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Noxafil

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Noxafil

Noxafil Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

Noxafil (posaconazole) is used to prevent fungal infections in people with weak immune systems resulting from chemotherapy or stem cell transplantation. It is a triazole antifungal agent. Common side effects include nausea, vomiting, diarrhea, headache, abdominal pain, dizziness, trouble sleeping, or stomach upset.

Dosing and frequency of Noxafil varies depending on the fungal infection being treated. Doses range from 100 mg (2.5 mL) to 400 mg (10 mL), taken one to three times a day. Noxafil may interact with arsenic trioxide, cimetidine, cyclosporine, digoxin, droperidol, esomeprazole, midazolam, phenytoin, antibiotics, antidepressants, anti-malaria medications, calcium channel blockers, cancer medicines, cholesterol-lowering medicines, heart rhythm medications, HIV medications, medicine to prevent or treat nausea and vomiting, medicines to treat psychiatric disorders, migraine headache medicines, or narcotics. Tell your doctor all medications and supplements you use. During pregnancy, Noxafil should be used only when prescribed. It is unknown if this drug passes into breast milk. Consult your doctor before breastfeeding.

Our Noxafil (posaconazole) 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 Patient Information in Detail?

Easy-to-read and understand detailed drug information and pill images for the patient or caregiver from Cerner Multum.

Noxafil in Detail - Patient Information: Side Effects

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

Call your doctor at once if you have a serious side effect such as:

  • headache with chest pain and severe dizziness, fainting, fast or pounding heartbeats;
  • slow heartbeats;
  • signs of an infection such as fever, chills, sore throat, flu symptoms, vomiting, mouth sores;
  • pale skin, easy bruising or bleeding, feeling light-headed or short of breath, rapid heart rate, trouble concentrating;
  • low potassium (confusion, uneven heart rate, extreme thirst, increased urination, leg discomfort, muscle weakness or limp feeling);
  • feeling like you might pass out;
  • nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or
  • dangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, anxiety, chest pain, shortness of breath, seizure).

Less serious side effects may include:

  • mild headache, dizziness;
  • tired feeling
  • swelling of your ankles or feet;
  • diarrhea, constipation, stomach pain;
  • joint or muscle pain; or
  • sleep problems (insomnia).

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 Noxafil (Posaconazole Oral Suspension) »

What is Prescribing information?

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

Noxafil FDA Prescribing Information: Side Effects
(Adverse Reactions)

SIDE EFFECTS

Serious And Otherwise Important Adverse Reactions

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

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. In clinical trials, the type of adverse reactions reported for posaconazole injection and posaconazole delayed-release tablets were generally similar to that reported in trials of posaconazole oral suspension.

Clinical Trial Experience with Posaconazole Injection

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

The safety of posaconazole injection has been assessed in 268 patients in a clinical trial. Patients were enrolled in a non-comparative pharmacokinetic and safety trial of posaconazole injection when given as antifungal prophylaxis (Posaconazole Injection Study 1). 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 posaconazole 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 4 presents treatment-emergent adverse reactions observed in patients treated with posaconazole injection 300 mg daily dose in the posaconazole injection study. Each patient received a loading dose, 300 mg twice on Day 1. Following posaconazole intravenous therapy, patients received posaconazole oral suspension to complete 28 days of total posaconazole therapy.

Table 4: Posaconazole Injection Study 1: Number (%) of Subjects Treated with Posaconazole Injection 300 mg Daily Dose Reporting Treatment-Emergent Adverse Reactions: Frequency of at Least 10%

Body System
Preferred Term
Posaconazole Injection Treatment Phase
n=237 (%)*
Posaconazole Injection Treatment Phase or Subsequent 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 posaconazole 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 posaconazole therapy.

The most frequently reported adverse reactions with an onset during the posaconazole 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 Posaconazole Delayed-Release Tablets

The safety of posaconazole delayed-release tablets has been assessed in 230 patients in clinical trials. Patients were enrolled in a non-comparative pharmacokinetic and safety trial of posaconazole delayed-release tablets when given as antifungal prophylaxis (Delayed-Release Tablet Study 1). 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 5 presents treatment-emergent adverse reactions observed in patients treated with 300 mg daily dose at an incidence of ≥ 10% in posaconazole delayed-release tablet study.

Table 5: Posaconazole Delayed-Release Tablet Study 1: Number (%) of Subjects Treated with 300 mg Daily Dose Reporting Treatment-Emergent Adverse Reactions: Frequency of at Least 10%

Body System
Preferred Term
Posaconazole delayed-release tablet (300 mg)
(n=210)
Subjects Reporting any Adverse Reaction 201 (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 posaconazole delayed-release tablets 300 mg once daily were diarrhea, pyrexia, and nausea.

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

Clinical Trial Safety Experience with Posaconazole Oral Suspension

The safety of posaconazole 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 nonneutropenic 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). Posaconazole therapy was given to 171 patients for ≥ 6 months, with 58 patients receiving posaconazole therapy for ≥ 12 months. Table 6 presents treatment-emergent adverse reactions observed at an incidence of > 10% in posaconazole prophylaxis studies. Table 7 presents treatment-emergent 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 (Oral Suspension Studies 1 and 2), the safety of posaconazole 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 posaconazole in the prophylaxis studies were associated with GI disorders, specifically, nausea (2%), vomiting (2%), and hepatic enzymes increased (2%).

Table 6: Posaconazole Oral Suspension Study 1 and Study 2. Number (%) of Randomized Subjects Reporting Treatment-Emergent Adverse Reactions: Frequency of at Least 10% in the Posaconazole Oral Suspension or Fluconazole Treatment Groups (Pooled Prophylaxis Safety Analysis)

Body System Preferred Term Posaconazole (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 posaconazole oral suspension at a dose of less than or equal to 400 mg QD in 557 HIV-infected patients was compared to the safety of fluconazole in 262 HIV-infected patients at a dose of 100 mg QD.

An additional 239 HIV-infected patients with refractory OPC received posaconazole 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 QD 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 posaconazole 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 posaconazole were AIDS (7%) and respiratory impairment (3%).

Table 7: Treatment-Emergent Adverse Reactions with Frequency of at Least 10% in OPC Studies with Posaconazole Oral Suspension (Treated Population)

Body System
Preferred Term
Number (%) of Subjects
Controlled OPC Pool Refractory OPC Pool
Posaconazole
n=557
Fluconazole
n=262
Posaconazole
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 treatment-emergent 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%).

Less Common Adverse Reactions: Clinically significant adverse reactions reported during clinical trials in prophylaxis, OPC/rOPC or other trials with posaconazole which occurred in less than 5% of patients are listed below:

Clinical Laboratory Values: In healthy volunteers and patients, elevation of liver function 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 function 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 8.

Table 8: Posaconazole Oral Suspension Study 1 and Study 2. Changes in Liver Function Test Results from CTC Grade 0, 1, or 2 at Baseline to Grade 3 or 4

Number (%) of Patients With Change* Oral Suspension Study 1
Laboratory Parameter Posaconazole
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)
Oral Suspension Study 2
Laboratory Parameter Posaconazole (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 function test (LFT) abnormalities at any time during the studies is provided in Table 9 (LFT abnormalities were present in some of these patients prior to initiation of the study drug).

Table 9: Posaconazole Oral Suspension Studies: Clinically Significant Laboratory Test Abnormalities without Regard to Baseline Value

Laboratory Test Controlled Refractory
Posaconazole
n=557(%)
Fluconazole
n=262(%)
Posaconazole
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.

Postmarketing Experience

No clinically significant postmarketing adverse reactions were identified that have not previously been reported during clinical trials experience.

Read the entire FDA prescribing information for Noxafil (Posaconazole Oral Suspension) »

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