoglobin, Platelets, or Neutrophils in Study 2

  IMBRUVICA
(N=195)
Ofatumumab
(N=191)
All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%)
Neutrophils Decreased 51 23 57 26
Platelets Decreased 52 5 45 10
Hemoglobin Decreased 36 0 21 0
* Based on laboratory measurements per IWCLL criteria

Read the entire FDA prescribing information for Imbruvica (Ibrutinib Capsules) »

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