Copiktra

Last updated on RxList: 9/8/2020
Copiktra Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Copiktra?

Copiktra (duvelisib) is a kinase inhibitor indicated for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least two prior therapies, and for the treatment of relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies.

What Are Side Effects of Copiktra?

Common side effects of Copiktra include:

Dosage for Copiktra

The dose of Copiktra is 25 mg orally, twice daily.

What Drugs, Substances, or Supplements Interact with Copiktra?

Copiktra may interact with strong CYP3A4 inducers (such as rifampicin, carbamazepine, phenytoin, and others), strong CYP3A inhibitors (such as protease inhibitors, macrolide antibiotics, azole antifungals, and others) and CYP3A4 substrates (immunosuppressants, chemotherapy drugs, antidepressants, antipsychotics, narcotics, and others).

Copiktra During Pregnancy and Breastfeeding

Tell your doctor all medications and supplements you use. Tell your doctor if you are pregnant or plan to become pregnant before using Copiktra; it can harm a fetus. It is unknown if Copiktra passes into breast milk. Because of the potential for serious adverse reactions in a breastfed child, breastfeeding is not recommended while using Copiktra and for at least 1 month after the last dose.

Additional Information

Our Copiktra (duvelisib), Capsules for Oral Use 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.

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Copiktra Consumer Information

Get emergency medical help if you have signs of an allergic reaction (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).

Call your doctor at once if you have:

  • severe diarrhea (more than 6 bowel movements in 1 day);
  • severe stomach pain, new or worsening diarrhea with blood or mucus;
  • liver problems--stomach pain (upper right side), dark urine, jaundice (yellowing of the skin or eyes); or
  • low blood cell counts--fever, chills, tiredness, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands and feet, feeling light-headed or short of breath.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

Common side effects may include:

  • diarrhea, nausea;
  • low blood cell counts;
  • bone pain, muscle pain;
  • fever, cough, tiredness; or
  • cold symptoms such as stuffy nose, sneezing, sore throat.

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.

Read the entire detailed patient monograph for Copiktra (Duvelisi Capsules)

QUESTION

What is leukemia? See Answer
Copiktra Professional Information

SIDE EFFECTS

The following adverse reactions have been associated with COPIKTRA in clinical trials and are discussed in greater detail in other sections of the prescribing information:

  • Infections [see WARNINGS AND PRECAUTIONS]
  • Diarrhea or Colitis [see WARNINGS AND PRECAUTIONS]
  • Cutaneous Reactions [see WARNINGS AND PRECAUTIONS]
  • Pneumonitis [see WARNINGS AND PRECAUTIONS]
  • Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
  • Neutropenia [see WARNINGS AND PRECAUTIONS]

Clinical Trial Experience

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

Summary Of Clinical Trial Experience In B-cell Malignancies

The data described below reflect exposure to COPIKTRA in two single-arm, open-label clinical trials, one open-label extension clinical trial, and one randomized, open-label, actively controlled clinical trial totaling 442 patients with previously treated hematologic malignancies primarily including CLL/SLL (69%) and FL (22%). Patients were treated with COPIKTRA 25 mg BID until unacceptable toxicity or progressive disease. The median duration of exposure was 9 months (range: 0.1 to 53 months), with 36% (160/442) of patients having at least 12 months of exposure.

For the 442 patients, the median age was 67 years (range: 30 to 90 years), 65% were male, 92% were White, and 93% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Patients had a median of 2 prior therapies. The trials required hepatic transaminases at least ≤ 3 times upper limit of normal (ULN), total bilirubin ≤ 1.5 times ULN, and serum creatinine ≤ 1.5 times ULN. Patients were excluded for prior exposure to a PI3K inhibitor within 4 weeks.

Fatal adverse reactions within 30 days of the last dose occurred in 36 patients (8%) treated with COPIKTRA 25 mg BID.

Serious adverse reactions were reported in 289 patients (65%). The most frequent serious adverse reactions that occurred were infection (31%), diarrhea or colitis (18%), pneumonia (17%), rash (5%), and pneumonitis (5%).

Adverse reactions resulted in treatment discontinuation in 156 patients (35%), most often due to diarrhea or colitis, infection, and rash. COPIKTRA was dose reduced in 104 patients (24%) due to adverse reactions, most often due to diarrhea or colitis and transaminase elevation. The median time to first dose modification or discontinuation was 4 months (range: 0.1 to 27 months), with 75% of patients having their first dose modification or discontinuation within 7 months.

Common Adverse Reactions

Table 3 summarizes common adverse reactions in patients receiving COPIKTRA 25 mg BID, and Table 4 summarizes the treatment-emergent laboratory abnormalities. The most common adverse reactions (reported in ≥ 20% of patients) were diarrhea or colitis, neutropenia, rash, fatigue, pyrexia, cough, nausea, upper respiratory infection, pneumonia, musculoskeletal pain, and anemia.

Table 3: Common Adverse Reactions (≥ 10% Incidence) in Patients with B-cell Malignancies Receiving COPIKTRA

Adverse ReactionsCOPIKTRA 25 mg BID
(N = 442)
Any Grade n (%)Grade ≥ 3 n (%)
Blood and lymphatic system disorders
Neutropenia †151 (34)132(30)
Anemia †90 (20)48(11)
Thrombocytopenia †74 (17)46 (10)
Gastrointestinal disorders
Diarrhea or colitis †a222 (50)101 (23)
Nausea †104 (24)4 (< 1)
Abdominal pain78 (18)9 (2)
Vomiting69 (16)6 (1)
Mucositis61 (14)6 (1)
Constipation57 (13)1 (< 1)
General disorders and administration site conditions
Fatigue †126 (29)22 (5)
Pyrexia115(26)7 (2)
Hepatobiliary disorders
Transaminase elevation †b67 (15)34 (8)
Infections and infestations
Upper respiratory tract infection †94 (21)2 (< 1)
Pneumonia †c91 (21)67 (15)
Lower respiratory tract infection †46 (10)11 (3)
Metabolism and nutrition disorders
Decreased appetite63 (14)2 (< 1)
Edema †60 (14)6 (1)
Hypokalemia †45 (10)17 (4)
Musculoskeletal and connective tissue disorders
Musculoskeletal pain†90 (20)6 (1)
Arthralgia46 (10)1 (< 1)
Nervous system disorders
Headache †55 (12)1 (< 1)
Respiratory, thoracic and mediastinal disorders
Cough†111 (25)2 (< 1)
Dyspnea†52 (12)8 (2)
Skin and subcutaneous tissue disorders
Rash †d136 (31)41 (9)
†Grouped term for reactions with multiple preferred terms
aDiarrhea or colitis includes the preferred terms: colitis, enterocolitis, colitis microscopic, colitis ulcerative, diarrhea, diarrhea hemorrhagic
bTransaminase elevation includes the preferred terms: alanine aminotransferase increased, aspartate aminotransferase increased, transaminases increased, hypertransaminasemia, hepatocellular injury, hepatotoxicity
cPneumonia includes the preferred terms: All preferred terms containing “pneumonia” except for “pneumonia aspiration”; bronchopneumonia, bronchopulmonary aspergillosis
dRash includes the preferred terms: dermatitis (including allergic, exfoliative, perivascular), erythema (including multiforme), rash (including exfoliative, erythematous, follicular, generalized, macular & papular, pruritic, pustular), toxic epidermal necrolysis and toxic skin eruption, drug reaction with eosinophilia and systemic symptoms, drug eruption, Stevens-Johnson syndrome

Grade 4 adverse reactions occurring in ≥ 2% of recipients of COPIKTRA included neutropenia (18%), thrombocytopenia (6%), sepsis (3%), hypokalemia and increased lipase (2% each), and pneumonia and pneumonitis (2% each).

Table 4: Most Common New or Worsening Laboratory Abnormalities (≥ 20% Any Grade) in Patients with B-cell Malignancies Receiving COPIKTRA

Laboratory ParameteraCOPIKTRA 25 mg BID
(N = 442)
Any Grade n (%)bGrade ≥ 3 n (%)b
Hematology abnormalities
Neutropenia276 (63)184(42)
Anemia198 (45)66 (15)
Thrombocytopenia170(39)65 (15)
Lymphocytosis132(30)92 (21)
Leukopenia129(29)34 (8)
Lymphopenia90 (21)39 (9)
Chemistry abnormalities
ALT increased177 (40)34 (8)
AST increased163 (37)24 (6)
Lipase increased133(36)58 (16)
Hypophosphatemia136 (31)23 (5)
ALP increased128(29)7 (2)
Serum amylase increased101(28)16 (4)
Hyponatremia116 (27)30 (7)
Hyperkalemia114 (26)14 (3)
Hypoalbuminemia111 (25)7 (2)
Creatinine increased106 (24)7 (2)
Hypocalcemia100 (23)12 (3)
aIncludes laboratory abnormalities that are new or worsening in grade or with worsening from baseline unknown.
bPercentages are based on number of patients with at least one post-baseline assessment; not all patients were evaluable.

Grade 4 laboratory abnormalities developing in ≥ 2% of patients included neutropenia (24%), thrombocytopenia (7%), lipase increase (4%), lymphocytopenia (3%), and leukopenia (2%).

Summary Of Clinical Trial Experience In CLL/SLL

Study 1

The safety data below reflects exposure in a randomized, open-label, actively controlled clinical trial for adult patients with CLL or SLL who received at least one prior therapy. Of 313 patients treated, 158 received COPIKTRA monotherapy and 155 received ofatumumab. The 442-patient safety analysis above includes patients from Study 1.

COPIKTRA was administered at 25 mg BID in 28-day treatment cycles until unacceptable toxicity or progressive disease. The comparator group received 12 doses of ofatumumab with an initial dose of 300 mg intravenous (IV) on Day 1 followed a week later by 7 weekly doses of 2000 mg IV, followed 4 weeks later by 2000 mg IV every 4 weeks for 4 doses.

In the total study population, the median age was 69 years (range: 39 to 90 years), 60% were male, 92% were White, and 91% had an ECOG performance status of 0 to 1. Patients had a median of 2 prior therapies, with 61% of patients having received 2 or more prior therapies. The trial required a hemoglobin ≥ 8 g/dL and platelets ≥ 10,000 μL with or without transfusion support, hepatic transaminases ≤ 3 times upper limit of normal (ULN), total bilirubin ≤ 1.5 times ULN, and serum creatinine ≤ 2 times ULN. The trial excluded patients with prior autologous transplant within 6 months or allogeneic transplant, prior exposure to a PI3K inhibitor or a Bruton's tyrosine kinase (BTK) inhibitor, and uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura.

During randomized treatment, the median duration of exposure to COPIKTRA was 11.6 months with 72% (114/158) exposed for ≥ 6 months and 49% (77/158) exposed for ≥ 1 year. The median duration of exposure to ofatumumab was 5.3 months, with 77% (120/155) receiving at least 10 of 12 doses.

Fatal adverse reactions within 30 days of the last dose occurred in 12% (19/158) of patients treated with COPIKTRA and in 4% (7/155) of patients treated with ofatumumab.

Serious adverse reactions were reported in 73% (115/158) of patients treated with COPIKTRA and most often involved infection (38% of patients; 60/158) and diarrhea or colitis (23% of patients; 36/158).

COPIKTRA was discontinued in 57 patients (36%), most often due to diarrhea or colitis, infection, and rash. COPIKTRA was dose reduced in 46 patients (29%) due to adverse reactions, most often due to diarrhea or colitis and rash.

Common Adverse Reactions

Table 5 summarizes selected adverse reactions in Study 1, and Table 6 summarizes treatment-emergent laboratory abnormalities. The most common adverse reactions with COPIKTRA (reported in ≥ 20% of patients) were diarrhea or colitis, neutropenia, pyrexia, upper respiratory tract infection, pneumonia, rash, fatigue, nausea, anemia and cough.

Table 5: Common Nonhematologic Adverse Reactions (≥ 10% Incidence) in Patients with CLL/SLL Receiving COPIKTRA (Study 1)

Adverse ReactionsCOPIKTRA
N =158
Ofatumumab
N =155
Any Grade (%)Grade ≥ 3 (%)Any Grade (%)Grade ≥ 3 (%)
Gastrointestinal disorders
Diarrhea or colitis †a5725142
Nausea †230110
Constipation17<180
Abdominal pain16370
Vomiting15070
General disorders and administration site conditions
Pyrexia29310<1
Fatigue †254234
Hepatobiliary disorders
Transaminase elevation †d1164<1
Infections and infestations
Upper respiratory tract infection †28016<1
Pneumonia †b272283
Lower respiratory tract infection†184101
Investigations
Weight decreased11020
Metabolism and nutrition disorders
Decreased appetite1303<1
Edema †11150
Musculoskeletal and connective tissue disorders
Musculoskeletal pain †17112<1
Respiratory, thoracic and mediastinal disorders
Cough†231160
Dyspnea12370
Skin and subcutaneous tissue disorders
Rash †c271115<1
Grades were obtained per CTCAE version 4.03.
†Grouped term for reactions with multiple preferred terms
aDiarrhea or colitis includes the preferred terms: colitis, enterocolitis, colitis microscopic, colitis ulcerative, diarrhea
bPneumonia includes the preferred terms: All preferred term containing “pneumonia” except for “pneumonia aspiration”; bronchopneumonia, bronchopulmonary aspergillosis
cRash includes the preferred terms: dermatitis (including allergic, exfoliative, perivascular), erythema (including multiforme), rash (including exfoliative, erythematous, follicular, generalized, macular & papular, pruritic, pustular), toxic skin eruption, drug eruption
dTransaminase elevation includes the preferred terms: alanine aminotransferase increased, aspartate aminotransferase increased, transaminases increased, hepatotoxicity

Table 6: Most Common New or Worsening Laboratory Abnormalities (≥ 20% Any Grade) in Patients with CLL/SLL Receiving COPIKTRA (Study 1)

Laboratory ParameterCOPIKTRA
N = 158
Ofatumumab
N = 155
Any Grade (%)Grade ≥ 3 (%)Any Grade (%)Grade ≥ 3 (%)
Hematology abnormalities
Neutropenia67495237
Anemia5520367
Thrombocytopenia4316348
Lymphocytosis3022116
Chemistry abnormalities
ALT increased427120
Lipase increased3712153
AST increased363141
Phosphate decreased343203
Hyperkalemia314241
Hyponatremia317183
Amylase increased315101
Hypoalbuminemia312151
Creatinine increased291310
Alkaline phosphatase increased270140
Hypocalcemia251171
Hypokalemia20880
Grades were obtained per CTCAE version 4.03.

Grade 4 laboratory abnormalities that developed in ≥ 2% of COPIKTRA treated patients included neutropenia (32%), thrombocytopenia (6%), lymphopenia (3%), and hypokalemia (2%).

The data above are not an adequate basis for comparison of rates between the study drug and the active control.

Summary Of Clinical Trial Experience In FL

The data described below reflect the exposure to COPIKTRA 25 mg BID in 96 patients with relapsed or refractory FL. These patients were included in the 442-patient safety analysis presented above. The median duration of treatment was 24 weeks, with 46% of patients exposed for ≥ 6 months and 19% exposed for ≥ 1 year.

The median age was 64 years (range: 30 to 82 years), and 93% had an ECOG performance status of 0 to 1. Patients had a median of 3 prior systemic therapies.

Serious adverse reactions were reported in 58% and most often involved diarrhea or colitis, pneumonia, renal insufficiency, rash, and sepsis. The most common adverse reactions (≥ 20% of patients) were diarrhea or colitis, nausea, fatigue, musculoskeletal pain, rash, neutropenia, cough, anemia, pyrexia, headache, mucositis, abdominal pain, vomiting, transaminase elevation, and thrombocytopenia.

Adverse reactions resulted in COPIKTRA discontinuation in 29% of patients, most often due to diarrhea or colitis and rash. COPIKTRA was dose reduced in 23% due to adverse reactions, most often due to transaminase elevation, diarrhea or colitis, lipase increased, and infection.

Read the entire FDA prescribing information for Copiktra (Duvelisi Capsules)

© Copiktra Patient Information is supplied by Cerner Multum, Inc. and Copiktra Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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