Noxafil (Posaconazole)
Triazole Antifungal Agent
⚡ Quick Facts
Key Takeaways
- Noxafil (posaconazole) is a broad-spectrum triazole antifungal with activity against Aspergillus, Candida, Fusarium, Zygomycetes, and other molds, offering one of the widest antifungal spectrums available.
- It is approved for both prophylaxis of invasive fungal infections in high-risk immunocompromised patients and as salvage therapy for serious infections that have not responded to other antifungals.
- Gastro-resistant tablets provide significantly better and more predictable absorption compared to the oral suspension and should be the preferred formulation when available.
- Posaconazole is a potent CYP3A4 inhibitor with numerous significant drug interactions; always inform your doctor about all medications you are taking before starting treatment.
- Liver function tests should be monitored at the start of and during treatment, as hepatotoxicity including rare cases of hepatic failure has been reported.
What Is Noxafil and What Is It Used For?
Quick answer: Noxafil (posaconazole) is a triazole antifungal medicine that works by blocking the production of ergosterol, a vital part of fungal cell membranes. It is used to prevent and treat serious fungal infections in patients with weakened immune systems.
Posaconazole is a second-generation triazole antifungal agent that was first approved by the European Medicines Agency (EMA) in 2005 and by the U.S. Food and Drug Administration (FDA) in 2006. It belongs to the same drug class as fluconazole, itraconazole, and voriconazole, but is distinguished by its exceptionally broad spectrum of antifungal activity. Posaconazole is effective against a wider range of fungal pathogens than many other triazoles, including species of Aspergillus, Candida, Coccidioides, Fonsecaea, Fusarium, and certain Zygomycetes (Mucorales), which are notoriously difficult to treat.
The mechanism of action of posaconazole involves the inhibition of the enzyme lanosterol 14-alpha-demethylase (also known as CYP51), which is a critical enzyme in the fungal ergosterol biosynthesis pathway. Ergosterol is an essential structural component of the fungal cell membrane, analogous to cholesterol in human cells. By blocking the production of ergosterol, posaconazole causes the accumulation of toxic methylated sterol precursors within the fungal cell, disrupting membrane integrity and function. This leads to increased membrane permeability, leakage of cellular contents, and ultimately fungal cell death. Because human cells use cholesterol rather than ergosterol, posaconazole has selective toxicity for fungal organisms, although some cross-reactivity with human enzymes contributes to its side effect profile.
Noxafil is authorized for several clinical indications. As a prophylactic agent, it is used to prevent invasive fungal infections in patients who are at high risk due to severe immunosuppression. This includes patients undergoing remission-induction chemotherapy for acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) who are expected to develop prolonged neutropenia, and patients receiving high-dose immunosuppressive therapy following hematopoietic stem cell transplantation (HSCT), particularly those with graft-versus-host disease (GVHD). Landmark clinical trials published in the New England Journal of Medicine in 2007 demonstrated that posaconazole was superior to both fluconazole and itraconazole for antifungal prophylaxis in these populations, significantly reducing the incidence of invasive aspergillosis and improving overall survival.
As a therapeutic agent, Noxafil is indicated for the treatment of several invasive fungal infections in adult patients who are refractory to, or intolerant of, first-line antifungal therapy. These include invasive aspergillosis (in patients unresponsive to amphotericin B or itraconazole), fusariosis (in patients unresponsive to amphotericin B), chromoblastomycosis and mycetoma (in patients unresponsive to itraconazole), and coccidioidomycosis (in patients unresponsive to amphotericin B, itraconazole, or fluconazole). These treatment indications are classified as salvage therapy, meaning posaconazole is reserved for patients who have failed or cannot tolerate other antifungal treatments. The gastro-resistant tablet formulation has also been approved for use in children aged 2 years and older, expanding its availability to the pediatric population.
Noxafil is available in two oral formulations: gastro-resistant tablets containing 100 mg of posaconazole, and a powder for oral suspension containing 300 mg of posaconazole per sachet (to be reconstituted with water). The gastro-resistant tablet formulation, introduced after the original oral suspension, provides significantly improved and more predictable bioavailability compared to the oral suspension. The tablets are not affected by food intake or gastric pH to the same extent as the suspension, making them the preferred oral formulation in clinical practice. A concentrate for solution for intravenous infusion is also available for patients who cannot take oral medication, though this article focuses on the oral formulations.
What Should You Know Before Taking Noxafil?
Quick answer: Before taking Noxafil, inform your doctor about all medications you use, any liver or heart conditions, and whether you are pregnant or breastfeeding. Several medications are strictly contraindicated with posaconazole due to the risk of life-threatening interactions.
Contraindications
Noxafil must not be taken if you are allergic to posaconazole or to any of the other ingredients in the medicine. Additionally, posaconazole is strictly contraindicated in combination with a number of other medications due to the risk of serious, potentially life-threatening adverse effects. Posaconazole is a potent inhibitor of the cytochrome P450 3A4 (CYP3A4) enzyme, which means it can dramatically increase the blood levels of drugs metabolized by this pathway.
The following medications must not be taken together with Noxafil:
- Terfenadine and astemizole (antihistamines) – increased plasma levels may cause QTc prolongation and potentially fatal cardiac arrhythmias including torsades de pointes.
- Cisapride (gastrointestinal motility agent) – increased levels may cause QTc prolongation and serious cardiac arrhythmias.
- Pimozide (antipsychotic) – increased levels may cause QTc prolongation and cardiac arrhythmias.
- Halofantrin (antimalarial) – increased levels may cause QTc prolongation and cardiac arrhythmias.
- Quinidine (antiarrhythmic) – increased levels may cause QTc prolongation and torsades de pointes.
- Ergot alkaloids (ergotamine, dihydroergotamine) – increased levels may cause ergotism (vasospasm, ischemia of the extremities).
- Simvastatin, atorvastatin, and lovastatin (HMG-CoA reductase inhibitors) – increased statin levels raise the risk of rhabdomyolysis, a potentially fatal breakdown of muscle tissue.
- Venetoclax (cancer medicine) – during the dose ramp-up phase for chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), co-administration is contraindicated due to risk of tumor lysis syndrome.
Warnings and Precautions
Before starting treatment with Noxafil, it is essential that your doctor is fully aware of your medical history. Special caution is required in the following situations:
Liver problems: Posaconazole is primarily metabolized and eliminated through the liver. Cases of serious hepatic reactions have been reported during treatment, including rare instances of hepatic failure leading to death. These have occurred predominantly in patients with serious underlying medical conditions such as hematological malignancies. Your doctor should perform liver function tests (including bilirubin, AST, ALT, and alkaline phosphatase) before starting treatment and at regular intervals during therapy. If liver function test results become significantly abnormal during treatment, your doctor will carefully assess whether the benefits of continuing posaconazole outweigh the risks of liver damage. Treatment may need to be discontinued if clinical signs of liver disease develop.
Heart conditions and QTc prolongation: Posaconazole should be used with caution in patients with pre-existing heart conditions that predispose to arrhythmias, such as congenital or acquired QTc prolongation, cardiomyopathy (particularly when accompanied by heart failure), sinus bradycardia, symptomatic arrhythmias, or any condition associated with clinically significant cardiac events. Electrolyte disturbances, especially involving potassium, magnesium, or calcium, should be corrected before initiating treatment, as these can increase the risk of QTc prolongation and dangerous arrhythmias.
Diarrhea or vomiting: Gastrointestinal disturbances such as severe diarrhea or vomiting may reduce absorption of posaconazole, particularly with the oral suspension formulation. If you experience significant gastrointestinal symptoms, your doctor may want to monitor your posaconazole blood levels more closely. The gastro-resistant tablet formulation generally provides better absorption even in the presence of gastrointestinal disturbances, but monitoring remains important.
Sun sensitivity: Posaconazole may increase your sensitivity to sunlight and ultraviolet radiation. You should minimize exposure to direct sunlight, avoid tanning beds, and use appropriate sun protection (high SPF sunscreen, protective clothing) during treatment. Contact your doctor if you develop skin reactions such as rash or sunburn-like symptoms.
Pregnancy and Breastfeeding
Noxafil should not be used during pregnancy unless the potential benefit to the mother clearly outweighs the possible risk to the unborn child. Animal studies have demonstrated reproductive toxicity, including skeletal malformations in offspring. There are no adequate and well-controlled studies of posaconazole in pregnant women. Women of childbearing potential must use effective contraception during treatment with posaconazole. If you become pregnant while taking Noxafil, contact your doctor immediately.
It is not known whether posaconazole passes into human breast milk, although animal studies have shown excretion into milk. As a precaution, breastfeeding should be discontinued when treatment with Noxafil begins. The decision to either discontinue breastfeeding or discontinue posaconazole therapy should be made in consultation with your doctor, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the mother.
Driving and Operating Machinery
Noxafil may cause side effects such as dizziness, somnolence (sleepiness), and visual disturbances, which could affect your ability to drive or operate machinery safely. If you experience any of these effects, you should refrain from driving or using machines until the symptoms resolve. It is advisable to assess your individual response to posaconazole before undertaking activities that require alertness and coordination.
How Does Noxafil Interact with Other Drugs?
Quick answer: Noxafil (posaconazole) is a potent inhibitor of the CYP3A4 enzyme and has numerous significant drug interactions. Some combinations are strictly contraindicated, while others require dose adjustments or close monitoring.
Posaconazole is primarily metabolized via UDP-glucuronidation (phase II enzymes) and is a substrate of P-glycoprotein efflux. Importantly, it is a potent inhibitor of CYP3A4, which is the most abundant cytochrome P450 enzyme in the human body and is responsible for the metabolism of approximately 50% of all clinically used drugs. This CYP3A4 inhibitory activity is the basis for the majority of posaconazole's clinically significant drug interactions. When posaconazole inhibits CYP3A4, the blood levels of drugs metabolized by this enzyme can increase substantially, potentially leading to increased toxicity.
Major Interactions (Contraindicated)
The following combinations are strictly contraindicated and must never be used together with Noxafil:
| Drug | Interaction Type | Clinical Effect |
|---|---|---|
| Terfenadine | CYP3A4 substrate – increased levels | QTc prolongation, risk of torsades de pointes and sudden cardiac death |
| Astemizole | CYP3A4 substrate – increased levels | QTc prolongation, risk of torsades de pointes and sudden cardiac death |
| Cisapride | CYP3A4 substrate – increased levels | QTc prolongation, risk of serious ventricular arrhythmias |
| Pimozide | CYP3A4 substrate – increased levels | QTc prolongation, risk of cardiac arrhythmias |
| Halofantrin | CYP3A4 substrate – increased levels | QTc prolongation, risk of fatal arrhythmias |
| Quinidine | CYP3A4 substrate – increased levels | QTc prolongation, torsades de pointes |
| Ergotamine / Dihydroergotamine | CYP3A4 substrate – increased levels | Ergotism: severe vasospasm, peripheral ischemia, gangrene |
| Simvastatin / Lovastatin / Atorvastatin | CYP3A4 substrate – increased levels | Rhabdomyolysis: life-threatening muscle breakdown, renal failure |
| Venetoclax (during CLL dose ramp-up) | CYP3A4 substrate – markedly increased levels | Tumor lysis syndrome: metabolic emergency, renal failure, cardiac arrest |
Drugs That Reduce Noxafil Effectiveness
Several medications can reduce the plasma concentration of posaconazole by inducing enzymes or affecting absorption, potentially leading to treatment failure. Co-administration with potent enzyme inducers should be avoided unless the benefit clearly outweighs the risk of reduced antifungal efficacy:
- Rifabutin – reduces posaconazole plasma levels while posaconazole increases rifabutin levels; avoid co-administration if possible. If combination is necessary, monitor for both reduced antifungal efficacy and rifabutin toxicity (uveitis, leukopenia).
- Rifampicin – a potent CYP inducer that can dramatically reduce posaconazole plasma concentrations. Co-administration should be avoided.
- Phenytoin – reduces posaconazole levels while posaconazole increases phenytoin levels. If co-administration is unavoidable, monitor phenytoin levels and posaconazole therapeutic drug monitoring is recommended.
- Carbamazepine – enzyme inducer that may significantly reduce posaconazole concentrations. Avoid concurrent use.
- Phenobarbital – potent enzyme inducer that decreases posaconazole exposure. Avoid use together.
- Efavirenz – reduces posaconazole levels substantially. Alternative antiretroviral agents should be considered.
- Fosamprenavir – decreases posaconazole concentrations. Therapeutic drug monitoring recommended if the combination cannot be avoided.
- Flucloxacillin – may reduce posaconazole levels through enzyme induction. Monitor posaconazole levels if used concomitantly.
Drugs Whose Levels May Be Increased by Noxafil
Because posaconazole is a potent CYP3A4 inhibitor, it can significantly increase the plasma concentrations of many drugs metabolized by this enzyme. The following medications require dose adjustments or enhanced monitoring when co-administered with Noxafil:
- Vincristine and vinblastine – posaconazole may increase vinca alkaloid levels, leading to increased risk of neurotoxicity (peripheral neuropathy, seizures, paralytic ileus). Dose reduction of the vinca alkaloid should be considered.
- Ciclosporin – posaconazole increases ciclosporin whole blood trough concentrations. The ciclosporin dose should be reduced (typically to about 75% of the original dose) at initiation of posaconazole, with frequent therapeutic drug monitoring and dose adjustments as needed.
- Tacrolimus – posaconazole increases tacrolimus trough concentrations by approximately 121%. The tacrolimus dose should be reduced (typically to about one-third of the original dose) at initiation of posaconazole therapy, with close therapeutic drug monitoring.
- Sirolimus – co-administration is generally not recommended as posaconazole can increase sirolimus blood levels by up to 9-fold. If the combination is unavoidable, sirolimus dose must be dramatically reduced with intensive monitoring.
- Midazolam and other benzodiazepines – posaconazole can increase midazolam levels approximately 5-fold. Dose reduction and careful monitoring for excessive sedation and respiratory depression are required. Consideration of alternative sedative agents is advised.
- Calcium channel blockers (felodipine, nifedipine, verapamil, diltiazem) – increased levels may cause hypotension, edema, and other cardiovascular effects. Dose adjustment and frequent monitoring of blood pressure and heart rate are recommended.
- Digoxin – posaconazole may increase digoxin levels through inhibition of P-glycoprotein. Monitoring of digoxin serum concentrations is advised.
- Sulfonylureas (glipizide, glyburide) – increased levels may cause hypoglycemia. Blood glucose monitoring should be intensified, and the sulfonylurea dose may need to be reduced.
What Is the Correct Dosage of Noxafil?
Quick answer: For adults using gastro-resistant tablets, the standard dose is 300 mg (three 100 mg tablets) twice on the first day (loading dose), followed by 300 mg once daily thereafter. Dosing for children is based on body weight.
Noxafil should always be taken as prescribed by your doctor. The correct dosage depends on your age, body weight, the formulation used, and the condition being treated or prevented. Do not change your dose or stop taking posaconazole without consulting your doctor, as inadequate dosing may lead to subtherapeutic drug levels and treatment failure.
Adults – Gastro-resistant Tablets
Loading Dose (Day 1)
300 mg (three 100 mg tablets) taken twice on the first day, approximately 12 hours apart. Take with or without food. Tablets should be swallowed whole with water – do not crush, chew, or break the tablets, as this will destroy the gastro-resistant coating and may alter absorption and tolerability.
Maintenance Dose (Day 2 onwards)
300 mg (three 100 mg tablets) taken once daily. Continue treatment for the duration prescribed by your doctor. For prophylaxis, treatment is typically continued throughout the period of immunosuppression (i.e., during neutropenia or immunosuppressive therapy for GVHD). For treatment of invasive fungal infections, the duration depends on clinical response and microbiological recovery.
Adults – Oral Suspension
For prophylaxis of invasive fungal infections, the recommended dose of the oral suspension is 200 mg (5 mL) taken three times daily. Each dose should ideally be taken during or immediately after a full meal or a nutritional supplement to enhance absorption. If the patient is unable to eat, consider using the gastro-resistant tablets or intravenous formulation instead, as the oral suspension has significantly reduced bioavailability in the fasted state.
For treatment of invasive fungal infections (salvage therapy), the oral suspension dose is 200 mg (5 mL) taken four times daily for patients who can eat a full meal or nutritional supplement with each dose. Alternatively, 400 mg (10 mL) twice daily may be used for patients who cannot tolerate food, although absorption will be reduced.
Children (2 to 17 years) – Gastro-resistant Tablets
The dosage for children aged 2 years and older is based on body weight. The gastro-resistant tablets are the preferred formulation for pediatric use when the child is able to swallow tablets whole. The following weight-based dosing applies for prophylaxis of invasive fungal infections:
| Body Weight | Loading Dose (Day 1) | Maintenance Dose (Day 2+) |
|---|---|---|
| 14 kg to <20 kg | 100 mg (1 tablet) twice on Day 1 | 100 mg (1 tablet) once daily |
| 20 kg to <30 kg | 200 mg (2 tablets) twice on Day 1 | 100 mg (1 tablet) once daily |
| 30 kg to <40 kg | 200 mg (2 tablets) twice on Day 1 | 200 mg (2 tablets) once daily |
| ≥40 kg | 300 mg (3 tablets) twice on Day 1 | 300 mg (3 tablets) once daily |
Children – Powder for Oral Suspension
The powder for oral suspension (300 mg per sachet) is available for children who cannot swallow tablets. Each sachet is reconstituted with water to form an oral suspension. Dosing is based on body weight:
| Body Weight | Dose | Volume of Reconstituted Suspension |
|---|---|---|
| 14 kg to <20 kg | 120 mg once daily (after loading) | 4.8 mL once daily |
| 20 kg to <30 kg | 160 mg once daily (after loading) | 6.4 mL once daily |
| 30 kg to <40 kg | 220 mg once daily (after loading) | 8.8 mL once daily |
| ≥40 kg | 300 mg once daily (after loading) | 12 mL once daily |
Pediatric dosing should always be determined and supervised by a physician experienced in the management of fungal infections in children. Loading doses on Day 1 are typically twice the maintenance dose given twice that day. Therapeutic drug monitoring (measurement of posaconazole blood levels) may be recommended, particularly in children, to ensure adequate drug exposure.
Missed Dose
If you forget to take a dose of Noxafil, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to compensate for a forgotten dose. If you are unsure about what to do after missing a dose, contact your doctor or pharmacist for advice. Maintaining consistent posaconazole blood levels is important for effective prophylaxis and treatment of fungal infections.
Overdose
If you take more Noxafil than prescribed, or if someone else accidentally takes your medicine, seek immediate medical attention or contact your local poison control center. There is no specific antidote for posaconazole overdose. Treatment is supportive and symptomatic. Posaconazole is not removed by hemodialysis, so dialysis will not be effective in removing the drug from the body. In clinical studies, posaconazole plasma concentrations have not been shown to increase beyond a ceiling level with doses above the recommended range, but overdose-related toxicities may still occur.
What Are the Side Effects of Noxafil?
Quick answer: Common side effects of Noxafil include nausea, vomiting, diarrhea, headache, and changes in blood test results (especially liver enzymes and electrolyte levels). Serious but less common side effects include liver damage, QTc prolongation, and severe allergic reactions.
Like all medicines, Noxafil can cause side effects, although not everybody gets them. Some side effects may be serious and require immediate medical attention. The side effects are categorized below by frequency according to standard medical convention. Tell your doctor immediately if you notice any side effects, particularly those listed under serious side effects.
Common Side Effects
- Headache
- Nausea
- Vomiting
- Diarrhea
- Abdominal pain
- Rash
- Fatigue and weakness
- Dizziness
- Changes in electrolyte levels (low potassium, low magnesium)
- Neutropenia (low white blood cell count)
- Fever (pyrexia)
- Elevated liver enzymes (ALT, AST, bilirubin, alkaline phosphatase)
- Decreased appetite
- Taste disturbance (dysgeusia)
- Flatulence
- Dry mouth
Uncommon Side Effects
- Anemia (low red blood cell count)
- Thrombocytopenia (low platelet count)
- Pancreatitis (inflammation of the pancreas)
- QTc prolongation on ECG
- Seizures (convulsions)
- Peripheral neuropathy (numbness, tingling in hands and feet)
- Visual disturbances (blurred vision, photophobia)
- Hair loss (alopecia)
- Renal impairment (increased creatinine, proteinuria)
- Hepatitis (inflammation of the liver)
- Jaundice (yellowing of skin and eyes)
- Hypertension (high blood pressure)
- Tremor
- Somnolence (excessive sleepiness)
- Musculoskeletal pain
Rare Side Effects
- Pulmonary hypertension (elevated pressure in lung blood vessels)
- Hemolytic uremic syndrome (HUS)
- Thrombotic thrombocytopenic purpura (TTP)
- Heart failure
- Cerebrovascular accident (stroke)
- Deep vein thrombosis (DVT)
- Pulmonary embolism (PE)
- Adrenal insufficiency
- Pseudoaldosteronism (mineralocorticoid excess)
- Hepatic failure
- Hepatic necrosis
- Stevens-Johnson syndrome (severe skin reaction)
Contact your doctor immediately or go to the nearest emergency department if you experience any of the following serious symptoms while taking Noxafil:
- Signs of liver problems: persistent nausea, vomiting, loss of appetite, stomach pain, yellowing of the skin or eyes (jaundice), unusually dark urine, or pale stools.
- Signs of severe allergic reaction (anaphylaxis): swelling of the face, lips, tongue or throat, difficulty breathing or swallowing, hives, rapid heartbeat, or sudden drop in blood pressure.
- Signs of heart rhythm problems: unusually fast, slow, or irregular heartbeat, fainting or near-fainting episodes, dizziness, or chest pain.
- Signs of severe skin reactions: widespread rash with blistering or peeling, especially involving the mouth, eyes, or genitals.
- Signs of adrenal insufficiency: extreme fatigue, muscle weakness, weight loss, dizziness on standing, darkening of the skin.
How Should You Store Noxafil?
Quick answer: Store Noxafil gastro-resistant tablets at room temperature (below 30°C) in the original packaging. No special storage conditions are required for the tablets, but the oral suspension should be used within a specified period after reconstitution.
Noxafil gastro-resistant tablets do not require any special storage conditions. Store the tablets in the original blister packaging to protect them from moisture. Keep the medicine at room temperature, typically below 30°C (86°F), and away from excessive heat or direct sunlight. Do not store the tablets in the bathroom or other damp environments, as humidity may affect the gastro-resistant coating.
The powder for oral suspension should be stored in its original sachet until ready for use. Once reconstituted with water according to the instructions, the suspension should be used within the timeframe specified in the patient information leaflet (typically within 30 minutes). Any unused reconstituted suspension should be discarded – do not save it for later use.
Keep Noxafil out of the sight and reach of children. Do not use this medicine after the expiry date stated on the packaging (the expiry date refers to the last day of that month). Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. These measures will help protect the environment and prevent accidental ingestion by children, pets, or others.
What Does Noxafil Contain?
Quick answer: Each Noxafil gastro-resistant tablet contains 100 mg of the active substance posaconazole. Each sachet of powder for oral suspension contains 300 mg of posaconazole. The tablets contain several excipients including hypromellose acetate succinate and microcrystalline cellulose.
Gastro-resistant Tablets (100 mg)
Each gastro-resistant tablet contains 100 mg of posaconazole as the active ingredient. The tablets also contain the following excipients (inactive ingredients):
- Tablet core: Hypromellose acetate succinate, microcrystalline cellulose, hydroxypropylcellulose (low substituted), silica colloidal anhydrous, croscarmellose sodium, magnesium stearate
- Tablet coating: Poly(vinyl alcohol), macrogol 3350, titanium dioxide (E171), talc, iron oxide yellow (E172)
The gastro-resistant coating is designed to prevent the tablet from dissolving in the acidic environment of the stomach. Instead, the tablet passes intact through the stomach and dissolves in the higher pH environment of the small intestine, where posaconazole is efficiently absorbed. This is why it is crucial not to crush, chew, or break the tablets, as this would destroy the enteric coating and alter both the pharmacokinetics and tolerability of the medication.
Powder for Oral Suspension (300 mg)
Each sachet of powder for oral suspension contains 300 mg of posaconazole. The powder also contains excipients including acetyl tributyl citrate, maltodextrin, leucine, silica colloidal anhydrous, croscarmellose sodium, methacrylic acid and ethyl acrylate copolymer (a pH-dependent polymer for delayed release), hydroxypropylcellulose, and natural orange flavoring. When reconstituted with water, the resulting suspension allows for weight-based dosing in patients, particularly children, who cannot swallow tablets. The diluent is purified water, and once mixed, the suspension should be taken promptly.
If you have been told by your doctor that you have an intolerance to certain sugars or food additives, speak to your doctor or pharmacist before taking this medicine. The tablets contain sodium (as croscarmellose sodium), and the powder for oral suspension contains maltodextrin, which is a source of glucose. Patients with rare hereditary conditions affecting the metabolism of these substances should consult their healthcare provider.
Frequently Asked Questions
Noxafil (posaconazole) is used to treat several types of serious invasive fungal infections as salvage therapy in adult patients who have not responded to, or cannot tolerate, other antifungal treatments. These include invasive aspergillosis, fusariosis, chromoblastomycosis, mycetoma, and coccidioidomycosis. Additionally, and perhaps more commonly in clinical practice, Noxafil is used for prophylaxis (prevention) of invasive fungal infections in high-risk immunocompromised patients, such as those receiving chemotherapy for acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), and those with graft-versus-host disease following hematopoietic stem cell transplantation. Clinical trials have demonstrated that posaconazole prophylaxis significantly reduces the incidence of invasive aspergillosis and improves overall survival in these populations compared to fluconazole or itraconazole.
Noxafil should not be used during pregnancy unless the potential benefit to the mother clearly outweighs the possible risk to the unborn child. Animal reproductive studies have shown evidence of toxicity, including skeletal malformations, at doses similar to therapeutic exposure in humans. There are no adequate and well-controlled studies in pregnant women. Women of childbearing potential must use effective contraception throughout treatment and should notify their doctor immediately if they become pregnant. Posaconazole may also pass into breast milk, so breastfeeding should be discontinued during treatment. The decision regarding whether to discontinue breastfeeding or therapy should involve careful discussion with your healthcare provider about the relative benefits and risks.
If you miss a dose of Noxafil, take it as soon as you remember. If it is nearly time for your next dose, skip the missed dose and take your next dose at the usual time. Do not take a double dose to make up for the forgotten one. Maintaining consistent blood levels of posaconazole is important for effective protection against or treatment of fungal infections. If you frequently forget doses, consider setting an alarm or using a pill organizer to help you remember. If you have missed several doses and are concerned about reduced efficacy, contact your doctor, who may recommend checking your posaconazole blood levels through therapeutic drug monitoring.
Noxafil (posaconazole) distinguishes itself from other antifungals in several important ways. Within the triazole class, it has the broadest spectrum of antifungal activity, including coverage against Aspergillus, Candida, Fusarium, and some Mucorales species – the latter being particularly important as Mucorales can cause devastating mucormycosis infections and are resistant to many other antifungals. Compared to voriconazole (another broad-spectrum triazole), posaconazole has activity against some Mucorales but may be less potent against certain Aspergillus species. Unlike the echinocandins (such as caspofungin), posaconazole is available in oral formulations, allowing outpatient treatment and long-term prophylaxis. Compared to amphotericin B, posaconazole has a much more favorable side effect profile, particularly regarding kidney toxicity. The gastro-resistant tablet formulation has greatly improved its bioavailability compared to the earlier oral suspension, making it a more reliable oral option than itraconazole, which has historically suffered from variable absorption.
The most critical drug interactions with Noxafil fall into two categories. First, contraindicated combinations that must never be used together: terfenadine, astemizole, cisapride, pimozide, halofantrin, and quinidine (all risk QTc prolongation and fatal arrhythmias); ergot alkaloids such as ergotamine (risk of ergotism and peripheral ischemia); simvastatin, lovastatin, and atorvastatin (risk of rhabdomyolysis); and venetoclax during the CLL dose ramp-up phase (risk of tumor lysis syndrome). Second, drugs that reduce posaconazole levels and may cause treatment failure: rifampicin, rifabutin, phenytoin, carbamazepine, phenobarbital, and efavirenz. Additionally, posaconazole significantly increases levels of immunosuppressants such as ciclosporin, tacrolimus, and sirolimus, requiring substantial dose reductions and close therapeutic drug monitoring. Always provide your doctor with a complete list of all medications, supplements, and herbal products you are taking before starting Noxafil.
References
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- Walsh TJ, Raad I, Patterson TF, et al. Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: an externally controlled trial. Clinical Infectious Diseases. 2007;44(1):2-12. doi:10.1086/508774
- Cornely OA, Maertens J, Winston DJ, et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. New England Journal of Medicine. 2007;356(4):348-359. doi:10.1056/NEJMoa061094
- Ullmann AJ, Lipton JH, Vesole DH, et al. Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. New England Journal of Medicine. 2007;356(4):335-347. doi:10.1056/NEJMoa061098
- Patterson TF, Thompson GR 3rd, Denning DW, et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America (IDSA). Clinical Infectious Diseases. 2016;63(4):e1-e60. doi:10.1093/cid/ciw326
- World Health Organization. WHO Model List of Essential Medicines – 23rd List, 2023. Geneva: World Health Organization; 2023. Available at: https://www.who.int/publications/i/item/WHO-MHP-HPS-EML-2023.02
- Cornely OA, Robertson MN, Haider S, et al. Pharmacokinetics and safety results from the Phase 3 randomized, open-label, study of intravenous posaconazole in patients at risk for invasive fungal disease. Journal of Antimicrobial Chemotherapy. 2017;72(12):3406-3413. doi:10.1093/jac/dkx263
- Tissot F, Agrawal S, Pagano L, et al. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica. 2017;102(3):433-444. doi:10.3324/haematol.2016.152900
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