NOXAFIL SIDE EFFECTS

Last updated on MDtodate: 10/9/2022

SIDE EFFECTS

The following serious and otherwise important adverse reactions are discussed in detail in another section of the labeling:

• Hypersensitivity
• Arrhythmias and QT Prolongation
• Hepatic Toxicity

Clinical Trials Experience

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

Clinical Trial Experience In Adults

Clinical Trial Experience With Noxafil Injection And Noxafil Delayed-Release Tablets For The Treatment Of Invasive Aspergillosis

The safety of Noxafil injection and Noxafil delayed-release tablet was assessed in a randomized, double-blind, active-controlled clinical study of Noxafil injection and Noxafil delayed-release tablets versus voriconazole for treatment of invasive aspergillosis (Aspergillosis Treatment Study). A total of 575 (288 in Noxafil arm, 287 in voriconazole arm) adult and pediatric patients 13 years of age and older with proven, probable or possible invasive aspergillosis were included. The median duration of treatment was 67 days for Noxafil injection or Noxafil delayed-release tablet and 64 days for voriconazole, with 55% to 60% of subjects starting treatment with the IV formulation of either drug. The median duration of the first instance of IV treatment (before switching to oral treatment or discontinuing or completing study treatment) was 9 days for both groups. Table 7 presents adverse reactions reported at an incidence of ≥10% in either one of the groups in Aspergillosis Treatment Study.

Adverse reactions leading to treatment discontinuation were reported for 33.9% of subjects. The most commonly reported adverse reactions (>2% of subjects) leading to treatment discontinuation were septic shock, respiratory failure, and bronchopulmonary aspergillosis in the Noxafil arm, and septic shock and acute myeloid leukemia in the voriconazole arm.

Table 1: Noxafil Invasive Aspergillosis Treatment Study: Adverse Reactions in at Least 10% of Subjects Treated with Noxafil Injection or Noxafil Delayed-Release Tablets

System Organ Class	Noxafil injection or tablet (N = 288), n (%)	Voriconazole injection or oral (N = 287), n (%)
Blood and lymphatic system disorders
Anemia	25 (8.7)	29 (10.1)
Febrile neutropenia	42 (14.6)	38 (13.2)
Gastrointestinal disorders
Abdominal pain	29 (10.1)	24 (8.4)
Constipation	32 (11.1)	23 (8.0)
Diarrhea	52 (18.1)	52 (18.1)
Nausea	65 (22.6)	51 (17.8)
Vomiting	52 (18.1)	39 (13.6)
General disorders and administration site conditions
Edema peripheral	32 (11.1)	24 (8.4)
Pyrexia	81 (28.1)	72 (25.1)
Infections and infestations
Pneumonia	36 (12.5)	26 (9.1)
Investigations
Alanine aminotransferase increased	42 (14.6)	37 (12.9)
Aspartate aminotransferase increased	38 (13.2)	36 (12.5)
Blood alkaline phosphatase increased	21 (7.3)	29 (10.1)
Metabolism and nutrition disorders
Hypokalemia	82 (28.5)	49 (17.1)
Hypomagnesemia	29 (10.1)	18 (6.3)
Nervous system disorders
Headache	35 (12.2)	25 (8.7)
Respiratory, thoracic and mediastinal disorders
Cough	30 (10.4)	24 (8.4)
Epistaxis	32 (11.1)	17 (5.9)

 

The most frequently reported adverse reactions in the Noxafil-treated group were pyrexia (28%), hypokalemia (28%), and nausea (23%).

Clinical Trial Experience With Noxafil Injection For Prophylaxis

Multiple doses of Noxafil injection administered via a peripheral venous catheter were associated with thrombophlebitis (60% incidence). Therefore, in subsequent studies, Noxafil injection was administered via central venous catheter.

The safety of Noxafil injection has been assessed in 268 patients in a clinical trial. Patients were enrolled in a non-comparative pharmacokinetic and safety trial of Noxafil injection when given as antifungal prophylaxis (Noxafil Injection Study). Patients were immunocompromised with underlying conditions including hematological malignancy, neutropenia post-chemotherapy, GVHD, and post HSCT. This patient population was 55% male, had a mean age of 51 years (range 18-82 years, 19% of patients were ≥65 years of age), and were 95% white and 8% Hispanic. Ten patients received a single dose of 200 mg Noxafil injection, 21 patients received 200 mg daily dose for a median of 14 days, and 237 patients received 300 mg daily dose for a median of 9 days.

Table 8 presents adverse reactions observed in patients treated with Noxafil injection 300 mg daily dose in the Noxafil Injection Study. Each patient received a loading dose, 300 mg twice on Day 1. Following Noxafil intravenous therapy, patients received Noxafil oral suspension to complete 28 days of total Noxafil therapy.

Table 1: Noxafil Injection Study: Adverse Reactions in at Least 10% of Subjects Treated withNoxafil Injection 300 mg Daily Dose

Body System	Noxafil Injection Treatment Phase n=237 (%)*	Noxafil Injection Treatment Phase or Subsequent Noxafil Oral Suspension Treatment Phase n=237 (%)†
Subjects Reporting any Adverse Reaction	220(93)	235(99)
Blood and Lymphatic System Disorder
Anemia	16(7)	23(10)
Thrombocytopenia	17(7)	25(11)
Gastrointestinal Disorders
Abdominal Pain Upper	15(6)	25(11)
Abdominal Pain	30(13)	41(17)
Constipation	18(8)	31(13)
Diarrhea	75(32)	93(39)
Nausea	46(19)	70(30)
Vomiting	29(12)	45(19)
General Disorders and Administration Site Conditions
Fatigue	19(8)	24(10)
Chills	28(12)	38(16)
Edema Peripheral	28(12)	35(15)
Pyrexia	49(21)	73(31)
Metabolism and Nutrition Disorders
Decreased appetite	23(10)	29(12)
Hypokalemia	51(22)	67(28)
Hypomagnesemia	25(11)	30(13)
Nervous System Disorders
Headache	33(14)	49(21)
Respiratory, Thoracic and Mediastinal Disorders
Cough	21(9)	31(13)
Dyspnea	16(7)	24(10)
Epistaxis	34(14)	40(17)
Skin and Subcutaneous Tissue Disorders
Petechiae	20(8)	24(10)
Rash	35(15)	56(24)
Vascular Disorders
Hypertension	20(8)	26(11)
*Adverse reactions reported in patients with an onset during the Noxafil intravenous dosing phase of the study. †Adverse reactions reported with an onset at any time during the study in patients who were treated for up to 28 days of Noxafil therapy.

 

The most frequently reported adverse reactions with an onset during the Noxafil intravenous phase of dosing with 300 mg once daily were diarrhea (32%), hypokalemia (22%), pyrexia (21%), and nausea (19%). These adverse reactions were consistent with those seen in studies with Noxafil oral suspension.

Clinical Trial Experience With Noxafil Delayed-Release Tablets For Prophylaxis

The safety of Noxafil delayed-release tablets has been assessed in 230 patients in clinical trials. Patients were enrolled in a non-comparative pharmacokinetic and safety trial of Noxafil delayed-release tablets when given as antifungal prophylaxis (Noxafil Delayed-Release Tablet Study). Patients were immunocompromised with underlying conditions including hematological malignancy, neutropenia post-chemotherapy, GVHD, and post HSCT. This patient population was 62% male, had a mean age of 51 years (range 19-78 years, 17% of patients were ≥65 years of age), and were 93% white and 16% Hispanic. Posaconazole therapy was given for a median duration of 28 days. Twenty patients received 200 mg daily dose and 210 patients received 300 mg daily dose (following twice daily dosing on Day 1 in each cohort). Table 9 presents adverse reactions observed in patients treated with 300 mg daily dose at an incidence of ≥10% in Noxafil Delayed-Release Tablet Study.

Table 2: Noxafil Delayed-Release Tablet Study: Adverse Reactions in at Least 10% of Subjects Treated with 300 mg Daily Dose

Body System	Noxafil delayed-release tablet
	(300 mg) n=210(%)
Subjects Reporting any Adverse Reaction	207(99)
Blood and Lymphatic System Disorder
Anemia	22(10)
Thrombocytopenia	29(14)
Gastrointestinal Disorders
Abdominal Pain	23(11)
Constipation	20(10)
Diarrhea	61(29)
Nausea	56(27)
Vomiting	28(13)
General Disorders and Administration Site Conditions
Asthenia	20(10)
Chills	22(10)
Mucosal Inflammation	29(14)
Edema Peripheral	33(16)
Pyrexia	59(28)
Metabolism and Nutrition Disorders
Hypokalemia	46(22)
Hypomagnesemia	20(10)
Nervous System Disorders
Headache	30(14)
Respiratory, Thoracic and Mediastinal Disorders
Cough	35(17)
Epistaxis	30(14)
Skin and Subcutaneous Tissue Disorders
Rash	34(16)
Vascular Disorders
Hypertension	23(11)

 

The most frequently reported adverse reactions (>25%) with Noxafil delayed-release tablets 300 mg once daily were diarrhea, pyrexia, and nausea.

The most common adverse reaction leading to discontinuation of Noxafil delayed-release tablets 300 mg once daily was nausea (2%).

Clinical Trial Safety Experience With Noxafil Oral Suspension

The safety of Noxafil oral suspension has been assessed in 1844 patients. This includes 605 patients in the active-controlled prophylaxis studies, 557 patients in the active-controlled OPC studies, 239 patients in refractory OPC studies, and 443 patients from other indications. This represents a heterogeneous population, including immunocompromised patients, e.g., patients with hematological malignancy, neutropenia post-chemotherapy, GVHD post HSCT, and HIV infection, as well as non-neutropenic patients. This patient population was 71% male, had a mean age of 42 years (range 8-84 years, 6% of patients were ≥65 years of age and 1% was <18 years of age), and were 64% white, 16% Hispanic, and 36% non-white (including 14% black). Noxafil therapy was given to 171 patients for ≥6 months, with 58 patients receiving Noxafil therapy for ≥12 months. Table 10 presents adverse reactions observed at an incidence of >10% in Noxafil prophylaxis studies. Table 11 presents adverse reactions observed at an incidence of at least 10% in the OPC/rOPC studies.

Prophylaxis Of Aspergillus And Candida

In the 2 randomized, comparative prophylaxis studies (Noxafil Oral Suspension Study 1 and 2), the safety of Noxafil oral suspension 200 mg three times a day was compared to fluconazole 400 mg once daily or itraconazole 200 mg twice a day in severely immunocompromised patients.

The most frequently reported adverse reactions (>30%) in the prophylaxis clinical trials were fever, diarrhea, and nausea.

The most common adverse reactions leading to discontinuation of Noxafil in the prophylaxis studies were associated with GI disorders, specifically, nausea (2%), vomiting (2%), and hepatic enzymes increased (2%).

Table 3: Noxafil Oral Suspension Study 1 and Study 2. Adverse Reactions in at Least 10% of theNoxafil Oral Suspension or Fluconazole Treatment Groups (Pooled Prophylaxis Safety Analysis)

Body System	Noxafil Oral Suspension n=605(%)	Fluconazole n=539(%)	Itraconazole n=58 (%)
Subjects Reporting any Adverse Reaction	595(98)	531(99)	58(100)
Body as a Whole – General Disorders
Fever	274(45)	254(47)	32(55)
Headache	171(28)	141(26)	23(40)
Rigors	122(20)	87(16)	17(29)
Fatigue	101(17)	98(18)	5(9)
Edema Legs	93(15)	67(12)	11(19)
Anorexia	92(15)	94(17)	16(28)
Dizziness	64(11)	56(10)	5(9)
Edema	54(9)	68(13)	8(14)
Weakness	51(8)	52(10)	2(3)
Cardiovascular Disorders, General
Hypertension	106(18)	88(16)	3(5)
Hypotension	83(14)	79(15)	10(17)
Disorders of Blood and Lymphatic System
Anemia	149(25)	124(23)	16(28)
Neutropenia	141(23)	122(23)	23(40)
Disorders of the Reproductive System and Breast
Vaginal Hemorrhage*	24(10)	20(9)	3(12)
Gastrointestinal System Disorders
Diarrhea	256(42)	212(39)	35(60)
Nausea	232(38)	198(37)	30(52)
Vomiting	174(29)	173(32)	24(41)
Abdominal Pain	161(27)	147(27)	21(36)
Constipation	126(21)	94(17)	10(17)
Dyspepsia	61(10)	50(9)	6(10)
Heart Rate and Rhythm Disorders
Tachycardia	72(12)	75(14)	3(5)
Infection and Infestations
Pharyngitis	71(12)	60(11)	12(21)
Liver and Biliary System Disorders
Bilirubinemia	59(10)	51(9)	11(19)
Metabolic and Nutritional Disorders
Hypokalemia	181(30)	142(26)	30(52)
Hypomagnesemia	110(18)	84(16)	11(19)
Hyperglycemia	68(11)	76(14)	2(3)
Hypocalcemia	56(9)	55(10)	5(9)
Musculoskeletal System Disorders
Musculoskeletal Pain	95(16)	82(15)	9(16)
Arthralgia	69(11)	67(12)	5(9)
Back Pain	63(10)	66(12)	4(7)
Platelet, Bleeding and Clotting Disorders
Thrombocytopenia	175(29)	146(27)	20(34)
Petechiae	64(11)	54(10)	9(16)
Psychiatric Disorders
Insomnia	103(17)	92(17)	11(19)
Respiratory System Disorders
Coughing	146(24)	130(24)	14(24)
Dyspnea	121(20)	116(22)	15(26)
Epistaxis	82(14)	73(14)	12(21)
Skin and Subcutaneous Tissue Disorders
Rash	113(19)	96(18)	25(43)
Pruritus	69(11)	62(12)	11(19)
* Percentages of sex-specific adverse reactions are based on the number of males/females.

 

HIV Infected Subjects With OPC

In 2 randomized comparative studies in OPC, the safety of Noxafil oral suspension at a dose of less than or equal to 400 mg once daily in 557 HIV-infected patients was compared to the safety of fluconazole in 262 HIV-infected patients at a dose of 100 mg once daily.

An additional 239 HIV-infected patients with refractory OPC received Noxafil oral suspension in 2 non-comparative trials for refractory OPC (rOPC). Of these subjects, 149 received the 800-mg/day dose and the remainder received the less than or equal to 400-mg once daily dose.

In the OPC/rOPC studies, the most common adverse reactions were fever, diarrhea, nausea, headache, vomiting, and coughing.

The most common adverse reactions that led to treatment discontinuation of Noxafil in the Controlled OPC Pool included respiratory impairment (1%) and pneumonia (1%). In the refractory OPC pool, the most common adverse reactions that led to treatment discontinuation of Noxafil were AIDS (7%) and respiratory impairment (3%).

Table 4: Adverse Reactions in at Least 10% of the Treated Population in OPC Studies with Noxafil Oral Suspension

Body System	Number (%) of Subjects
	Controlled OPC Pool		Refractory OPC Pool
	Noxafil Oral Suspension n=557	Fluconazole n=262	Noxafil Oral Suspension n=239
Subjects Reporting any Adverse Reaction*	356 (64)	175 (67)	221 (92)
Body as a Whole – General Disorders
Fever	34 (6)	22 (8)	82 (34)
Headache	44 (8)	23 (9)	47 (20)
Anorexia	10 (2)	4 (2)	46 (19)
Fatigue	18 (3)	12 (5)	31 (13)
Asthenia	9 (2)	5 (2)	31 (13)
Rigors	2 (<1)	4 (2)	29 (12)
Pain	4 (1)	2 (1)	27 (11)
Disorders of Blood and Lymphatic System
Neutropenia	21 (4)	8 (3)	39 (16)
Anemia	11 (2)	5 (2)	34 (14)
Gastrointestinal System Disorders
Diarrhea	58 (10)	34 (13)	70 (29)
Nausea	48 (9)	30 (11)	70 (29)
Vomiting	37 (7)	18 (7)	67 (28)
Abdominal Pain	27 (5)	17 (6)	43 (18)
Infection and Infestations
Candidiasis, Oral	3 (1)	1 (<1)	28 (12)
Herpes Simplex	16 (3)	8 (3)	26 (11)
Pneumonia	17 (3)	6 (2)	25 (10)
Metabolic and Nutritional Disorders
Weight Decrease	4 (1)	2 (1)	33 (14)
Dehydration	4 (1)	7 (3)	27 (11)
Psychiatric Disorders
Insomnia	8 (1)	3 (1)	39 (16)
Respiratory System Disorders
Coughing	18 (3)	11 (4)	60 (25)
Dyspnea	8 (1)	8 (3)	28 (12)
Skin and Subcutaneous Tissue Disorders
Rash	15 (3)	10 (4)	36 (15)
Sweating Increased	13 (2)	5 (2)	23 (10)
OPC=oropharyngeal candidiasis * Number of subjects reporting adverse reactions at least once during the study, without regard to relationship to treatment. Subjects may have reported more than 1 event.

 

Adverse reactions were reported more frequently in the pool of patients with refractory OPC. Among these highly immunocompromised patients with advanced HIV disease, serious adverse reactions (SARs) were reported in 55% (132/239). The most commonly reported SARs were fever (13%) and neutropenia (10%).

Other clinically significant adverse reactions reported in less than 5% of patients in clinical trials of Noxafil are listed below:

• Blood and lymphatic system disorders: hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, neutropenia aggravated
• Endocrine disorders: adrenal insufficiency
• Nervous system disorders: paresthesia
• Immune system disorders: allergic reaction
• Cardiac disorders: torsades de pointes
• Vascular disorders: pulmonary embolism
• Gastrointestinal disorders: pancreatitis
• Liver and Biliary System Disorders: hepatic enzymes increased, hepatic function abnormal, hepatitis, hepatomegaly, jaundice
• Renal & Urinary System Disorders: renal failure acute

Clinical Laboratory Values

In healthy volunteers and patients, elevation of liver test values did not appear to be associated with higher plasma concentrations of posaconazole.

For the prophylaxis studies, the number of patients with changes in liver tests from Common Toxicity Criteria (CTC) Grade 0, 1, or 2 at baseline to Grade 3 or 4 during the study is presented in Table 5.

Table 5: Noxafil Oral Suspension Study 1 and Study 2. Changes in Liver Test Results from CTCGrade 0, 1, or 2 at Baseline to Grade 3 or 4

Number (%) of Patients with Change*
Noxafil Oral Suspension Study 1
Laboratory Parameter	Noxafil Oral Suspension n=301	Fluconazole n=299
AST	11/266 (4)	13/266 (5)
ALT	47/271 (17)	39/272 (14)
Bilirubin	24/271 (9)	20/275 (7)
Alkaline Phosphatase	9/271 (3)	8/271 (3)
Noxafil Oral Suspension Study 2
Laboratory Parameter	Noxafil Oral Suspension (n=304)	Fluconazole/Itraconazole (n=298)
AST	9/286 (3)	5/280 (2)
ALT	18/289 (6)	13/284 (5)
Bilirubin	20/290 (7)	25/285 (9)
Alkaline Phosphatase	4/281 (1)	1/276 (<1)
*Change from Grade 0 to 2 at baseline to Grade 3 or 4 during the study. These data are presented in the form X/Y, where X represents the number of patients who met the criterion as indicated, and Y represents the number of patients who had a baseline observation and at least one post-baseline observation. CTC = Common Toxicity Criteria; AST= Aspartate Aminotransferase; ALT= Alanine Aminotransferase.

 

The number of patients treated for OPC with clinically significant liver test abnormalities at any time  during the studies is provided in Table 13 (liver test abnormalities were present in some of these patients  prior to initiation of the study drug).

Table 6 : Noxafil Oral Suspension Studies: Clinically Significant Laboratory Test Abnormalities without Regard to Baseline Value

Laboratory Test	Controlled		Refractory
	Noxafil Oral Suspension n=557(%)	Fluconazole n=262(%)	Noxafil Oral Suspension n=239(%)
ALT > 3.0 x ULN	16/537 (3)	13/254 (5)	25/226 (11)
AST > 3.0 x ULN	33/537 (6)	26/254 (10)	39/223 (17)
Total Bilirubin > 1.5 x ULN	15/536 (3)	5/254 (2)	9/197 (5)
Alkaline Phosphatase > 3.0 x ULN	17/535 (3)	15/253 (6)	24/190 (13)
ALT= Alanine Aminotransferase; AST= Aspartate Aminotransferase.

 

The number of patients treated for invasive aspergillosis with clinically significant liver test abnormalities at any time during the Aspergillosis Treatment Study is provided in Table 7. Liver test abnormalities present prior to the initiation of study drug included ALT (22%), AST (13%), and bilirubin (13%).

Table 7: Aspergillosis Treatment Study: Changes in Liver Test Results from CTC Grade 0, 1, or 2 at Baseline to Grade 3 or 4

Number (%) of Patients with Change*
Laboratory Parameter	Noxafil n/N (%)	Voriconazole n/N (%)
AST	22/281 (8)	21/285 (7)
ALT	29/281(10)	23/282 (8)
Bilirubin	26/280 (9)	25/284 (9)
Alkaline Phosphatase	12/282 (4)	20/284 (7)
*Change from Grade 0 to 2 at baseline to Grade 3 or 4 during the study. These data are presented in the form n/N, where n represents the number of patients who met the criterion as indicated, and N represents the number of patients who had a baseline observation and at least one post-baseline observation. N=Number of subjects for a given laboratory test with a baseline value of CTC Grade 0, 1, or 2 and at least one post-baseline value. CTC = Common Toxicity Criteria; AST= Aspartate Aminotransferase; ALT= Alanine Aminotransferase.

 

Clinical Trial Experience In Pediatrics

Clinical Trial Experience In Pediatric Patients (2 to less than 18 Years of Age)

The safety of Noxafil injection and Noxafil PowderMix for delayed-release oral suspension for prophylaxis of invasive fungal infections has been assessed in an open label uncontrolled dose-ranging PK and safety study (Noxafil injection/ Noxafil PowderMix for delayed-release oral suspension Pediatric Study 1, NCT02452034); hereinafter referred to as Noxafil Pediatric Study) in 115 immunocompromised pediatric patients 2 to less than 18 years of age with known or expected neutropenia. Noxafil injection and Noxafil PowderMix for delayed-release oral suspension was administered at daily doses of up to 6 mg/kg (twice daily on day 1) in three dose cohorts. All 115 subjects initially received Noxafil injection for at least 7 days, and 63 subjects were transitioned to Noxafil PowderMix for delayed-release oral suspension. The mean overall treatment duration for all treated subjects was 20.6 days with 14.3 days (range: 1 to 28 days) on Noxafil injection and 11.6 days (range: 2 to 18 days) on Noxafil PowderMix for delayed-release oral suspension.

Table 8 presents adverse reactions observed in greater than or equal to 10% of pediatric patients treated with Noxafil in the Noxafil Pediatric Study.

Reported adverse reaction profile of Noxafil in pediatric patients was consistent with the safety profile of Noxafil in adults. The most common adverse reactions (occurring in greater than 20% of pediatric patients receiving 6 mg/kg Noxafil injection and Noxafil PowderMix for delayed-release oral suspension daily dose) were pyrexia, febrile neutropenia, vomiting, mucosal inflammation, pruritus, hypertension, hypokalemia, and stomatitis.

Table 8: Adverse Reactions in at Least 10% of Pediatric Patients Treated with Noxafil Injectionand Noxafil PowderMix for Delayed-Release Oral Suspension

Adverse Reaction	Noxafil Injection and Noxafil PowderMix for Delayed-Release Oral Suspension 6 mg/kg Dose Cohort n=49 (%)	Noxafil Injection and Noxafil PowderMix for Delayed-Release Oral Suspension All Dose Cohorts n=115 (%)
Pyrexia	16(33)	50 (43)
Febrile neutropenia	15(31)	25 (22)
Vomiting	12(24)	30 (26)
Mucosal inflammation	11 (22)	32 (28)
Pruritus	11 (22)	18(16)
Hypertension	10(20)	20(17)
Hypokalemia	10(20)	16(14)
Stomatitis	10(20)	13(11)
Diarrhea	9(18)	25 (22)
Nausea	9(18)	18(16)
Abdominal pain	8(16)	20(17)
Decreased appetite	7(14)	17(15)
Rash	7(14)	18(16)
Alanine aminotransferase increased	6(12)	8 (7)
Headache	6(12)	16(14)
Aspartate aminotransferase increased	5(10)	8 (7)

 

The number of patients receiving Noxafil in the Noxafil Pediatric Study who had changes in liver tests from Grade 0, 1, or 2 at baseline to Grade 3 or 4 is presented in Table 9.

Table 9: Noxafil Pediatric Study: Changes in Liver Tests from CTC Grade 0, 1, or 2 at Baseline toGrade 3 or 4

Number (%) of Patients with Change* Pediatric Study 1
Laboratory Parameter	Noxafil Injection and Noxafil PowderMix for Delayed-Release Oral Suspension (6 mg/kg daily) n=49 (%)
AST	2/49 (4)
ALT	3/49 (6)
Bilirubin	0/48 (0)
Alkaline Phosphatase	0/48 (0)
*Change from Grade 0 to 2 at baseline to Grade 3 or 4 during the study. These data are presented in the form X/Y, where X represents the number of patients who met the criterion as indicated, and Y represents the number of patients who had a baseline observation and at least one post-baseline observation. CTC = Common Toxicity Criteria; AST= Aspartate Aminotransferase; ALT= Alanine Aminotransferase

 

Postmarketing Experience

The following adverse reaction has been identified during the post-approval use of Noxafil. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency.

Endocrine Disorders: Pseudoaldosteronism