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Pharmacologic class: Triazole
Therapeutic class: Antifungal
Pregnancy risk category C
Inhibits fungal ergosterol synthesis (key component of fungal cell membrane) by inhibiting lanosterol 14-alpha demethylase and causing methylated sterol precursors to accumulate
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
• Esophageal candidiasis
• Fusarium infection
• Hypersensitivity to drug or its components
• Concurrent use of astemizole, cisapride, ergot alkaloids, halofantrine, pimozide, quinidine, sirolimus, or terfenadine
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).
• 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.
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
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
• 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.
• 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.
Time/action profile (blood levels)
|PO||unknown||3–5 hr||8 hr|
Adverse Reactions/Side Effects
Central nervous system
- headache (most frequent)
- torsades de pointes (life-threatening)
- QT interval prolongation
- hepatocellular damage (life-threatening)
- diarrhea (most frequent)
- nausea (most frequent)
- vomiting (most frequent)
- adrenal insufficiency
- cough (most frequent)
- allergic reactions (life-threatening)
- fever (most frequent)
Drug-Drug interactionPosaconazole 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.
- 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 DiagnosesRisk for infection (Indications)
- 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.
- 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.
- Resolution of clinical and laboratory indications of fungal infections. Duration of therapy is based on recovery from infection or neutropenia or immunosuppression.