Posaconazole (Oral)

Posaconazole, marketed under the brand name Noxafil, is an anti-fungal medication in the triazole family, and is used to treat active fungal infections such as invasive aspergillosis or oropharyngeal candidiasis, particularly in patients with compromised immune systems because of underlying health conditions.

Overview

Posaconazole, which is marketed under the brand Noxafil or Posaron, was first approved in 2006 for the treatment of fungal infections that primarily affect patients with compromised immune systems caused by disease or other health conditions. This medication can be used to treat an ongoing infection, but its primary application is prophylactic. It is often prescribed for these patients to prevent fungal infections from occurring. Posaconazole is effective in treating or preventing infections caused by fungi in the aspergillus, candida and zygomycetes species. This would include infections like invasive aspergillosis and oropharyneal candidiasis.

Posaconazole is often prescribed as part of an overall treatment plan for patients with diseases like HIV/AIDS, HVCT or cancers of the blood as fungal infections represent a great risk for these patients.

Posaconazole may also be prescribed for the treatment of oral thrush and mucormycosis. There is not definitive evidence that this medication is effective in the treatment of fusariosis, a fungal infection from Fusarium species

Noxafil comes in several different delivery platforms including injection (given by intravenous line and available since 2014), oral tablet and delayed release tablets, which became available in 2013. Dosing levels vary depending on the severity of the infection or if it is prescribed as a preventative. It also varies by condition and the ability of the patient to tolerate the medication. For infections like oral thrush, the length of treatment is approximately two week. In prophylactic cases, the treatment period is open-ended and this medication may be taken for quite a prolonged period.

This medication interacts with many medications, most especially statin drugs and medications used to treat migraine headaches. Posaconazole should not be taken concomitantly with either of these families of medicines. Given the limited information regarding the impact this medication has on pregnant women and the unborn child, pregnant women should not use this drug unless absolutely necessary.

It should also always be taken with a full meal. In the event that the patient is not able to eat a meal, it should be administered with a liquid nutritional supplement. Taking this medication on an empty stomach limits the efficacy of the medicine itself and can exacerbate the symptoms and side effects that it may cause.

Conditions Treated

  • Fungal infections, particularly from Aspergillus species and Candida species
  • Candidiasis, oropharyngeal
  • Candidiasis, esophageal
  • Coccidioidomycosis
  • Prophylaxis of infection, Candida and Aspergillus species
  • Mucormycosis
  • Pulmonary cryptococcosis infection
  • Bronchopulmonary aspergillosis, invasive

Type Of Medication

  • Triazole anti-fungal agent

Side Effects

Posaconazole can cause side effects. Some of these are not particularly serious or dangerous and do not require additional medical attention. Generally, these side effects are tolerable for the patient and would not indicate that the patient needs to discontinue its use. Patients may experience one or more of the following:

  • Heartburn
  • Acidic stomach
  • Joint pain
  • Belching and sour stomach
  • Stiff muscles
  • Trouble sleeping
  • Lower back pain
  • Constipation and difficult bowel movement
  • Changes in taste, particularly unpleasant or bad taste response

Posaconazole may cause other, more serious side effects that do require medical attention. In some cases, the patient's response to this medication may require its discontinuation and/or emergency medical treatment. Patients who experience one or more of the following responses to posaconazole should seek medical advice and attention:

  • Unusual body aches or sharp pain
  • Severe abdominal pain
  • Disorientation and confusion
  • Diarrhea
  • Tarry or black stools
  • Lightheadedness when getting up from a seated or lying position
  • Persistent cough
  • Blurry vision
  • Dizziness
  • Frequent bloody nose
  • Fever
  • Sleepiness
  • Difficulty breathing
  • Chills
  • Unusual thirst
  • Unexplained hoarseness or laryngitis
  • Off cycle spotting or heavy vaginal bleeding
  • Unusually sweet breath (fruity)
  • More frequent urination
  • Muscle spasms
  • Heart arrhythmia
  • Nausea
  • Pounding in the ears
  • Sores or blisters, particularly around the mouth and lips
  • Blisters or rash around eyes or genitals
  • Numbness in extremities
  • Painful urination
  • Idiopathic trembling
  • Unusual skin rash
  • Difficulty in swallowing
  • Swollen glands in the neck
  • Yellowing of the skin or eyes
  • Excessive sweating
  • Ulcers inside the mouth
  • Feeling of tightness in the chest or chest pain
  • Sudden weight loss
  • Syncope or fainting
  • Increased levels of anxiety
  • Shortness of breath, sudden onset
  • Mood swings
  • Convulsions or seizures
  • Increased depression
  • Unexplained weakness
  • Edema of the lower legs, feet or fingers
  • Darkened skin
  • Swollen eyes

Dosage

The typical dosing levels to treat adults with Invasive Aspergillus depend on the mechanism of delivery of the medication:

If given intravenously, recommended dosing is 300mg twice daily on day one. The remainder of the prescribed treatment should be injected at a rate of 300mg once daily.

If given through delayed release tablet, the recommended dose is 300 mg taken twice daily on the first day. The remainder of the prescribed treatment should be taken 300mg a day once daily.

If given through oral suspension, the recommended dose is 200mg taken three times daily.

The length of the prescription depends on the severity of the underlying conditions, neutropenia, and the patient's response to treatment.

Oral delayed release tablets are the more preferred method. Posaconazole (Noxafil) may used to treat this infection or given prophylactically to prevent its onset.

For pediatric patients who have or at risk of developing Invasive aspergillus, the dosing levels stay the same. However, this medication is not recommended for use in children under thirteen years old.

The typical prescription and dosing levels for the treatment of Oropharyngeal candidiasis delivered through oral delayed release tablets is 200 mg taken over two doses on the initial day. Following the initial treatment, patients take 100mg once daily for thirteen days.

For pediatric patients suffering from or at risk of developing Oropharyngeal candidiasis, dosing levels are the same as for adult patients. It is not recommended for children under thirteen at any dosing level.

If the patient suffers from the form of Oropharyngeal candidiasis that is refractory to itraconazole, the recommended dose is 400mg taken twice daily. The length of this treatment depends on the patient's response to treatment and the severity of the compromised immunity.

This medication should be taken with food to increase absorption of medication and maximize its effectiveness.

Interactions

Posaconazole interacts with many other medications, 630 different drugs in total. Some of those interactions are more significant than others and in some cases, use of posaconazole is contraindicated when in combination with other medications. Major drug interactions include:

  • Abemaciclib
  • Caffeine
  • Phenylephrine
  • Acalabrutinib
  • Alfentanil
  • Acetaminophen
  • Oxycodone
  • Chlorpheniramine
  • Amlodipine
  • Hydrocodone
  • Alfuzosin
  • Arsenic trioxide
  • Aspirin
  • Lumefantrine
  • Alprazolam
  • Atorvastatin
  • Apixaban
  • Amiodaron
  • Artemether
  • Anagrelide
  • Avanafil
  • Astemizole
  • Ezetimibe
  • Axitinib
  • Fluticasone (nasal)
  • Azelastine
  • Bepridil
  • Pseudoephedrine
  • Bedaquiline
  • Brigatinib
  • Belladonna
  • Budesonide
  • Ergotamine
  • Brompheniramine
  • Bosutinib
  • Formoterol
  • Phenobarbital
  • Lidocaine
  • Brexpiprazole
  • Fentanyl
  • Butorphanol
  • Bupivacaine
  • Pentobarbital
  • Triamcinolon
  • Carbinoxamine
  • Cariprazine
  • Guaifenesin
  • Cisapride
  • Colchicine
  • Ceritinib
  • Clozapine
  • Probenacid
  • Cerivastatin
  • Conivaptan
  • Cyclosporine
  • Cilostazol
  • Crizotinib
  • Citalopram
  • Copanlisib
  • Daclatasvir
  • Dexchlorpheniramine
  • Quinidine
  • Darifenacin
  • Docetaxel
  • Dihydroergotamine
  • Dasatinib
  • Dextromethorphan
  • Diphenhydramine
  • Deflazacort
  • Droperidol
  • Dexbrompheniramine
  • Dutasteride
  • Dronedarone
  • Dofetilide
  • Tamsulosin
  • Disopyramide
  • Dolasetrone
  • Eletriptan
  • Ergonovine
  • Elbasvir / grazoprevir
  • Erythromycin and sulfisoxazole
  • Eliglustat
  • Simvastatin
  • Eszopiclone
  • Eplerenone
  • Ezetimibe
  • Escitalopram
  • Everolimus
  • Umeclidinium
  • Ropivacaine
  • Flibanserin
  • Salmeterol
  • Fesoterodine
  • Vilanterol
  • Fingolimod
  • Grepafloxacin
  • Pyrilamine
  • Gatifloxacin
  • Guanfacine
  • Tripolidine
  • Halofantrine
  • Ibuprofen
  • Homatropine
  • Potassium guaiacolsulfonate
  • Haloperidol
  • Ibrutinib
  • Irinotecan
  • Ivacaftor
  • Isavuconazonium
  • Iloperidone
  • Lumacaftor
  • Ibutilide
  • Ivabradine
  • Lomitapide
  • Leflunomide
  • Lovastatin
  • Ribociclib
  • Levomethadyl acetate
  • Simethicone
  • Lurasidone
  • Loperamide
  • Niacin
  • Methylergonovine
  • Macitentan
  • Mipomersen
  • Midazolam
  • Maraviroc
  • Midostaurin
  • Mesoridazine
  • Methysergide maleate
  • Methadone
  • Mifepristine
  • Moxifloxacin
  • Methylprednisolone
  • Nilotinib
  • Naloxane
  • Naloxegol
  • Nimodipine
  • Naltrexone
  • Neratinib
  • Olaparib
  • Simvastatin
  • Osimertinib
  • Pasireotide
  • Pimozide
  • Panobinostat
  • Procainamide
  • Terfenadine
  • Palbociclib
  • Pimvanserin
  • Papaverine
  • Quetiapine
  • Rivaroxaban
  • Red yeast rice
  • Ranolazine
  • Ruxolitinib
  • Simeprevir
  • Saquinavir
  • Sitagliptin
  • Solifenacin
  • Silodosin
  • Sonidegib
  • Sirolimus
  • Sparfloxacin
  • Sirolimus
  • Sotalol
  • Suvorexant
  • Ticagrelor
  • Tacrolimus
  • Teriflunomide
  • Tolvaptan
  • Temsirolimus
  • Trabectedin
  • Thioridazine
  • Toremifene
  • Tofacitinib
  • Vemurafenib
  • Valbenazine
  • Vinorelbine
  • Vincristine liposome
  • Venetoclax
  • Vorapaxar
  • Vandetanib
  • Vinblastine
  • Ziprasidone

The following medicines interact with posaconazole, but less significantly. Generally, the following medications may be taken in conjunction with posaconazole:

  • Abarelix
  • Magnesium hydroxide
  • Propoxyphene
  • Abiraterone
  • Adenosine
  • Albuterol
  • Ipratropium
  • Ado-trastuzumab emtansine
  • Aliskiren
  • Albendazole
  • Almotriptan
  • Calcium carbonate
  • Aminophylline
  • Aluminum hydroxide
  • Potassium iodide
  • Mineral oil
  • Perphenazine
  • Perindopril
  • Benazepril
  • Amitryptyline
  • Telmisartan
  • Amoxapine
  • Omeprazole
  • Anisindione
  • Amoxicillin
  • Anhydrous calcium iodide
  • Aprepitant
  • Amprenavir
  • Clarithromycin
  • Arformoterol
  • Apomorphine
  • Atazanavir
  • = aripiprazole
  • Atomoxetine
  • Cobicistat
  • Propoxyphene
  • Asenapine
  • Hyoscyamine
  • Azithromycin
  • Scopolamine
  • Atropine
  • Trovafloxacin
  • Betrixaban
  • Baclofen
  • Bisacodyl
  • Black cohosh
  • Flurbiprofen
  • Betamethasone
  • Magnesium citrate
  • Bazedoxifene
  • Sodium bicarbonate
  • Conjugated estrogens
  • Bicalutamide
  • Bitolterol
  • Brentuximab
  • Potassium chloride
  • Boceprevir
  • Polyethylene glycol 3350
  • Bosentan
  • Budesonide (nasal)
  • Bortezomib
  • Busulfan
  • Bromocriptine
  • Cabazitaxel
  • Famotidine
  • Casanthranol
  • Cevimeline
  • Cabozantinib
  • Carbamazepine
  • Docusate
  • Magnesium hydroxide
  • Cascara sagrada
  • Calcium carbonate
  • Phenolphthalein
  • Chloroquine
  • Ciclesonide (nasal)
  • Castor oil
  • Chlorpromazine
  • Cimetidine
  • Ceftriaxone
  • Citric acid
  • Chlorotrianisene
  • Clofarabine
  • Cinacalcet
  • Clarithromycin
  • Ciprofloxacin
  • Codeine
  • Clofazimine
  • Medroxyprogesterone
  • Cortisone
  • Cobicistat
  • Promethazine
  • Meprobamate
  • Promethazine
  • Daunorubicin liposomal
  • Darunavir
  • Cortisone
  • Methyltestosterone
  • Cytarabine liposomal
  • Dapagliflozin
  • Dabigatran
  • Paritaprevir
  • Dabrafenib
  • Desipramine
  • Saxagliptin
  • Ombitasvir
  • Ethinyl estradiol
  • Diazepam
  • Dasabuvir
  • Dexlansoprazole
  • Dicumarol
  • Ritonavir
  • Dienestrol topical
  • Deutetrabenazine
  • Digoxin
  • Dienogest
  • Diethylstilbestrol
  • Doxepin
  • Diltiazem
  • Senna
  • Rilpivirine
  • Doxorubici
  • Dyphylline
  • Dolutegravir
  • Levomefolate calcium
  • Dutasteride
  • Efavirenz
  • Enzalutamide
  • Eluxadoline
  • Felodipine
  • Emtricitabine
  • Hydroxyzine
  • Erlotinib
  • Epinephrine
  • Esomeprazole
  • Eribulin
  • Esterified estrogens
  • Epirubicin
  • Norethindrone (topical)
  • Estrone
  • Testosterone
  • Etonogestrel
  • Estropipate
  • Folic acid
  • Norgestimate
  • Etravirine
  • Ethosuximide
  • Levonorgestrel
  • Ezogabine
  • Etoposide
  • Flecainide
  • Fludrocortisone
  • Olanzapine
  • Fluphenazine
  • Fosaprepitant
  • Flunisolide
  • Flutamide
  • Fosamprenavir
  • Galantamine
  • Ginger
  • Gemifloxacin
  • Metformin
  • Gefitinib
  • Goserelin
  • Glipizide
  • Glycopyrrelate
  • Glycerin
  • Granisetron
  • Indacaterol
  • Histrelin
  • Hydroxyzine
  • Methylene blue
  • Halothane
  • Hydrocortisone
  • Imatinib
  • Idelalisib
  • Interferon beta -1a
  • Idarubicin
  • Isoetharine
  • Inotuzumab ozogamicin
  • Ivermectin
  • Isoniazid
  • Isradipine
  • Isoproterenol
  • Ixabepilone
  • Ketoconazole
  • Lanolin
  • Lapatinib
  • Lactulose
  • Sofosbuvir
  • Lansoprazole
  • Levalbuterol
  • Lenvatinib
  • Levobupivacaine
  • Oxytetracycline
  • Leuprolide
  • Levomilnacipran
  • Lithium
  • Levofloxacin
  • Lomefloxacin
  • Lopinavir
  • Maprotiline
  • Meperidine
  • Metaproterenol
  • Mefloquine
  • Methanimine
  • Methotrimeprazine
  • Mitoxantrone
  • Metoclopramide
  • Mometasone nasal
  • Naldemedine
  • Nilutamide
  • Nefazodone
  • Nizatidine
  • Netupitant
  • Ospemifene
  • Omeprazole
  • Ondansetron
  • Oxaliplatin
  • Paclitaxel
  • Ponatinib
  • Psyllium
  • Prednisolone
  • Pirbuterol
  • Quinestrol
  • Riociguat
  • Regorafenib
  • Rabeprazole
  • Rolapitant
  • Sertraline
  • Sunitinib
  • Tretinoin
  • Tamoxifen
  • Telithromycin
  • Thioguanine
  • Umeclidinium
  • Venlafaxine
  • Voriconazole
  • Vilanterol
  • Vilazodone
  • Vardenafil
  • Warfarin
  • Zonisamide
  • Zaleplon

Posaconazole also can interact negatively with several diseases, either by exacerbating those symptoms, worsening the condition itself or interfering with medication necessary for the treatment of these conditions. These interactions are rated as moderate hazards, so the concomitant use of posaconazole is not contraindicated, but it is not generally recommended unless no adequate alternative treatment can be found. These diseases include:

  • Hepatic impairment and liver disease
  • Heart disease, including QT Prolongation, arrhythmia, or torsade de pointes
  • Renal impairment and kidney disease

Posaconazole interacts positively with food. For maximum effectiveness, this medication should be taken with a full meal. If that is not possible, a liquid nutritional supplement may substitute. It should not be taken without food or on an empty stomach as this reduces the drug's efficacy.

Warnings

Posaconazole should always be taken with a full meal, as it helps maximize absorption of the medication and lessens some of the side effects that can be associated with it. If a patient is unable to eat a full meal, he or she should take posaconazole with supplemental nutrition such as Ensure.

Patients should not take posaconazole (Noxafil) in combination with statin medications that are prescribed to lower cholesterol.

It is also contraindicated in conjunction with ergot medications such as ergotamine that are used to treat migraine headaches.

Physicians should prescribe this medication with caution in any patient who also suffers from a heart arrhythmia, has had an organ transplant and takes medication to prevent its rejection, has a kidney or liver condition for which he or she takes medication or has a history of Long QT Syndrome.

For organ transplant patients, the concentration of those anti-rejection medications, such as cyclosporine, is increased. Dosage of those medicines may need to be reduced during the treatment period of posaconazole.

There is insufficient data available on the effect posaconazole may have on an unborn child if used by the mother. It is also not clear if this medication passes through breast milk to a nursing infant. In cases of pregnancy, an alternative medication may be a better choice. Nursing mothers should discontinue nursing during the treatment period.

For patients who take posaconazole over prolonged periods of time, especially if it is being used to prevent infection, physicians and health care providers need to monitor for breakthrough infections and any impact it may be having on red blood cell counts. For patients with some impaired kidney or liver function, frequent testing of those functions is also indicated as worsening symptoms may indicate a need for reduced dosage or discontinuation of use altogether.

Patients with renal impairment should not be given the injectable form of posaconazole.

Storage

Storage requirements of posaconazole vary depending on the platform of delivery method.

The oral suspension should be stored at room temperature (65 to 75 degrees Fahrenheit). It should not be exposed to excessive heat or freezing temperatures.

The delayed-release tablets should also be stored at room temperature (65 to 75 degrees Fahrenheit). It should not be exposed to excessive heat or freezing temperatures.

The injection (given intravenously) should be kept refrigerated once the solution has been reconstituted. It can be stored for up to 24 hours, and should then be disposed of.

This medication should be stored safely and securely in its original container until administered. Any unused medication should be disposed of with care. Posaconazole should be kept away from children and animals. If overdose is suspected, contact poison control and seek medical attention. If the patient is unconscious or unresponsive, call 911 immediately.

Summary

Posaconazole has been available for the treatment of certain fungal infections since 2006. This medication is effective in the treatment of infection caused by fungi in the aspergillus, zygomycetes and candida families. Its most common application is in preventing these infections in patients with compromised immune systems. This would include patients suffering from malignant hematologic conditions, HIV/AIDS, HVCT or patients who have received an organ transplant and are on a regimen of anti-rejection medication. These patients are more at risk of developing these sorts of fungal infections. In some cases, such as invasive aspergillosis, pulmonary cryptococcosis infection, or bronchopulmonary aspergillosis, these infections may prove fatal so prophylactic treatment is indicated when possible. This medication is also used for the treatment of oral thrush in adults and children over the age of thirteen. This medication is not recommended for use in any patient under the age of thirteen. It is also not recommended for women who are pregnant or nursing.

Posaconazole is available in several different delivery methods. Most commonly, patients take it as an oral tablet, either once a day or twice a day. It may also be given as an intravenous injections, which is most likely in HIV/AIDS patients. Regardless of the form of the medication, it should always be taken with plenty of food to insure maximum effectiveness and absorption of the medication.

This medication does interact with a variety of medications, but should not be taken in conjunctions with statin medications prescribed for lowering cholesterol or ergot medications that are prescribed for migraine or throbbing headaches. It should also be prescribed with great caution for patients who also suffer from hepatic or renal impairment as it may exacerbate the dysfunction. Liver and kidney function should be monitored closely for the length of the treatment period. Posaconazole may also not be a good choice for patients with heart arrhythmias or a history of Long QT Syndrome, as this medication can impact heart rate and rhythm.