June 29, 2016
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Noxafil

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Noxafil




Indications
Dosage
How Supplied

INDICATIONS

Prophylaxis Of Invasive Aspergillus And Candida Infections

Noxafil® injection, delayed-release tablets, and oral suspension are indicated for prophylaxis of invasive Aspergillus and Candida infections in patients who are at high risk of developing these infections due to being severely immunocompromised, such as hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD) or those with hematologic malignancies with prolonged neutropenia from chemotherapy.

Noxafil injection is indicated in patients 18 years of age and older.

Noxafil delayed-release tablets and oral suspension are indicated in patients 13 years of age and older.

Treatment Of Oropharyngeal Candidiasis Including Oropharyngeal Candidiasis Refractory To Itraconazole And/Or Fluconazole

Noxafil oral suspension is indicated for the treatment of oropharyngeal candidiasis, including oropharyngeal candidiasis refractory to itraconazole and/or fluconazole.

DOSAGE AND ADMINISTRATION

Important Administration Instructions For Noxafil Injection, Noxafil Delayed-Release Tablets And Noxafil Oral Suspension

Noxafil delayed-release tablets and oral suspension are not to be used interchangeably due to the differences in the dosing of each formulation [see below].

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 below].
  • If a central venous catheter is not available, Noxafil injection may be administered through a peripheral venous catheter by slow intravenous infusion over 30 minutes only as a single dose in advance of central venous line placement or to bridge the period during which a central venous line is replaced or is in use for other intravenous treatment.
  • When multiple dosing is required, the infusion should be done via a central venous line.
  • Never administer Noxafil injection as an intravenous bolus injection.
Noxafil Delayed-Release Tablets
  • Swallow tablets whole. Do not divide, crush, or chew.
  • Administer with food [see CLINICAL PHARMACOLOGY].
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.
  • Co-administration of drugs that can decrease the plasma concentrations of posaconazole should generally be avoided unless the benefit outweighs the risk. If such drugs are necessary, patients should be monitored closely for breakthrough fungal infections [see DRUG INTERACTIONS]
Noxafil Delayed-Release Tablets And Noxafil Oral Suspension
  • Patients who have severe diarrhea or vomiting should be monitored closely for breakthrough fungal infections when receiving Noxafil delayed-release tablets or oral suspension.

Dosage, Preparation, Intravenous Line Compatibility And Administration Of Noxafil Injection

Dosage

Table 1: Dosage for Noxafil Injection

Indication Dose and Duration of Therapy
Prophylaxis of invasive Aspergillus and Candida infections 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. Duration of therapy is based on recovery from neutropenia or immunosuppression.

Preparation
  • Equilibrate the refrigerated vial of Noxafil (posaconazole) injection to room temperature.
  • To prepare the required dose, aseptically transfer one vial (16.7 mL) of Noxafil injection (containing 300 mg of posaconazole in solution) to an intravenous bag (or bottle) of a compatible admixture diluent (as described in Table 2), to achieve a final concentration of posaconazole that is between 1 mg/mL and 2 mg/mL. Use of other diluents is not recommended because they may result in particulate formation.
  • Noxafil injection is a single dose sterile solution without preservatives. Once admixed, the product should be used immediately. If not used immediately, the solution can be stored up to 24 hours refrigerated 2-8°C (36-46°F). Noxafil injection is for single use only and any unused solution should be discarded.
  • Parenteral drug products should be inspected visually for particulate matter prior to administration, whenever solution and container permit. Once admixed, the solution of Noxafil ranges from colorless to yellow. Variations of color within this range do not affect the quality of the product.
Intravenous Line Compatibility

A study was conducted to evaluate physical compatibility of Noxafil injection with injectable drug products and commonly used intravenous diluents during simulated Y-site infusion. Compatibility was determined through visual observations, measurement of particulate matter and turbidity. Compatible diluents and drug products are listed in Tables 2 and 3 below. Any diluents or drug products not listed in the tables below should not be co-administered through the same intravenous line (or cannula).

Noxafil injection can be infused at the same time through the same intravenous line (or cannula) with the following compatible diluents:

Table 2: Compatible Diluents

0.45% sodium chloride
0.9% sodium chloride
5% dextrose in water
5% dextrose and 0.45% sodium chloride
5% dextrose and 0.9% sodium chloride

5% dextrose and 20 mEq potassium chloride

  • Noxafil injection can be infused at the same time through the same intravenous line (or cannula) with the following drug products prepared in 5% dextrose in water or sodium chloride 0.9%. Coadministration of drug products prepared in other diluents may result in particulate formation.

Table 3: Compatible Drugs

Amikacin sulfate
Caspofungin
Ciprofloxacin
Daptomycin
Dobutamine hydrochloride
Famotidine
Filgrastim
Gentamicin sulfate
Hydromorphone hydrochloride
Levofloxacin
Lorazepam
Meropenem
Micafungin
Morphine sulfate
Norepinephrine bitartrate
Potassium chloride
Vancomycin hydrochloride
Incompatible Diluents

Noxafil injection must not be diluted with the following diluents:

Lactated Ringer's solution
5% dextrose with Lactated Ringer's solution
4.2% sodium bicarbonate

Administration

  • Noxafil injection must be administered through a 0.22 micron polyethersulfone (PES) or polyvinylidene difluoride (PVDF) filter.
  • Administer via a central venous line, including a central venous catheter or PICC by slow infusion over approximately 90 minutes. Noxafil injection is not for bolus administration.
  • If a central venous catheter is not available, Noxafil injection may be administered through a peripheral venous catheter only as a single dose in advance of central venous line placement or to bridge the period during which a central venous line is replaced or is in use for other treatment.
  • When multiple dosing is required, the infusion should be done via a central venous line. When administered through a peripheral venous catheter, the infusion should be administered over approximately 30 minutes. Note: In clinical trials, multiple peripheral infusions given through the same vein resulted in infusion site reactions [see ADVERSE REACTIONS].

Dosage And Administration Instructions For Noxafil Delayed-Release Tablets

Dosage

Table 4: Dosage for Noxafil Delayed-Release Tablets

Indication Dose and Duration of Therapy
Prophylaxis of invasive Aspergillus and Candida infections 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. Duration of therapy is based on recovery from neutropenia or immunosuppression.

Administration Instructions for Noxafil Delayed-Release Tablets
  • Swallow tablets whole. Do not divide, crush, or chew.
  • Administer Noxafil delayed-release tablets with food to enhance the oral absorption of posaconazole and optimize plasma concentrations [see CLINICAL PHARMACOLOGY].
  • Noxafil delayed-release tablets should be used only for the prophylaxis indication.
  • Noxafil delayed-release tablets generally provide higher plasma drug exposures than Noxafil oral suspension under both fed and fasted conditions, and therefore is the preferred oral formulation for the prophylaxis indication.

Dosage And Administration Instructions For Noxafil Oral Suspension

Dosage

Table 5: Dosage for Noxafil Oral Suspension

Indication Dose and Duration of Therapy
Prophylaxis of invasive Aspergillus and Candida infections 200 mg (5 mL) three times a day. The duration of therapy is based on recovery from neutropenia or immunosuppression.
Oropharyngeal Candidiasis Loading dose: 100 mg (2.5 mL) twice a day on the first day.
Maintenance dose: 100 mg (2.5 mL) once a day for 13 days.
Oropharyngeal Candidiasis Refractory to Itraconazole and/or Fluconazole 400 mg (10 mL) twice a day. Duration of therapy should be based on the severity of the patient’s underlying disease and clinical response.

Administration Instructions for Noxafil Oral Suspension
  • Shake Noxafil oral suspension well before use. Administer with measured dosing spoon (see Figure 1) provided.

Figure 1: A measured dosing spoon is provided, marked for doses of 2.5 mL and 5 mL.

Measured dosing spoon - Illustration

  • Rinse the spoon with water after each administration and before storage.
  • Administer each dose of Noxafil oral suspension during or immediately (i.e., within 20 minutes) following a full meal to enhance the oral absorption of Noxafil and optimize plasma concentrations [see CLINICAL PHARMACOLOGY].
  • For patients who cannot eat a full meal, Noxafil delayed-release tablets should be used instead of Noxafil oral suspension. Noxafil delayed-release tablets should be used only for the prophylaxis indication. Noxafil delayed-release tablets provide higher plasma drug exposures than Noxafil oral suspension under fasted conditions.
  • 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).
  • For patients who cannot eat a full meal or tolerate an oral nutritional supplement or an acidic carbonated beverage and who do not have the option of taking Noxafil delayed-release tablets or Noxafil injection, an alternative antifungal therapy should be considered or patients should be monitored closely for breakthrough fungal infections.

Non-Interchangeability Between Noxafil Delayed-Release Tablets And Noxafil Oral Suspension

Noxafil delayed-release tablets and oral suspension are not to be used interchangeably due to the differences in the dosing of each formulation. Therefore, follow the specific dosage recommendations for each of the formulations.

Dosage Adjustments In Patients With Renal Impairment

The pharmacokinetics of Noxafil oral suspension and delayed-release tablets are not significantly affected by renal impairment. Therefore, no adjustment is necessary for oral dosing in patients with mild to severe renal impairment.

  • Noxafil injection should be avoided in patients with moderate or severe renal impairment (eGFR < 50 mL/min), unless an assessment of the benefit/risk to the patient justifies the use of Noxafil injection.
  • In patients with moderate or severe renal impairment (estimated glomerular filtration rate (eGFR) < 50 mL/min), receiving the Noxafil injection, accumulation of the intravenous vehicle, Betadex Sulfobutyl Ether Sodium (SBECD), is expected to occur. Serum creatinine levels should be closely monitored in these patients, and, if increases occur, consideration should be given to changing to oral Noxafil therapy.

HOW SUPPLIED

Dosage Forms And Strengths

Noxafil injection is available in Type I glass vials closed with bromobutyl rubber stopper and aluminum seal containing 300 mg per 16.7 mL of solution (18 mg of posaconazole per mL).

Noxafil 100 mg delayed-release tablets are available as yellow, coated, oblong tablets, debossed with “100” on one side.

Noxafil oral suspension is available in 4-ounce (123 mL) amber glass bottles with child-resistant closures containing 105 mL of suspension (40 mg of posaconazole per mL).

Storage And Handling

Injection

Noxafil injection is available in Type I glass vials closed with bromobutyl rubber stopper and aluminum seal (NDC 0085-4331-01) containing 300 mg per 16.7 mL of solution (18 mg of posaconazole per mL). Store refrigerated at 2-8°C (36-46°F).

Delayed-Release Tablets

Noxafil 100 mg delayed-release tablets; yellow, coated, oblong, debossed with “100” on one side. Bottles with child-resistant closures of 60 delayed-release tablets (NDC 0085-4324-02). Store at 20-25°C (68-77°F), excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature].

Oral Suspension

Noxafil oral suspension is available in 4-ounce (123 mL) amber glass bottles with child-resistant closures (NDC 0085-1328-01) containing 105 mL of suspension (40 mg of posaconazole per mL).

Supplied with each oral suspension bottle is a plastic dosing spoon calibrated for measuring 2.5-mL and 5-mL doses. Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. DO NOT FREEZE.

Manuf. for: MERCK SHARP & Dohme Corp., a subsidiary of MERCK & CO., INC., whitehouse Station, NJ 08889, USA. Revised: Nov 2015

This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 12/11/2015

Indications
Dosage
How Supplied

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