Zykadia

Medical Editor: John P. Cunha, DO, FACOEP Last updated on RxList: 10/25/2021
Zykadia Side Effects Center

What Is Zykadia?

Zykadia (ceritinib) is a tyrosine kinase inhibitor used to treat patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib.

What Are Side Effects of Zykadia?

Common side effects of Zykadia include:

  • diarrhea,
  • nausea,
  • vomiting,
  • abdominal pain,
  • constipation,
  • fatigue,
  • decreased appetite,
  • rash,
  • decreased hemoglobin,
  • increased liver enzymes,
  • increase in blood creatinine,
  • numbness and tingling,
  • muscle weakness,
  • vision problems, and
  • slow heart rate,
  • non-cardiac chest pain,
  • back pain,
  • pain in extremities,
  • musculoskeletal pain,
  • itching,
  • fever,
  • weight loss,
  • cough,
  • headache,
  • dizziness,
  • heart rhythm disorder, and
  • inflammation of the sac around the heart (pericarditis).

Dosage for Zykadia

The recommended dose of Zykadia is 750 mg orally once daily on an empty stomach until disease progression or unacceptable toxicity.

What Drugs, Substances, or Supplements Interact with Zykadia?

Zykadia may interact with antivirals, macrolide antibiotics, antifungals, nefazodone, grapefruit and grapefruit juice, carbamazepine, phenytoin, rifampin, St. John's Wort, alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, phenytoin, and warfarin. Tell your doctor all medications and supplements you use.

Zykadia During Pregnancy and Breastfeeding

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

Additional Information

Our Zykadia (ceritinib) 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.

SLIDESHOW

Lung Cancer: Early Signs, Symptoms, Stages See Slideshow
Zykadia Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Ceritinib usually causes side effects on your stomach (nausea, vomiting, diarrhea, stomach pain) that can be severe. Call your doctor if you have severe or ongoing stomach symptoms.

Also call your doctor at once if you have:

  • severe pain in your upper stomach spreading to your back;
  • slow heartbeats, weak pulse, weak or shallow breathing;
  • sudden chest pain or discomfort, fever, dry cough or cough with mucus, feeling short of breath;
  • fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness (like you might pass out);
  • high blood sugar--increased thirst, increased urination, hunger, fruity breath odor, headaches, thinking problems, blurred vision, feeling tired; or
  • high blood sugar--increased thirst, increased urination, dry mouth, fruity breath odor; o
  • liver problems--right-sided-stomach pain, loss of appetite, unusual tiredness, itching, easy bruising or bleeding, dark urine, or yellowing of the skin or eyes.

Common side effects may include:

  • stomach pain, loss of appetite;
  • nausea, vomiting, diarrhea;
  • feeling tired; or
  • weight loss.

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 Zykadia (Ceritinib Hard-gelatin Capsules)

QUESTION

Lung cancer is a disease in which lung cells grow abnormally in an uncontrolled way. See Answer
Zykadia Professional Information

SIDE EFFECTS

The following clinically significant adverse reactions are described elsewhere in the labeling:

  • Gastrointestinal Adverse Reactions [see WARNINGS AND PRECAUTIONS]
  • Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
  • Interstitial Lung Disease/Pneumonitis [see WARNINGS AND PRECAUTIONS]
  • QT Interval Prolongation [see WARNINGS AND PRECAUTIONS]
  • Hyperglycemia [see WARNINGS AND PRECAUTIONS]
  • Bradycardia [see WARNINGS AND PRECAUTIONS]
  • Pancreatitis [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

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

The data in the Warnings and Precautions section reflect exposure to ZYKADIA 750 mg once daily under fasted conditions in 925 patients with ALK-positive NSCLC across seven clinical studies, including ASCEND-4 and ASCEND1, described below, a randomized active-controlled study, two single arm studies, and two dose-escalation studies. The majority of patients enrolled in these studies had received prior treatment with chemotherapy and/or crizotinib for NSCLC. Among these 925 patients, the most common adverse reactions (≥ 25% incidence) were diarrhea, nausea, vomiting, fatigue, abdominal pain, decreased appetite, and weight loss. Approximately 45% of patients initiating treatment with ZYKADIA 750 mg under fasted conditions had an adverse reaction that required at least one dose reduction and 66% of patients had an adverse reaction that required at least one dose interruption. The median time to first dose reduction due to any reason was 7 weeks.

Dose Optimization Study

Dosing Regimen of 450 mg Daily With Food

In ASCEND-8, a dose optimization study, ZYKADIA 450 mg daily with food (N = 108) was compared to 750 mg daily under fasted conditions (N = 110) in both previously treated and untreated patients with ALK-positive NSCLC. The overall safety profile of ZYKADIA 450 mg with food was consistent with ZYKADIA 750 mg fasted, except for a reduction in gastrointestinal adverse reactions, while achieving comparable steady-state exposure [see CLINICAL PHARMACOLOGY]. The most common adverse reactions (≥ 25% incidence) in the 450 mg with food arm were diarrhea, nausea, abdominal pain, vomiting, and fatigue. The incidence and severity of gastrointestinal adverse reactions (diarrhea 59%, nausea 43%, and vomiting 38%) were reduced for patients treated with ZYKADIA 450 mg with food; Grade ≥ 3 adverse reactions were reported in two patients (1.9%): Grade 3 diarrhea and Grade 3 vomiting in one patient each [see WARNINGS AND PRECAUTIONS].

In patients treated with ZYKADIA 450 mg with food, 24% of patients had an adverse reaction that required at least one dose reduction and 56% of patients had an adverse reaction that required at least one dose interruption. The median time to first dose reduction due to any reason was 8 weeks.

Previously Untreated ALK-Positive Metastatic NSCLC

The safety of ZYKADIA was evaluated in ASCEND-4, an open-label, randomized, active-controlled multicenter study of 376 previously untreated ALK-positive NSCLC patients [see Clinical Studies]. Patients received ZYKADIA 750 mg daily (N = 189) under fasted conditions or chemotherapy and maintenance chemotherapy (N = 187). Chemotherapy regimens were pemetrexed (500 mg/m2) and investigator’s choice of cisplatin (75 mg/m2) or carboplatin [area under the curve (AUC) of 5 - 6 mg*min/mL] administered every 21 days. Patients who completed 4 cycles of chemotherapy without progressive disease received pemetrexed (500 mg/m2) as single-agent maintenance therapy every 21 days. The median duration of exposure to ZYKADIA was 18 months.

The demographic characteristics of the study population were 57% female, median age 54 years (range, 22 to 81 years), 22% age 65 years or older, 54% white, 42% Asian, 2% black, and 2% other races. Patients were enrolled in Europe (53%), Asia Pacific (42%), and South America (5%) regions. The majority of patients had adenocarcinoma (97%), never smoked (61%), and 32% had brain metastases at screening.

The following fatal adverse reactions occurred in 4 patients treated with ZYKADIA: myocardial infarction, respiratory tract infection, pneumonitis, and unknown cause.

Serious adverse reactions were reported in 38% of patients treated with ZYKADIA. The most frequent serious adverse reactions were pneumonia (4%), pleural effusion (4%), vomiting (4%), nausea (3%), dyspnea (3%), hyperglycemia (3%), AST increased (2%), lung infection (2%), and pericardial effusion (2%).

Among patients treated with ZYKADIA, dose interruptions due to adverse reactions occurred in 77%, dose reductions were required in 66%, and adverse reactions that led to discontinuation of therapy occurred in 12% of patients. The most frequent adverse reactions, reported in at least 10% of patients treated with ZYKADIA, that led to dose interruptions or reductions were: increased ALT (48%), increased AST (34%), vomiting (15%), increased blood creatinine (14%), increased gamma-glutamyl transpeptidase (GGT) (13%), diarrhea (13%), and nausea (13%). The most frequent adverse reactions that led to discontinuation of ZYKADIA in 1% or more of patients in ASCEND-4 were increased blood creatinine (2.1%), increased amylase (1.1%), and increased lipase (1.1%).

Tables 3 and 4 summarize adverse reactions and laboratory abnormalities, respectively, in ASCEND-4.

Table 3: Adverse Reactions (> 10% for All Grades* or ≥ 2% for Grades 3-4) of Patients in ASCEND-4

ZYKADIA
N = 189
Chemotherapy
N = 175a
All Grades Grade 3-4 All Grades Grade 3-4
% % % %
Gastrointestinal**
  Diarrhea 85 4.8 11 1.1
  Nausea 69 2.6 55 5
  Vomiting 67 5 36 6
  Abdominal painb 40 3.7 13 0
  Constipation 20 0 22 0
  Esophageal disorderc 15 0.5 8 0.6
General
  Fatigued 45 7 49 6
  Non-cardiac chest pain 21 1.1 10 0.6
  Back pain 19 1.6 18 2.3
  Pyrexia 19 0 14 1.1
  Pain in extremity 13 0 7 0
  Musculoskeletal pain 11 0.5 6 0.6
  Pruritus 11 0.5 5 0
Metabolism and Nutrition
  Decreased appetite 34 1.1 32 1.1
  Weight loss 24 3.7 15 0.6
Respiratory
  Cough 25 0 17 0
Skin
  Rashe 21 1.1 8 0.6
Neurologic
  Headache 19 0.5 13 1.1
  Dizziness 12 1.1 10 0.6
Cardiac
  Prolonged QT interval 12 2.6 1.1 0.6
  Pericarditisf 4.2 1.6 2.3 1.1
*National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03).
**For frequency of gastrointestinal adverse reactions at the recommended dose of 450 mg with food [see WARNINGS AND PRECAUTIONS , Clinical Trials Experience].
aTwelve patients randomized to chemotherapy did not receive study drug.
bAbdominal pain (abdominal pain, abdominal pain upper, abdominal discomfort, and epigastric discomfort).
cEsophageal disorder (dyspepsia, gastroesophageal reflux disease, and dysphagia).
dFatigue (fatigue and asthenia).
eRash (rash, dermatitis acneiform, rash maculo-papular).
fPericarditis (pericardial effusion and pericarditis).

Additional clinically significant adverse reactions occurring in 2% or more of patients treated with ZYKADIA 750 mg under fasted conditions included: vision disorder (4% comprised of vision impairment, blurred vision, photopsia, accommodation disorder, presbyopia, reduced visual acuity, or vitreous floaters), bradycardia (4%), ILD/pneumonitis (2%), hepatotoxicity (2%), and renal failure (2%).

Table 4: Laboratory Abnormalities Occurring in > 10% (All Grades*) of Patients in ASCEND-4

ZYKADIA
N = 189
Chemotherapy
N = 175a
All Grades Grade 3-4 All Grades Grade 3-4
% % % %
Chemistry
  Increased ALT 91 34 65 3.4
  Increased AST 86 21 58 2.3
  Increased GGT 84 49 67 10
  Increased alkaline phosphatase 81 12 47 1.7
  Increased creatinine 77 4.2 37 0.6
  Hyperglycemia 53 10 67 10
  Hypophosphatemia 38 3.7 27 4.0
  Increased amylase 37 8 43 4.5
  Hyperbilirubinemia (total) 15 0.5 6 0.6
  Increased lipaseb 13 6 7 0.6
Hematology
  Anemia 67 4.2 84 11
  Neutropenia 27 2.1 58 20
  Thrombocytopenia 16 1.0 38 4.6
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma-glutamyl transpeptidase.
*National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03).
aTwelve patients randomized to chemotherapy did not receive study drug.
bIn the ZYKADIA arm, no patients had baseline lipase laboratory assessments, 112 had post-baseline assessments. In the chemotherapy arm, one patient had baseline lipase laboratory assessments but no post-baseline assessment; 49 patients had post-baseline assessments.

Previously Treated ALK-Positive Metastatic NSCLC

The safety of ZYKADIA was evaluated in ASCEND-1, a multicenter, single-arm, open-label clinical study of 255 ALK-positive patients (246 patients with NSCLC and 9 patients with other cancers who received ZYKADIA at a dose of 750 mg daily under fasted conditions) [see Clinical Studies]. The median duration of exposure to ZYKADIA was 6 months.

The study population characteristics were: median age 53 years, age less than 65 (84%), female (53%), white (63%), Asian (34%), NSCLC adenocarcinoma histology (90%), never or former smoker (97%), Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1 (89%), brain metastases (49%), and number of prior therapies 2 or more (67%).

Fatal adverse reactions in patients treated with ZYKADIA occurred in 5% of patients, consisting of: pneumonia (4 patients), respiratory failure, ILD/pneumonitis, pneumothorax, gastric hemorrhage, general physical health deterioration, pulmonary tuberculosis, cardiac tamponade, and sepsis (1 patient each).

Serious adverse reactions reported in 2% or more of patients in ASCEND-1 were convulsion, pneumonia, ILD/pneumonitis, dyspnea, dehydration, hyperglycemia, and nausea.

Dose reductions due to adverse reactions occurred in 59% of patients treated with ZYKADIA. The most frequent adverse reactions, reported in at least 10% of patients, that led to dose reductions or interruptions were: increased ALT (29%), nausea (20%), increased AST (16%), diarrhea (16%), and vomiting (16%). Discontinuation of therapy due to adverse reactions occurred in 10% of patients treated with ZYKADIA. The most frequent adverse reactions that led to discontinuation in 1% or more of patients in ASCEND-1 were pneumonia, ILD/pneumonitis, and decreased appetite.

Tables 5 and 6 summarize adverse reactions and laboratory abnormalities, respectively, in ASCEND-1.

Table 5: Adverse Reactions (> 10% for All Grades* or ≥ 2% for Grades 3-4) in ALK-Positive Patients Treated with ZYKADIA in ASCEND-1

ZYKADIA
N = 255
All Grades Grade 3-4
% %
Gastrointestinal**
  Diarrhea 86 6
  Nausea 80 4
  Vomiting 60 4
  Abdominal paina 54 2
  Constipation 29 0
  Esophageal disorderb 16 1
General
  Fatiguec 52 5
Metabolism and Nutrition
  Decreased appetite 34 1
Skin
  Rashd 16 0
Respiratory
  Interstitial lung disease/pneumonitis 4 3
Abbreviation: ALK, anaplastic lymphoma kinase.
*National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03).
**For frequency of gastrointestinal adverse reactions at the recommended dose of 450 mg with food [see WARNINGS AND PRECAUTIONS , Clinical Trials Experience].
aAbdominal pain (abdominal pain, upper abdominal pain, abdominal discomfort, and epigastric discomfort).
bEsophageal disorder (dyspepsia, gastroesophageal reflux disease, and dysphagia).
cFatigue (fatigue and asthenia).
dRash (rash, maculopapular rash, and acneiform dermatitis).

Additional clinically significant adverse reactions occurring in 2% or more of patients treated with ZYKADIA 750 mg under fasted conditions included neuropathy (17% comprised of paresthesia, muscular weakness, gait disturbance, peripheral neuropathy, hypoesthesia, peripheral sensory neuropathy, dysesthesia, neuralgia, peripheral motor neuropathy, hypotonia, or polyneuropathy), vision disorder (9% comprised of vision impairment, blurred vision, photopsia, accommodation disorder, presbyopia, or reduced visual acuity), prolonged QT interval (4%), and bradycardia (3%).

Table 6: Key Laboratory Abnormalities Occurring in > 10% (All Grades*) of ALK-Positive Patients Treated with ZYKADIA in ASCEND-1

ZYKADIA
N = 255
All Grades Grade 3-4
% %
Hematology
  Anemia 84 5
Chemistry
  Increased ALT 80 27
  Increased AST 75 13
  Increased creatinine 58 2
  Hyperglycemia 49 13
  Hypophosphatemia 36 7
  Increased lipase 28 10
  Hyperbilirubinemia (total) 15 1
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALK, anaplastic lymphoma kinase.
*National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03).

DRUG INTERACTIONS

Effect Of Other Drugs On ZYKADIA

Strong CYP3A Inhibitors

A strong CYP3A4/P-gp inhibitor (ketoconazole) increased the systemic exposure of ceritinib [see CLINICAL PHARMACOLOGY], which may increase the incidence and severity of adverse reactions of ZYKADIA. Avoid concurrent use of strong CYP3A inhibitors during treatment with ZYKADIA. If concurrent use of strong CYP3A inhibitors is unavoidable, reduce the ZYKADIA dose [see DOSAGE AND ADMINISTRATION].

Do not consume grapefruit and grapefruit juice as they may inhibit CYP3A.

Strong CYP3A Inducers

A strong CYP3A4/P-gp inducer (rifampin) decreased the systemic exposure of ceritinib [see CLINICAL PHARMACOLOGY], which may decrease the efficacy of ZYKADIA. Avoid concurrent use of strong CYP3A inducers during treatment with ZYKADIA.

Effect Of ZYKADIA On Other Drugs

CYP3A Substrates

Ceritinib increased the systemic exposure of a sensitive CYP3A substrate (midazolam) [see CLINICAL PHARMACOLOGY]. Avoid coadministration of ZYKADIA with sensitive CYP3A substrates. If concomitant use is unavoidable, consider dose reduction of the sensitive CYP3A substrate(s). If ZYKADIA is coadministered with other CYP3A substrates, refer to the CYP3A substrate labeling for dosage recommendation with strong CYP3A inhibitors.

CYP2C9 Substrates

Ceritinib increased the systemic exposure of a CYP2C9 substrate (warfarin) [see CLINICAL PHARMACOLOGY]. Increase the frequency of INR monitoring if coadministration with warfarin is unavoidable as the anti-coagulant effect of warfarin may be enhanced.

Avoid coadministration of ZYKADIA with CYP2C9 substrates for which minimal concentration changes may lead to serious toxicities. If concomitant use of such CYP2C9 substrates is unavoidable, consider dose reduction for the coadministered CYP2C9 substrates.

Drugs That Prolong QT Interval

ZYKADIA causes concentration-dependent increases in the QTc interval. When possible, avoid coadministration of ZYKADIA with other products with a known potential to prolong the QTc interval [see WARNINGS AND PRECAUTIONS, CLINICAL PHARMACOLOGY].

Drugs That Cause Bradycardia

ZYKADIA can cause bradycardia. When possible, avoid coadministration of ZYKADIA with other products known to cause bradycardia [see WARNINGS AND PRECAUTIONS , CLINICAL PHARMACOLOGY].

Read the entire FDA prescribing information for Zykadia (Ceritinib Hard-gelatin Capsules)

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

Health Solutions From Our Sponsors