AKEEGA
Generic: NIRAPARIB TOSYLATE MONOHYDRATE AND ABIRATERONE ACETATE
Basic Information
Manufacturer
Janssen Biotech, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
8245a990-3268-4613-b5c5-9537858a1eb9
Indications & Usage
1 INDICATIONS AND USAGE AKEEGA with prednisone is indicated for the treatment of adult patients with deleterious or suspected deleterious BRCA2 -mutated ( BRCA2 m) metastatic castration-sensitive prostate cancer (mCSPC).
AKEEGA with prednisone is indicated for the treatment of adult patients with deleterious or suspected deleterious BRCA -mutated ( BRCA m) metastatic castration-resistant prostate cancer (mCRPC).
Select patients for therapy based on an FDA-approved test for AKEEGA [see Dosage and Administration (2.1) ] .
AKEEGA is a combination of niraparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, and abiraterone acetate, a CYP17 inhibitor indicated with prednisone for the treatment of adult patients with: deleterious or suspected deleterious BRCA2 -mutated ( BRCA2 m) metastatic castration-sensitive prostate cancer (mCSPC).
deleterious or suspected deleterious BRCA -mutated ( BRCA m) metastatic castration-resistant prostate cancer (mCRPC).
Select patients for therapy based on an FDA-approved test for AKEEGA.
( 1 , 2.1 )
AKEEGA with prednisone is indicated for the treatment of adult patients with deleterious or suspected deleterious BRCA -mutated ( BRCA m) metastatic castration-resistant prostate cancer (mCRPC).
Select patients for therapy based on an FDA-approved test for AKEEGA [see Dosage and Administration (2.1) ] .
AKEEGA is a combination of niraparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, and abiraterone acetate, a CYP17 inhibitor indicated with prednisone for the treatment of adult patients with: deleterious or suspected deleterious BRCA2 -mutated ( BRCA2 m) metastatic castration-sensitive prostate cancer (mCSPC).
deleterious or suspected deleterious BRCA -mutated ( BRCA m) metastatic castration-resistant prostate cancer (mCRPC).
Select patients for therapy based on an FDA-approved test for AKEEGA.
( 1 , 2.1 )
Adverse Reactions
6 ADVERSE REACTIONS The following adverse reactions are discussed elsewhere in the labeling: Myelodysplastic syndrome/acute myeloid leukemia [see Warnings and Precautions (5.1) ] Myelosuppression [see Warnings and Precautions (5.2) ] Hypokalemia, fluid retention, and cardiovascular adverse reactions [see Warnings and Precautions (5.3) ] Hepatotoxicity [see Warnings and Precautions (5.4) ] Adrenocortical insufficiency [see Warnings and Precautions (5.5) ] Hypoglycemia [see Warnings and Precautions (5.6) ] Increased fractures and mortality in combination with Radium 223 Dichloride [see Warnings and Precautions (5.7) ] Posterior reversible encephalopathy syndrome [see Warnings and Precautions (5.8) ] The most common adverse reactions (≥20%), including laboratory abnormalities, are decreased hemoglobin, decreased lymphocytes, musculoskeletal pain, fatigue, decreased platelets, increased alkaline phosphatase, constipation, hypertension, nausea, decreased neutrophils, increased creatinine, increased potassium, decreased potassium, increased AST, fluid retention/edema, increased bilirubin, respiratory tract infection and arrhythmia.
( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Biotech, Inc.
at 1-800-526-7736 (1-800-JANSSEN) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trial 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 safety population described in the WARNINGS and PRECAUTIONS reflect exposure to AKEEGA (niraparib 200 mg and abiraterone acetate 1,000 mg) in BRCA2 m patients (N=162) in the AMPLITUDE study and in BRCA m patients in Cohort 1 (N=113) in the MAGNITUDE study unless otherwise specified.
BRCA2 -mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC) The safety of AKEEGA in patients with BRCA2 m mCSPC was evaluated in AMPLITUDE [see Clinical Studies (14.1) ].
Patients were randomized to receive either AKEEGA (niraparib 200 mg and abiraterone acetate 1,000 mg once daily) (n=162), or placebo and abiraterone acetate (n=161) until unacceptable toxicity or progression.
Patients in both arms also received prednisone 5 mg daily.
The median duration of exposure for AKEEGA was 26 months (range: 0 to 48 months).
Serious adverse reactions occurred in 36% of patients who received AKEEGA.
Serious adverse reactions reported in >2% of patients included anemia (4.9%), and pneumonia (3.7%).
Fatal adverse reactions occurred in 4.9% of patients who received AKEEGA, including sudden death (1.9%), COVID-19 pneumonia (1.2%), pneumocystis jirovecii pneumonia (0.6%), pneumonia (0.6%), and cardio-respiratory arrest (0.6%).
Permanent discontinuation of any component of AKEEGA due to an adverse reaction occurred in 13% of patients.
Dosage interruptions of any component of AKEEGA due to an adverse reaction occurred in 67% of patients.
Adverse reactions which required dosage interruption in >2% of patients included anemia (30%), COVID-19 (10%), hypertension (9%), neutropenia (8%), thrombocytopenia (8%), hypokalemia (7%), vomiting (4.9%), fatigue (4.3%), diarrhea (2.5%), and pneumonia (2.5%).
Dose reductions of any component of AKEEGA due to an adverse reaction occurred in 25% of patients.
Adverse reactions which required dose reductions in >2% of patients included anemia (17%).
The most common adverse reactions (>20%), including laboratory abnormalities, in patients who received AKEEGA were decreased hemoglobin, decreased lymphocyte count, hypertension, decreased neutrophil count, musculoskeletal pain, decreased platelet count, constipation, fatigue, decreased potassium, increase creatinine, nausea, increased alkaline phosphate, increased aspartate aminotransferase, respiratory tract infection, arrhythmia, increased blood bilirubin, and fluid retention/edema.
Table 2: Adverse Reactions (>20%) in Patients with BRCA2m mCSPC Who Received AKEEGA (with a Difference of ≥5% Compared to Placebo) in AMPLITUDE Adverse Reaction AKEEGA (N=162) Placebo with Abiraterone Acetate (N=161) All Grades % Grade 3 or 4 % All Grades % Grade 3 or 4 % Vascular disorders Hypertension Grouped terms including multiple similar terms 51 31 36 19 Musculoskeletal and connective tissue disorders Musculoskeletal pain 45 6 58 4.3 Gastrointestinal disorders Constipation 41 0 17 0.6 Nausea 30 0 17 0 General disorders and administration Fatigue 39 4.3 29 3.1 Respiratory, thoracic and mediastinal disorders Respiratory Tract Infection 23 0.6 13 0.6 Cardiac disorders Arrhythmia 23 3.7 9 2.5 Clinically relevant adverse reactions that occurred in ≤20% of patients receiving AKEEGA plus prednisone were hot flush (18%), vomiting (17%), dizziness (17%), abdominal pain (15%), weight decreased (14%), diarrhea (14%), decreased appetite (12%), headache (12%), hemorrhage (12%), dyspnea (10%), urinary tract infection (8%), pneumonia (7%), osteoporosis (4.9%), rash (3.7%), cardiac failure (3.1%), ischemic heart disease (4.9%), acute kidney injury (2.5%), pulmonary embolism (2.5%), and urosepsis (0.6%).
The most common select laboratory abnormalities (>20%) that worsened from baseline in patients who received AKEEGA are in Table 3.
Table 3: Select Laboratory Abnormalities (>20%) That Worsened from Baseline in Patients with BRCA2m mCSPC Who Received AKEEGA in AMPLITUDE Laboratory Abnormality AKEEGA The denominator used to calculate the rate varied from 160 to 161 for placebo with abiraterone acetate plus prednisone and 159 to 162 for AKEEGA with prednisone based on the number of patients with a baseline value and at least one post-treatment value.
(N=162) Placebo with Abiraterone Acetate (N=161) All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Hematology Decreased Hemoglobin 74 29 53 1.9 Decreased Lymphocyte Count 59 20 37 13 Decreased Neutrophil Count 49 10 19 3.1 Decreased Platelet Count 41 4.9 23 0.6 Chemistry Decreased Potassium 38 9 29 10 Increased Creatinine 30 1.3 16 2.5 Increased Alkaline Phosphatase 28 0.6 24 3.1 Increased Aspartate Aminotransferase 24 1.3 33 2.5 Increased Blood Bilirubin 22 0 11 0 BRCA -mutated Metastatic Castration-Resistant Prostate Cancer The safety of AKEEGA in patients with BRCA m mCRPC was evaluated in Cohort 1 of MAGNITUDE [see Clinical Studies (14.2) ].
Patients were randomized to receive either AKEEGA (niraparib 200 mg and abiraterone acetate 1,000 mg once daily) (n=113), or placebo and abiraterone acetate (n=112) until unacceptable toxicity or progression.
Patients in both arms also received prednisone 10 mg daily.
The median duration of exposure for AKEEGA was 18 months (range: 0 to 37 months).
Serious adverse reactions occurred in 41% of patients who received AKEEGA.
Serious adverse reactions reported in >2% of patients included COVID-19 (7%), anemia (4.4%), pneumonia (3.5%), and hemorrhage (3.5%).
Fatal adverse reactions occurred in 9% of patients who received AKEEGA, including COVID-19 (5%), cardiopulmonary arrest (1%), dyspnea (1%), pneumonia (1%), and septic shock (1%).
Permanent discontinuation of any component of AKEEGA due to an adverse reaction occurred in 15% of patients.
Adverse reactions which resulted in permanent discontinuation of AKEEGA in > 2% of patients included COVID-19 (4.4%), anemia (2.7%), asthenia (2.7%), and vomiting (2.7%).
Dosage interruptions of any component of AKEEGA due to an adverse reaction occurred in 50% of patients.
Adverse reactions which required dosage interruption in > 2% of patients included anemia (23%), thrombocytopenia (12%), neutropenia (7%), COVID-19 (6%), fatigue (3.5%), asthenia (3.5%), nausea (3.5%), pneumonia (2.7%), hematuria (2.7%), and vomiting (2.7%).
Dose reductions of any component of AKEEGA due to an adverse reaction occurred in 28% of patients.
Adverse reactions which required dose reductions in > 2% of patients included anemia (12%), thrombocytopenia (4.4%), and fatigue (2.7%).
The most common adverse reactions (>20%), including laboratory abnormalities, in patients who received AKEEGA were hemoglobin decreased, lymphocyte decreased, musculoskeletal pain, fatigue, platelets decreased, constipation, alkaline phosphatase increased, hypertension, nausea, neutrophils decreased, creatinine increased, potassium increased, potassium decreased, and aspartate aminotransferase increased.
Tables 4 and 5 summarize adverse reactions and laboratory abnormalities for patients with BRCA m mCRPC in MAGNITUDE, respectively.
Table 4: Adverse Reactions (>10%) in Patients with BRCAm mCRPC Who Received AKEEGA in MAGNITUDE AKEEGA (N=113) Placebo with Abiraterone Acetate (N=112) Adverse Reaction All Grades % Grade 3 or 4 % All Grades % Grade 3 or 4 % Musculoskeletal and connective tissue disorders Musculoskeletal pain Grouped terms including multiple similar terms.
44 4 42 5 General disorders and administration site conditions Fatigue 43 5 30 4 Edema 17 0 9 0 Pyrexia 10 2 6 0 Gastrointestinal disorders Constipation 34 1 20 0 Vomiting 15 0 7 1 Nausea 33 1 21 0 Abdominal pain 12 2 12 1 Vascular disorders Hypertension 33 14 27 17 Hemorrhage 12 2 8 1 Respiratory, thoracic and mediastinal disorders Dyspnea 15 1 8 3 Cough 12 0 6 0 Metabolism and nutrition disorders Decreased appetite 15 2 8 0 Nervous system disorders Dizziness 14 0 10 0 Headache 12 1 9 0 Infections and infestations COVID-19 13 7 9 4 Urinary tract infection 12 3 9 1 Psychiatric disorders Insomnia 12 0 4 0 Investigations Weight decreased 10 1 4 1 Cardiac disorders Arrhythmia 10 2 4 1 Injury, poisoning and procedural complications Fall 10 1 13 4 Clinically relevant adverse events that occurred in <10% of patients receiving AKEEGA plus prednisone were rash (7%), alanine aminotransferase increased (5%), aspartate aminotransferase increased (5%), cerebrovascular accident (4.4%), pulmonary embolism (2.7%), deep vein thrombosis (2.7%), and acute kidney injury (2.7%).
Table 5: Select Laboratory Abnormalities (>20%) That Worsened from Baseline in Patients with BRCAm mCRPC Who Received AKEEGA in MAGNITUDE AKEEGA The denominator used to calculate the rate varied from 111 to 112 for placebo with abiraterone acetate plus prednisone and 113 for AKEEGA with prednisone based on the number of patients with a baseline value and at least one post-treatment value.
(N=113) Placebo with Abiraterone Acetate (N=112) Laboratory Abnormality All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Hematology Hemoglobin decreased 67 26 53 7 Lymphocyte decreased 55 22 32 13 Platelets decreased 37 8 22 1.8 Neutrophils decreased 32 7 16 2.7 Chemistry Alkaline Phosphatase increased 34 1.8 29 1.8 Creatinine increased 30 0 13 1.8 Potassium increased 25 0.9 21 3.6 Potassium decreased 20 5 20 5 Aspartate Aminotransferase increased 20 1.8 25 2.7 Other Clinical Trial Experience The following adverse reactions have been reported with the individual components of AKEEGA but were not observed in AMPLITUDE or MAGNITUDE Cohort 1: myopathy, rhabdomyolysis, adrenal insufficiency, allergic alveolitis, febrile neutropenia, anaphylactic reaction, posterior reversible encephalopathy (PRES), and hypertensive crisis.
( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Biotech, Inc.
at 1-800-526-7736 (1-800-JANSSEN) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trial 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 safety population described in the WARNINGS and PRECAUTIONS reflect exposure to AKEEGA (niraparib 200 mg and abiraterone acetate 1,000 mg) in BRCA2 m patients (N=162) in the AMPLITUDE study and in BRCA m patients in Cohort 1 (N=113) in the MAGNITUDE study unless otherwise specified.
BRCA2 -mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC) The safety of AKEEGA in patients with BRCA2 m mCSPC was evaluated in AMPLITUDE [see Clinical Studies (14.1) ].
Patients were randomized to receive either AKEEGA (niraparib 200 mg and abiraterone acetate 1,000 mg once daily) (n=162), or placebo and abiraterone acetate (n=161) until unacceptable toxicity or progression.
Patients in both arms also received prednisone 5 mg daily.
The median duration of exposure for AKEEGA was 26 months (range: 0 to 48 months).
Serious adverse reactions occurred in 36% of patients who received AKEEGA.
Serious adverse reactions reported in >2% of patients included anemia (4.9%), and pneumonia (3.7%).
Fatal adverse reactions occurred in 4.9% of patients who received AKEEGA, including sudden death (1.9%), COVID-19 pneumonia (1.2%), pneumocystis jirovecii pneumonia (0.6%), pneumonia (0.6%), and cardio-respiratory arrest (0.6%).
Permanent discontinuation of any component of AKEEGA due to an adverse reaction occurred in 13% of patients.
Dosage interruptions of any component of AKEEGA due to an adverse reaction occurred in 67% of patients.
Adverse reactions which required dosage interruption in >2% of patients included anemia (30%), COVID-19 (10%), hypertension (9%), neutropenia (8%), thrombocytopenia (8%), hypokalemia (7%), vomiting (4.9%), fatigue (4.3%), diarrhea (2.5%), and pneumonia (2.5%).
Dose reductions of any component of AKEEGA due to an adverse reaction occurred in 25% of patients.
Adverse reactions which required dose reductions in >2% of patients included anemia (17%).
The most common adverse reactions (>20%), including laboratory abnormalities, in patients who received AKEEGA were decreased hemoglobin, decreased lymphocyte count, hypertension, decreased neutrophil count, musculoskeletal pain, decreased platelet count, constipation, fatigue, decreased potassium, increase creatinine, nausea, increased alkaline phosphate, increased aspartate aminotransferase, respiratory tract infection, arrhythmia, increased blood bilirubin, and fluid retention/edema.
Table 2: Adverse Reactions (>20%) in Patients with BRCA2m mCSPC Who Received AKEEGA (with a Difference of ≥5% Compared to Placebo) in AMPLITUDE Adverse Reaction AKEEGA (N=162) Placebo with Abiraterone Acetate (N=161) All Grades % Grade 3 or 4 % All Grades % Grade 3 or 4 % Vascular disorders Hypertension Grouped terms including multiple similar terms 51 31 36 19 Musculoskeletal and connective tissue disorders Musculoskeletal pain 45 6 58 4.3 Gastrointestinal disorders Constipation 41 0 17 0.6 Nausea 30 0 17 0 General disorders and administration Fatigue 39 4.3 29 3.1 Respiratory, thoracic and mediastinal disorders Respiratory Tract Infection 23 0.6 13 0.6 Cardiac disorders Arrhythmia 23 3.7 9 2.5 Clinically relevant adverse reactions that occurred in ≤20% of patients receiving AKEEGA plus prednisone were hot flush (18%), vomiting (17%), dizziness (17%), abdominal pain (15%), weight decreased (14%), diarrhea (14%), decreased appetite (12%), headache (12%), hemorrhage (12%), dyspnea (10%), urinary tract infection (8%), pneumonia (7%), osteoporosis (4.9%), rash (3.7%), cardiac failure (3.1%), ischemic heart disease (4.9%), acute kidney injury (2.5%), pulmonary embolism (2.5%), and urosepsis (0.6%).
The most common select laboratory abnormalities (>20%) that worsened from baseline in patients who received AKEEGA are in Table 3.
Table 3: Select Laboratory Abnormalities (>20%) That Worsened from Baseline in Patients with BRCA2m mCSPC Who Received AKEEGA in AMPLITUDE Laboratory Abnormality AKEEGA The denominator used to calculate the rate varied from 160 to 161 for placebo with abiraterone acetate plus prednisone and 159 to 162 for AKEEGA with prednisone based on the number of patients with a baseline value and at least one post-treatment value.
(N=162) Placebo with Abiraterone Acetate (N=161) All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Hematology Decreased Hemoglobin 74 29 53 1.9 Decreased Lymphocyte Count 59 20 37 13 Decreased Neutrophil Count 49 10 19 3.1 Decreased Platelet Count 41 4.9 23 0.6 Chemistry Decreased Potassium 38 9 29 10 Increased Creatinine 30 1.3 16 2.5 Increased Alkaline Phosphatase 28 0.6 24 3.1 Increased Aspartate Aminotransferase 24 1.3 33 2.5 Increased Blood Bilirubin 22 0 11 0 BRCA -mutated Metastatic Castration-Resistant Prostate Cancer The safety of AKEEGA in patients with BRCA m mCRPC was evaluated in Cohort 1 of MAGNITUDE [see Clinical Studies (14.2) ].
Patients were randomized to receive either AKEEGA (niraparib 200 mg and abiraterone acetate 1,000 mg once daily) (n=113), or placebo and abiraterone acetate (n=112) until unacceptable toxicity or progression.
Patients in both arms also received prednisone 10 mg daily.
The median duration of exposure for AKEEGA was 18 months (range: 0 to 37 months).
Serious adverse reactions occurred in 41% of patients who received AKEEGA.
Serious adverse reactions reported in >2% of patients included COVID-19 (7%), anemia (4.4%), pneumonia (3.5%), and hemorrhage (3.5%).
Fatal adverse reactions occurred in 9% of patients who received AKEEGA, including COVID-19 (5%), cardiopulmonary arrest (1%), dyspnea (1%), pneumonia (1%), and septic shock (1%).
Permanent discontinuation of any component of AKEEGA due to an adverse reaction occurred in 15% of patients.
Adverse reactions which resulted in permanent discontinuation of AKEEGA in > 2% of patients included COVID-19 (4.4%), anemia (2.7%), asthenia (2.7%), and vomiting (2.7%).
Dosage interruptions of any component of AKEEGA due to an adverse reaction occurred in 50% of patients.
Adverse reactions which required dosage interruption in > 2% of patients included anemia (23%), thrombocytopenia (12%), neutropenia (7%), COVID-19 (6%), fatigue (3.5%), asthenia (3.5%), nausea (3.5%), pneumonia (2.7%), hematuria (2.7%), and vomiting (2.7%).
Dose reductions of any component of AKEEGA due to an adverse reaction occurred in 28% of patients.
Adverse reactions which required dose reductions in > 2% of patients included anemia (12%), thrombocytopenia (4.4%), and fatigue (2.7%).
The most common adverse reactions (>20%), including laboratory abnormalities, in patients who received AKEEGA were hemoglobin decreased, lymphocyte decreased, musculoskeletal pain, fatigue, platelets decreased, constipation, alkaline phosphatase increased, hypertension, nausea, neutrophils decreased, creatinine increased, potassium increased, potassium decreased, and aspartate aminotransferase increased.
Tables 4 and 5 summarize adverse reactions and laboratory abnormalities for patients with BRCA m mCRPC in MAGNITUDE, respectively.
Table 4: Adverse Reactions (>10%) in Patients with BRCAm mCRPC Who Received AKEEGA in MAGNITUDE AKEEGA (N=113) Placebo with Abiraterone Acetate (N=112) Adverse Reaction All Grades % Grade 3 or 4 % All Grades % Grade 3 or 4 % Musculoskeletal and connective tissue disorders Musculoskeletal pain Grouped terms including multiple similar terms.
44 4 42 5 General disorders and administration site conditions Fatigue 43 5 30 4 Edema 17 0 9 0 Pyrexia 10 2 6 0 Gastrointestinal disorders Constipation 34 1 20 0 Vomiting 15 0 7 1 Nausea 33 1 21 0 Abdominal pain 12 2 12 1 Vascular disorders Hypertension 33 14 27 17 Hemorrhage 12 2 8 1 Respiratory, thoracic and mediastinal disorders Dyspnea 15 1 8 3 Cough 12 0 6 0 Metabolism and nutrition disorders Decreased appetite 15 2 8 0 Nervous system disorders Dizziness 14 0 10 0 Headache 12 1 9 0 Infections and infestations COVID-19 13 7 9 4 Urinary tract infection 12 3 9 1 Psychiatric disorders Insomnia 12 0 4 0 Investigations Weight decreased 10 1 4 1 Cardiac disorders Arrhythmia 10 2 4 1 Injury, poisoning and procedural complications Fall 10 1 13 4 Clinically relevant adverse events that occurred in <10% of patients receiving AKEEGA plus prednisone were rash (7%), alanine aminotransferase increased (5%), aspartate aminotransferase increased (5%), cerebrovascular accident (4.4%), pulmonary embolism (2.7%), deep vein thrombosis (2.7%), and acute kidney injury (2.7%).
Table 5: Select Laboratory Abnormalities (>20%) That Worsened from Baseline in Patients with BRCAm mCRPC Who Received AKEEGA in MAGNITUDE AKEEGA The denominator used to calculate the rate varied from 111 to 112 for placebo with abiraterone acetate plus prednisone and 113 for AKEEGA with prednisone based on the number of patients with a baseline value and at least one post-treatment value.
(N=113) Placebo with Abiraterone Acetate (N=112) Laboratory Abnormality All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Hematology Hemoglobin decreased 67 26 53 7 Lymphocyte decreased 55 22 32 13 Platelets decreased 37 8 22 1.8 Neutrophils decreased 32 7 16 2.7 Chemistry Alkaline Phosphatase increased 34 1.8 29 1.8 Creatinine increased 30 0 13 1.8 Potassium increased 25 0.9 21 3.6 Potassium decreased 20 5 20 5 Aspartate Aminotransferase increased 20 1.8 25 2.7 Other Clinical Trial Experience The following adverse reactions have been reported with the individual components of AKEEGA but were not observed in AMPLITUDE or MAGNITUDE Cohort 1: myopathy, rhabdomyolysis, adrenal insufficiency, allergic alveolitis, febrile neutropenia, anaphylactic reaction, posterior reversible encephalopathy (PRES), and hypertensive crisis.