Posaconazole 18 mg/mL Injection, Solution, 1 vial
Other active recalls for Posaconazole (different manufacturers) — 1 · tap to view
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Azole Antifungal class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Posaconazole injection is used to prevent serious fungal infections that can spread throughout the body in adults and children 2 years of age and older with a weakened ability to fight infection. Posaconazole injection is also used to treat invasive aspergillosis (a serious fungal infection that begins in the lungs and spreads through the bloodstream to other organs) in adults and teenagers 13 years of age and older. Posaconazole injection is in a class of medications called azole antifungals. It works by slowing the growth of fungi that cause infection.
Read the full MedlinePlus article ↗- Posaconazole fights serious fungal infections, not bacterial ones. Depending on your situation, you may be taking it to treat invasive aspergillosis — a mold infection that can aff...
- What exactly is posaconazole treating — what kind of infection is this?
- It depends on which form you have. The delayed-release tablets can be taken with or without food — that's one of their advantages. But if you have the oral suspension (the liquid),...
- Does it matter if I take the tablets with food or not?
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UNII 2PP9364507
A modified form of beta-cyclodextrin, a natural sugar-like molecule. It helps dissolve and stabilize drugs in liquid medicines and improves how well the body absorbs certain medications.
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UNII 7FLD91C86K
Edetate disodium is a chemical compound that binds and removes certain metal ions. In medicines, it acts as a preservative and stabilizer by preventing metals like calcium from interfering with the product's shelf life and consistency.
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A strong acid used to adjust and maintain the proper pH level in liquid medicines, ensuring stability and preventing breakdown of active ingredients.
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UNII 55X04QC32I
A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
5 inactive ingredients listed in the exact product block matched to this NDC.
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J1837 | $0.342 / J1837 unit | — |
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🧾 Billing & reimbursement
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Noxafil 18 mg/mL 00085-4331-01 | Merck | 1 vial | — | — | FDA listed | — |
| Posaconazole 18 mg/mL 31722-0370-31 | Camber | 1 vial | — | AP | FDA listed | — |
| Posaconazole 18 mg/mL 42023-0195-01 | Par | 1 vial | — | AP | FDA listed | — |
| Posaconazole 18 mg/mL 55150-0388-01 | Eugia | 1 vial | — | AP | FDA listed | — |
| Posaconazole 18 mg/mLthis 63323-0685-17 | Fresensius | 1 vial | — | AP | FDA listed | — |
| posaconazole 18 mg/mL 67457-0665-20 | Mylan | 1 vial | — | AP | FDA listed | — |
| posaconazole 18 mg/mL 68083-0577-01 | Gland | 1 vial | — | AP | FDA listed | — |
| posaconazole 18 mg/mL 68462-0904-01 | GLENMARK | 1 vial | — | AP | FDA listed | — |
| posaconazole 18 mg/mL 68462-0911-01 | GLENMARK | 1 vial | — | AP | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 63323-0685-17 You're viewing this | 1 VIAL, SINGLE-DOSE in 1 CARTON (63323-685-17) / 16.7 mL in 1 VIAL, SINGLE-DOSE | 2023-12-26 | Active |
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Posaconazole is an azole antifungal indicated as follows: Posaconazole injection is indicated for the treatment of invasive aspergillosis in adults and pediatric patients 13 years of age and older. ( 1.1 ) Posaconazole is indicated for the 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 as follows: ( 1.2 ) Posaconazole injection: adults and pediatric patients 2 years of age and older
1.1Treatment of Invasive Aspergillosis Posaconazole injection is indicated for the treatment of invasive aspergillosis in adults and pediatric patients 13 years of age and older.
1.2Prophylaxis of Invasive Aspergillus and Candida Infections Posaconazole is indicated for the 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 [see Clinical Studies ( 14.1 )] as follows: Posaconazole injection: adults and pediatric patients 2 years of age and older
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Posaconazole injection must be administered through an in-line filter. Administer Posaconazole injection by intravenous infusion over approximately 90 minutes via a central venous line. ( 2.1 ) Do NOT administer Posaconazole injection as intravenous bolus injection.
( 2.1 ) Table 1 : Recommended Dosage in Adult Patients Indication Dosage Form, Dose, and Duration of Therapy Treatment of invasive Aspergillosis Posaconazole Injection: Loading dose : 300 mg Posaconazole injection intravenously twice a day on the first day. Maintenance dose : 300 mg Posaconazole injection intravenously once a day thereafter. Recommended total duration of therapy is 6 to 12 weeks.
( 2.2 ) Prophylaxis of Posaconazole Injection: invasive Loading dose : 300 mg Posaconazole injection Aspergillus and intravenously twice a day on the first day. Candida Maintenance dose : 300 mg Posaconazole injection intravenously once a day thereafter infections Duration of therapy is based on recovery from neutropenia or immunosuppression. ( 2.2 , 2.3 ) For pediatric patients, see the Full Prescribing Information for dosing recommendations for Posaconazole injection , based on the age and indication associated with the dosage form.
( 1.1 , 1.2 , 2.1 , 2.3 )
2.1Important Administration Instructions Posaconazole 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 ( 2.4 )] . If a central venous catheter is not available, Posaconazole 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. Do NOT administer Posaconazole injection as an intravenous bolus injection.
2.2Dosing Regimen in Adult Patients Table 1: Dosing Regimens in Adult Patients Indication Dose and Frequency Duration of Therapy Treatment of invasive Aspergillosis Posaconazole Injection: Loading dose: 300 mg Posaconazole injection intravenously twice a day on the first day. Maintenance dose: 300 mg Posaconazole injection intravenously once a day, starting on the second day. Switching between the intravenous and delayed-release tablets is acceptable.
A loading dose is not required when switching between formulations. Loading dose: 1 day Maintenance dose: Recommended total duration of therapy is 6 to 12 weeks. Prophylaxis of invasive Aspergillus and Candida infections Posaconazole Injection: Loading dose : 300 mg Posaconazole injection intravenously twice a day on the first day.
Maintenance dose : 300 mg Posaconazole injection intravenously once a day thereafter. Loading dose: 1 day Maintenance dose: Duration of therapy is based on recovery from neutropenia or immunosuppression.
2.3Dosing Regimen in Pediatric Patients (ages 2 to less than 18 years of age) The recommended dosing regimen of Posaconazole for pediatric patients 2 to less than 18 years of age is shown in Table 2 [see Clinical Pharmacology ( 12.3 )]. Table 2: Posaconazole Injection Dosing Regimens for Pediatric Patients (ages 2 to less than 18 years of age) Recommended Pediatric Dosage and Formulation Indication Age Injection Duration of therapy Prophylaxis of invasive Aspergillus and Candida infections Less than or equal to 40 kg (2 to less than 18 years of age) Greater than 40 kg (2 to less than 18 years of age) Loading dose: 6 mg/kg up to a maximum of 300 mg twice daily on the first day Maintenance dose: 6 mg/kg up to a maximum of 300 mg once daily Duration of therapy is based on recovery from neutropenia or immunosuppression.
Treatment of invasive Aspergillosis 13 to less than 18 years of age regardless of weight. Loading dose :…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Posaconazole injection: 300 mg per vial (18 mg per mL) in a single dose vial ( 3 ) Posaconazole injection Posaconazole injection (300 mg per vial) is available as a clear, to yellow sterile liquid in a single-dose vial.
⛔ Contraindications ▾
4 CONTRAINDICATIONS Known hypersensitivity to posaconazole or other azole antifungal agents. ( 4.1 ) Coadministration of Posaconazole with the following drugs is contraindicated; Posaconazole increases concentrations and toxicities of: Sirolimus: ( 4.2 , 5.1 , 7.1 ) CYP3A4 substrates (pimozide, quinidine): can result in QTc interval prolongation and cases of torsades de pointes (TdP) ( 4.3 , 5.2 , 7.2 ) HMG-CoA Reductase Inhibitors Primarily Metabolized through CYP3A4 ( 4.4 , 7.3 ) Ergot alkaloids ( 4.5 , 7.4 ) Venetoclax: in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) at initiation and during the ramp of phase ( 4.6 , 5.10 , 7.16 )
4.1Hypersensitivity Posaconazole is contraindicated in persons with known hypersensitivity to posaconazole or other azole antifungal agents.
4.2Use with Sirolimus Posaconazole is contraindicated with sirolimus. Concomitant administration of Posaconazole with sirolimus increases the sirolimus blood concentrations by approximately 9-fold and can result in sirolimus toxicity [see Drug Interactions ( 7.1 ) and Clinical Pharmacology ( 12.3 )] .
4.3QT Prolongation with Concomitant Use with CYP3A4 Substrates Posaconazole is contraindicated with CYP3A4 substrates that prolong the QT interval. Concomitant administration of Posaconazole with the CYP3A4 substrates, pimozide and quinidine may result in increased plasma concentrations of these drugs, leading to QTc prolongation and cases of torsades de pointes [see Warnings and Precautions ( 5.2 ) and Drug Interactions ( 7.2 )] .
4.4HMG-CoA Reductase Inhibitors Primarily Metabolized Through CYP3A4 Coadministration with the HMG-CoA reductase inhibitors that are primarily metabolized through CYP3A4 (e.g., atorvastatin, lovastatin, and simvastatin) is contraindicated since increased plasma concentration of these drugs can lead to rhabdomyolysis [see Drug Interactions ( 7.3 ) and Clinical Pharmacology ( 12.3 )] .
4.5Use with Ergot Alkaloids Posaconazole may increase the plasma concentrations of ergot alkaloids (ergotamine and dihydroergotamine) which may lead to ergotism [see Drug Interactions ( 7.4 )] .
4.6Use with Venetoclax Coadministration of Posaconzole with venetoclax at initiation and during the ramp-up phase is contraindicated in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) due to the potential for increased risk of tumor lysis syndrome [see Warnings and Precautions ( 5.10 ) and Drug Interactions ( 7.16 )].
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Calcineurin-Inhibitor Toxicity : Posaconazole increases concentrations of cyclosporine or tacrolimus; reduce dose of cyclosporine and tacrolimus and monitor concentrations frequently. ( 5.1 ) Arrhythmias and QTc Prolongation : Posaconazole has been shown to prolong the QTc interval and cause cases of TdP. Administer with caution to patients with potentially proarrhythmic conditions.
Do not administer with drugs known to prolong QTc interval and metabolized through CYP3A4. ( 5.2 ) Electrolyte Disturbances : Monitor and correct, especially those involving potassium (K+), magnesium (Mg++), and calcium (Ca++), before and during Posaconazole therapy. ( 5.3 ) Hepatic Toxicity : Elevations in liver tests may occur.
Discontinuation should be considered in patients who develop abnormal liver tests or monitor liver tests during treatment. ( 5.4 ) Renal Impairment : Posaconazole injection should be avoided in patients with moderate or severe renal impairment (creatinine clearance <50 mL/min), unless an assessment of the benefit/risk to the patient justifies the use of Posaconazole injection. ( 5.5 , 8.6 ) Concomitant Use with Midazolam : Posaconazole can prolong hypnotic/sedative effects.
Monitor patients and benzodiazepine receptor antagonists should be available. ( 5.6 , 7.5 ) Vincristine Toxicity : Concomitant administration of azole antifungals, including Posaconazole , with vincristine has been associated with neurotoxicity and other serious adverse reactions; reserve azole antifungals, including Posaconazole, for patients receiving a vinca alkaloid, including vincristine, who have no alternative antifungal treatment options. ( 5.7 , 7.10 ) Venetoclax Toxicity : Concomitant administration of Posaconazole with venetoclax may increase venetoclax toxicities, including the risk of tumor lysis syndrome, neutropenia, and serious infections; monitor for toxicity and reduce venetoclax dose.
( 4.6 , 5.10 , 7.16 )
5.1Calcineurin-Inhibitor Toxicity Concomitant administration of Posaconazole with cyclosporine or tacrolimus increases the whole blood trough concentrations of these calcineurin-inhibitors [see Drug Interactions ( 7.1 ) and Clinical Pharmacology ( 12.3 )] . Nephrotoxicity and leukoencephalopathy (including deaths) have been reported in clinical efficacy studies in patients with elevated cyclosporine or tacrolimus concentrations. Frequent monitoring of tacrolimus or cyclosporine whole blood trough concentrations should be performed during and at discontinuation of Posaconazole treatment and the tacrolimus or cyclosporine dose adjusted accordingly.
5.2Arrhythmias and QT Prolongation Some azoles, including Posaconazole, have been associated with prolongation of the QT interval on the electrocardiogram. In addition, cases of torsades de pointes have been reported in patients taking Posaconazole. Results from a multiple time-matched ECG analysis in healthy volunteers did not show any increase in the mean of the QTc interval.
Multiple, time-matched ECGs collected over a 12-hour period were recorded at baseline and steady-state from 173 healthy male and female volunteers (18-85 years of age) administered Noxafil ® oral suspension 400 mg twice daily with a high-fat meal. In this pooled analysis, the mean QTc (Fridericia) interval change from baseline was –5 msec following administration of the recommended clinical dose. A decrease in the QTc(F) interval (–3 msec) was also observed in a small number of subjects (n=16) administered placebo.
The placebo-adjusted mean maximum QTc(F) interval change from baseline was <0 msec (–8 msec). No healthy subject administered Posaconazole had a QTc(F) interval ≥500 msec or an increase ≥60 msec in their QTc(F) interval from baseline. Posaconazole should be administered with caution to patients with potentially proarrhythmic conditions.
Do not administer with drugs that are known to prolong the QTc interval and are metabolized through CYP3A4 [see Contraindications ( 4.3 ) and D…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following serious and otherwise important adverse reactions are discussed in detail in another section of the labeling: Hypersensitivity [see Contraindications ( 4.1 )] Arrhythmias and QT Prolongation [see Warnings and Precautions ( 5.2 )] Hepatic Toxicity [see Warnings and Precautions ( 5.4 )] Adult Patients: Common adverse reactions in studies with Posaconazole in adults are diarrhea, nausea, fever, vomiting, headache, coughing, and hypokalemia. ( 6.1 ) Pediatric Patients: Common adverse reactions (incidence >20% receiving 6 mg/kg Posaconazole injection in a study in pediatric patients are pyrexia, febrile neutropenia, vomiting, mucosal inflammation, pruritus, hypertension, hypokalemia, and stomatitis.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of Posaconazole cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Clinical Trial Experience in Adults Clinical Trial Experience with Posaconazole Injection and Noxafil ® Delayed-Release Tablets for the Treatment of Invasive Aspergillosis The safety of Posaconazole injection and Noxafil ® delayed-release tablet was assessed in a randomized, double-blind, active-controlled clinical study of Posaconazole injection and Noxafil ® delayed-release tablets versus voriconazole for treatment of invasive aspergillosis (Aspergillosis Treatment Study).
A total of 575 (288 in Posaconazole arm, 287 in voriconazole arm) adult and pediatric patients 13 years of age and older with proven, probable or possible invasive aspergillosis were included. The median duration of treatment was 67 days for Posaconazole injection or Noxafil ® delayed-release tablet and 64 days for voriconazole, with 55% to 60% of subjects starting treatment with the IV formulation of either drug. The median duration of the first instance of IV treatment (before switching to oral treatment or discontinuing or completing study treatment) was 9 days for both groups.
Table 7 presents adverse reactions reported at an incidence of ≥10% in either one of the groups in Aspergillosis Treatment Study. Adverse reactions leading to treatment discontinuation were reported for 33.9% of subjects. The most commonly reported adverse reactions (>2% of subjects) leading to treatment discontinuation were septic shock, respiratory failure, and bronchopulmonary aspergillosis in the Posaconazole arm, and septic shock and acute myeloid leukemia in the voriconazole arm.
Table 7: Posaconazole Invasive Aspergillosis Treatment Study: Adverse Reactions in at Least 10% of Subjects Treated with Posaconazole Injection or Noxafil ® Delayed-Release Tablets System Organ Class Posaconazole injection or tablet (N = 288), n (%) Voriconazole injection or oral (N = 287), n (%) Blood and lymphatic system disorders Anemia 25 (8.7) 29 (10.1) Febrile neutropenia 42 (14.6) 38 (13.2) Gastrointestinal disorders Abdominal pain 29 (10.1) 24 (8.4) Constipation 32 (11.1) 23 (8.0) Diarrhea 52 (18.1) 52 (18.1) Nausea 65 (22.6) 51 (17.8) Vomiting 52 (18.1) 39 (13.6) General disorders and administration site conditions Edema peripheral 32 (11.1) 24 (8.4) Pyrexia 81 (28.1) 72 (25.1) Infections and infestations Pneumonia 36 (12.5) 26 (9.1) Investigations Alanine aminotransferase increased 42 (14.6) 37 (12.9) Aspartate aminotransferase increased 38 (13.2) 36 (12.5) Blood alkaline phosphatase increased 21 (7.3) 29 (10.1) Metabolism and nutrition disorders Hypokalemia 82 (28.5) 49 (17.1) Hypomagnesemia 29 (10.1) 18 (6.3) Nervous system disorders Headache 35 (12.2) 25 (8.7) Respiratory, thoracic and mediastinal disorders Cough 30 (10.4) 24 (8.4) Epistaxis 32 (11.1) 17 (5.9) The most frequently reported adverse reactions in the Posaconazole-t…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Posaconazole is primarily metabolized via UDP glucuronosyltransferase and is a substrate of p- glycoprotein (P-gp) efflux. Therefore, inhibitors or inducers of these clearance pathways may affect posaconazole plasma concentrations. Coadministration 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. Posaconazole is also a strong inhibitor of CYP3A4. Therefore, plasma concentrations of drugs predominantly metabolized by CYP3A4 may be increased by posaconazole [see Clinical Pharmacology ( 12.3 )] .
The following information was derived from data with Noxafil ® oral suspension or early tablet formulation unless otherwise noted. All drug interactions with Noxafil ® oral suspension, except for those that affect the absorption of posaconazole (via gastric pH and motility), are considered relevant to Posaconazole injection, Noxafil ® delayed-release tablet, and Noxafil ® PowderMix for delayed-release oral suspension as well. Interaction Drug Interaction Rifabutin, phenytoin, efavirenz Avoid coadministration unless the benefit outweighs the risks ( 7.6 , 7.7 , 7.8 ) Other drugs metabolized by CYP3A4 Consider dosage adjustment and monitor for adverse effects and toxicity ( 7.1 , 7.10 , 7.11 ) Digoxin Monitor digoxin plasma concentrations ( 7.12 ) Fosamprenavir Monitor for breakthrough fungal infections ( 7.6 )
7.1Immunosuppressants Metabolized by CYP3A4 Sirolimus: Concomitant administration of Posaconazole with sirolimus increases the sirolimus blood concentrations by approximately 9-fold and can result in sirolimus toxicity. Therefore, posaconazole is contraindicated with sirolimus [see Contraindications ( 4.2 ) and Clinical Pharmacology ( 12.3 )] . Tacrolimus: Posaconazole has been shown to significantly increase the Cmax and AUC of tacrolimus.
At initiation of posaconazole treatment, reduce the tacrolimus dose to approximately one-third of the original dose. Frequent monitoring of tacrolimus whole blood trough concentrations should be performed during and at discontinuation of Posaconazole treatment and the tacrolimus dose adjusted accordingly [see Warnings and Precautions ( 5.1 ) and Clinical Pharmacology ( 12.3 )] . Cyclosporine: Posaconazole has been shown to increase cyclosporine whole blood concentrations in heart transplant patients upon initiation of Posaconazole treatment.
It is recommended to reduce cyclosporine dose to approximately three-fourths of the original dose upon initiation of Posaconazole treatment. Frequent monitoring of cyclosporine whole blood trough concentrations should be performed during and at discontinuation of Posaconazole treatment and the cyclosporine dose adjusted accordingly [see Warnings and Precautions ( 5.1 ) and Clinical Pharmacology ( 12.3 )] .
7.2CYP3A4 Substrates Concomitant administration of Posaconazole with CYP3A4 substrates such as pimozide and quinidine may result in increased plasma concentrations of these drugs, leading to QTc prolongation and cases of torsades de pointes. Therefore, Posaconazole is contraindicated with these drugs [see Contraindications ( 4.3 ) and Warnings and Precautions ( 5.2 )] .
7.3HMG-CoA Reductase Inhibitors (Statins) Primarily Metabolized Through CYP3A4 Concomitant administration of Posaconazole with simvastatin increases the simvastatin plasma concentrations by approximately 10-fold. Therefore, Posaconazole is contraindicated with HMG-CoA reductase inhibitors primarily metabolized through CYP3A4 [see Contraindications ( 4.4 ) and Clinical Pharmacology ( 12.3 )] .
7.4Ergot Alkaloids Most of the ergot alkaloids are substrates of CYP3A4. Posaconazole may increase the plasma concentrations of ergot alkaloids (ergotamine and dihydroergotamine) which may lead to ergotism. Therefore, Posaconazole is contraindicated with ergot alkaloids [see Contraindications (…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data, may cause fetal harm. ( 8.1 ) Pediatrics: Safety and effectiveness in patients younger than 2 years of age have not been established. ( 8.4 ) Severe Renal Impairment: Monitor closely for breakthrough fungal infections. ( 8.6 )
8.1Pregnancy Risk Summary Based on findings from animal data, Posaconazole may cause fetal harm when administered to pregnant women. Available data for use of Posaconazole in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, skeletal malformations (cranial malformations and missing ribs) and maternal toxicity (reduced food consumption and reduced body weight gain) were observed when posaconazole was dosed orally to pregnant rats during organogenesis at doses ≥1.4 times the 400 mg twice daily oral suspension regimen based on steady-state plasma concentrations of Posaconazole in healthy volunteers.
In pregnant rabbits dosed orally during organogenesis, increased resorptions, reduced litter size, and reduced body weight gain of females were seen at doses 5 times the exposure achieved with the 400 mg twice daily oral suspension regimen. Doses of ≥ 3 times the clinical exposure caused an increase in resorptions in these rabbits (see Data ) . Based on animal data, advise pregnant women of the potential risk to a fetus.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data Animal Data Posaconazole resulted in maternal toxicity (reduced food consumption and reduced body weight gain) and skeletal malformations (cranial malformations and missing ribs) when given orally to pregnant rats during organogenesis (Gestational Days 6 through 15) at doses ≥27 mg/kg (≥1.4 times the 400 mg twice daily oral suspension regimen based on steady-state plasma concentrations of drug in healthy volunteers). The no-effect dose for malformations and maternal toxicity in rats was 9 mg/kg, which is 0.7 times the exposure achieved with the 400 mg twice daily oral suspension regimen.
No malformations were seen in rabbits dosed during organogenesis (Gestational Days 7 through 19) at doses up to 80 mg/kg (5 times the exposure achieved with the 400 mg twice daily oral suspension regimen). In the rabbit, the no-effect dose was 20 mg/kg, while high doses of 40 mg/kg and 80 mg/kg (3 or 5 times the clinical exposure) caused an increase in resorptions. In rabbits dosed at 80 mg/kg, a reduction in body weight gain of females and a reduction in litter size were seen.
8.2Lactation Risk Summary There are no data on the presence of posaconazole in human milk, the effects on the breastfed infant, or the effects on milk production. Posaconazole is excreted in the milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk.
The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Posaconazole and any potential adverse effects on the breastfed child from Posaconazole or from the underlying maternal condition.
8.4Pediatric Use The safety and effectiveness of Posaconazole injection for the prophylaxis of invasive Aspergillus and Candida infections have been established in pediatric patients aged 2 and older who are at high risk of developing these infections due to being severely immunocompromised, such as HSCT recipients with GVHD or those with hematologic malignancies with prolonged neutropenia from chemotherapy. The safety and effectiveness of Posaconazole injection for the treatment of invasive aspergillosis have been establ…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Based on findings from animal data, Posaconazole may cause fetal harm when administered to pregnant women. Available data for use of Posaconazole in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, skeletal malformations (cranial malformations and missing ribs) and maternal toxicity (reduced food consumption and reduced body weight gain) were observed when posaconazole was dosed orally to pregnant rats during organogenesis at doses ≥1.4 times the 400 mg twice daily oral suspension regimen based on steady-state plasma concentrations of Posaconazole in healthy volunteers.
In pregnant rabbits dosed orally during organogenesis, increased resorptions, reduced litter size, and reduced body weight gain of females were seen at doses 5 times the exposure achieved with the 400 mg twice daily oral suspension regimen. Doses of ≥ 3 times the clinical exposure caused an increase in resorptions in these rabbits (see Data ) . Based on animal data, advise pregnant women of the potential risk to a fetus.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data Animal Data Posaconazole resulted in maternal toxicity (reduced food consumption and reduced body weight gain) and skeletal malformations (cranial malformations and missing ribs) when given orally to pregnant rats during organogenesis (Gestational Days 6 through 15) at doses ≥27 mg/kg (≥1.4 times the 400 mg twice daily oral suspension regimen based on steady-state plasma concentrations of drug in healthy volunteers). The no-effect dose for malformations and maternal toxicity in rats was 9 mg/kg, which is 0.7 times the exposure achieved with the 400 mg twice daily oral suspension regimen.
No malformations were seen in rabbits dosed during organogenesis (Gestational Days 7 through 19) at doses up to 80 mg/kg (5 times the exposure achieved with the 400 mg twice daily oral suspension regimen). In the rabbit, the no-effect dose was 20 mg/kg, while high doses of 40 mg/kg and 80 mg/kg (3 or 5 times the clinical exposure) caused an increase in resorptions. In rabbits dosed at 80 mg/kg, a reduction in body weight gain of females and a reduction in litter size were seen.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of Posaconazole injection for the prophylaxis of invasive Aspergillus and Candida infections have been established in pediatric patients aged 2 and older who are at high risk of developing these infections due to being severely immunocompromised, such as HSCT recipients with GVHD or those with hematologic malignancies with prolonged neutropenia from chemotherapy. The safety and effectiveness of Posaconazole injection for the treatment of invasive aspergillosis have been established in pediatric patients aged 13 years and older.
Use of Posaconazole in these age groups is supported by evidence from adequate and well-controlled studies of Posaconazole in adult and pediatric patients and additional pharmacokinetic and safety data in pediatric patients 2 years of age and older [see Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.3 ) and Clinical Studies ( 14 )] . The safety and effectiveness of Posaconazole have not been established in pediatric patients younger than 2 years of age.
🧓 Geriatric Use ▾
8.5Geriatric Use No overall differences in the safety of Posaconazole injection were observed between geriatric patients and younger adult patients in the clinical trials; therefore, no dosage adjustment is recommended for any formulation of Posaconazole in geriatric patients. No clinically meaningful differences in the pharmacokinetics of Posaconazole were observed in geriatric patients compared to younger adult patients during clinical trials [see Clinical Pharmacology ( 12.3 )] . Of the 279 patients treated with Posaconazole injection in the Posaconazole Injection Study, 52 (19%) were greater than 65 years of age.
Of the 230 patients treated with Noxafil ® delayed-release tablets , 38 (17%) were greater than 65 years of age. Of the 288 patients randomized to Posaconazole injection/ Noxafil ® delayed-release tablets in the Aspergillosis Treatment Study, 85 (29%) were ≥65 years of age. No overall differences in the pharmacokinetics and safety were observed between elderly and young subjects during clinical trials, but greater sensitivity of some older individuals cannot be ruled out.
🆘 Overdosage ▾
10 OVERDOSAGE There is no experience with overdosage of Posaconazole injection. During the clinical trials, some patients received Noxafil ® 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 twice daily Noxafil ® oral suspension for 3 days.
No related adverse reactions were noted by the investigator. Posaconazole is not removed by hemodialysis.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Posaconazole is an azole antifungal agent [see Clinical Pharmacology ( 12.4 )] .
12.2Pharmacodynamics Exposure Response Relationship Prophylaxis: In clinical studies of neutropenic patients who were receiving cytotoxic chemotherapy for acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS) or hematopoietic stem cell transplant (HSCT) recipients with Graft versus Host Disease (GVHD), a wide range of plasma exposures to posaconazole was noted following administration of Noxafil ® oral suspension. A pharmacokinetic-pharmacodynamic analysis of patient data revealed an apparent association between average posaconazole concentrations (Cavg) and prophylactic efficacy ( Table 17 ).
A lower Cavg may be associated with an increased risk of treatment failure, defined as treatment discontinuation, use of empiric systemic antifungal therapy (SAF), or occurrence of breakthrough invasive fungal infections. Table 17: Noxafil ® Oral Suspension Exposure Analysis (Cavg) in Prophylaxis Trials Cavg = the average posaconazole concentration when measured at steady state * Neutropenic patients who were receiving cytotoxic chemotherapy for AML or MDS † HSCT recipients with GVHD ‡ Defined as treatment discontinuation, use of empiric systemic antifungal therapy (SAF), or occurrence of breakthrough invasive fungal infections Prophylaxis in AML/MDS* Prophylaxis in GVHD † Cavg Range (ng/mL) Treatment Failure ‡ (%) Cavg Range (ng/mL) Treatment Failure ‡ (%) Quartile 1 90-322 54.7 22-557
44.4Quartile 2 322-490 37.0 557-915
20.6Quartile 3 490-734 46.8 915-1563
17.5Quartile 4 734-2200 27.8 1563-3650
17.5Exposure Response Relationship Treatment of Invasive Aspergillosis: Across a range of posaconazole plasma minimum concentrations (Cmin, range: 244 to 5663 ng/mL) following administration of Posaconazole injection and Noxafil ® delayed-release tablets in patients treated for invasive aspergillosis in Aspergillosis Treatment Study, there was no association between posaconazole Cmin and treatment efficacy [see Clinical Pharmacology ( 12.3 ) and Clinical Studies ( 14.1 )] . Similarly, across a range of population pharmacokinetic model-predicted steady-state plasma average concentrations (Cavg, range: 589 to 6315 ng/mL), there was no association between posaconazole Cavg and treatment efficacy.
12.3Pharmacokinetics General Pharmacokinetic Characteristics Posaconazole Injection Posaconazole injection exhibits dose proportional pharmacokinetics after single doses between 200 and 300 mg in healthy volunteers and patients. The mean pharmacokinetic parameters after single doses with Posaconazole injection in healthy volunteers and patients are shown in Table 18 . Table 18: Summary of Mean Pharmacokinetic Parameters (%CV) in Healthy Volunteers (30-minute infusion via peripheral venous line) and Patients (90 minute infusion via central venous line) after Dosing with Posaconazole Injection on Day 1 AUC 0-∞ = Area under the plasma concentration-time curve from time zero to infinity; AUC 0-12 = Area under the plasma concentration- time curve from time zero to 12 hr after the first dose on Day 1; C max = maximum observed concentration; t ½ = terminal phase half- life; CL = total body clearance; N/D = Not Determined Dose (mg) n AUC 0-∞ (ng·hr/mL) AUC 0-12 (ng·hr/mL) C max (ng/mL) t 1/2 (hr) CL (L/hr) Healthy Volunteers 200 9 35400 (50) 8840 (20) 2250 (29) 23.6 (23) 6.5 (32) 300 9 46400 (26) 13000 (13) 2840 (30) 24.6 (20) 6.9 (27) Patients 200 30 N/D 5570 (32) 954 (44) N/D N/D 300 22 N/D 8240 (26) 1590 (62) N/D N/D Table 19 displays the pharmacokinetic parameters of posaconazole in patients following administration of Posaconazole injection 300 mg taken once a day for 10 or 14 days following twice daily dosing on Day 1.
Table 19: Arithmetic Mean (%CV) of PK Parameters in Serial PK-Evaluable Patients Following Dosing of Posaconazole Injection (300 mg)* AUC 0-24 = area under the concentration-time curve over the…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Posaconazole is an azole antifungal agent [see Clinical Pharmacology ( 12.4 )] .
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied Injection Posaconazole Injection is available in Type I glass vials closed with chlorobutyl rubber stopper and aluminum seal. Product Code Unit of Sale Strength Each 685017 NDC 63323-685-17 Individually packaged 300 mg per 16.7 mL of solution (18 mg of Posaconazole per mL) 300 mg per 16.7 mL (18 mg per mL) Single-Dose Vial
16.2Storage and Handling Posaconazole Injection Posaconazole injection vial should be stored refrigerated at 2° to 8°C (36° to 46°F). Storage conditions for the diluted solution are presented in another section of the prescribing information [see Dosage and Administration ( 2.4 )] .
16.1How Supplied Injection Posaconazole Injection is available in Type I glass vials closed with chlorobutyl rubber stopper and aluminum seal. Product Code Unit of Sale Strength Each 685017 NDC 63323-685-17 Individually packaged 300 mg per 16.7 mL of solution (18 mg of Posaconazole per mL) 300 mg per 16.7 mL (18 mg per mL) Single-Dose Vial
📦 Storage and Handling ▾
16.2Storage and Handling Posaconazole Injection Posaconazole injection vial should be stored refrigerated at 2° to 8°C (36° to 46°F). Storage conditions for the diluted solution are presented in another section of the prescribing information [see Dosage and Administration ( 2.4 )] .
📋 Description ▾
11 DESCRIPTION Posaconazole is an azole antifungal agent. Posaconazole is available as injection solution to be diluted before intravenous administration. Posaconazole is designated chemically as 4-[4-[4-[4-[[ (3 R ,5 R )-5- (2,4-difluorophenyl)tetrahydro-5• (1 H -1,2,4-triazol-1-ylmethyl)-3-furanyl]methoxy]phenyl]-1-piperazinyl]phenyl]-2-[(1 S ,2 S )-1-ethyl-2• hydroxypropyl]-2,4-dihydro-3 H -1,2,4-triazol-3-one with an empirical formula of C 37 H 42 F 2 N 8 O 4 and a molecular weight of 700.8.
The chemical structure is: Posaconazole is a white powder with a low aqueous solubility. Posaconazole 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.
Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). 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.
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