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Medication Safety Issues
Sound-alike/look-alike issues:
Noxafil® may be confused with minoxidil
International issues:
Noxafil® may be confused with Noxidil® which is a brand name for minoxidil in Thailand
Pronunciation
(poe sa KON a zole)
U.S. Brand Names
Index Terms
Generic Available
No
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Prophylaxis of invasive Aspergillus and Candida infections in severely-immunocompromised patients [eg, hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD) or those with prolonged neutropenia secondary to chemotherapy for hematologic malignancies]; treatment of oropharyngeal candidiasis (including patients refractory to itraconazole and/or fluconazole)
Use: Dental
Treatment of oropharyngeal candidiasis (including patients refractory to itraconazole and/or fluconazole)
Use: Unlabeled/Investigational
Salvage therapy of refractory invasive fungal infections; mucormycosis
Pregnancy Risk Factor
C
Pregnancy Considerations
Posaconazole has been shown to be teratogenic in animal studies. There are no adequate and well-controlled studies in pregnant women. Use only if the benefit to the mother justifies potential risk to the fetus.
Lactation
Excretion in breast milk unknown/not recommended
Breast-Feeding Considerations
Excretion in breast milk has not been investigated; use only if the benefit to the mother justifies potential risk to the fetus.
Contraindications
Hypersensitivity to posaconazole or any component of the formulation; coadministration of cisapride, ergot alkaloids, pimozide, quinidine, or sirolimus
Warnings/Precautions
Concerns related to adverse effects:
• Azole hypersensitivity: Use with caution in patients with hypersensitivity to other azole antifungal agents; cross-reaction may occur, but has not been established.
• Hepatic effects: Hepatic dysfunction has occurred, ranging from reversible mild/moderate increases of ALT, AST, alkaline phosphatase, total bilirubin, and/or clinical hepatitis to severe reactions (cholestasis, hepatic failure including death). Consider discontinuation of therapy in patients who develop clinical evidence of liver disease that may be secondary to posaconazole.
Disease-related concerns:
• Arrhythmias: Use caution in patients with an increased risk of arrhythmia (long QT syndrome, concurrent QTc-prolonging drugs, hypokalemia). Correct electrolyte abnormalities (eg, potassium, magnesium, and calcium) before initiating therapy.
• GI disturbances: Monitor closely for breakthrough fungal infections in patients with severe diarrhea or vomiting.
• Renal impairment: Monitor closely for breakthrough fungal infections in patients with severe renal impairment due to variability in posaconazole exposure.
Concurrent drug therapy issues:
• Cyclosporine: Concurrent use may significantly increase cyclosporine levels and may result in rare serious adverse events (eg, nephrotoxicity, leukoencephalopathy, and death); dose reduction and close monitoring are recommended with initiation of posaconazole therapy.
• High potential for interactions: Consider alternative therapy or closely monitor for breakthrough fungal infections in patients receiving drugs that decrease absorption or increase the metabolism of posaconazole.
Special populations:
• Patients unable to take or tolerate nutritional supplements: Consider alternative antifungal therapy or closely monitor for breakthrough fungal infections in any patient unable to eat or tolerate an oral liquid nutritional supplement.
• Pediatrics: Safety and efficacy have not been established in children <13 years of age.
Adverse Reactions
Note: A higher frequency of adverse reactions was observed in studies with refractory oropharyngeal candidiasis patients and percentages are included below.
>10%: Gastrointestinal: Diarrhea (3% to 11%)
1% to 10%:
Cardiovascular: QTc prolongation (?4%), hypertension (?1%)
Central nervous system: Headache (1% to 8%), dizziness (1% to 3%), fatigue (1% to 3%), insomnia (1% to 3%), fever (?3%), somnolence (?1%)
Dermatologic: Rash (1% to 4%), pruritus (1% to 2%)
Endocrine & metabolic: Hypokalemia (?3%)
Gastrointestinal: Nausea (5% to 8%), vomiting (4% to 7%), abdominal pain (1% to 5%), flatulence (1% to 5%), anorexia (1% to 3%), mucositis (?2%), dyspepsia (1% to 2%), xerostomia (1% to 2%), constipation (?1%), taste perversion (?1%)
Hematologic: Neutropenia (2% to 8%), anemia (?3%), thrombocytopenia (?2%)
Hepatic: ALT increased (2% to 17%), AST increased (2% to 17%), alkaline phosphatase increased (1% to 13%), bilirubin increased (2% to 9%), GGT increased (2% to 3%), hepatocellular damage (?1%)
Neuromuscular & skeletal: Weakness (1% to 3%), myalgia (?2%), tremor (?1%)
Ocular: Blurred vision (?1%)
Renal: Serum creatinine increased (?2%)
<1%, postmarketing, and/or case reports: Adrenal insufficiency, allergic/hypersensitivity reactions, atrial fibrillation, cholestasis, ejection fraction decreased, hemolytic uremic syndrome, hepatic failure, hepatitis, jaundice, pulmonary embolus, syncope, thrombotic thrombocytopenic purpura, torsade de pointes
Metabolism/Transport Effects
Inhibits CYP3A4 (strong)
Drug Interactions
Alfentanil: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Alfentanil. Risk D: Consider therapy modification
Alfuzosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alfuzosin. Risk X: Avoid combination
Almotriptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Almotriptan. Management: Limit initial almotriptan adult dose to 6.25 mg and maximum adult dose to 12.5 mg/24-hrs when used with a strong CYP3A4 inhibitor. Avoid concurrent use in patients with impaired hepatic or renal function. Risk D: Consider therapy modification
Alosetron: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alosetron. Risk C: Monitor therapy
Amphotericin B: Antifungal Agents (Azole Derivatives, Systemic) may diminish the therapeutic effect of Amphotericin B. Risk C: Monitor therapy
Antacids: May decrease the absorption of Antifungal Agents (Azole Derivatives, Systemic). Risk D: Consider therapy modification
Antineoplastic Agents (Vinca Alkaloids): Posaconazole may enhance the adverse/toxic effect of Antineoplastic Agents (Vinca Alkaloids). Posaconazole may increase the serum concentration of Antineoplastic Agents (Vinca Alkaloids). Risk D: Consider therapy modification
Aprepitant: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Aprepitant. Risk C: Monitor therapy
Benzodiazepines (metabolized by oxidation): Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Benzodiazepines (metabolized by oxidation). Exceptions: Quazepam. Risk D: Consider therapy modification
Bosentan: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Bosentan. Risk C: Monitor therapy
Brinzolamide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brinzolamide. Risk C: Monitor therapy
BusPIRone: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of BusPIRone. Risk D: Consider therapy modification
Busulfan: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Busulfan. Risk C: Monitor therapy
Calcium Channel Blockers: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Calcium Channel Blockers. Exceptions: Clevidipine. Risk D: Consider therapy modification
CarBAMazepine: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of CarBAMazepine. Risk C: Monitor therapy
Cardiac Glycosides: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Cardiac Glycosides. Risk D: Consider therapy modification
Ciclesonide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ciclesonide. Specifically, concentrations of the active des-ciclesonide metabolite may be increased. Risk C: Monitor therapy
Cilostazol: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Cilostazol. Risk D: Consider therapy modification
Cinacalcet: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Cinacalcet. Risk C: Monitor therapy
Cisapride: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Cisapride. Risk X: Avoid combination
Colchicine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Colchicine. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a strong CYP3A4 inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Risk D: Consider therapy modification
Conivaptan: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Conivaptan. Risk X: Avoid combination
Corticosteroids (Orally Inhaled): Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Corticosteroids (Orally Inhaled). Exceptions: Beclomethasone; Flunisolide; Triamcinolone. Risk C: Monitor therapy
Corticosteroids (Systemic): Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Corticosteroids (Systemic). Risk C: Monitor therapy
CycloSPORINE: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of CycloSPORINE. Risk D: Consider therapy modification
CYP3A4 Substrates: CYP3A4 Inhibitors (Strong) may decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Didanosine: May decrease the absorption of Antifungal Agents (Azole Derivatives, Systemic). Enteric coated didanosine capsules are not expected to affect these antifungals. Risk D: Consider therapy modification
Docetaxel: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Docetaxel. Risk D: Consider therapy modification
Dofetilide: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Dofetilide. Risk X: Avoid combination
Dronedarone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronedarone. Risk X: Avoid combination
Dutasteride: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dutasteride. Risk C: Monitor therapy
Efavirenz: May decrease the serum concentration of Posaconazole. Risk X: Avoid combination
Eletriptan: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Eletriptan. Risk D: Consider therapy modification
Eplerenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eplerenone. Risk X: Avoid combination
Eplerenone: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Eplerenone. Risk D: Consider therapy modification
Ergot Derivatives: Posaconazole may increase the serum concentration of Ergot Derivatives. Risk X: Avoid combination
Erlotinib: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Erlotinib. Risk C: Monitor therapy
Eszopiclone: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Eszopiclone. Risk C: Monitor therapy
Everolimus: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Everolimus. Risk X: Avoid combination
FentaNYL: CYP3A4 Inhibitors (Strong) may increase the serum concentration of FentaNYL. Risk D: Consider therapy modification
Fesoterodine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fesoterodine. Management: Avoid fesoterodine doses greater than 4 mg daily in adult patients who are also receiving strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Fosaprepitant: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Fosaprepitant. Specifically, concentrations of aprepitant are likely to be increased. Risk C: Monitor therapy
Gefitinib: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Gefitinib. Risk C: Monitor therapy
Grapefruit Juice: May increase the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). This specifically applies to oral antifungal administration, and the interaction may be different depending on specific dosage form being used. Risk C: Monitor therapy
H2-Antagonists: May decrease the absorption of Antifungal Agents (Azole Derivatives, Systemic). Risk D: Consider therapy modification
Halofantrine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Halofantrine. Risk X: Avoid combination
HMG-CoA Reductase Inhibitors: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of HMG-CoA Reductase Inhibitors. Exceptions: Fluvastatin; Pitavastatin; Rosuvastatin. Risk D: Consider therapy modification
Imatinib: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Imatinib. Risk C: Monitor therapy
Irinotecan: Antifungal Agents (Azole Derivatives, Systemic) may enhance the adverse/toxic effect of Irinotecan. Risk D: Consider therapy modification
Ixabepilone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ixabepilone. Risk D: Consider therapy modification
Losartan: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Losartan. Risk C: Monitor therapy
Macrolide Antibiotics: May decrease the metabolism of Antifungal Agents (Azole Derivatives, Systemic). Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Macrolide Antibiotics. Exceptions: Azithromycin; Dirithromycin [Off Market]; Spiramycin. Risk D: Consider therapy modification
Maraviroc: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc. Management: When used with a strong CYP3A4 inhibitor, the adult dose of maraviroc should be decreased to 150 mg twice daily. Risk D: Consider therapy modification
Methadone: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Methadone. Risk C: Monitor therapy
Metoclopramide: May decrease the serum concentration of Posaconazole. Risk C: Monitor therapy
Nilotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib. Risk X: Avoid combination
Nisoldipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nisoldipine. Risk X: Avoid combination
Paricalcitol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Paricalcitol. Risk C: Monitor therapy
Pazopanib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pazopanib. Management: Avoid concurrent use of pazopanib with strong inhibitors of CYP3A4 whenever possible. If it is not possible to avoid such a combination, reduce pazopanib dose to 400 mg. Further dose reductions may also be required. Risk D: Consider therapy modification
Phenytoin: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Risk D: Consider therapy modification
Phosphodiesterase 5 Inhibitors: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Phosphodiesterase 5 Inhibitors. Risk D: Consider therapy modification
Pimecrolimus: CYP3A4 Inhibitors (Strong) may decrease the metabolism of Pimecrolimus. Risk C: Monitor therapy
Pimozide: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Pimozide. Risk X: Avoid combination
Prasugrel: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Prasugrel. Risk C: Monitor therapy
Protease Inhibitors: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Protease Inhibitors. Protease Inhibitors may increase the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Management: Limit indinavir adult dose to 600 mg every 8 hours with itraconazole or ketoconazole. With ritonavir, limit ketoconazole adult dose to 200 mg/day. Limit fluconazole, itraconazole, and ketoconazole to 200 mg (adult dose) with tipranavir/ritonavir. Risk D: Consider therapy modification
Proton Pump Inhibitors: May decrease the serum concentration of Posaconazole. Risk X: Avoid combination
QuiNIDine: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of QuiNIDine. Management: Itraconazole, voriconazole, and posaconazole are specifically contraindicated with quinidine. Use of quinidine with any azole antifungal may require quinidine dose adjustment and should be done with caution and close monitoring. Risk X: Avoid combination
Ramelteon: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Ramelteon. Risk C: Monitor therapy
Ranolazine: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Ranolazine. Risk X: Avoid combination
Ranolazine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ranolazine. Risk X: Avoid combination
Repaglinide: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Repaglinide. Management: Concurrent use of an azole antifungal with both repaglinide and gemfibrozil should be avoided. Risk C: Monitor therapy
Rifamycin Derivatives: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Rifamycin Derivatives. Only rifabutin appears to be affected. Rifamycin Derivatives may decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Risk D: Consider therapy modification
Rivaroxaban: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rivaroxaban. Risk X: Avoid combination
Saccharomyces boulardii: Antifungal Agents may diminish the therapeutic effect of Saccharomyces boulardii. Risk D: Consider therapy modification
Salmeterol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Salmeterol. Risk X: Avoid combination
Saxagliptin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Saxagliptin. Management: Limit saxagliptin adult dose to 2.5 mg/day and monitor for increased saxagliptin levels/effects (e.g., hypoglycemia) when used with a strong CYP3A4 inhibitor. Monitor for decreased saxagliptin levels/effects if discontinuing CYP3A4 inhibitor. Risk D: Consider therapy modification
Silodosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Silodosin. Risk X: Avoid combination
Sirolimus: Posaconazole may increase the serum concentration of Sirolimus. Risk X: Avoid combination
Solifenacin: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Solifenacin. Risk D: Consider therapy modification
Sorafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sorafenib. Risk C: Monitor therapy
Sucralfate: May decrease the absorption of Antifungal Agents (Azole Derivatives, Systemic). Risk C: Monitor therapy
Sunitinib: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Sunitinib. Risk D: Consider therapy modification
Tacrolimus: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Tacrolimus. Risk D: Consider therapy modification
Tadalafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tadalafil. Management: Erectile dysfunction: tadalafil max = 2.5 mg/day (daily use) or 10 mg/72 hrs (as needed use) (adult doses). Avoid use of tadalafil with a strong CYP3A4 inhibitor for treatment of pulmonary arterial hypertension. Risk D: Consider therapy modification
Temsirolimus: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Temsirolimus. Concentrations of the active metabolite, sirolimus, are likely to be increased more substantially than those of the parent temsirolimus. Risk D: Consider therapy modification
Tolterodine: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Tolterodine. This is likely only of concern in CYP2D6-deficient patients (ie, "poor metabolizers") Risk D: Consider therapy modification
Tolvaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolvaptan. Risk X: Avoid combination
Trimetrexate: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Trimetrexate. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Posaconazole may increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy
Ziprasidone: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Ziprasidone. Risk C: Monitor therapy
Zolpidem: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Zolpidem. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Food: Bioavailability increased ~3 times when posaconazole is administered with a nonfat meal or an oral liquid nutritional supplement; increased ~4 times when administered with a high-fat meal. Grapefruit juice may decrease the levels/effects of posaconazole; concurrent use should be avoided.
Storage
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°C to 86°C). Do not freeze.
Mechanism of Action
Interferes with fungal cytochrome P450 (latosterol-14?-demethylase) activity, decreasing ergosterol synthesis (principal sterol in fungal cell membrane) and inhibiting fungal cell membrane formation.
Pharmacodynamics/Kinetics
Absorption: Coadministration with food, liquid nutritional supplements, and/or acidic carbonated beverages (eg, ginger ale) increases absorption; fasting states do not provide sufficient absorption to ensure adequate plasma concentrations.
Distribution: Vd: 465-1774 L
Protein binding: >98%; predominantly bound to albumin
Metabolism: Not significantly metabolized; ~15% to 17% undergoes non-CYP-mediated metabolism, primarily via hepatic glucuronidation into metabolites
Half-life elimination: 35 hours (range: 20-66 hours)
Time to peak, plasma: ~3-5 hours
Excretion: Feces 71% to 77% (~66% of the total dose as unchanged drug); urine 13% to 14% (<0.2% of the total dose as unchanged drug)
Dosage
Oral:
Children ?13 years and Adults:
Aspergillosis, invasive:
Prophylaxis: 200 mg 3 times/day
Salvage treatment of refractory infection (unlabeled use): 200 mg 4 times/day initially; after disease stabilization may decrease frequency to 400 mg twice daily (Walsh, 2007). Note: Duration of therapy should be a minimum of 6-12 weeks or throughout period of immunosuppression.
Candidal infections:
Prophylaxis: 200 mg 3 times/day
Treatment of oropharyngeal infection: Initial: 100 mg twice daily for 1 day; maintenance: 100 mg once daily for 13 days
Treatment of refractory oropharyngeal infection: 400 mg twice daily
Adults: Mucormycosis (unlabeled use): 800 mg/day in 2 or 4 divided doses (Greenburg, 2006)
Dosage adjustment in renal impairment:
Mild-to-moderate renal insufficiency (Clcr 20-80 mL/minute): No adjustment necessary
Severe renal insufficiency (Clcr <20 mL/minute): No adjustment necessary; however, monitor for breakthrough fungal infections due to variability in posaconazole exposure.
Dosage adjustment in hepatic impairment:
Mild-to-severe hepatic insufficiency (Child-Pugh classes A, B, and C): No adjustment necessary
Clinical signs and symptoms of liver disease due to posaconazole: Consider discontinuing therapy
Dental Usual Dosing
Children ?13 years and Adults: Oral:
Oropharyngeal candidiasis: Initial: 100 mg twice daily for 1 day; maintenance dose: 100 mg once daily for 13 days
Refractory oropharyngeal candidiasis: 400 mg twice daily
Administration: Oral
Shake well before use. Must be administered during or within 20 minutes following a full meal or an oral liquid nutritional supplement; alternatively, posaconazole may be administered with an acidic carbonated beverage (eg, ginger ale). In patients able to swallow, administer oral suspension using dosing spoon provided by the manufacturer; spoon should be rinsed clean with water after each use and before storage.
Monitoring Parameters
Hepatic function (eg, AST/ALT, alkaline phosphatase and bilirubin) prior to initiation and during treatment; renal function; electrolyte disturbances (eg, calcium, magnesium, potassium); CBC
Dietary Considerations
Give during or within 20 minutes following a full meal or liquid nutritional supplement; alternatively, posaconazole may be administered with an acidic carbonated beverage (eg, ginger ale). Consider alternative antifungal therapy in patients with inadequate oral intake or severe diarrhea/vomiting; if alternative therapy is not an option, closely monitoring for breakthrough fungal infections. Adequate posaconazole absorption from GI tract and subsequent plasma concentrations are dependent on food for efficacy. Lower average plasma concentrations have been associated with an increased risk of treatment failure.
Patient Education
Do not take any new prescription or OTC medications or herbal products during therapy without consulting prescriber. Take exactly as directed, preferably during or immediately after a full meal or liquid nutritional supplement (can alternatively be taken with an acidic carbonated beverage, such as ginger ale). Take full course of medication as ordered; do not discontinue without consulting prescriber (fungal infections may take weeks or months of therapy). Maintain adequate hydration unless instructed to restrict fluid intake. You may experience nausea, vomiting, abdominal pain, or loss of appetite (frequent oral care, sucking lozenges, or chewing gum may help); constipation (increased dietary fiber, liquids, or exercise may help); or headache, dizziness, blurred vision, or insomnia (use caution when driving or engaging in tasks that require alertness until response to drug is known). Report immediately chest pain or palpitations, unusual muscle pain or weakness, severe diarrhea or vomiting, urinary pattern changes, yellowing of skin or eyes, changes in color of stool or urine, or any other persistent side effects. Breast-feeding precaution: Breast-feeding is not recommended.
Geriatric Considerations
Dosage adjustment not necessary.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation), abnormal taste, mucositis.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Dental Comment
This drug is known to prolong the QT interval. The QT interval is measured as the time and distance between the Q point of the QRS complex and the end of the T wave in the ECG tracing. After adjustment for heart rate, the QT interval is defined as prolonged if it is more than 450 msec in men and 460 msec in women. A long QT syndrome was first described in the 1950s and 60s as a congenital syndrome involving QT interval prolongation and syncope and sudden death. Some of the congenital long QT syndromes were characterized by a peculiar electrocardiographic appearance of the QRS complex involving a premature atria beat followed by a pause, then a subsequent sinus beat showing marked QT prolongation and deformity. This type of cardiac arrhythmia was originally termed “torsade de pointes” (translated from the French as “twisting of the points”).
Prolongation of the QT interval is thought to result from delayed ventricular repolarization. The repolarization process within the myocardial cell is due to the efflux of intracellular potassium. The channels associated with this current can be blocked by many drugs and predispose the electrical propagation cycle to torsade de pointes.
Posaconazole is one of the drugs confirmed to prolong the QT interval and is accepted as having a risk of causing torsade de pointes. The risk of drug-induced torsade de pointes is extremely low when a single QT interval prolonging drug is prescribed. In terms of epinephrine, it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval. Until more information is obtained, it is suggested that the clinician consult with the physician prior to the use of a vasoconstrictor in suspected patients, and that the vasoconstrictor (epinephrine, levonordefrin [Neo-Cobefrin®]) be used with caution.
Mental Health: Effects on Mental Status
May cause dizziness, fatigue, or insomnia
Mental Health: Effects on Psychiatric Treatment
Contraindicated with pimozide and ergot alkaloids. Diarrhea and other GI side effects are common and may be worse with combined use of lithium, valproic acid, carbamazepine, or SSRIs. May cause neutropenia; use caution with clozapine. May cause thrombocytopenia; use caution with valproic acid. May increase level of some benzodiazepines, mirtazapine, nefazodone, or venlafaxine; monitor for increased effects and/or toxicity.
Nursing: Physical Assessment/Monitoring
Assess allergy history prior to beginning therapy. Use caution in presence of hepatic or renal dysfunction or risk of arrhythmia. Assess other pharmacological or herbal products patient may be taking for potential interactions or toxicity; dosing adjustments may be necessary. Evaluate results of laboratory tests prior to and during therapy; electrolyte abnormalities should be corrected prior to beginning therapy. Assess therapeutic effectiveness (resolution of fungal infection) and adverse response (eg, gastrointestinal disturbance, vision changes, hepatic toxicity, CNS changes) on a regular basis during therapy. Teach patient proper use, possible side effects/appropriate interventions, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, oral:
Noxafil®: 40 mg/mL (123 mL) [contains sodium benzoate; delivers 105 mL of suspension; cherry flavor; packaged with calibrated dosing spoon]
References
Cornely OA, Maertens J, Winston DJ, et al, “Posaconazole vs. Fluconazole or Itraconazole Prophylaxis in Patients With Neutropenia,” N Engl J Med, 2007, 356(4):348-59.
Greenberg RN, Mullane K, van Burik JA, et al, “Posaconazole as Salvage Therapy for Zygomycosis,” Antimicrob Agents Chemother, 2006, 50(1):126-33.
Herbrecht R, “Posaconazole: A Potent, Extended-Spectrum Triazole Anti-Fungal for the Treatment of Serious Fungal Infections,” Int J Clin Pract, 2004, 58(6): 612-24.
Keating G, “Posaconazole,” Drugs, 2005, 65(11):1553-67.
Krieter P, Flannery B, Musick T, et al, “Disposition of Posaconazole Following Single-Dose Oral Administration in Healthy Subjects,” Antimicrob Agents Chemother, 2004, 48(9):3543-51.
National Comprehensive Cancer Network® (NCCN), “Clinical Practice Guidelines in Oncology™: Prevention and Treatment of Cancer-Related Infections,” Version 1.2008. Available at http://www.nccn.org/professionals/physician_gls/PDF/infections.pdf.
Raad II, Graybill JR, Bustamante AB, “Safety of Long-Term Oral Posaconazole Use in the Treatment of Refractory Invasive Fungal Infections,” Clin Infect Dis, 2006, 42(12):1726-34.
Ullmann AJ, Lipton JH, Vesole DH, et al, “Posaconazole or Fluconazole for Prophylaxis in Severe Graft-Versus-Host Disease,” N Engl J Med, 2007, 356(4):335-47.
Walsh TJ, Anaissie EJ, Denning DW, et al, “Treatment of Aspergillosis: Clinical Practice Guidelines of the Infectious Diseases Society of America,” Clin Infect Dis, 2008, 46(3):327-60.
Walsh RJ, Raad I, Patterson TF, “Treatment of Invasive Aspergillosis With Posaconazole in Patients Who are Refractory to or Intolerant of Conventional Therapy: An Externally Controlled Trial,” Clin Infect Dis, 2007, 44(1):2-12.
International Brand Names
Lexi-Comp.com
Last full review/revision November 2009
Content last modified November 2009
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