posaconazole

REMS

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).

Action ⬆ ⬇

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

Therapeutic effects:

Fungistatic/fungicidal action against susceptible fungi.

Spectrum:

Aspergillus spp.,
Candida spp.

Pharmacokinetics ⬆ ⬇

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.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO (suspension)	unknown	3–5 hr	8 hr
PO-ER	unknown	4–5 hr	24 hr
IV	unknown	2 hr	24 hr

Contraind./Precautions ⬆ ⬇

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).

Adv. Reactions/Side Effects ⬆ ⬇

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

Interactions ⬆ ⬇

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.

Route/Dosage ⬆ ⬇

The oral suspension is NOT interchangeable with delayed-release tablets.

Treatment of Invasive Aspergillosis

May switch between use of IV and delayed-release tablets (another loading dose is not needed when switching between formulations).
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.

Availability ⬆ ⬇

(Generic available)

Delayed-release tablets: 100 mg
Oral suspensioncherry flavor: 40 mg/mL
Solution for injection: 18 mg/mL

Assessment ⬆ ⬇

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

Lab Test Considerations:

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.

Implementation ⬆ ⬇

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. Diluent: 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.

Patient/Family Teaching ⬆ ⬇

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.
Rep: 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.

Evaluation/Desired Outcomes ⬆ ⬇

Fungistatic/fungicidal action against susceptible fungi.

US Brand Names ⬆ ⬇

Canadian Brand Names ⬆ ⬇

Code ⬆

NDC Code

0085- Merck Sharp and Dohme Corp.
- 0085-1328- NOXAFIL
  - 0085-1328-01- 1 BOTTLE, GLASS in 1 CARTON (0085-1328-01) > 105 mL in 1 BOTTLE, GLASS

0085- Merck Sharp and Dohme Corp.
- 0085-4324- NOXAFIL
  - 0085-4324-02- 60 TABLET, COATED in 1 BOTTLE (0085-4324-02)

0085- Merck Sharp and Dohme Corp.
- 0085-4331- NOXAFIL
  - 0085-4331-01- 1 VIAL, GLASS in 1 CARTON (0085-4331-01) > 16.7 mL in 1 VIAL, GLASS

0254- Par Pharmaceutical Inc.
- 0254-2045- POSACONAZOLE
  - 0254-2045-02- 60 TABLET, COATED in 1 BOTTLE (0254-2045-02)

0527- Lannett Company Inc.
- 0527-2133- POSACONAZOLE
  - 0527-2133-35- 60 TABLET, DELAYED RELEASE in 1 BOTTLE (0527-2133-35)

0527- Lannett Company Inc.
- 0527-2133- POSACONAZOLE
  - 0527-2133-43- 1000 TABLET, DELAYED RELEASE in 1 BOTTLE (0527-2133-43)

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇