Noxafil

What is Noxafil?

Noxafil (which refers to injection, delayed-release tablets, and oral suspension) and Noxafil PowderMix (for delayed-release oral suspension) are prescription medicines used in adults and children to help prevent or treat fungal infections that can spread throughout your body (invasive fungal infections).

These infections are caused by fungi called Aspergillus or Candida. Noxafil and Noxafil PowderMix are used in people who have an increased chance of getting these infections due to a weak immune system. These include people who have had a hematopoietic stem cell transplantation (bone marrow transplant) with graft versus host disease or those with a low white blood cell count due to chemotherapy for blood cancers (hematologic malignancies).

Description

Noxafil (posaconazole) is an azole antifungal agent. Noxafil is available as an injection solution to be diluted before intravenous administration, delayed-release tablet, oral suspension, and for delayed-release oral suspension intended for oral administration. Noxafil PowderMix for delayed-release oral suspension must be reconstituted before oral administration.

Posaconazole is designated chemically as 4-[4-[4-[4-[[ (3R,5R)-5- (2,4-difluorophenyl)tetrahydro-5- (1H-1,2,4-triazol-1-ylmethyl)-3-furanyl]methoxy]phenyl]-1-piperazinyl]phenyl]-2-[(1S,2S)-1-ethyl-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one with an empirical formula of C37H42F2N8O4 and a molecular weight of 700.8. The chemical structure is:

Noxafil Injection

Noxafil injection is available as a clear colorless to yellow, sterile liquid essentially free of foreign matter. Each vial contains 300 mg of posaconazole and the following inactive ingredients: 6.68 g Betadex Sulfobutyl Ether Sodium (SBECD), 0.0033 g edetate disodium, hydrochloric acid and sodium hydroxide to adjust the pH to 2.6, and water for injection.

Noxafil Delayed-Release Tablets

Noxafil delayed-release tablet is a yellow, coated, oblong tablet containing 100 mg of posaconazole. Each delayed-release tablet contains the inactive ingredients: croscarmellose sodium, hydroxypropylcellulose, hypromellose acetate succinate, iron oxide yellow, Macrogol/PEG 3350, magnesium stearate, microcrystalline cellulose, polyvinyl alcohol partially hydrolyzed, silicon dioxide, talc, and titanium dioxide.

Noxafil Oral Suspension

Noxafil oral suspension is a white, cherry-flavored immediate-release suspension containing 40 mg of posaconazole per mL and the following inactive ingredients: artificial cherry flavor, citric acid monohydrate, glycerin, liquid glucose, polysorbate 80, purified water, simethicone, sodium benzoate, sodium citrate dihydrate, titanium dioxide, and xanthan gum.

Noxafil PowderMix for Delayed-Release Oral Suspension

Noxafil PowderMix for delayed-release oral suspension is supplied as a component of a kit. Each kit contains Noxafil as an off-white to yellowish powder for delayed-release oral suspension, a bottle of mixing liquid, two 3 mL (green) notched tip syringes, two 10 mL (blue) notched tip syringes, two mixing cups, and one bottle adapter for the mixing liquid bottle. Noxafil PowderMix for delayed-release oral suspension contains 300 mg of posaconazole and the following inactive ingredient: hypromellose acetate succinate. The mixing liquid contains: anhydrous citric acid, antifoam Af emulsion, berry citrus sweet flavor, carboxymethylcellulose sodium, carrageenan calcium sulfate trisodium phosphate, glycerin, methylparaben, microcrystalline cellulose, potassium sorbate, propylparaben, purified water, sodium citrate, sodium phosphate monobasic monohydrate, sodium saccharin, sorbitol solution, and xanthan gum. Once reconstituted, the Noxafil PowderMix for delayed-release oral suspension will be cloudy and free of clumps.

Noxafil injection is used for:

• prevention of fungal infections in adults and children 2 years of age and older.
• treatment of fungal infections in adults and children 13 years of age and older.

Noxafil delayed-release tablets are used for:

• prevention of fungal infections in adults and children 2 years of age and older who weigh greater than 88 lbs (40 kg).
• treatment of fungal infections in adults and children 13 years of age and older.

Noxafil oral suspension is used for:

• prevention of fungal infections in adults and children 13 years of age and older.

Noxafil PowderMix for delayed-release oral suspension is used for:

• prevention of fungal infections in children 2 years of age and older who weigh 88 lbs (40 kg) or less.

Noxafil oral suspension is also used to treat a fungal infection called “thrush” caused by Candida in your mouth or throat area. Noxafil oral suspension can be used as the first treatment for thrush, or as another treatment for thrush after itraconazole or fluconazole treatment has not worked.

Noxafil oral suspension is for adults and children 13 years of age and older.

It is not known if Noxafil or Noxafil PowderMix is safe and effective in children under 2 years of age.

Who should not take Noxafil?

Do not take Noxafil or Noxafil PowderMix if you:

• are allergic to posaconazole, any of the ingredients in Noxafil or Noxafil PowderMix, or other azole antifungal medicines. See the end of this leaflet for a complete list of ingredients in Noxafil and Noxafil PowderMix.
• are taking any of the following medicines:
  • sirolimus
  • pimozide
  • quinidine
  • certain statin medicines that lower cholesterol (atorvastatin, lovastatin, simvastatin)
  • ergot alkaloids (ergotamine, dihydroergotamine)
  • are taking Noxafil PowderMix for delayed-release oral suspension and have hereditary fructose intolerance.

Ask your healthcare provider or pharmacist if you are not sure if you are taking any of these medicines.
Do not start taking a new medicine without talking to your healthcare provider or pharmacist.

What should I tell my healthcare provider before taking Noxafil?

Before you take Noxafil or Noxafil PowderMix, tell your healthcare provider if you:

• are taking certain medicines that lower your immune system like cyclosporine or tacrolimus.
• are taking certain drugs for HIV infection, such as ritonavir, atazanavir, efavirenz, or fosamprenavir. Efavirenz and fosamprenavir can cause a decrease in the Noxafil levels in your body. Efavirenz and fosamprenavir should not be taken with Noxafil or Noxafil PowderMix.
• are taking midazolam, a hypnotic and sedative medicine.
• are taking vincristine, vinblastine and other “vinca alkaloids” (medicines used to treat cancer).
• have or had liver problems.
• have or had kidney problems.
• have or had an abnormal heart rate or rhythm, heart problems, or blood circulation problems.
• are pregnant or plan to become pregnant. It is not known if Noxafil will harm your unborn baby.
• are breastfeeding or plan to breastfeed. It is not known if Noxafil passes into your breast milk. You and your healthcare provider should decide if you will take Noxafil or breastfeed. You should not do both.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Noxafil and Noxafil PowderMix can affect the way other medicines work, and other medicines can affect the way Noxafil and Noxafil PowderMix work, and can cause serious side effects.

Especially tell your healthcare provider if you take:

• rifabutin or phenytoin. If you are taking these medicines, you should not take Noxafil delayed-release tablets, Noxafil oral suspension, or Noxafil PowderMix for delayed-release oral suspension.
• cimetidine or esomeprazole. If you are taking these medicines, you should not take Noxafil oral suspension.

Ask your healthcare provider or pharmacist for a list of these medicines if you are not sure.
Know the medicines you take. Keep a list of them with you to show your healthcare provider or pharmacist when you get a new medicine.

How should I take Noxafil?

• Do not switch between Noxafil oral suspension and Noxafil delayed-release tablets or Noxafil PowderMix for delayed-release oral suspension.
• Take Noxafil or Noxafil PowderMix exactly as your healthcare provider tells you to take it.
• Your healthcare provider will tell you how much Noxafil or Noxafil PowderMix to take and when to take it.
• Take Noxafil or Noxafil PowderMix for as long as your healthcare provider tells you to take it.
• If you take too much Noxafil or Noxafil PowderMix, call your healthcare provider or go to the nearest hospital emergency room right away.
• Noxafil injection is usually given over 30 to 90 minutes through a plastic tube placed in your vein.
• Noxafil delayed-release tablets:
  • Take Noxafil delayed-release tablets with or without food.
  • Take Noxafil delayed-release tablets whole. Do not break, crush, or chew Noxafil delayed-release tablets before swallowing. If you cannot swallow Noxafil delayed-release tablets whole, tell your healthcare provider. You may need a different medicine.
  • If you miss a dose, take it as soon as you remember and then take your next scheduled dose at its regular time. If it is within 12 hours of your next dose, do not take the missed dose. Skip the missed dose and go back to your regular schedule. Do not double your next dose or take more than your prescribed dose.
• Noxafil oral suspension:
  • Shake Noxafil oral suspension well before use.
  • Take each dose of Noxafil oral suspension during or within 20 minutes after a full meal. If you cannot eat a full meal, take each dose of Noxafil oral suspension with a liquid nutritional supplement or an acidic carbonated beverage, like ginger ale.
  • A measured dosing spoon comes with your Noxafil oral suspension and is marked for doses of 2.5 mL and 5 mL. See Figure A.
  • Rinse the spoon with water after each dose of Noxafil oral suspension and before you store it away.
  • If you miss a dose, take it as soon as you remember. However, if it is almost time for the next dose, skip the missed dose and go back to the regular dosing schedule. Do not take a double dose to make up for the missed dose.

Figure A

• Noxafil PowderMix for delayed-release oral suspension:
  • Before giving the first dose of Noxafil PowderMix for delayed-release oral suspension, read the Instructions for Use booklet that comes with Noxafil PowderMix for delayed-release oral suspension for information about the correct way to mix and give a dose of Noxafil PowderMix for delayed-release oral suspension to your child. Keep the booklet and follow it each time you prepare the medicine. Bring this booklet to your child’s appointments.
  • If you have questions about how to mix or give Noxafil PowderMix, talk with your doctor or pharmacist.
  • Only use the mixing liquid that comes with the kit to prepare Noxafil PowderMix.
  • Once mixed, measure the prescribed dose with notched tip syringe provided with the kit. Only use the notched tip syringes that come with the kit to prepare and administer the medicine.
  • Give the dose within 1 hour of mixing the suspension. Give with food.
  • If your child does not take all of the prescribed dose or spits some of it out, call your doctor to find out what to do.

Follow the instructions from your healthcare provider on how much Noxafil or Noxafil PowderMix you should take and when to take it.

What are the possible side effects of Noxafil?

Noxafil or Noxafil PowderMix may cause serious side effects, including:

• drug interactions with cyclosporine or tacrolimus. If you take Noxafil or Noxafil PowderMix with cyclosporine or tacrolimus, your blood levels of cyclosporine or tacrolimus may increase. Serious side effects can happen in your kidney or brain if you have high levels of cyclosporine or tacrolimus in your blood. Your healthcare provider should do blood tests to check your levels of cyclosporine or tacrolimus if you are taking these medicines while taking Noxafil or Noxafil PowderMix. Tell your healthcare provider right away if you have swelling in your arm or leg or shortness of breath.
• problems with the electrical system of your heart (arrhythmias and QTc prolongation). Certain medicines used to treat fungus called azoles, including posaconazole, the active ingredient in Noxafil and Noxafil PowderMix, may cause heart rhythm problems. People who have certain heart problems or who take certain medicines have a higher chance for this problem. Tell your healthcare provider right away if your heartbeat becomes fast or irregular.
• liver problems. Some people who also have other serious medical problems may have severe liver problems that may lead to death, especially if you take certain doses of Noxafil or Noxafil PowderMix. Your healthcare provider should do blood tests to check your liver while you are taking Noxafil or Noxafil PowderMix. Call your healthcare provider right away if you have any of the following symptoms of liver problems:
  • itchy skin
  • nausea or vomiting
  • yellowing of your eyes
  • feeling very tired
  • flu-like symptoms
• increased amounts of midazolam in your blood. If you take Noxafil or Noxafil PowderMix with midazolam, Noxafil or Noxafil PowderMix increases the amount of midazolam in your blood. This can make your sleepiness last longer. Your healthcare provider should check you closely for side effects if you take midazolam with Noxafil or Noxafil PowderMix.

The most common side effects of Noxafil in adults include:

• diarrhea
• nausea
• fever
• vomiting
• headache
• coughing
• low potassium levels in the blood

The most common side effects of Noxafil injection and Noxafil PowderMix in children include:

• fever
• fever with low white blood cell count (febrile neutropenia)
• vomiting
• redness and sores of the lining of the mouth, lips, throat, stomach, and genitals (mucositis or stomatitis)
• itching
• high blood pressure
• low potassium levels in the blood

If you take Noxafil delayed-release tablets, Noxafil oral suspension, or Noxafil PowderMix for delayed-release oral suspension, tell your healthcare provider right away if you have diarrhea or vomiting.

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Noxafil or Noxafil PowderMix. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of Noxafil

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Noxafil or Noxafil PowderMix for a condition for which it was not prescribed. Do not give Noxafil or Noxafil PowderMix to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about Noxafil or Noxafil PowderMix that is written for health professionals.

How should I store Noxafil?

Noxafil injection

• Store Noxafil injection refrigerated at 36°F to 46°F (2°C to 8°C).

Noxafil delayed-release tablets

• Store Noxafil delayed-release tablets at room temperature between 68°F to 77°F (20°C to 25°C).

Noxafil oral suspension

• Store Noxafil oral suspension at room temperature between 68°F to 77°F (20°C to 25°C).
• Do not freeze Noxafil oral suspension.

Noxafil PowderMix for delayed-release oral suspension

• Store the entire kit at room temperature between 68°F to 77°F (20°C to 25°C) in a clean, dry place.
• Do not open the foil packet until ready for use.

Safely throw away medicine that is out of date or no longer needed.

Keep Noxafil and Noxafil PowderMix and all medicines out of the reach of children.

What are the ingredients in Noxafil?

Active ingredient: posaconazole

Inactive ingredients:

Noxafil injection: Betadex Sulfobutyl Ether Sodium (SBECD), edetate sodium, hydrochloric acid, sodium hydroxide, and water for injection.

Noxafil delayed-release tablets: croscarmellose sodium, hydroxypropylcellulose, hypromellose acetate succinate, iron oxide yellow, Macrogol/PEG 3350, magnesium stearate, microcrystalline cellulose, polyvinyl alcohol partially hydrolyzed, silicon dioxide, talc, and titanium dioxide.

Noxafil oral suspension: artificial cherry flavor, citric acid monohydrate, glycerin, liquid glucose, polysorbate 80, purified water, simethicone, sodium benzoate, sodium citrate dihydrate, titanium dioxide, and xanthan gum.

Noxafil PowderMix for delayed-release oral suspension: hypromellose acetate succinate.
The mixing liquid contains: anhydrous citric acid, antifoam Af emulsion, berry citrus sweet flavor, carboxymethylcellulose sodium, carrageenan calcium sulfate trisodium phosphate, glycerin, methylparaben, microcrystalline cellulose, potassium sorbate, propylparaben, purified water, sodium citrate, sodium phosphate monobasic monohydrate, sodium saccharin, sorbitol solution, and xanthan gum.

For more information, go to www.noxafil.com or call 1-800-672-6372.

Instructions for use for Noxafil

Noxafil PowderMix (posaconazole)
for delayed-release oral suspension

For caregivers and healthcare providers of toddlers and children

Before you start

Before you start, be sure that you read and understand all of these instructions. They may be different than those for medicines that you have used in the past. It is important that you make all measurements very carefully. Before you give Noxafil PowderMix, check all 3 expiration dates. The expiration date is printed on the box, the Noxafil PowderMix packets, and the mixing liquid. Do not open the Noxafil PowderMix packets until you are ready to mix the dose. Give Noxafil PowderMix with food.

• The amount of Noxafil PowderMix you give depends on your child’s weight. Your healthcare provider will tell you the right dose to give your child. Be sure to keep your healthcare provider’s appointments so you get new dosing information as your child grows.
• This booklet tells you how to:
  • Make the Noxafil PowderMix into a liquid form.
  • Measure the right dose using the included notched-tip oral syringe. Only use the notched-tip syringes supplied
    with the kit. Do not use other oral syringes.
  • Give the Noxafil PowderMix to your child.
  • Clean up.

Kit contents

Prescription (on Noxafil PowderMix box)		2 mixing cups
Instructions for Use (this booklet)		8 packets of Noxafil PowderMix
Package insert		Bottle adapter
4 syringes (shown below)		Bottle of Mixing Liquid for use with Noxafil PowderMix

2 blue (10 mL) syringes	2 green (3 mL) syringes

Get to know the oral syringes

Before you prepare a dose, review the parts of the syringe and how to use them. If you have any questions about measuring with a syringe, call your healthcare provider. Make sure the plunger is pushed all the way into the barrel before you start to measure the dose.

• Look for the number on the measuring scale that matches the amount of mixing liquid or Noxafil PowderMix that you need.
• Be sure to follow the directions in this booklet to remove air bubbles from the syringe. Air bubbles can affect the amount of medicine that the child gets.

Step 1. Get the mixing liquid ready.

When you use the mixing liquid for the first time:

• Open the bottle and remove the safety seal.
• Place the bottle adapter on top of the bottle with the small hole facing up.
• Push the bottle adapter all the way down.
• After it is in place, the bottle adapter stays in the bottle.
• Put the cap back on the bottle.

Step 2. Gather all your supplies and put on a clean surface.

1 mixing cup (Using the tab on the mixing cup, pull open the lid.)	1 packet of Noxafil PowderMix powder	Mixing liquid	2 syringes (Have 1 of each size ready, but you may only use 1, depending on the dose.)	Scissors (not included with kit: use sharp household scissors or kitchen scissors)
		The Noxafil PowderMix box has a mixing cup holder inside to help tilt the cup when you are measuring the dose.

Step 3. Add Noxafil PowderMix to the mixing cup

Take 1 packet of Noxafil PowderMix and shake the powder to the bottom of the packet.
Cut open the packet of Noxafil PowderMix at the dotted line and add all of the Noxafil PowderMix to the mixing cup. Make sure the packet of Noxafil PowderMix is completely empty.

Step 4. Shake the mixing liquid bottle.

Shake the mixing liquid well before each time you prepare Noxafil PowderMix.

Step 5. Fill the blue syringe with 9 mL of mixing liquid.

Push the plunger of the blue syringe into the syringe barrel as far as it goes. Remove the cap from the bottle of mixing liquid. Push the notched tip of the syringe into the bottle adapter. With the syringe attached to the bottle, turn.the bottle and syringe upside down. With your other hand, pull back the plunger to draw the mixing liquid back into the syringe. Stop when you get to the 9 mL line. Turn the bottle back over and remove the syringe to check your measurement.

Step 6. Check for air bubbles.

Hold the syringe with notched tip up. Tap it with your finger to move any air bubbles up. Slowly push the plunger to make the air come out.
	Re-check the measurement of mixing liquid in the syringe. If it is less than 9 mL, put the notched tip back into the mixing liquid and pull the plunger back until you get to the 9 mL mark.

Step 7. Add the 9 mL of mixing liquid to the Noxafil PowderMix.

• Add the 9 mL of mixing liquid to the Noxafil PowderMix in the mixing cup by pushing all the way down on the plunger.

Step 8. Mix the Noxafil PowderMix.

Snap the lid of the mixing cup shut. Shake the mixing cup really hard for 45 seconds to mix the Noxafil PowderMix.
	Check to make sure the Noxafil PowderMix powder is mixed. If it is not mixed, shake the mixing cup some more. Noxafil PowderMix should look cloudy and free of clumps.

Step 9. Check your prescription label.

Find the dose amount (look for the ‘mL’ written on the prescription label on the box from your healthcare provider).

Step 10. Choose the syringe you need.

For 1 mL to 3 mL Green

For 3 mL to 10 mL Blue

• Then find the mL mark on the syringe that matches your child’s dose.

Step 11. Measure the Noxafil PowderMix.

Push the plunger into the dosing syringe as far as it goes. Tilt the cup by hand or use the mixing cup holder inside the Noxafil PowderMix box. Put the notched tip of the dosing syringe into the lowest part of the cup with the Noxafil PowderMix and pull back the plunger. Stop when you get to the line showing the prescribed dose.

Step 12. Check for air bubbles.

Be sure to follow the directions to remove air bubbles from the syringe. Air bubbles can affect the amount of medicine that the child gets. Hold the syringe with notched tip up. Tap it with your finger to move any air bubbles up. Check for air gaps in the tip of the syringe. Slowly push the plunger to make the air bubbles or air gaps come out.
	Re-check the measurement of Noxafil PowderMix in the syringe. If it is less than the prescribed dose, put the notched tip back into the mixing cup with the Noxafil PowderMix and pull the plunger back until you get to the right dose mark.

Step 13. Give the Noxafil PowderMix to your child.

Gently place the syringe inside your child’s mouth so that the notched tip touches one of his or her cheeks. Slowly push down on the plunger to give the dose of Noxafil PowderMix. It is important that your child takes all of the dose of Noxafil PowderMix (a little left in the syringe notched tip is ok).

Step 14. Clean the cup and syringes.

Pour the leftover Noxafil PowderMix from the mixing cup into the trash. Do not pour it into the sink. Pull the plungers out of any syringes you used. Hand wash the syringes, plungers, and mixing cup with warm water and dish soap. Do not wash in the dishwasher. Rinse with water and air dry. Put everything in a clean, dry place.

Step 15. After all packets of Noxafil PowderMix have been used.

• After you have used the last Noxafil PowderMix packet in this box, you will have leftover mixing liquid in the bottle. Throw away the leftover mixing liquid and all components of the kit.

How should I store Noxafil PowderMix?

• Store the entire kit at room temperature between 68°F to 77°F (20°C to 25°C) in a clean, dry place.
• Keep the mixing liquid at room temperature.
• Do not open the Noxafil PowderMix packet until you are ready to mix a dose.

Keep Noxafil PowderMix and all medicines out of the reach of children.

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