posaconazole


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posaconazole

Noxafil, Posanol (CA)

Pharmacologic class: Triazole

Therapeutic class: Antifungal

Pregnancy risk category C

Action

Inhibits fungal ergosterol synthesis (key component of fungal cell membrane) by inhibiting lanosterol 14-alpha demethylase and causing methylated sterol precursors to accumulate

Availability

Oral suspension (immediate-release): 40 mg/ml in 123-ml bottle

Indications and dosages

Prophylaxis of invasive Aspergillus and Candida infections in patients at risk for these infections because of severe immunocompromise (such as hematopoietic stem-cell transplant recipients with graft-versus-host disease and those who have hematologic cancers with prolonged neutropenia from chemotherapy)

Adults and children age 13 and older: 200 mg (5 ml) P.O. three times daily for duration of therapy based on recovery from neutropenia or immunosuppression

Oropharyngeal candidiasis

Adults and children age 13 and older: Loading dose of 100 mg (2.5 ml) P.O. twice daily on first day, then 100 mg P.O. once daily for 13 days

Oropharyngeal candidiasis refractory to itraconazole or fluconazole

Adults and children age 13 and older: 400 mg (10 ml) P.O. twice daily for duration of therapy based on disease severity and clinical response

Off-label uses

• Esophageal candidiasis
Fusarium infection
• Mycosis

Contraindications

• Hypersensitivity to drug or its components
• Concurrent use of astemizole, cisapride, ergot alkaloids, halofantrine, pimozide, quinidine, sirolimus, or terfenadine

Precautions

Use cautiously in:
• hypersensitivity to other azoles
• potentially proarrhythmic conditions, severe underlying medical conditions (such as hematologic cancers), preexisting hepatic impairment
• pregnant or breastfeeding patients
• children younger than age 13 (safety and efficacy not established).

Administration

• Before starting drug, make rigorous attempts to correct potassium, magnesium, and calcium imbalances.
• Advise patient to take each dose with full meal or liquid nutritional supplement to enhance drug absorption.

Don't give concurrently with astemizole, cisapride, ergot alkaloids, halofantrine, pimozide, quinidine, or terfenadine.

Adverse reactions

CNS: seizure, insomnia, anxiety, headache, fatigue, dizziness, weakness

CV: prolonged QT interval, hypertension, hypotension, tachycardia

EENT: blurred vision, epistaxis, pharyngitis

GI: nausea, vomiting, diarrhea, constipation, abdominal pain, dyspepsia, flatulence, mucositis, dry mouth, oral candidiasis, anorexia

GU: vaginal hemorrhage

Hematologic: anemia, neutropenia, febrile neutropenia, thrombocytopenia

Hepatic: cholestasis, hepatic damage, hepatic failure

Metabolic: adrenal insufficiency (rare), dehydration

Musculoskeletal: arthralgia, back pain

Respiratory: cough, dyspnea, upper respiratory tract infection, pneumonia

Skin: rash, pruritus, petechiae

Other: unusual taste, weight loss, fever, bacteremia, herpes simplex, edema, leg edema, rigors, cytomegalovirus infection

Interactions

Drug-drug.Astemizole, cisapride, halofantrine, pimozide, quinidine, terfenadine: elevated blood levels of these drugs, leading to prolonged QT interval and increased risk of life-threatening arrhythmias (including torsades de pointes)

Benzodiazepines metabolized through CYP3A4 (such as midazolam), pheny-toin, rifabutin: increased blood levels of these drugs

Calcium channel blockers metabolized through CYP3A4 (such as amlodipine, diltiazem, felodipine): increased blood levels of these drugs, causing increased toxicity risk

Cimetidine, phenytoin, rifabutin: decreased posaconazole blood level

Cyclosporine, sirolimus, tacrolimus: elevated blood levels of these drugs, causing increased risk of nephrotoxicity and other serious adverse reactions

Ergot derivatives (dihydroergotamine, ergotamine): increased blood levels of these drugs, causing increased ergotism risk

HMG-CoA reductase inhibitors metabolized through CYP3A4 (such as atorvas-tatin, fluvastatin, lovastatin): increased blood levels of these drugs, causing increased risk of rhabdomyolysis

Vinca alkaloids (such as vinblastine, vincristine): increased vinca alkaloid blood levels, causing increased neuro-toxicity risk

Drug-diagnostic tests.Alanine amino-transferase, alkaline phosphatase, aspartate aminotransferase, bilirubin, gamma-glutamyltransferase, serum creatinine: increased levels

Drug-food.Nonfat, high-fat, or liquid nutritional supplements: approximately three-to four-fold increase in drug mean Cmax and area under the curve values

Patient monitoring

• Monitor serum potassium, magnesium, and calcium levels before and frequently during therapy.
• Obtain liver function tests and bilirubin level at start of therapy and periodically throughout. If liver function tests become abnormal during therapy, stay alert for signs and symptoms of more severe hepatic injury; consider withdrawing drug if these occur.
• Monitor blood drug levels frequently if patient is receiving concurrent cyclosporine, sirolimus, or tacrolimus. Consider reducing dosage as appropriate.

Monitor ECG if patient has potentially proarrhythmic condition or is receiving concurrent drugs that may prolong QT interval and are metabolized through CYP3A4. Stay alert for prolonged QT interval.
• Watch for breakthrough fungal infections in patients with severe diarrhea, vomiting, or severe renal impairment and in those receiving drugs that may decrease blood drug level or who can't eat a full meal or tolerate oral nutritional supplements.

Patient teaching

• Instruct patient to take each dose with full meal or liquid nutritional supplement.
• Advise patient to inform prescriber of all drugs he is taking because serious interactions may occur.

Urge patient to contact prescriber immediately if he develops signs or symptoms of liver impairment, such as unusual tiredness, weakness, nausea, itching, yellowing of eyes or skin, upper right abdominal tenderness, or flulike symptoms.

Tell patient to contact prescriber immediately if he develops irregular heartbeats or other cardiac symptoms.

Advise patient to notify prescriber of severe diarrhea or vomiting, because these conditions may alter blood drug level.
• Stress importance of keeping appointments for follow-up laboratory tests.
• Caution patient to avoid driving and other hazardous activities because drug may alter vision.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and foods mentioned above.

posaconazole

(po-sa-kon-a-zole) ,

Noxafil

(trade name),

Posanol

(trade name)

Classification

Therapeutic: antifungals
Pharmacologic: triazoles
Pregnancy Category: C

Indications

Prevention of invasive aspergillus and candida infections in severely immunocompromised patients.Treatment of orpharyngeal candidiasis (including candidiasis unresponsive to itraconazole or fluconazole).

Action

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

Therapeutic effects

Fungistatic/fungicidal action against susceptible fungi.

Pharmacokinetics

Absorption: Well absorbed following oral administration; absorption is optimized by food.
Distribution: Extensive extravascular distribution and penetration into body tissues.
Protein Binding: >98%.
Metabolism and Excretion: Some metabolism via UDP glucuronidation; 66% eliminated unchanged in feces, 13% in urine (mostly as metabolites).
Half-life: 35 hr.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
POunknown3–5 hr8 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity to posaconazole or other azole antifungals;Concurrent use of pimozide, quinidine, ergot alkaloids, sirolimus, simvastatin, atorvastatin, or lovastatin.
Use Cautiously in: History of/predisposition to QTc prolongation including congenital QTc prolongation, concurrent medications that prolong QTc, high cumulative anthracycline history or electrolyte abnormalities (hypokalemia, hypomagnesemia); correct pre-existing abnormalities prior to administration;Severe diarrhea, vomiting, or renal impairment (monitor for breakthrough fungal infections); Obstetric / Lactation: Use only if maternal benefit outweighs risk to child; Pediatric: Children <13 yr (safety not established).

Adverse Reactions/Side Effects

Central nervous system

  • headache (most frequent)

Cardiovascular

  • torsades de pointes (life-threatening)
  • QT interval prolongation

Gastrointestinal

  • hepatocellular damage (life-threatening)
  • diarrhea (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)

Endocrinologic

  • adrenal insufficiency

Respiratory

  • cough (most frequent)

Metabolic

  • allergic reactions (life-threatening)

Miscellaneous

  • fever (most frequent)

Interactions

Drug-Drug interaction

Posaconazole inhibits the CYP3A4 enzyme systems and should be expected to interact with other drugs affected by this system.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.Rifabutin, phenytoin, cimetidine, and efavirenz ↓ levels and may ↓ antifungal effectiveness; avoid concurrent use.Fosamprenavir ↓ levels and may ↓ antifungal effectiveness; monitor for breakthrough antifungal infectionsEsomeprazole and metoclopramide may ↓ levels and may ↓ antifungal effectiveness.↑ rifabutin levels; avoid concurrent use.May ↑ digoxin levels; monitor levels frequently.↑ phenytoin, midazolam, ritonavir, and atazanavir levels; monitor for excess clinical effect.↑ levels and risk of neurotoxicity of vinca alkaloids, including vincristine and vinblastine ; consider dose adjustment.↑ levels and risk of toxicity of HMG CoA reductase inhibitors (statins) ; consider ↓ statin dose.May ↑ levels and risk of adverse cardiovascular reactions to calcium channel blockers ; consider dosage reduction.

Route/Dosage

Oral (Adults and Children ≥13 yr) Prophylaxis of invasive fungal infections—200 mg 3 times daily.
Oral (Adults) Oropharyngeal candidiasis—100 mg 2 times daily for 1 day, then 100 mg daily for 13 days; Refractory oropharyngeal candidiasis—400 mg 2 times daily.

Availability

Oral suspensioncherry: 40 mg/mL

Nursing implications

Nursing assessment

  • Assess for signs and symptoms of 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.

Potential Nursing Diagnoses

Risk for infection (Indications)

Implementation

  • Oral: Shake suspension well before use. Administer with a full meal, liquid nutritional supplement or an acidic carbonated beverage (ginger ale) to enhance 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.

Patient/Family Teaching

  • 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 read the Patient Information before taking posaconazole and with each Rx refill; may be new information.
  • Advise patient to notify health care professional if severe diarrhea or vomiting occur; may decrease posaconazole blood levels and allow breakthrough fungal infections or if signs and symptoms of liver injury (itching, yellow eyes or skin, fatigue, flu-like symptoms) occur.
  • 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 pregnancy is planned or suspected or if breast feeding.

Evaluation/Desired Outcomes

  • Resolution of clinical and laboratory indications of fungal infections. Duration of therapy is based on recovery from infection or neutropenia or immunosuppression.

posaconazole

a systemic antifungal.
indications This drug is used for prevention of aspergillus, Candida infection, and oropharyngeal candidiasis in the immunocompromised.
contraindications Fungal meningitis, onychomycosis or dermatomycosis in cardiac dysfunction, and hypersensitivity to this drug or other systemic antifungals or azoles prohibit its use.
adverse effects Adverse effects of this drug include insomnia, fever, rigors, weakness, anxiety, hypertension, hypotension, tachycardia, anemia, cramps, abdominal pain, flatulence, gynecomastia, impotence, decreased libido, malaise, hypokalemia, and tinnitus. Life-threatening side effects include GI bleeding, hepatotoxicity, toxic epidermal necrolysis, and rhabdomyolysis. Common side effects include headache, dizziness, nausea, vomiting, anorexia, diarrhea, pruritus, edema, and fatigue.

posaconazole

An extended-spectrum triazole antifungal drug active in vitro against a wide range of fungi including candida species, aspergillus species, fusarium species and zygomycetes.
References in periodicals archive ?
Any of these medicines (if taken by mouth or injection): clarithromycin (Biaxin), erythromycin (E-Mycin, Eryc, Ery-Tab, PCE, Pediazole, Ilosone), fluconazole (Diflucan), itraconazole (Sporanox), ketoconazole (Nizoral), methadone (Dolophine), posaconazole (Noxafil), telithromycin (Ketek), voriconazole (Vfend)
guilliermondii strains exhibited high rates of azole MICs above ECVs (fluconazole, 17%; voriconazole and posaconazole, 24%; Table 3).
Supply of Syrup Posaconazole, Abacavir Tab 300 mg, Efavirenz Tab 200 mg, Dexamethasone 4 mg Tab, Intravenous aminoacid, Saccharomyces boulardii Capsule, Injection Acetaminophen, Mefenamic acid suspension, Inj Acetyl Cysteine, etc.
Benznidazole and posaconazole in experimental Chagas disease: positive interaction in concomitant and sequential treatments.
Intravenous liposomal amphotericin B, intravenous echinocandins such as caspofungin and micafungin, and oral triazoles such as posaconazole and itraconazole can be used as alternative (salvage) therapy.
Other useful agents may be voriconazole (VFend), caspofungin (Cancidas), micafungin (Mycamine), or posaconazole (Noxafil).
The ergosterol-synthesis inhibitor posaconazole proved ineffective at eliminating Trypanosoma cruzi DNA from the blood of patients with chronic Chagas' disease, according to a report published online May 14 in the New England Journal of Medicine.
In the management of fusariosis, conventional or liposomal Amp B may be used singly; successful results were achieved also by combining it with voriconazole or posaconazole (8), (9), (10).
In other research, rapid treatment with amphotericin B or posaconazole led to the best outcomes.
More recently, voriconazole and then posaconazole have been shown to be efficacious in patients who had failed itraconazole.
41) Posaconazole, a structural analogue of itraconazole, was approved for use in USA in 2006.