Noxafil

Name: Noxafil

Warnings

Contraindications

Hypersensitivity to posaconazole or other azoles

Coadministration with sirolimus; increases sirolimus blood concentrations by ~9-fold

CYP3A4 substrates that prolong the QT interval (eg, pimozide, quinidine); posaconazole inhibits CYP3A4 isoenzyme

Coadministration with the HMG-CoA reductase inhibitors (statins) that are primarily metabolized through CYP3A4 (eg, atorvastatin, lovastatin, simvastatin); increased statin plasma concentration can lead to rhabdomyolysis

May increase plasma concentrations of ergot alkaloids (ergotamine and dihydroergotamine) which may lead to ergotism

Cautions

Coadministration with calcineurin inhibitors (eg, cyclosporine, tacrolimus); increases whole concentrations of calcineurin inhibitors

Coadministration with midazolam increases midazolam plasma concentrations by ~5-fold; increased risk of prolonged hypnotic and sedative effects

May prolong QT interval; cases of torsades de pointes reported

Hepatic reactions reported including mild-to-moderate elevations in ALT, AST, alkaline phosphatase, total bilirubin, and clinical hepatitis; consider discontinuing therapy in patients who develop abnormal LFTs or monitor LFTs during treatment

coadministration of azole antifungals, including posaconazole, with vincristine has been associated with neurotoxicity and other serious adverse reactions,including seizures, peripheral neuropathy, syndrome of inappropriate antidiuretic hormone secretion, and paralytic ileus; Reserve azole antifungals, including posaconazole, for patients receiving a vinca alkaloid, including vincristine, who have no alternative antifungal treatment options

What special precautions should I follow?

Before taking posaconazole,

  • tell your doctor and pharmacist if you are allergic to posaconazole; other antifungal medications such as fluconazole (Diflucan), isavuconazonium (Cresemba), itraconazole (Onmel, Sporanox), ketoconazole (Extina, Nizoral, Xolegel), or voriconazole (Vfend); simethicone; any other medications; or any of the ingredients in posaconazole products. Ask your pharmacist for a list of the ingredients.
  • tell your doctor if you taking any of the following medications: atorvastatin (Lipitor, in Caduet), ergot-type medications such as bromocriptine (Cycloset, Parlodel), cabergoline, dihydroergotamine (D.H.E. 45, Migranal), ergoloid mesylates (Hydergine), ergonovine, ergotamine (Ergomar, in Cafergot, in Migergot), and methylergonovine (Methergine); lovastatin (Altoprev, in Advicor); pimozide (Orap); quinidine (in Nuedexta); simvastatin (Zocor, in Simcor, in Vytorin); or sirolimus (Rapamune). Your doctor will probably tell you not to take posaconazole if you are taking one or more of these medications.
  • tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: benzodiazepines such as alprazolam (Xanax), diazepam (Valium), midazolam, and triazolam (Halcion); calcium channel blockers such as diltiazem (Cardizem, Cartia, Tiazac, others), felodipine, nicardipine (Cardene), nifedipine (Adalat, Afeditab CR, Procardia), and verapamil (Calan, Covera, Verelan, others); cyclosporine (Gengraf, Neoral, Sandimmune); digoxin (Lanoxin); efavirenz (Sustiva, in Atripla); erythromycin (E.E.S., ERYC, Erythrocin, others), fosamprenavir (Lexiva); glipizide (Glucotrol); phenytoin (Dilantin, Phenytek); rifabutin (Mycobutin); ritonavir (Norvir) taken with atazanavir (Reyataz); tacrolimus (Astagraf, Envarsus XR, Prograf); vinblastine; and vincristine (Marquibo Kit). If you are taking the posaconazole oral suspension, also tell your doctor if you are taking cimetidine (Tagamet), esomeprazole (Nexium, in Vimovo), or metoclopramide (Reglan). Many other medications may also interact with posaconazole, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
  • tell your doctor if you have or have ever had a slow or irregular heartbeat; a prolonged QT interval (a rare heart problem that may cause irregular heartbeat, fainting, or sudden death); problems with blood circulation; low levels of calcium, magnesium, or potassium in your blood; or kidney, or liver disease.
  • tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking posaconazole, call your doctor.

Side Effects of Noxafil

Serious side effects have been reported. See "Drug Precautions" section.

The most common side effects of Noxafil delayed-release tablets include:

  • diarrhea
  • fever
  • nausea

The most common side effects of Noxafil oral suspension include:

  • diarrhea
  • nausea
  • headache
  • vomiting
  • fever

The most common side effects of Noxafil injection  include:

  • anemia
  • abdominal pain
  • diarrhea
  • nausea
  • 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. For more information, ask your healthcare provider or pharmacist.

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

Noxafil Precautions

Noxafil may cause serious side effects, including:

  • drug interactions with cyclosporine or tacrolimus. If you take Noxafil 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. 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 Noxafil, the active ingredient in Noxafil, 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. Your healthcare provider should do blood tests to check your liver while you are taking Noxafil. 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 with midazolam, Noxafil 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.

Noxafil and Pregnancy

Tell your doctor if you are pregnant or plan to become pregnant. The FDA categorizes medications based on safety for use during pregnancy.

Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy. 

Noxafil falls into category C. There are no well-controlled studies in pregnant women. Noxafil should be used during pregnancy only if the possible benefit outweighs the possible risk to the unborn baby

How should I take posaconazole?

The liquid and tablet forms of posaconazole are not equivalent and may not have the same dose or schedule. Ask your pharmacist if you have any questions about the kind of posaconazole you receive at the pharmacy.

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Do not crush, chew, dissolve, or break a delayed-release tablet. Swallow it whole.

Shake the oral suspension (liquid) well just before you measure a dose. Measure the liquid with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.

The posaconazole delayed-release tablet works best if you take it with food. Take the oral suspension within 20 minutes after a full meal. If you cannot eat a full meal, take the oral suspension with a nutritional supplement (such as BOOST) or with an acidic carbonated drink such as ginger ale.

Use this medicine for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Skipping doses may also increase your risk of further infection that is resistant to antifungal medicine. Posaconazole will not treat a viral infection such as the flu or a common cold.

Call your doctor if you have ongoing vomiting or diarrhea. Posaconazole may not work as well while during this time.

While using posaconazole, you may need frequent blood tests.

Store at room temperature away from moisture and heat. Do not freeze. Keep the bottle tightly closed when not in use.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Noxafil 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 Dosage and Administration (2.3, 2.4, 2.5)].

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 (2.2)].
  • 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 Dosage and Administration (2.3) and Clinical Pharmacology (12.3)].

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 (2.4)]
  • 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 (7.6, 7.7, 7.8, 7.9, 7.13)]

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%. Co-administration 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 (6.2)].

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 (12.3)].
  • 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.

  • 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 (12.3)].
  • 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 [See Dosage and Administration (2.5)].
  • 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 [see Dosage and Administration (2.3, 2.4)].

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.

Overdosage

There is no experience with overdosage of posaconazole injection and delayed-release tablets.

During the clinical trials, some patients received posaconazole oral suspension up to 1600 mg/day with no adverse reactions noted that were different from the lower doses. In addition, accidental overdose was noted in one patient who took 1200 mg BID posaconazole oral suspension for 3 days. No related adverse reactions were noted by the investigator.

Posaconazole is not removed by hemodialysis.

Noxafil Description

Noxafil is an azole antifungal agent available as concentrated solution to be diluted before intravenous administration, delayed-release tablet, or suspension for 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:

Posaconazole is a white powder with a low aqueous solubility.

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), 0.003 g edetate disodium, hydrochloric acid and sodium hydroxide to adjust the pH to 2.6, and water for injection.

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

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

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

No drug-related neoplasms were recorded in rats or mice treated with posaconazole for 2 years at doses higher than the clinical dose. In a 2-year carcinogenicity study, rats were given posaconazole orally at doses up to 20 mg/kg (females), or 30 mg/kg (males). These doses are equivalent to 3.9- or 3.5-times the exposure achieved with a 400-mg BID oral suspension regimen, respectively, based on steady-state AUC in healthy volunteers administered a high-fat meal (400-mg BID oral suspension regimen). In the mouse study, mice were treated at oral doses up to 60 mg/kg/day or 4.8-times the exposure achieved with a 400-mg BID oral suspension regimen.

Posaconazole was not genotoxic or clastogenic when evaluated in bacterial mutagenicity (Ames), a chromosome aberration study in human peripheral blood lymphocytes, a Chinese hamster ovary cell mutagenicity study, and a mouse bone marrow micronucleus study.

Posaconazole had no effect on fertility of male rats at a dose up to 180 mg/kg (1.7 × the 400-mg BID oral suspension regimen based on steady-state plasma concentrations in healthy volunteers) or female rats at a dose up to 45 mg/kg (2.2 × the 400-mg BID oral suspension regimen).

Animal Toxicology and/or Pharmacology

In a nonclinical study using intravenous administration of posaconazole in very young dogs (dosed from 2 to 8 weeks of age), an increase in the incidence of brain ventricle enlargement was observed in treated animals as compared with concurrent control animals. No difference in the incidence of brain ventricle enlargement between control and treated animals was observed following the subsequent 5-month treatment-free period. There were no neurologic, behavioral or developmental abnormalities in the dogs with this finding, and a similar brain finding was not seen with oral posaconazole administration to juvenile dogs (4 days to 9 months of age).

The clinical significance of this finding is unknown; therefore, the use of posaconazole injection to patients under 18 years of age is not recommended.

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Administration

Noxafil Delayed-Release Tablets

Advise patients to take Noxafil delayed-release tablets with food.

Advise patients that Noxafil delayed-release tablets must be swallowed whole and not divided, crushed, or chewed.

Instruct patients that if they miss a dose, they should take it as soon as they remember. If they do not remember until it is within 12 hours of the next dose, they should be instructed to skip the missed dose and go back to the regular schedule. Patients should not double their next dose or take more than the prescribed dose.

Noxafil Oral Suspension

Advise patients to take each dose of Noxafil oral suspension during or immediately (i.e., within 20 minutes) following a full meal. In patients who cannot eat a full meal, each dose of Noxafil oral suspension should be administered with a liquid nutritional supplement or an acidic carbonated beverage (e.g., ginger ale) in order to enhance absorption.

Instruct patients that if they miss a dose, they should take it as soon as they remember. However, if it is almost time for the next dose, they should be instructed to skip the missed dose and go back to the regular schedule. Patients should not double their next dose or take more than the prescribed dose.

Drug Interactions

Advise patients to inform their physician immediately if they:

  • develop severe diarrhea or vomiting.
  • are currently taking drugs that are known to prolong the QTc interval and are metabolized through CYP3A4.
  • are currently taking a cyclosporine or tacrolimus, or they notice swelling in an arm or leg or shortness of breath.
  • are taking other drugs or before they begin taking other drugs as certain drugs can decrease or increase the plasma concentrations of posaconazole.

Serious and Potentially Serious Adverse Reactions

Advise patients to inform their physician immediately if they:

  • notice a change in heart rate or heart rhythm, or have a heart condition or circulatory disease. Posaconazole can be administered with caution to patients with potentially proarrhythmic conditions.
  • are pregnant, plan to become pregnant, or are nursing.
  • have liver disease or develop itching, nausea or vomiting, their eyes or skin turn yellow, they feel more tired than usual or feel like they have the flu.
  • have ever had an allergic reaction to other antifungal medicines such as ketoconazole, fluconazole, itraconazole, or voriconazole.

Manuf. for: Merck Sharp & Dohme Corp., a subsidiary of
MERCK & CO., INC., Whitehouse Station, NJ 08889, USA

Injection: Manuf. by: MSD International GmbH, Brinny, Innishannon, County Cork, Ireland

Delayed-Release Tablets: Manuf. by: N. V. Organon, Kloosterstraat 6, 5349 AB Oss, Netherlands

Oral Suspension: Manuf. by: Patheon Inc., Whitby, Ontario, Canada L1N 5Z5

For patent information: www.merck.com/product/patent/home.html

The trademarks referenced herein are owned by their respective companies.

Copyright © 2006-2017 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
All rights reserved.

uspi-mk5592-mf-1708r038

This Patient Information has been approved by the U.S. Food and Drug Administration.                                                              Revised: 08/2017
Patient Information
Noxafil® (NOX-a-fil)
(posaconazole) injection
Noxafil® (NOX-a-fil)
(posaconazole) delayed-release tablets
Noxafil® (NOX-a-fil)
(posaconazole) oral suspension
What is Noxafil?
Noxafil injection, delayed-release tablets, and oral suspension are prescription medicines used to help prevent fungal infections that can spread throughout your body (invasive fungal infections). These infections are caused by fungi called Aspergillus or Candida. Noxafil is 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
  • a low white blood cell count due to chemotherapy for blood cancers (hematologic malignancy)
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 injection is for adults over 18 years of age. It is not known if Noxafil injection is safe and effective in children under 18 years of age.
Noxafil delayed-release tablets and oral suspension are for adults and children over 13 years of age.
It is not known if Noxafil oral suspension and delayed-release tablets are safe and effective in children under 13 years of age.
Who should not take Noxafil?
Do not take Noxafil if you:
  • are allergic to posaconazole, any of the ingredients in Noxafil, or other azole antifungal medicines. See the end of this leaflet for a complete list of ingredients in Noxafil.
  • are taking any of the following medicines:
    • sirolimus
    • pimozide
    • quinidine
    • certain statin medicines that lower cholesterol (atorvastatin, lovastatin, simvastatin)
    • ergot alkaloids (ergotamine, dihydroergotamine)
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, 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.
  • 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 can affect the way other medicines work, and other medicines can affect the way Noxafil works, 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 or Noxafil 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 will I take Noxafil?

  • Do not switch between taking Noxafil delayed-release tablets and Noxafil oral suspension without talking to your healthcare provider.
  • Take Noxafil exactly as your healthcare provider tells you to take it.
  • Your healthcare provider will tell you how much Noxafil to take and when to take it.
  • Take Noxafil for as long as your healthcare provider tells you to take it.
  • If you take too much Noxafil, 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 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.

                                                                                       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 forgotten dose.

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

What are the possible side effects of Noxafil?

Noxafil may cause serious side effects, including:

  • drug interactions with cyclosporine or tacrolimus. If you take Noxafil 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. 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, 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. Your healthcare provider should do blood tests to check your liver while you are taking Noxafil. 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 with midazolam, Noxafil 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.

The most common side effects of Noxafil include:

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

If you take Noxafil delayed-release tablets or Noxafil 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. 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.

How should I store Noxafil?

  • Store Noxafil injection refrigerated at 36°F to 46°F (2°C to 8°C).
  • Store Noxafil delayed-release tablets and oral suspension at room temperature between 68°F to 77°F (20°C to 25°C).
  • Do not freeze Noxafil oral suspension.
  • Safely throw away medicine that is out of date or no longer needed.

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

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 for a condition for which it was not prescribed. Do not give Noxafil 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 that is written for health professionals.

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: hypromellose acetate succinate, microcrystalline cellulose, hydroxypropylcellulose, silicon dioxide, croscarmellose sodium, magnesium stearate, and Opadry® II Yellow (consists of the following ingredients: polyvinyl alcohol partially hydrolyzed, Macrogol/PEG 3350, titanium dioxide, talc, and iron oxide yellow)
Noxafil oral suspension: polysorbate 80, simethicone, sodium benzoate, sodium citrate dihydrate, citric acid monohydrate, glycerin, xanthan gum, liquid glucose, titanium dioxide, artificial cherry flavor, and purified water

Manuf. for: Merck Sharp & Dohme Corp., a subsidiary of
MERCK & CO., INC., Whitehouse Station, NJ 08889, USA
Injection: MSD International GmbH, Brinny, Innishannon, County Cork, Ireland
Delayed-Release Tablets: Manuf. by: N. V. Organon, Kloosterstraat 6, 5349 AB Oss, Netherlands
Oral Suspension: Manuf. by: Patheon Inc., Whitby, Ontario, Canada L1N 5Z5
For patent information: www.merck.com/product/patent/home.html
The trademarks depicted in this piece are owned by their respective companies.
Copyright © 2006-2017 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
All rights reserved.
usppi-mk5592-mf-1703r017
For more information, go to www.Noxafil.com or call 1-800-672-6372.

PRINCIPAL DISPLAY PANEL - 300 mg Vial Carton

NDC 0085-4331-01

Noxafil®
(posaconazole)
Injection

300 mg/16.7 mL
(18 mg/mL)

For Intravenous Use Only

Requires further dilution prior to infusion.

Rx only
Single-Dose Vial

Noxafil 
posaconazole suspension
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0085-1328
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
posaconazole (posaconazole) posaconazole 40 mg  in 1 mL
Inactive Ingredients
Ingredient Name Strength
polysorbate 80  
sodium benzoate  
trisodium citrate dihydrate  
citric acid monohydrate  
glycerin  
xanthan gum  
anhydrous dextrose  
titanium dioxide  
water  
Product Characteristics
Color      Score     
Shape Size
Flavor CHERRY Imprint Code
Contains     
Packaging
# Item Code Package Description
1 NDC:0085-1328-01 1 BOTTLE, GLASS in 1 CARTON
1 105 mL in 1 BOTTLE, GLASS
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA022003 09/15/2006
Noxafil 
posaconazole tablet, coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0085-4324
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
posaconazole (posaconazole) posaconazole 100 mg
Inactive Ingredients
Ingredient Name Strength
HYPROMELLOSE ACETATE SUCCINATE 06081224 (3 MM2/S)  
MICROCRYSTALLINE CELLULOSE  
HYDROXYPROPYL CELLULOSE (1200000 MW)  
SILICON DIOXIDE  
CROSCARMELLOSE SODIUM  
MAGNESIUM STEARATE  
POLYVINYL ALCOHOL, UNSPECIFIED  
POLYETHYLENE GLYCOL 3350  
TITANIUM DIOXIDE  
TALC  
FERRIC OXIDE YELLOW  
Product Characteristics
Color YELLOW Score no score
Shape OVAL (oblong) Size 17mm
Flavor Imprint Code 100
Contains     
Packaging
# Item Code Package Description
1 NDC:0085-4324-02 60 TABLET, COATED in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA205053 11/25/2013
Noxafil 
posaconazole solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0085-4331
Route of Administration INTRAVENOUS DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
posaconazole (posaconazole) posaconazole 18 mg  in 1 mL
Inactive Ingredients
Ingredient Name Strength
BETADEX SULFOBUTYL ETHER SODIUM  
EDETATE DISODIUM  
HYDROCHLORIC ACID  
SODIUM HYDROXIDE  
WATER  
Packaging
# Item Code Package Description
1 NDC:0085-4331-01 1 VIAL, GLASS in 1 CARTON
1 16.7 mL in 1 VIAL, GLASS
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA205596 03/13/2014
Labeler - Merck Sharp & Dohme Corp. (001317601)
Revised: 08/2017   Merck Sharp & Dohme Corp.

How should I take Noxafil?

Take Noxafil exactly as prescribed by your doctor. Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

The liquid and tablet forms of posaconazole are not equivalent and may not have the same dose or schedule. Ask your pharmacist if you have any questions about the kind of Noxafil you receive at the pharmacy.

Do not crush, chew, dissolve, or break a delayed-release tablet. Swallow it whole.

Shake the oral suspension (liquid) well just before you measure a dose. Measure the liquid with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.

Noxafil delayed-release tablets work best if you take it with food. Take the oral suspension within 20 minutes after a full meal. If you cannot eat a full meal, take the oral suspension with a nutritional supplement (such as BOOST) or with an acidic carbonated drink such as ginger ale.

Use this medicine for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Skipping doses may also increase your risk of further infection that is resistant to antifungal medicine. Posaconazole will not treat a viral infection such as the flu or a common cold.

Call your doctor if you have ongoing vomiting or diarrhea. Noxafil may not work as well while during this time.

While using Noxafil, you may need frequent blood tests.

Store at room temperature away from moisture and heat. Do not freeze. Keep the bottle tightly closed when not in use.

For Healthcare Professionals

Applies to posaconazole: intravenous solution, oral delayed release tablet, oral suspension

General

Thrombophlebitis was very common when multiple doses of the injection were administered via peripheral venous catheter, leading to administration via central venous catheter in later studies. The most common side effects reported with the IV injection were diarrhea, hypokalemia, pyrexia, and nausea.

The most common side effects reported with the delayed-release tablets were diarrhea, pyrexia, and nausea. The most common side effect leading to discontinuation of the delayed-release tablets was nausea (2%).

The most common side effects reported with the oral suspension in the prophylaxis clinical trials were fever, diarrhea, and nausea. The most common side effects leading to discontinuation of the oral suspension in these trials were associated with gastrointestinal disorders, including nausea (2%), vomiting (2%), and increased liver enzymes (2%).

The most common side effects reported with the oral suspension in the oropharyngeal candidiasis and refractory oropharyngeal candidiasis trials were fever, diarrhea, nausea, headache, vomiting, and coughing. The most common side effects leading to discontinuation of the oral suspension were respiratory impairment (1%) and pneumonia (1%) in patients with oropharyngeal candidiasis and AIDS (7%) and respiratory impairment (3%) in patients with refractory oropharyngeal candidiasis. Side effects occurred more often in patients with refractory oropharyngeal candidiasis. Serious side effects were reported in 55% of highly immunocompromised patients with advanced HIV disease. Fever (13%) and neutropenia (10%) were the serious side effects reported most often in these patients. Other serious side effects included altered drug levels (of other products), increased hepatic enzymes, nausea, rash, vomiting, bilirubinemia, and hepatocellular damage.[Ref]

Gastrointestinal

Very common (10% or more): Diarrhea (up to 42%), nausea (up to 38%), vomiting (up to 29%), abdominal pain (up to 27%), constipation (up to 21%), oral candidiasis (up to 12%), upper abdominal pain (up to 11%)
Common (1% to 10%): Dyspepsia, dry mouth, flatulence
Uncommon (0.1% to 1%): Mucositis, taste perversion, pancreatitis, mouth ulceration, loose stools, abdominal distension, dysphagia, ascites, eructation, gastritis, gastroesophageal reflux disease, esophagitis, tongue edema, tongue discoloration, tooth discoloration, mouth edema
Rare (less than 0.1%): Gastrointestinal hemorrhage, ileus, esophageal candidiasis, increased amylase, increased lipase, abdominal tenderness, cheilitis, hemorrhagic diarrhea, esophageal ulceration, hemorrhagic gastritis, odynophagia, increased pancreatic enzymes, proctalgia, retching, aphthous stomatitis, tenesmus, melena, gingivitis, glossitis, stomatitis[Ref]

Other

Very common (10% or more): Fever/pyrexia (up to 45%), rigors (up to 20%), fatigue (up to 17%), peripheral edema (16%), chills (up to 16%), leg edema (15%), mucosal inflammation (14%), asthenia (up to 13%), herpes simplex (up to 11%), pain (up to 11%)
Common (1% to 10%): Edema, weakness
Uncommon (0.1% to 1%): Altered drug levels, malaise, flushing, hot flushes, thirst, drug toxicity
Rare (less than 0.1%): Face edema, catheter-related infection, non-herpetic cold sores
Frequency not reported: Bacteremia, cytomegalovirus infection[Ref]

Metabolic

Very common (10% or more): Hypokalemia (up to 30%), anorexia (up to 19%), hypomagnesemia (up to 18%), decreased weight (up to 14%), decreased appetite (up to 12%), hyperglycemia (up to 11%), dehydration (up to 11%)
Common (1% to 10%): Hypocalcemia, electrolyte imbalance
Uncommon (0.1% to 1%): Hypertriglyceridemia, hyperuricemia, increased LDH
Rare (less than 0.1%): Hypercholesterolemia, hyperlipemia, hyperproteinemia, hypoalbuminemia, metabolic acidosis, vitamin K deficiency, increased weight[Ref]

Hematologic

Rare occurrences of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura have been reported, generally in patients with concurrent cyclosporine or tacrolimus therapy for the prevention of transplant rejection or graft versus host disease.[Ref]

Very common (10% or more): Thrombocytopenia (up to 29%), anemia (up to 25%), neutropenia (up to 23%)
Common (1% to 10%): Hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, aggravated neutropenia
Uncommon (0.1% to 1%): Leukopenia, eosinophilia, lymphadenopathy
Rare (less than 0.1%): Pancytopenia, coagulopathy/coagulation disorder, hemorrhage, abnormal blood gases, neutrophilia, increased platelet count, decreased prothrombin, prolonged prothrombin time, purpura
Frequency not reported: Febrile neutropenia[Ref]

Nervous system

Very common (10% or more): Headache (up to 28%), dizziness (up to 11%)
Common (1% to 10%): Paresthesia, somnolence
Uncommon (0.1% to 1%): Tremor, convulsions, neuropathy, hypoesthesia, earache, vertigo, aphasia
Rare (less than 0.1%): Cerebrovascular accident, encephalopathy, peripheral neuropathy, syncope, hearing impairment, areflexia, ataxia, impaired cognition, dysphonia, dystonia, hemiparesis, hyperkinesia, hyperreflexia, hyporeflexia, hypotonia, impaired concentration, memory impairment, meningism, mononeuritis, restless leg syndrome, sciatica, tinnitus[Ref]

Respiratory

Very common (10% or more): Coughing (up to 25%), dyspnea (up to 20%), epistaxis (up to 17%), pharyngitis (up to 12%)
Common (1% to 10%): Pneumonia, pulmonary embolism
Uncommon (0.1% to 1%): Sinusitis, chest pain, nasal congestion, hiccups, pleuritic pain
Rare (less than 0.1%): Pulmonary hypertension, interstitial pneumonia, pneumonitis, upper respiratory tract infection, atelectasis, dry throat, nasal irritation, postnasal drip, pulmonary infiltration, rales, rhinitis, rhinorrhea[Ref]

Rare occurrences of pulmonary embolus have been reported, generally in patients with concurrent cyclosporine or tacrolimus therapy for the prevention of transplant rejection or graft versus host disease.[Ref]

Dermatologic

Very common (10% or more): Rash (up to 24%), pruritus (up to 11%), petechiae (up to 11%)
Common (1% to 10%): Increased sweating
Uncommon (0.1% to 1%): Alopecia, dry skin, maculopapular rash, urticaria, furunculosis, acne, pruritic rash
Rare (less than 0.1%): Stevens-Johnson syndrome, vesicular rash, dermatitis, erythema, erythematous rash, follicular rash, macular rash, night sweats, seborrhea, skin nodule, ecchymoses[Ref]

Cardiovascular

Very common (10% or more): Hypertension (up to 18%), hypotension (up to 14%), tachycardia (up to 12%)
Common (1% to 10%): Torsades de pointes
Uncommon (0.1% to 1%): Long QT syndrome, abnormal ECG, palpitations, bradycardia, QT/QTc prolongation, atrial fibrillation, atrial flutter, bundle branch block, extrasystoles, ventricular hypertrophy, supraventricular extrasystoles, vasculitis
Rare (less than 0.1%): Deep vein thrombosis, sudden death, ventricular tachycardia, cardiorespiratory arrest, cardiac failure, myocardial infarction, aortic valve sclerosis, cardiomegaly, decreased ejection fraction, mitral valve disease, supraventricular tachycardia, premature atrial contractions, premature ventricular contractions, atrioventricular block, atherosclerosis, ischemia, hematoma[Ref]

One patient taking posaconazole during a clinical trial developed torsades de pointes. This severely ill patient had a history of palpitations, recent cardiotoxic chemotherapy, hypokalemia, and hypomagnesemia; risk factors that may have contributed to or confounded the patient's condition.[Ref]

Hepatic

Very common (10% or more): Increased AST (up to 17%), changes in ALT (up to 17%), increased alkaline phosphatase (up to 13%), increased ALT (up to 11%)
Common (1% to 10%): Bilirubinemia, changes in bilirubin, increased total bilirubin, increased hepatic enzymes, abnormal hepatic function, hepatitis, hepatomegaly, jaundice, changes in AST, changes in alkaline phosphatase, increased gamma-glutamyl transpeptidase
Uncommon (0.1% to 1%): Hepatocellular damage
Rare (less than 0.1%): Hepatic failure, cholestatic hepatitis, cholestasis, hepatosplenomegaly, liver tenderness, asterixis, splenomegaly
Postmarketing reports: Severe hepatic injury with fatal outcome[Ref]

Clinically significant liver function test abnormalities during oropharyngeal candidiasis studies included increased AST, alkaline phosphatase, ALT, and total bilirubin. The majority of abnormal liver function tests in patients and healthy subjects were minor, transient, and did not lead to therapy discontinuation.

Changes in liver function tests from Grade 0, 1, or 2 at baseline to Grade 3 or 4 during prophylaxis studies included changes in ALT, bilirubin, AST, and alkaline phosphatase.

Total bilirubin greater than 1.5 times ULN (up to 22%), AST greater than 3 times ULN (up to 17%), alkaline phosphatase greater than 3 times ULN (up to 14%), and ALT greater than 3 times ULN (up to 11%) were reported.[Ref]

Psychiatric

Very common (10% or more): Insomnia (up to 17%)
Common (1% to 10%): Anxiety
Uncommon (0.1% to 1%): Altered mental status, confusion
Rare (less than 0.1%): Psychotic disorder, depression, amnesia, abnormal dreaming, emotional lability, decreased libido, paroniria, psychosis, delirium
Frequency not reported: Confusional state[Ref]

Musculoskeletal

Very common (10% or more): Musculoskeletal pain (up to 16%), arthralgia (up to 11%)
Common (1% to 10%): Back pain
Uncommon (0.1% to 1%): Myalgia, flank pain, muscle weakness, pain in extremity
Rare (less than 0.1%): Bone pain, chest wall pain, fasciitis, neck stiffness, cramps in the extremities, muscle cramps[Ref]

Genitourinary

Very common (10% or more): Vaginal hemorrhage (10%)
Uncommon (0.1% to 1%): Menstrual disorder, albuminuria, altered micturition frequency, dysuria, hematuria, nocturia
Rare (less than 0.1%): Breast pain, urinary tract infection, micturition disorder, urinary tract obstruction, leukorrhea[Ref]

Renal

Common (1% to 10%): Acute renal failure
Uncommon (0.1% to 1%): Increased blood creatinine, renal failure, renal insufficiency
Rare (less than 0.1%): Renal tubular acidosis, interstitial nephritis, increased BUN, renal calculus[Ref]

Endocrine

Common (1% to 10%): Adrenal insufficiency
Rare (less than 0.1%): Decreased blood gonadotropins[Ref]

Hypersensitivity

Common (1% to 10%): Allergic reaction
Rare (less than 0.1%): Hypersensitivity reactions[Ref]

Ocular

Uncommon (0.1% to 1%): Blurred vision, conjunctivitis
Rare (less than 0.1%): Diplopia, scotoma, eye pain, dry eyes, periorbital edema, photophobia[Ref]

Some side effects of Noxafil may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Posaconazole Pregnancy Warnings

Animal studies have revealed evidence of embryotoxicity and teratogenicity. There are no controlled data in human pregnancy. AU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

This drug should not be used during pregnancy unless the benefit outweighs the risk to the fetus. AU TGA pregnancy category: B3 US FDA pregnancy category: C Comments: Effective contraception is recommended during therapy and for at least 2 weeks after the last dose; local protocol should be consulted regarding contraception timing.

(web3)