Posaconazole

Reviewed on 10/26/2021

What Is Posaconazole and How Does It Work?

Posaconazole is a prescription medication used to treat the symptoms of Invasive Aspergillus, Candida Infections and Oropharyngeal Candidiasis

  • Posaconazole is available under the following different brand names: Noxafil

What Are Dosages of Posaconazole?

Adult and Pediatric dosage

Oral suspension

Adult dosage

  • 40mg/mL (105mL)

Pediatric dosage

  • 300mg
  • Reconstituted concentration:30 mg/mL

Tablet, delayed-release

  • 100mg

Injectable solution

  • 18mg/mL (300mg/16.7mL-vial)

Invasive Aspergillus and Candida Infections

Adult dosage

  • Oral suspension: 200 mg (5 mL) orally three times daily
  • Tablet: 300 mg orally twice daily on day 1, then 300 mg orally once daily
  • IV: 300 mg IV twice daily on day 1, then 300 mg IV once daily 

Pediatric dosage

IV

  • Younger than 2 years of age: safety and efficacy not established
  • Loading dose: 6 mg/kg IV twice daily on day 1; not to exceed 300 mg twice daily
  • Maintenance dose: 6 mg/kg IV each day starting on the day 2; not to exceed 300 mg each day

Tablets

  • Younger than 2 years of age: safety and efficacy not established
  • Older than 2 years of age, and weighing over 40 kg: loading dose: 300 mg orally twice daily on day 1, then maintenance dose: 300 mg orally once daily starting on day 2

Oral suspension

  • Younger than 13 years of age: safety and efficacy not established
  • Older than 13 years of age: loading and maintenance dose: 200 mg orally three times daily

Delayed-release oral suspension

  • Younger than 2 years of age: safety and efficacy not established
  • Older than 2 years of age, weighing less than 40 kg:
    • 10 kg, less than 12 kg: 90 mg orally twice daily on day 1, then 90 mg orally daily starting on day 2
    • 12 kg, less than 17 kg: 120 mg orally twice daily on day 1, then 120 mg orally daily starting on day 2
    • 17 kg, less than 21 kg: 150 mg orally twice daily on day 1, then 150 mg orally daily starting on day 2
    • 21 kg, less than 26 kg: 180 mg orally twice daily on day 1, then 180 mg orally daily starting on day 2
    • 26 kg, less than 36 kg: 210 mg orally twice daily on day 1, then 210 mg orally daily starting on day 2
    • 36 kg to 40 kg: 240 mg orally twice daily on day 1, then 240 mg orally daily starting on day 2

Oropharyngeal Candidiasis

Adult dosage

  • 100 mg (2.5 mL) orally twice daily on day 1, then 100 mg orally each day for 13 days
  • Refractory to itraconazole and/or fluconazole: 400 mg (10 mL) orally twice daily

Pediatric dosage

  • Younger than 13 years of age: Safety and efficacy not established
  • Older than 13 years of age: 
  • Oral suspension: 100 mg (2.5 mL) orally twice daily on day 1, then 100 mg orally each day for 13 days
  • Refractory to itraconazole and/or fluconazole: 400 mg (10 mL) orally twice daily

Dosage Considerations – Should be Given as Follows: 

  • See "Dosages."

SLIDESHOW

Fungal Skin Infections: Types, Symptoms, and Treatments See Slideshow

What Are Side Effects Associated with Using Posaconazole?

Common side effects of Posaconazole include:

  • diarrhea, 
  • nausea, 
  • vomiting, 
  • low potassium
  • headache, 
  • fever, and 
  • cough

Serious side effects of Posaconazole include:

  • hives, 
  • difficulty breathing, 
  • swelling of the face, lips, tongue, or throat, 
  • fast or pounding heartbeats, 
  • fluttering in chest, 
  • shortness of breath, 
  • sudden dizziness, 
  • swelling in an arm or leg, 
  • shortness of breath, 
  • nausea, 
  • vomiting, 
  • itching, 
  • tiredness, 
  • yellowing of the skin or eyes (jaundice), 
  • leg cramps, 
  • constipation, 
  • dizziness, 
  • irregular heartbeats, 
  • increased thirst or urination, 
  • feeling jittery, 
  • muscle spasms or contractions, 
  • muscle weakness, 
  • numbness or tingling, 
  • cough, and
  • choking feeling

Rare side effects of Posaconazole include:

  • none 

This is not a complete list of side effects and other serious side effects or health problems may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

What Other Drugs Interact with Posaconazole?

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them.  Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first

  • Posaconazole has severe interactions with at least 29 other drugs. 
  • Posaconazole has serious interactions with at least 143 other drugs.
  • Posaconazole has moderate interactions with at least 303 other drugs.
  • Posaconazole has minor interactions with at least 72 other drugs.  

This information does not contain all possible interactions or adverse effects.  Visit the RxList Drug Interaction Checker for any drugs interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use.  Keep a list of all your medications with you, and share this information with your doctor and pharmacist.  Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns.

What Are Warnings and Precautions for Posaconazole?

Contraindications

  • Hypersensitivity to Posaconazole or other azoles 
  • Coadministration with sirolimus; increases sirolimus blood concentrations by ~9-fold
  • CYP3A4 substrates that prolong the QT interval (eg, pimozide, quinidine)
  • Coadministration with the HMG-CoA reductase inhibitors (statins) that are primarily metabolized through CYP3A4 (eg, atorvastatin, lovastatin, simvastatin)
  • Concurrent use with ergot alkaloids
  • Delayed-release oral suspension only: patients with known or suspected hereditary fructose intolerance (HFI)

Effects of drug abuse

  • None

Short-Term Effects

  • See "What are Side Effects Associated with Using Posaconazole?"

Long-Term Effects

  • See “What Are Side Effects Associated with Using Posaconazole?”

Cautions

  • May prolong QT interval; cases of torsades de pointes reported
  • Hepatic reactions reported including mild-to-moderate elevations in ALT, AST, alkaline phosphatase, total bilirubin, and clinical hepatitis; consider discontinuing therapy in patients who develop abnormal LFTs or monitor LFTs during treatment
  • Closely monitor patients with severe renal impairment for breakthrough fungal infections due to the variability in exposure of the delayed-release tablets and oral suspension; avoid use of injection in patients with moderate or severe renal impairment (eGFR <50 mL/min); unless benefit outweighs risks
  • Electrolyte disturbances, especially those involving potassium, magnesium or calcium levels, should be monitored and corrected as necessary before and during posaconazole therapy
  • Closely monitor patients who have severe diarrhea or vomiting for breakthrough fungal infections when receiving delayed-release tablets, oral suspension, or delayed-release oral suspension
  • Use of delayed-release oral suspension in patients with HFI
    • Delayed-release oral suspension contains sorbitol, an inactive ingredient, and may precipitate a metabolic crisis that may include, but is not limited to life-threatening hypoglycemia, hypophosphatemia, lactic acidosis, and hepatic failure in patients with HFI
    • Review patient history of HFI symptoms (nausea, vomiting, abdominal pain) with sorbitol/fructose/sucrose exposure before using the delayed-release oral suspension
    • Diagnosis of HFI may not yet be established in pediatric patients
  • Drug interactions overview
    • Posaconazole is a P-gp substrate and a strong CYP3A4 inhibitor; metabolized by UDP-glucuronidase
  • Rifabutin and phenytoin
    • Avoid unless benefit outweighs risks
    • Rifabutin and phenytoin may decrease posaconazole plasma concentrations by inducing UDP-glucuronidase
    • Posaconazole may also increase rifabutin and phenytoin levels by inhibiting CYP3A4
  • Antiretroviral agents
    • Efavirenz may induce UDP-glucuronidase and significantly decrease posaconazole plasma levels; avoid use
    • Ritonavir and atazanavir are CYP3A4 substrates; posaconazole may increase plasma concentrations of these drugs; closely monitor for posaconazole-related toxicities if concurrently used
    • Fosamprenavir may decrease posaconazole plasma concentration; closely monitor for breakthrough fungal infections
  • Benzodiazepines metabolized by CYP3A4
    • Closely monitor
    • Coadministration with midazolam increases midazolam plasma concentrations by ~5-fold; increased risk of prolonged hypnotic and sedative effects
  • CYP3A4 substrates that cause QT prolongation
    • Contraindicated
    • Coadministration with CYP3A4 substrates may result in increased plasma concentrations of these drugs, leading to QTc prolongation and cases of torsades de pointes
  • Immunosuppressants metabolized by CYP3A4
    • Coadministration posaconazole with calcineurin inhibitors (eg, sirolimus, tacrolimus, cyclosporine) increases blood concentrations of calcineurin inhibitors
    • Sirolimus: Contraindicated
    • Tacrolimus: Reduce tacrolimus dose to ~1/3 of original dose when initiating posaconazole; closely monitor tacrolimus trough concentrations during and at discontinuation of posaconazole treatment and adjust tacrolimus dose accordingly
    • Cyclosporine: Reduce cyclosporine dose to ~3/4 of original dose when initiating cyclosporine; closely monitor tacrolimus trough concentrations during and at discontinuation of posaconazole treatment and adjust tacrolimus dose accordingly
  • HMG-CoA reductase inhibitors primarily metabolized through CYP3A4
    • Contraindicated
    • May increase plasma concentrations of simvastatin by ~10-fold
  • Ergot alkaloids
    • Contraindicated
    • May increase the plasma concentrations of ergot alkaloids which may lead to ergotism
  • Cimetidine and esomeprazole
    • Oral suspension: Cimetidine (an H2-receptor antagonist) and esomeprazole (a proton pump inhibitor) decreased posaconazole plasma concentrations; avoid use of cimetidine and esomeprazole unless the benefit outweighs the risks
  • Vinca alkaloids
    • Use with vinca alkaloids (eg, vinblastine, vincristine) may increase the plasma concentrations of vinca alkaloids and risks of neurotoxicity and other serious adverse reactions
    • Reserve azole antifungals for patients receiving a vinca alkaloid, including vincristine, who have no alternative antifungal treatment options
  • Calcium channel blockers
    • May increase the plasma concentrations of calcium channel blockers metabolized by CYP3A4 (eg, verapamil, diltiazem, nifedipine, nicardipine, felodipine)
    • Closely monitor for adverse reactions and toxicity related to calcium channel blockers; consider dose reduction of calcium channel blockers
  • Digoxin
    • Increased plasma concentrations of digoxin reported in patients receiving digoxin and posaconazole; closely monitor digoxin levels

Pregnancy and Lactation

  • Available data in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes; based on findings from animal data, therapy may cause fetal harm when administered to pregnant women
  • There are no data on presence of drug in human milk, effects on breastfed infant, or on milk production; drug is excreted in milk of lactating rats; when a drug is present in animal milk, it is likely that the drug will be present in human milk; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for drug and any potential adverse effects on breastfed child from drug or from underlying maternal condition

QUESTION

Bowel regularity means a bowel movement every day. See Answer
References
https://reference.medscape.com/drug/noxafil-posaconazole-342588

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