Standard Dose
2 DOSAGE AND ADMINISTRATION Noxafil formulations are supplied in different dose strengths of posaconazole, are approved for different indications, age groups, and weights, have different dosages and duration of therapy; and have different preparation and administration instructions. ( 2.1 ) Noxafil oral suspension is not substitutable with Noxafil delayed-release tablets or Noxafil PowderMix for delayed-release oral suspension due to the differences in the dosing of each formulation. Therefore, follow the specific dosage recommendations for each of the formulations. ( 2.1 , 2.2 , 2.3 ) Noxafil injection must be administered through an in-line filter. ( 2.6 ) Administer Noxafil injection by intravenous infusion over approximately 90 minutes via a central venous line. ( 2.1 , 2.6 ) Do NOT administer Noxafil injection as an intravenous bolus injection. ( 2.1 ) Administer Noxafil delayed-release tablets with or without food. ( 2.1 ) Administer Noxafil oral suspension with a full meal. ( 2.1 ) Administer Noxafil PowderMix for delayed-release oral suspension with food. ( 2.1 ) Administer Noxafil PowderMix for delayed-release oral suspension with the provided notched tip syringes only. ( 2.1 ) See the full prescribing information for important administration instructions and preparation instructions for Noxafil (injection, delayed-release tablets, and oral suspension) and Noxafil PowderMix delayed-release oral suspension ( 2.5 , 2.6 , 2.7 , 2.8 , 2.9 , 2.10 ) For adult and pediatric patients aged 2 years of age and older, see the Full Prescribing Information for dosing recommendations for Noxafil injection, Noxafil delayed-release tablets, Noxafil oral suspension, and/or Noxafil PowderMix for delayed-release oral suspension based on the indication, age, and weight associated with the dosage form ( 1.1 , 1.2 , 1.3 , 2.1 , 2.2 , 2.3 , 2.4 ) 2.1 Important Administration Instructions Noxafil injection, Noxafil delayed-release tablets, Noxafil oral suspension and Noxafil PowderMix for delayed-release oral suspension are supplied in different dose strengths of posaconazole, are approved for different indications, age groups and weights; have different dosages and duration of therapy; and have different preparation and administration instructions. Therefore, select the recommended dosage form based on the indication, age group, and weight and carefully follow the recommended dosage, preparation and administration instructions described for each product [see Dosage and Administration (2.2 to 2.11) ] , and the following important administration instructions described below. Non-substitutable Noxafil oral suspension is not substitutable with Noxafil delayed-release tablets or Noxafil PowderMix for delayed-release oral suspension due to the differences in the dosing of each formulation. Therefore, follow the specific dosage recommendations for each of the formulations [see Dosage and Administration (2.2 , 2.3) ]. Noxafil injection Administer via a central venous line, including a central venous catheter or peripherally inserted central catheter (PICC), by slow intravenous infusion over approximately 90 minutes [see Dosage and Administration (2.6) ] . Do NOT administer Noxafil injection as an intravenous bolus injection. Noxafil delayed-release tablets Swallow tablets whole. Do not divide, crush, or chew. Administer with or without food [see Dosage and Administration (2.7) and Clinical Pharmacology (12.3) ] . For patients who cannot eat a full meal, Noxafil delayed-release tablets should be used instead of Noxafil oral suspension for the prophylaxis indication. Noxafil delayed-release tablets generally provide higher plasma drug exposures than Noxafil oral suspension under both fed and fasted conditions [see Dosage and Administration (2.8) ] . Noxafil oral suspension Administer with a full meal or with a liquid nutritional supplement or an acidic carbonated beverage (e.g., ginger ale) in patients who cannot eat a full meal [see Dosage and Administration (2.8) ]. Noxafil PowderMix for delayed-release oral suspension Administer with food [see Clinical Pharmacology (12.3) ] . To ensure delivery of the correct dose, ONLY the provided notched tip syringes must be used for preparation and administration. The design of the notched tip syringe prevents aggregation of the suspension during preparation and administration [see Dosage and Administration (2.10) ] . 2.2 Recommended Dosage of Noxafil in Adult Patients The recommended dosage of Noxafil (injection, delayed-release tablets, and oral suspension) in adult patients for the treatment of invasive aspergillosis, prophylaxis of invasive Aspergillus and Candida infections in patients who are at high risk of developing these infections due to being severely immunocompromised, or for the treatment of oropharyngeal candidiasis (OPC) is shown in Table 1 [see Dosage and Administration (2.5 , 2.6 , 2.7 , 2.8 , 2.9) and Clinical Pharmacology (12.3) ]. Noxafil PowderMix for delayed-release oral suspension is not recommended for use in adults [see Indications and Usage (1.1 , 1.2) ]. Table 1: Recommended Dosage of Noxafil Injection, Noxafil Delayed-Release Tablets, and Noxafil Oral Suspension in Adult Patients Dosage Duration of Therapy Treatment of Invasive Aspergillosis Switching between the Noxafil injection and delayed-release tablets is acceptable. A loading dose is not required when switching between dosage forms. Noxafil Injection: Loading dose : 300 mg Noxafil injection intravenously twice a day on the first day. Maintenance dose : 300 mg Noxafil injection intravenously once a day, starting on the second day. Noxafil Delayed-Release Tablets: Loading dose: 300 mg (three 100 mg delayed-release tablets) twice a day on the first day. Maintenance dose : 300 mg (three 100 mg delayed-release tablets) once a day, starting on the second day. Loading dose: 1 day Maintenance dose: Recommended total duration of therapy is 6 to 12 weeks. Prophylaxis of Invasive Aspergillus and Candida Infections Noxafil Injection: Loading dose : 300 mg Noxafil injection intravenously twice a day on the first day. Maintenance dose : 300 mg Noxafil injection intravenously once a day thereafter. Noxafil Delayed-Release Tablets: Loading dose : 300 mg (three 100 mg delayed-release tablets) twice a day on the first day. Maintenance dose : 300 mg (three 100 mg delayed-release tablets) once a day, starting on the second day. Noxafil Oral Suspension: 200 mg (5 mL) three times a day. Loading dose : 1 day Maintenance dose : Duration of therapy is based on recovery from neutropenia or immunosuppression Oropharyngeal Candidiasis (OPC) Noxafil Oral Suspension: Loading dose : 100 mg (2.5 mL) twice a day on the first day. Maintenance dose : 100 mg (2.5 mL) once a day thereafter. Loading dose : 1 day Maintenance dose : 13 days OPC Refractory (rOPC) to Itraconazole and/or Fluconazole Noxafil Oral Suspension: 400 mg (10 mL) twice a day. Duration of therapy is based on the severity of the patient’s underlying disease and clinical response. 2.3 Recommended Dosage of Noxafil for the Treatment of Invasive Aspergillosis and Prophylaxis of Invasive Aspergillus and Candida Infections in Pediatric Patients 2 Years of Age and Older Noxafil injection and Noxafil delayed-release tablets The recommended dosage of (1) Noxafil injection in pediatric patients 2 years of age and older who weigh 10 kg or greater, and (2) Noxafil delayed-release tablets in pediatric patients 2 years of age and older who weigh greater than 40 kg for the treatment of invasive aspergillosis and prophylaxis of invasive Aspergillus and Candida infections is shown in Table 2 [see Dosage and Administration (2.5 , 2.6 , 2.7 , 2.9 ) and Clinical Pharmacology (12.3) ]. Noxafil delayed-release tablets are not recommended for use in pediatric patients who weigh 40 kg or less because the recommended dosage cannot be achieved with this dosage form. Table 2: Recommended Dosage of Noxafil Injection and Noxafil Delayed-Release Tablets for the Treatment of Invasive Aspergillosis Switching between the intravenous and delayed-release tablets is acceptable. A loading dose is not required when switching between formulations. and Prophylaxis of Invasive Aspergillus and Candida Infections in Pediatric Patients (2 Years of Age and Older) Recommended Pediatric Dosage by Formulation Duration of Therapy Noxafil Injection (patients weighing 10 kg or greater): Loading dose : 6 mg/kg up to a maximum of 300 mg twice daily on the first day Maintenance dose : 6 mg/kg up to a maximum of 300 mg once daily, starting on the second day. Noxafil Delayed-Release Tablets (patients weighing greater than 40 kg): Loading dose: 300 mg (three 100 mg delayed-release tablets) twice a day on the first day. Maintenance dose : 300 mg (three 100 mg delayed-release tablets) once a day, starting on the second day. Treatment of invasive aspergillosis: Recommended total duration of therapy is 6 to 12 weeks Prophylaxis of invasive Aspergillus and Candida infections: Duration of therapy is based on recovery from neutropenia or immunosuppression. Noxafil Oral Suspension The recommended dosage of Noxafil oral suspension in pediatric patients 13 years of age and older for the prophylaxis of invasive Aspergillus and Candida Infections is shown in Table 3. Table 3: Recommended Dosage of Noxafil Oral Suspension for the Prophylaxis of Invasive Aspergillus and Candida Infections in Pediatric Patients (13 Years of Age and Older) Recommended Pediatric Dosage of Noxafil Oral Suspension Duration of Therapy 200 mg (5 mL) three times a day Duration of therapy is based on recovery from neutropenia or immunosuppression. Noxafil PowderMix The recommended dosage of Noxafil PowderMix for delayed-release oral suspension in pediatric patients 2 years of age and older who weigh 10 kg to 40 kg, for the treatment of invasive aspergillosis, and the prophylaxis of invasive Aspergillus and Candida infections, is shown in Table 4 and Table 5 . The dosing for these indications is the same, except for patients weighing 10 to less than 12 kg [see Dosage and Administration (2.9 , 2.10 ) and Clinical Pharmacology (12.3) ]. Noxafil PowderMix for delayed-release oral suspension is not recommended for use in pediatric patients who weigh greater than 40 kg because the recommended dosage cannot be achieved with this dosage form. Table 4: Recommended Dosage for Noxafil PowderMix for Delayed-Release Oral Suspension for the Treatment of Invasive Aspergillosis in Pediatric Patients (2 Years of Age and Older) Weight (kg) Recommended Pediatric Dosage of Noxafil PowderMix for Delayed-Release Oral Suspension Duration of Therapy 10 to less than 17 Loading Dose: 120 mg (4 mL) twice daily on the first day Maintenance Dose: 120 mg (4 mL) once daily Recommended total duration of therapy is 6 to 12 weeks. 17 to less than 21 Loading Dose: 150 mg (5 mL) twice daily on the first day Maintenance Dose: 150 mg (5 mL) once daily 21 to less than 26 Loading Dose: 180 mg (6 mL) twice daily on the first day Maintenance Dose: 180 mg (6 mL) once daily 26 to less than 36 Loading Dose: 210 mg (7 mL) twice daily on the first day Maintenance Dose: 210 mg (7 mL) once daily 36 to 40 Loading Dose: 240 mg (8 mL) twice daily on the first day Maintenance Dose: 240 mg (8 mL) once daily Table 5: Recommended Dosage for Noxafil PowderMix for Delayed-Release Oral Suspension for the Prophylaxis of Invasive Aspergillus and Candida infections in Pediatric Patients (2 Years of Age and Older ) Weight (kg) Recommended Pediatric Dosage of Noxafil PowderMix for Delayed-Release Oral Suspension Duration of Therapy 10 to less than 12 Loading Dose: 90 mg (3 mL) twice daily on the first day Maintenance Dose: 90 mg (3 mL) once daily Duration of therapy is based on recovery from neutropenia or immunosuppression . 12 to less than 17 Loading Dose: 120 mg (4 mL) twice daily on the first day Maintenance Dose: 120 mg (4 mL) once daily 17 to less than 21 Loading Dose: 150 mg (5 mL) twice daily on the first day Maintenance Dose: 150 mg (5 mL) once daily 21 to less than 26 Loading Dose: 180 mg (6 mL) twice daily on the first day Maintenance Dose: 180 mg (6 mL) once daily 26 to less than 36 Loading Dose: 210 mg (7 mL) twice daily on the first day Maintenance Dose: 210 mg (7 mL) once daily 36 to 40 Loading Dose: 240 mg (8 mL) twice daily on the first day Maintenance Dose: 240 mg (8 mL) once daily 2.4 Recommended Dosage of Noxafil Oral Suspension for the Treatment of Oropharyngeal Candidiasis in Pediatric Patients 13 Years of Age and Older The recommended dosage of Noxafil oral suspension for the treatment of oropharyngeal candidiasis (OPC) and OPC refractory (rOPC) to itraconazole and/or fluconazole in pediatric patients 13 years of age and older is shown in Table 6. The Noxafil injection, Noxafil delayed-release tablets, and Noxafil PowderMix for delayed-release oral suspension products are not approved for the treatment of oropharyngeal candidiasis in pediatric patients. Table 6: Recommended Dosage of Noxafil Oral Suspension for the Treatment of OPC and rOPC in Pediatric Patients (13 Years of Age and Older) Recommended Pediatric Dosage of Noxafil Oral Suspension Duration of Therapy Oropharyngeal Candidiasis (OPC) Loading Dose: 100 mg (2.5 mL) twice daily on the first day Maintenance Dose: 100 mg (2.5 mL) once daily Loading dose: 1 day Maintenance dose: 13 days OPC Refractory (rOPC) to Itraconazole and/or Fluconazole 400 mg (10 mL) twice daily Duration of therapy is based on the severity of the patient’s underlying disease and clinical response. 2.5 Preparation of Noxafil Injection Preparation of Noxafil Injection: Remove the vial of Noxafil injection from the refrigerator and allow to equilibrate to room temperature prior to use. To prepare the required dose, aseptically transfer one vial of Noxafil injection (containing 300 mg of posaconazole in 16.7 mL of solution) to an intravenous bag or bottle of one of the following compatible diluents to achieve a final posaconazole concentration between 1 mg/mL and 2 mg/mL: 0.45% Sodium Chloride Injection 0.9% Sodium Chloride Injection 5% Dextrose Injection 5% Dextrose and 0.45% Sodium Chloride Injection 5% Dextrose and 0.9% Sodium Chloride Injection 5% Dextrose and 20 mEq Potassium Chloride Injection Use of other diluents is not recommended because they may result in particulate formation. Discard any unused Noxafil injection from the vial. Parenteral drug products should be inspected visually for particulate matter prior to administration, whenever solution and container permit. Once admixed, the diluted Noxafil infusion solution ranges from colorless to yellow (variations of color within this range do not affect the quality of the product). Immediately use the diluted Noxafil infusion solution, once admixed. If not used immediately, refrigerate (2 to 8°C (36 to 46°F)) the diluted Noxafil infusion solution up to 24 hours. Discard any unused portion. Incompatible Diluents Co-administration of drug products besides the infusion solutions or products stated above are not recommended because this may result in particulate formation. The following diluents were determined to be incompatible with Noxafil injection; thus, do not dilute Noxafil injection with them: Lactated Ringer’s Injection Lactated Ringer's and 5% Dextrose Injection 4.2% Sodium Bicarbonate Injection 2.6 Administration of Diluted Noxafil Infusion Solution See Dosage and Administration (2.5) for the preparation instructions for the diluted Noxafil Solution. Important Administration Instructions for the Diluted Noxafil Infusion Solution Must administer diluted Noxafil Infusion Solution through a 0.22-micron polyethersulfone (PES) or polyvinylidene difluoride (PVDF) filter. Administer diluted Noxafil infusion solution via a central venous line, including a central venous catheter (CVC) or peripherally inserted central catheter (PICC), by slow intravenous infusion over approximately 90 minutes [see Adverse Reactions (6.1) ] . If a CVC or PICC are not available, may administer diluted Noxafil solution once through a peripheral venous catheter by intravenous infusion over approximately 30 minutes to bridge the period during which a CVC or PICC are replaced, inserted, or unavailable for use (e.g., the CVC is being used for intravenous treatment with another product). However, do not administer diluted Noxafil infusion solution more than once via peripheral venous catheter because in clinical trials, multiple peripheral infusions given through the same vein resulted in infusion site reactions [see Adverse Reactions (6.1) ]. When multiple dosing is required, the infusion should be done via a central venous line. Additional Administration Instructions for the Diluted Noxafil Infusion Solution Administer diluted Noxafil infusion solution intravenously through the same intravenous line (or cannula) with the following compatible infusion solutions: 0.45% Sodium Chloride Injection 0.9% Sodium Chloride Injection 5% Dextrose Injection 5% Dextrose and 0.45% Sodium Chloride Injection 5% Dextrose and 0.9% Sodium Chloride Injection 5% Dextrose and 20 mEq potassium chloride Injection Administer diluted Noxafil infusion solution intravenously at the same time through the same intravenous line (or cannula) with the following intravenous drug products prepared in 5% Dextrose Injection or 0.9% Sodium Chloride Injection: Amikacin Sulfate Injection Caspofungin Acetate for Injection Ciprofloxacin Injection Daptomycin for Injection Dobutamine Injection Famotidine Injection Filgrastim Injection Gentamicin Injection Hydromorphone Hydrochloride Injection Levofloxacin Injection Lorazepam Injection Meropenem for Injection Micafungin for Injection Morphine Sulfate Injection Norepinephrine Bitartrate Injection Potassium Chloride Injection Vancomycin Hydrochloride for Injection 2.7 Administration Instructions for Noxafil Delayed-Release Tablets Swallow the Noxafil delayed-release tablets whole. Do not divide, crush, or chew. Administer Noxafil delayed-release tablets orally with or without food [see Clinical Pharmacology (12.3) ]. 2.8 Administration Instructions for Noxafil Oral Suspension Administer Noxafil oral suspension with a full meal or with a liquid nutritional supplement or an acidic carbonated beverage (e.g., ginger ale) in patients who cannot eat a full meal. For patients who cannot eat a full meal, use Noxafil delayed-release tablets instead of the Noxafil oral suspension for the prophylaxis of invasive Aspergillus and Candida infections in those who are at high risk of developing these infections due to being severely immunocompromised. This is because Noxafil delayed-release tablets provide higher plasma drug exposures than Noxafil oral suspension under fasted condition [see Dosage and Administration (2.1) ]. For those patients using the Noxafil oral suspension: Shake Noxafil oral suspension well before use. Administer with measured dosing spoon provided in the package (see Figure 1 ). Figure 1: Measured dosing spoon provided in the package marked for doses of 2.5 mL and 5 mL. Administer each dose of Noxafil oral suspension during or immediately (i.e., within 20 minutes) following a full meal [see Clinical Pharmacology (12.3) ]. In patients who cannot eat a full meal and for whom Noxafil delayed-release tablets or Noxafil injection are not options, administer each dose of Noxafil oral suspension with a liquid nutritional supplement or an acidic carbonated beverage (e.g., ginger ale). If these patients cannot tolerate an oral nutritional supplement or an acidic carbonated beverage either use: An alternative antifungal therapy, or Noxafil oral suspension and closely monitor patients for breakthrough fungal infections. Rinse the spoon with water after each administration and before storage. Figure 1 2.9 Non-substitutability between Noxafil Oral Suspension and Other Formulations Noxafil oral suspension is not substitutable with Noxafil delayed-release tablets or Noxafil PowderMix for delayed-release oral suspension due to the differences in the dosing of each formulation. Therefore, follow the specific dosage recommendations for each of the formulations [see Dosage and Administration (2.2 , 2.3) ]. 2.10 Preparation and Administration Instructions for Noxafil PowderMix for Delayed-Release Oral Suspension For details on preparation and administration of Noxafil PowderMix for delayed-release oral suspension, see Instructions for Use . Preparation Instructions for Noxafil PowderMix for Delayed-Release Oral Suspension Do not open the Noxafil PowderMix packet until ready to prepare the drug. Remove cap from the mixing liquid and push the bottle adapter into the neck of the bottle. Once in place, the bottle adapter stays in the bottle. Remove 9 mL of mixing liquid using the provided blue syringe. Put the cap back on the bottle. Only use the mixing liquid in the kit to prepare Noxafil PowderMix. Using the provided mixing cup, combine 9 mL of mixing liquid and the entire contents of one packet in the Noxafil PowderMix kit and mix (containing 300 mg of posaconazole). Shake the mixing cup vigorously for 45 seconds to mix the powder and mixing liquid from the Noxafil PowderMix kit. The final concentration of the reconstituted Noxafil PowderMix delayed-release suspension is approximately 30 mg/mL of posaconazole. Check to make sure the powder is mixed (the mixture should look cloudy and free of clumps). Must use the reconstituted Noxafil PowderMix delayed-release suspension within 1 hour of reconstitution. Discard unused portion of the reconstituted Noxafil PowderMix delayed-release suspension. Administration Instructions for Noxafil PowderMix Delayed-Release Reconstituted Suspension To ensure delivery of the correct reconstituted Noxafil PowderMix Delayed-release dose, only use the provided notched tip syringes for preparation and administration because its design reduces the risk of aggregation of the product during preparation and administration. Choose the correct syringe based on the prescribed Noxafil PowderMix dose: Use 3 mL ( green ) notched tip syringe (provided with the kit) if dose is 3 mL or less. Use 10 mL ( blue ) notched tip syringe (provided with the kit) if dose is more than 3 mL. Administer reconstituted Noxafil PowderMix suspension orally with food within 1 hour of reconstitution [see Clinical Pharmacology (12.3) ]. The maximum dose that can be accurately withdrawn from the mixing cup after reconstitution is 240 mg (8 mL). Discarding Unused Reconstituted Noxafil PowderMix Suspension and Reuse of Syringes Not all the reconstituted Noxafil PowderMix suspension in the mixing cup will be used; there will be some left over in the mixing cup. Discard any remaining reconstituted Noxafil PowderMix suspension. The mixing cup may be hand washed and reused. Alternatively, the mixing cup may be discarded, and a similar mixing cup with a lid may be used for subsequent doses. The notched tip syringes may be hand washed and reused. 2.11 Dosage Modifications in Patients with Renal Impairment The recommended dosage of Noxafil oral suspension, Noxafil delayed-release tablets, and Noxafil PowderMix for delayed-release oral suspension is the same in patients with renal impairment compared to those with normal renal function. Avoid the use of Noxafil injection in patients with eGFR less than 50 mL/minute/1.73 m 2 , unless an assessment of the benefit/risk to the patient justifies its use. If the decision is made to use Noxafil injection in patients with eGFR less than 50 mL/minute/1.73 m 2 , closely monitor serum creatinine levels, and, if increases occur, consider changing to oral Noxafil therapy. The recommended dosage of Noxafil injection in patients with eGFR 50 to 90 mL/minute/1.73 m 2 is the same as those with normal renal function.