po-sa-KON-a-zole

Therapeutic Classification: antifungals

Pharmacologic Classification: triazoles

• PO, IV: Treatment of invasive aspergillosis (tablets and injection).
• PO, IV: Prevention of invasive Aspergillus and Candida infections in patients who are severely immunocompromised, such as hematopoietic stem cell transplant recipients with graft-versus-host disease or those with hematologic malignancies with prolonged neutropenia from chemotherapy (tablets, oral suspension, delayed-release oral suspension, and injection).
• PO: Treatment of oropharyngeal candidiasis (including candidiasis unresponsive to itraconazole or fluconazole) (oral suspension).

• Blocks ergosterol synthesis, a major component of fungal plasma membrane.

• Fungistatic/fungicidal action against susceptible fungi.

Spectrum:

• Aspergillus spp.,
• Candida spp.

Absorption: Well absorbed following oral administration; absorption is optimized by food; IV administration results in complete bioavailability.

Distribution: Extensive extravascular distribution and penetration into body tissues.

Protein Binding: >98%.

Metabolism/Excretion: Some metabolism via UDP glucuronidation; 66% eliminated unchanged in feces, 13% in urine (mostly as metabolites).

Half-life: 35 hr.

(plasma concentrations)

Contraindicated in:

• Hypersensitivity to posaconazole or other azole antifungals
• Concurrent use of atorvastatin, ergot alkaloids, lovastatin, pimozide, quinidine, simvastatin, or sirolimus
• Concurrent use of venetoclax at initiation and during the ramp-up phase
• Hereditary fructose intolerance (for delayed-release oral suspension only).

Use Cautiously in:

• History of/predisposition to QTc prolongation including congenital QTc prolongation, concurrent medications that prolong QTc, or electrolyte abnormalities (hypokalemia, hypomagnesemia); correct pre-existing abnormalities prior to administration
• Moderate to severe renal impairment (CCr <50 mL/min); use only if justified by risk/benefit assessment (IV form should be avoided, use oral form only)
• Severe diarrhea, vomiting, or renal impairment (monitor for breakthrough fungal infections)
• OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk
• Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant
• Pedi: Children <18 yr (IV) or <13 yr (oral) (safety and effectiveness not established).

CV: QT interval prolongation, TORSADES DE POINTES.

Endo: adrenal insufficiency.

F and E: hypokalemia, hypomagnesemia, hypocalcemia.

GI: diarrhea, nausea, vomiting, HEPATOCELLULAR DAMAGE, PANCREATITIS.

Neuro: headache.

Resp: cough.
Misc: fever, HYPERSENSITIVITY REACTIONS.

Drug-Drug:

• May ↑ cyclosporine, sirolimus, and tacrolimus levels and risk of toxicity; use with sirolimus contraindicated; for cyclosporine and tacrolimus, ↓ dose initially and monitor levels frequently.
• May ↑ quinidine and pimozide levels and the risk for arrhythmias; concurrent use contraindicated.
• May ↑ levels and risk of toxicity from ergot alkaloids, including ergotamine and dihydroergotamine; concurrent use contraindicated.
• May ↑ levels of simvastatin, atorvastatin, or lovastatin and the risk for rhabdomyolysis; concurrent use contraindicated.
• May ↑ risk of tumor lysis syndrome, neutropenia, and serious infection during initiation or the ramp-up phase of venetoclax in patients with chronic lymphocytic leukemia or small lymphocytic leukemia; concurrent use contraindicated.
• Rifabutin, phenytoin, cimetidine, and efavirenz may ↓ levels and may ↓ effectiveness; avoid concurrent use.
• Esomeprazole and metoclopramide may ↓ levels and effectiveness.
• May ↑ rifabutin levels and risk of toxicity; avoid concurrent use.
• QT interval prolonging drugs may ↑ risk for QT interval prolongation and torsades de pointes; avoid concurrent use.
• May ↑ digoxin levels and risk of toxicity; monitor levels frequently.
• May ↑ phenytoin, midazolam, ritonavir, and atazanavir levels and risk of toxicity; monitor for excess clinical effect.
• May ↑ levels of and risk of neurotoxicity, syndrome of inappropriate antidiuretic hormone, and paralytic ileus with concurrent use of vinca alkaloids, including vincristine and vinblastine; consider using an alternative nonazole antifungal.
• May ↑ levels and risk of adverse cardiovascular reactions to calcium channel blockers; consider dosage reduction.

Treatment of Invasive Aspergillosis

• PO (Adults and Children 13 yr): Delayed-release tablets: 300 mg twice daily on Day 1, then 300 mg once daily starting on Day 2 for a total of 6–12 wk.
• IV (Adults and Children 13 yr): 300 mg twice daily on Day 1, then 300 mg once daily starting on Day 2 for a total of 6–12 wk.

Prophylaxis of Invasive Aspergillus and Candida Infections

• PO (Adults and Children 13 yr): Oral suspension: 200 mg 3 times daily. Duration of therapy is based on recovery from neutropenia or immunosuppression.
• PO (Adults and Children 2 yr and >40 kg): Delayed-release tablets: 300 mg twice daily on Day 1, then 300 mg once daily starting on Day 2. Duration of therapy is based on recovery from neutropenia or immunosuppression.
• IV (Adults): 300 mg twice daily on Day 1, then 300 mg once daily starting on Day 2. Duration of therapy is based on recovery from neutropenia or immunosuppression.
• IV (Children 2 yr): 6 mg/kg (max = 300 mg) twice daily on Day 1, then 6 mg/kg (max = 300 mg) once daily starting on Day 2. Duration of therapy is based on recovery from neutropenia or immunosuppression.

Treatment of Oropharyngeal Candidiasis

• PO (Adults and Children 13 yr): Oral suspension: 100 mg twice daily on Day 1, then 100 mg once daily for the next 13 days. For refractory oropharyngeal candidiasis, give 400 mg twice daily; duration of therapy is based on the severity of the patient’s underlying disease and clinical response.

(Generic available)

• Delayed-release tablets: 100 mg;
• Oral suspension (cherry flavor): 40 mg/mL;
• Solution for injection: 18 mg/mL;

• Assess for signs and symptoms of fungal infection. If severe diarrhea or vomiting occurs, monitor closely for breakthrough fungal infection.

• Monitor liver function tests prior to and periodically during therapy. May cause ↑ ALT, AST, alkaline phosphatase, and total bilirubin levels; generally reversible on discontinuation. Discontinue posaconazole if clinical signs and symptoms of liver disease develop.
  • Monitor electrolyte levels (potassium, magnesium, calcium) before starting and during therapy. Correct as necessary before and during therapy.

• Delayed-release tablet and oral suspension are not interchangeable. Tablets are the preferred oral formulation for prophylaxis because they achieve higher plasma concentrations of drug.
• PO: Administer delayed-release tablets with food. DNC: Swallow tablets whole; do not divide, crush, or chew.
  • Shake suspension well before use. Use spoon provided to ensure accurate dose. Administer during or within 20 min of a full meal, liquid nutritional supplement, or an acidic carbonated beverage (e.g., ginger ale) to ↑ absorption. Rinse spoon for administration with water after each use. Alternative therapy or close monitoring for breakthrough fungal infections should be considered for patients unable to eat a full meal or tolerate a nutritional supplement.

IV Administration:

• Intermittent Infusion: Allow solution to reach room temperature before administering. Dilute in D5W, D5/0.45% NaCl, D5/0.9% NaCl, D5/20 mEq potassium, 0.45% NaCl, or 0.9% NaCl.1–2 mg/mL. Do not dilute with other solutions. Use immediately; stable for 24 hr if refrigerated. Discard unused solution. Solution is clear, colorless to yellow; do not administer solutions that are discolored or contain particulate matter. Administer through a 0.22-micron polyethersulfone or polyvinylidene difluoride filter via central venous line, including a central venous catheter or peripherally inserted central catheter line. If no central catheter available, may be administered through a peripheral venous catheter by slow intravenous infusion over 30 min 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.
• Rate: Infuse slowly over 90 min. Do not give as a bolus.
• Y-Site Compatibility:
  • amikacin
  • caspofungin
  • ciprofloxacin
  • daptomycin
  • dobutamine
  • famotidine
  • filgrastim
  • gentamicin
  • hydromorphone
  • levofloxacin
  • lorazepam
  • meropenem
  • micafungin
  • morphine
  • norepinephrine
  • potassium chloride
  • vancomycin.
• Y-Site Incompatibility:
  • acetaminophen
  • acyclovir
  • cefepime
  • furosemide
  • ganciclovir
  • imipenem/cilastatin/relebactam
  • insulin aspart
  • levetiracetam
  • methylprednisolone
  • metoclopramide
  • ondansetron
  • pantoprazole
  • piperacillin/tazobactam
.

• Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy. Instruct patient to take posaconazole during or immediately (within 20 min) following a full meal or liquid nutritional supplement in order to enhance absorption. Take missed doses as soon as remembered.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• Advise patient to notify health care professional if severe diarrhea or vomiting occurs (may ↓ posaconazole levels and allow breakthrough fungal infections) or if signs and symptoms of liver injury (itching, yellow eyes or skin, fatigue, flu-like symptoms) or change in HR or rhythm occur.
• May cause fetal harm. Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during therapy.

• Fungistatic/fungicidal action against susceptible fungi.

Noxafil

Posanol