posaconazole

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

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 interval prolongation including congenital QTc prolongation, concurrent medications that prolong the QTc interval, 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 <13 yr (oral suspension) or <3 yr (all other formulations) (safety and effectiveness not established).

Adv. Reactions/Side Effects ⬆ ⬇

CV: QT interval prolongation, TORSADES DE POINTES

Endo: adrenal insufficiency, pseudoaldosteronism

F and E: 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 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 non-azole 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 or delayed-release oral suspension.

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 ≥2 yr and >40 kg): 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.
PO (Children ≥2 yr and 36–40 kg): Powder for delayed-release oral suspension: 240 mg twice daily on Day 1; then 240 mg once daily starting on Day 2 for a total of 6–12 wk.
PO (Children ≥2 yr and 26–<36 kg): Powder for delayed-release oral suspension: 210 mg twice daily on Day 1; then 210 mg once daily starting on Day 2 for a total of 6–12 wk.
PO (Children ≥2 yr and 21–<26 kg): Powder for delayed-release oral suspension: 180 mg twice daily on Day 1; then 180 mg once daily starting on Day 2 for a total of 6–12 wk.
PO (Children ≥2 yr and 17–<21 kg): Powder for delayed-release oral suspension: 150 mg twice daily on Day 1; then 150 mg once daily starting on Day 2 for a total of 6–12 wk.
PO (Children ≥2 yr and 10–<17 kg): Powder for delayed-release oral suspension: 120 mg twice daily on Day 1; then 120 mg once daily starting on Day 2 for a total of 6–12 wk.
IV (Adults ): 300 mg twice daily on Day 1; then 300 mg once daily starting on Day 2 for a total of 6–12 wk.
IV (Children ≥2 yr and >10 kg): 6 mg/kg (max = 300 mg) twice daily on Day 1; then 6 mg/kg (max = 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.
PO (Children ≥2 yr and 36–40 kg): Powder for delayed-release oral suspension: 240 mg twice daily on Day 1; then 240 mg once daily starting on Day 2 for a total of 6–12 wk.
PO (Children ≥2 yr and 26–<36 kg): Powder for delayed-release oral suspension: 210 mg twice daily on Day 1; then 210 mg once daily starting on Day 2 for a total of 6–12 wk.
PO (Children ≥2 yr and 21–<26 kg): Powder for delayed-release oral suspension: 180 mg twice daily on Day 1; then 180 mg once daily starting on Day 2 for a total of 6–12 wk.
PO (Children ≥2 yr and 17–<21 kg): Powder for delayed-release oral suspension: 150 mg twice daily on Day 1; then 150 mg once daily starting on Day 2 for a total of 6–12 wk.
PO (Children ≥2 yr and 12–<17 kg): Powder for delayed-release oral suspension: 120 mg twice daily on Day 1; then 120 mg once daily starting on Day 2 for a total of 6–12 wk.
PO (Children ≥2 yr and 10–<12 kg): Powder for delayed-release oral suspension: 90 mg twice daily on Day 1; then 90 mg once daily starting on Day 2 for a total of 6–12 wk.
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 and ≥10 kg): 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 suspension cherry flavor: 40 mg/mL
Powder for delayed-release oral suspension: 300 mg/pkt
Solution for injection: 18 mg/mL

Assessment ⬆ ⬇

Assess for previous allergies to antifungal medicines (ketoconazole, fluconazole, itraconazole, voriconazole).
Assess for signs/ symptoms of fungal infection. If severe diarrhea or vomiting occurs, monitor closely for breakthrough fungal infection.
Assess for hypersensitivity reactions (rash; hives; swelling of mouth, face, lips, tongue, or throat). Implement supportive measures (epinephrine) as indicated.
Assess cardiac status. Obtain baseline ECG and periodically during therapy to monitor for arrhythmias and QT interval prolongation in high-risk patients.

Lab Test Considerations:

Monitor liver function tests before and periodically during therapy. May ↑ ALT, AST, alkaline phosphatase, and total bilirubin levels; generally reversible on discontinuation. If clinical signs/symptoms of liver disease develop, permanently discontinue posaconazole.
- May cause pseudoaldosteronism (new or exacerbation of hypertension and abnormal laboratory tests). Monitor for ↓ aldosterone, ↑ 11-deoxycortisol, ↓ potassium, and ↓ serum renin. If these occur, discontinue therapy, switch to another antifungal, or use of an aldosterone receptor antagonist may be necessary.
- Monitor electrolyte levels (may ↓ potassium, magnesium, and calcium) before starting and during therapy. Correct as necessary before and during therapy.

Implementation ⬆ ⬇

Posaconazole comes in different forms (injection, delayed-release tablets, oral suspension, and PowderMix), and are not interchangeable. Oral suspension must not be substituted for the delayed-release tablets or PowderMix because each formulation has different dosing.
PO: Administer delayed-release tablets with food. DNC: Swallow tablets whole; do not divide, crush, or chew.
- Oral suspension: 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 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.
- PowderMix for delayed-release oral suspension: Reconstitute immediately before use using only the supplied mixing liquid. Mix the entire contents of 1 packet (300 mg) with 9 mL of the provided mixing liquid and shake vigorously for 45 sec until the suspension is cloudy and free of clumps (final concentration 30 mg/mL). Use within 1 hr of reconstitution and discard any unused suspension. Use only the supplied notched-tip oral syringes to prepare and administer the reconstituted suspension. Select the 3 mL (green) syringe for doses ≤3 mL and the 10 mL (blue) syringe for doses >3 mL. Administer with food within 1 hr of reconstitution. The max withdrawable dose from a single reconstituted suspension is 240 mg (8 mL). Discard unused suspension after administration. The provided mixing cup and notched-tip oral syringes may be hand washed and reused (or the mixing cup may be replaced with a similar lidded cup).

IV Administration:

Intermittent Infusion: Allow solution to reach room temperature before administering. Diluent: Dilute in D5W, D5/0.45% NaCl, D5/0.9% NaCl, 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
- cefiderocol
- furosemide
- ganciclovir
- imipenem/cilastatin/relebactam
- insulin aspart
- levetiracetam
- methylprednisolone
- metoclopramide
- ondansetron
- pantoprazole
- tazobactam

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care provider before taking any new medications.
Advise patient to notify health care provider if severe diarrhea or vomiting occurs (may ↓ posaconazole levels and allow breakthrough fungal infections) or if signs/symptoms of liver injury (itching, yellow eyes or skin, fatigue, flu-like symptoms) or change in HR or rhythm occur.
Emphasize the need for routine laboratory and BP monitoring before and during therapy.
For Delayed-Release Tablets:If a dose is missed, take it as soon as remembered unless it is within 12 hr of the next scheduled dose; in that case, skip the missed dose and resume the regular dosing schedule. Do not double doses.
For Oral Suspension:Advise patient on proper administration. Advise if dose is missed, take it as soon as remembered unless it is almost time for the next scheduled dose. If so, skip the missed dose and resume the regular dosing schedule. Do not double doses or take more than the prescribed dose.
For PowderMix for Delayed-Release Oral Suspension:Advise patient to use only the supplied notched-tip oral syringes to administer PowderMix for delayed-release oral suspension. Administer with food. Advise patient/caregivers that PowderMix contains sorbitol.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected and to avoid breastfeeding during therapy.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇