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Pronunciation
(poe sa KON a zole)
Generic Available (U.S.)
No
Index Terms
Brand Names: U.S.
Brand Names: Canada
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
Salvage therapy of refractory or relapsed invasive fungal infections; mucormycosis; pulmonary infection (nonimmunosuppressed)
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, other azole antifungals, or any component of the formulation; coadministration of cisapride, ergot alkaloids, pimozide, quinidine, simvastatin, 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). Development of torsade de pointes has been reported. 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:
• Calcineurin inhibitors: Concurrent use with cyclosporine or tacrolimus may significantly increase the whole blood trough concentrations of cyclosporine or tacrolimus 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.
• Midazolam: Concurrent use may significantly increase midazolam concentrations and potentiate or prolong sedative or hypnotic effects. Reversal agents should be readily available.
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.
Adverse Reactions
Note: Percentages reflect data from use in comparator trials with multiple concomitant conditions and medications; some adverse reactions may be due to underlying condition(s).
>10%:
Cardiovascular: Hypertension (18%), edema (9% to 15%), hypotension (14%), tachycardia (12%)
Central nervous system: Fever (6% to 45%), headache (8% to 28%), fatigue (3% to 17%), insomnia (1% to 17%), dizziness (11%), pain (1% to 11%)
Endocrine & metabolic: Hypokalemia (≤30%), hypomagnesemia (18%), dehydration (1% to 11%), hyperglycemia (11%)
Gastrointestinal: Diarrhea (10% to 42%), nausea (9% to 38%), vomiting (7% to 29%), abdominal pain (5% to 27%), constipation (21%), anorexia (2% to 19%), mucositis (17%), weight loss (1% to 14%), oral candidiasis (1% to 12%)
Hematologic: Thrombocytopenia (29%), anemia (2% to 25%), neutropenia (4% to 23%), neutropenic fever (20%)
Hepatic: ALT increased (6% to 17%)
Neuromuscular & skeletal: Rigors (≤20%), musculoskeletal pain (16%), weakness (2% to 13%), arthralgia (11%)
Respiratory: Cough (3% to 25%), dyspnea (1% to 20%), epistaxis (14%), pharyngitis (12%)
Miscellaneous: Bacteremia (18%), herpes simplex (3% to 15%), CMV infection (14%)
1% to 10%:
Central nervous system: Anxiety (9%)
Endocrine & metabolic: Hypocalcemia (9%)
Gastrointestinal: Dyspepsia (10%)
Genitourinary: Vaginal hemorrhage (10%)
Hepatic: Hyperbilirubinemia (7% to 10%), AST increased (3% to 4%), alkaline phosphatase increased (1% to 3%)
Neuromuscular & skeletal: Back pain (10%)
Respiratory: Pneumonia (3% to 10%), upper respiratory infection (7%)
Miscellaneous: Diaphoresis (2% to 10%)
<1%, postmarketing, and/or case reports: Acute renal failure, adrenal insufficiency, allergic reaction, atrial fibrillation, cholestasis, ejection fraction decreased, hemolytic uremic syndrome, hepatic failure, hepatitis, hepatomegaly, hypersensitivity, jaundice, paresthesia, pulmonary embolus, QTc prolongation, 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
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). Management: Consider vinca alkaloid dose adjustment. Specific dose adjustment guidelines are not currently available. Monitor response to vinca alkaloid therapy, including development of vinca alkaloid toxicities (e.g., gastrointestinal toxicity, neurotoxicity). Risk D: Consider therapy modification
Aprepitant: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Aprepitant. Risk C: Monitor therapy
ARIPiprazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of ARIPiprazole. Management: Decrease aripiprazole dose to 50% of the usual dose with concomitant use of strong CYP3A4 inhibitors or to 25% of usual dose with concomitant use of strong CYP3A4 and 2D6 inhibitors or with use of a strong 3A4 inhibitor in a poor 2D6 metabolizer Risk D: Consider therapy modification
Axitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib. Management: Avoid concurrent use of axitinib with any strong CYP3A inhibitor whenever possible. If a strong CYP3A inhibitor must be used with axitinib, a 50% axitinib dose reduction is recommended. Risk X: Avoid combination
Benzodiazepines (metabolized by oxidation): Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Benzodiazepines (metabolized by oxidation). Management: The following combinations are specifically contraindicated: itraconazole with alprazolam, estazolam, oral midazolam, or triazolam; ketoconazole with alprazolam, estazolam, or triazolam. Consider initial dose reductions of other benzodiazepines. Exceptions: Quazepam. Risk D: Consider therapy modification
Boceprevir: May increase the serum concentration of Posaconazole. Posaconazole may increase the serum concentration of Boceprevir. Risk C: Monitor therapy
Bortezomib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bortezomib. Risk C: Monitor therapy
Bosentan: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Bosentan. Risk C: Monitor therapy
Brentuximab Vedotin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Risk C: Monitor therapy
Brinzolamide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brinzolamide. Risk C: Monitor therapy
Budesonide (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Nasal). Risk C: Monitor therapy
Budesonide (Systemic, Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Systemic, Oral Inhalation). Management: Consider reducing the oral budesonide dose when used together with a CYP3A4 inhibitor. This interaction is likely less severe with orally inhaled budesonide. Monitor patients closely for signs/symptoms of corticosteroid excess. Risk D: Consider therapy modification
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: Posaconazole may increase the serum concentration of Cardiac Glycosides. Risk C: Monitor therapy
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
Conivaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Conivaptan. Risk X: Avoid combination
Corticosteroids (Orally Inhaled): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Corticosteroids (Orally Inhaled). Management: Monitor for signs and symptoms of adrenal suppression if inhaled budesonide or mometasone are coadministered with a strong CYP3A4 inhibitor. Avoid combining inhaled fluticasone with any strong CYP3A4 inhibitor. Exceptions: Beclomethasone; Beclomethasone (Oral Inhalation); Triamcinolone; Triamcinolone (Systemic). Risk C: Monitor therapy
Corticosteroids (Systemic): Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Corticosteroids (Systemic). Risk C: Monitor therapy
Crizotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Crizotinib. Risk X: Avoid combination
CycloSPORINE: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of CycloSPORINE. Risk D: Consider therapy modification
CycloSPORINE (Systemic): Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of CycloSPORINE (Systemic). 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
Dienogest: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dienogest. Risk C: Monitor therapy
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: Posaconazole may increase the serum concentration of Eplerenone. Risk X: Avoid combination
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
Etravirine: May decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). This would be anticipated with itraconazole or ketoconazole. Etravirine may increase the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). This would be anticipated with voriconazole. Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Etravirine. Management: Monitor for increased effects/toxicity of etravirine. Antifungal dose adjustment may be needed for ketoconazole, itraconazole, or posaconazole but specific dosing guidelines are lacking. Risk D: Consider therapy modification
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. Management: Monitor patients extra closely for several days following initiation of the combination, and fentanyl dosage reductions should be made as appropriate. 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
Fluticasone (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Nasal). Risk C: Monitor therapy
Fluticasone (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Oral Inhalation). Risk X: Avoid combination
Fosamprenavir: Posaconazole may increase serum concentrations of the active metabolite(s) of Fosamprenavir. Fosamprenavir may decrease the serum concentration of Posaconazole. Risk C: Monitor therapy
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
Fosphenytoin: May decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Fosphenytoin. Risk D: Consider therapy modification
Gefitinib: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Gefitinib. Risk C: Monitor therapy
GlipiZIDE: Posaconazole may enhance the hypoglycemic effect of GlipiZIDE. Posaconazole may increase the serum concentration of GlipiZIDE. 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
GuanFACINE: CYP3A4 Inhibitors (Strong) may increase the serum concentration of GuanFACINE. Risk C: Monitor therapy
H2-Antagonists: May decrease the serum concentration of Posaconazole. Management: Avoid concurrent use whenever possible. Monitor patients closely for decreased antifungal effects if this combination is used. Consider using a noninteracting antifungal as appropriate. 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. Management: Consider use of HMG-CoA reductase inhibitors posing the least rhabdomyolysis risk (e.g. fluva- or pravastatin), and monitor for signs/symptoms of rhabdomyolysis. Do not use keto- or itraconazole with lova- or simvastatin, or posaconazole with simvastatin. Exceptions: Fluvastatin; Pitavastatin; Rosuvastatin. Risk D: Consider therapy modification
Iloperidone: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolites P88 and P95 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Iloperidone. Management: Reduce iloperidone dose by half when administered with a strong CYP3A4 inhibitor. 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
Ivacaftor: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivacaftor. Management: Decrease ivacaftor dose to 150 mg twice a week in patients also receiving strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Ixabepilone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ixabepilone. Risk D: Consider therapy modification
Lapatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lapatinib. Management: If an overlap in therapy cannot be avoided, consider reducing lapatinib dose to 500 mg/day during, and within 1 week of completing, treatment with the strong CYP3A4 inhibitor. Risk X: Avoid combination
Losartan: Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Losartan. Risk C: Monitor therapy
Lovastatin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lovastatin. Risk X: Avoid combination
Lumefantrine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lumefantrine. Risk C: Monitor therapy
Lurasidone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lurasidone. Risk X: Avoid combination
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; Azithromycin (Systemic); Fidaxomicin; Spiramycin. Risk D: Consider therapy modification
Maraviroc: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc. Management: Reduce the adult dose of maraviroc to 150 mg twice daily when used with a strong CYP3A4 inhibitor. Do not use maraviroc with strong CYP3A4 inhibitors in patients with Clcr less than 30 mL/min. Risk D: Consider therapy modification
Methadone: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Methadone. Risk C: Monitor therapy
MethylPREDNISolone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of MethylPREDNISolone. Management: Consider methylprednisolone dose titration and/or adjustments in patients receiving strong CYP3A4 inhibitors (eg, azole antifungals, protease inhibitors) and monitor for increased steroid related adverse effects. Risk D: Consider therapy modification
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 adult dose to 400 mg. Further dose reductions may also be required. Risk D: Consider therapy modification
Phenytoin: May decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Phenytoin. 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
Pimozide: CYP3A4 Inhibitors (Strong) may increase the serum concentration 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
Propafenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Propafenone. Risk C: Monitor therapy
Protease Inhibitors: May increase the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Protease Inhibitors. 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: May decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Rifamycin Derivatives. Only rifabutin appears to be affected. Risk D: Consider therapy modification
Rivaroxaban: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rivaroxaban. Risk X: Avoid combination
RomiDEPsin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of RomiDEPsin. Risk X: Avoid combination
Ruxolitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ruxolitinib. Management: Reduce ruxolitinib initial adult dose to 10 mg twice daily in patients receiving strong CYP3A4 inhibitors whose platelet count is 100*10^9/L or greater. Avoid in patients with lower platelet count. Risk D: Consider therapy modification
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
Sildenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sildenafil. Management: When used for treatment of pulmonary arterial hypertension, use of sildenafil with strong CYP3A4 inhibitors should be avoided. When used for erectile dysfunction, starting dose should be reduced to 25 mg. Max dose with ritonavir is 25 mg per 48 hours. Risk D: Consider therapy modification
Silodosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Silodosin. Risk X: Avoid combination
Simvastatin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simvastatin. 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: May enhance the adverse/toxic effect of Posaconazole. Posaconazole may increase the serum concentration of Tacrolimus. Management: Reduce tacrolimus dose to approximately one-third of original dose when starting posaconazole. Tacrolimus blood concentrations should be monitored closely during and at discontinuation of posaconazole. Risk D: Consider therapy modification
Tacrolimus (Systemic): Posaconazole may increase the serum concentration of Tacrolimus (Systemic). Management: Reduce tacrolimus dose to approximately one-third of original dose when starting posaconazole. Tacrolimus blood concentrations should be monitored closely during and at discontinuation of posaconazole. Risk D: Consider therapy modification
Tacrolimus (Topical): Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Tacrolimus (Topical). Risk C: Monitor therapy
Tadalafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tadalafil. Management: Recommendations regarding use of tadalafil in patients also receiving strong CYP3A4 inhibitors may vary based on indication and/or international labeling. Consult appropriate product labeling. Risk D: Consider therapy modification
Tamsulosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tamsulosin. Risk X: Avoid combination
Telaprevir: Posaconazole may increase the serum concentration of Telaprevir. Telaprevir may increase the serum concentration of Posaconazole. Risk C: Monitor therapy
Temsirolimus: Posaconazole may increase serum concentrations of the active metabolite(s) of Temsirolimus. Management: Consider temsirolimus dose reductions or alternatives to posaconazole. Monitor sirolimus concentrations in all patients receiving posaconazole or any systemic azole antifungal. Risk D: Consider therapy modification
Ticagrelor: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ticagrelor. Risk X: Avoid combination
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
Tolterodine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolterodine. Management: The maximum recommended dose of long-acting tolterodine is 2 mg/day when used together with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Tolvaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolvaptan. Risk X: Avoid combination
Toremifene: CYP3A4 Inhibitors (Strong) may enhance the adverse/toxic effect of Toremifene. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Toremifene. Risk X: Avoid combination
Vardenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vardenafil. Management: Recommendations regarding concomitant use of vardenafil with strong CYP3A4 inhibitors may vary depending on brand name (e.g., Levitra, Staxyn) or by international labeling. Consult appropriate product labeling for specific recommendations. Risk D: Consider therapy modification
Vemurafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vemurafenib. Risk C: Monitor therapy
Vilazodone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilazodone. Management: Limit maximum adult vilazodone dose to 20 mg/day in patients receiving strong CYP3A4 inhibitors. Risk D: Consider therapy modification
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 increase the serum concentration of Zolpidem. Management: Consider using a lower starting dose of zolpidem in patients receiving systemic azole antifungals. Monitor patients closely for increased magnitude and/or duration of zolpidem effects when using this combination. Risk D: Consider therapy modification
Zuclopenthixol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zuclopenthixol. Management: Consider zuclopenthixol dosage reduction with concomitant use of a strong CYP3A4 inhibitor (eg, ketoconazole) in poor CYP2D6 metabolizers or with strong CYP2D6 inhibitors (eg, paroxetine). Monitor for increased zuclopenthixol levels/toxicity. 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. Management: Must be administered with or within 20 minutes of a full meal or an oral liquid nutritional supplement, or 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. Avoid concurrent use of grapefruit juice.
Storage
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Do not freeze.
Mechanism of Action
Interferes with fungal cytochrome P450 (latosterol-14α-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; duration of therapy is based is based on recovery from neutropenia or immunosuppression
Salvage treatment of refractory infection (unlabeled use): 200 mg 4 times/day initially; after disease stabilization may decrease frequency to 400 mg 2 times/day (Walsh, 2007). Note: Duration of therapy should be a minimum of 6-12 weeks or throughout period of immunosuppression (Walsh, 2008).
Candidal infections:
Prophylaxis: 200 mg 3 times/day; duration of therapy is based on recovery from neutropenia or immunosuppression
Treatment of oropharyngeal infection: Initial: 100 mg 2 times/day for 1 day; maintenance: 100 mg once daily for 13 days
Treatment of refractory oropharyngeal infection: 400 mg 2 times/day; duration of therapy is based on underlying disease and clinical response
Adults:
Mucormycosis (unlabeled use): 800 mg/day in 2 or 4 divided doses; duration of therapy is based on response and risk of relapse due to immunosuppression (Greenburg, 2006)
Cryptococcal infections:
Pulmonary, nonimmunosuppressed (unlabeled use): 400 mg 2 times/day. Note: Fluconazole is considered first-line treatment (Perfect, 2010).
Salvage treatment of relapsed infection (unlabeled use): 400 mg 2 times/day (or 200 mg 4 times/day) for 10-12 weeks. Note: Salvage treatment should only be started after an appropriate course of an induction regimen (Perfect, 2010).
Dosage adjustment in renal impairment:
Mild-to-moderate renal insufficiency (Clcr 20-80 mL/minute/1.73 m2): No adjustment necessary
Severe renal insufficiency (Clcr <20 mL/minute/1.73 m2): 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
Take 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; 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, loss of appetite, constipation, headache, dizziness, blurred vision, or insomnia. Report immediately chest pain or palpitations, unusual muscle pain or weakness, severe diarrhea or vomiting, urinary pattern changes, yellowing of skin or eyes, or changes in color of stool or urine.
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. Electrolyte abnormalities should be corrected prior to beginning therapy. Monitor for gastrointestinal disturbance, vision changes, hepatic toxicity, and CNS changes on a regular basis during therapy.
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; cherry flavor; delivers 105 mL of suspension]
References
Centers for Disease Control and Prevention (CDC), “Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-infected Adults and Adolescents: Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America,” MMWR Recomm Rep, 2009, 58(4):1-207.
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.
Eiden C, Palenzuela G, Hillaire-Buys D, et al, “Posaconazole-Increased Vincristine Neurotoxicity in a Child: A Case Report,” J Pediatr Hematol Oncol, 2009, 31(4):292-5.
Freifeld AG, Bow EJ, Sepkowitz KA, et al, “Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients With Cancer: 2010 Update by the Infectious Diseases Society of America,” Clin Infect Dis, 2011, 52(4):e56-93.
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 2.2009. Available at http://www.nccn.org/professionals/physician_gls/PDF/infections.pdf
Pappas PG, Kauffman CA, Andes D, et al, “Clinical Practice Guidelines for the Management of Candidiasis: 2009 Update by the Infectious Diseases Society of America,” Clin Infect Dis, 2009, 48(5):503-35.
Perfect JR, Dismukes WE, Dromer F, et al, “Clinical Practice Guidelines for the Management of Cryptococcal Disease: 2010 Update by the Infectious Diseases Society of America,” Clin Infect Dis, 2010, 50(3):291-322.
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.
Skiest DJ, Vazquez JA, Anstead GM, et al, “Posaconazole for the Treatment of Azole-Refractory Oropharyngeal and Esophageal Candidiasis in Subjects With HIV Infection,” Clin Infect Dis, 2007, 44(4):607-14.
Tomblyn M, Chiller T, Einsele H, et al, “Guidelines for Preventing Infectious Complications Among Hematopoietic Cell Transplantation Recipients: a Global Perspective,” Biol Blood Marrow Transplant, 2009, 15(10):1143-238.
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.
Vasquez JA, Skiest DJ, Nieto L, et al, “A Multicenter Randomized Trial Evaluating Posaconazole Versus Fluconazole for the Treatment of Oropharyngeal Candidiasis in Subjects With HIV/AIDS,” Clin Infect Dis, 2006, 42(8):1179-86.
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 March 2012
Content last modified March 2012
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