| Item |
Information |
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Drug Groups
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approved; investigational |
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Description
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Posaconazole is a triazole antifungal drug that is used to treat invasive infections by Candida species and Aspergillus species in severely immunocompromised patients. |
| Indication |
For prophylaxis of invasive Aspergillus and Candida infections in patients, 13 years of age and older, who are at high risk of developing these infections due to being severely immunocompromised as a result of procedures such as hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD), or due to hematologic malignancies with prolonged neutropenia from chemotherapy. Also for the treatment of oropharyngeal candidiasis, including oropharyngeal candidiasis refractory to itraconazole and/or fluconazole. Posaconazole is used as an alternative treatment for invasive aspergillosis, Fusarium infections, and zygomycosis in patients who are intolerant of, or whose disease is refractory to, other antifungals. |
| Pharmacology |
Posaconazole is an antifungal agent structurally related to itraconazole. It is a drug derived from itraconzaole through the replacement of the chlorine substituents with flourine in the phenyl ring, as well as hydroxylation of the triazolone side chain. These modifications enhance the potency and spectrum of activity of the drug. Posaconazole can be either fungicial or fungistatic in action. |
| Toxicity |
During the clinical trials, some patients received posaconazole up to 1600 mg/day with no adverse events noted that were different from the lower doses. In addition, accidental overdose was noted in one patient who took 1200 mg BID for 3 days. No related adverse events were noted by the investigator. |
| Affected Organisms |
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Aspergillis, Candida and other fungi |
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| Biotransformation |
Posaconazole primarily circulates as the parent compound in plasma. Of the circulating metabolites, the majority are glucuronide conjugates formed via UDP glucuronidation (phase 2 enzymes). Posaconazole does not have any major circulating oxidative (CYP450 mediated) metabolites. The excreted metabolites in urine and feces account for ~17% of the administered radiolabeled dose. |
| Absorption |
Posaconazole is absorbed with a median Tmax of approximately 3 to 5 hours. |
| Half Life |
Posaconazole is eliminated with a mean half-life (t½) of 35 hours (range 20 to 66 hours). |
| Protein Binding |
Posaconazole is highly protein bound (>98%), predominantly to albumin. |
| Elimination |
The excreted metabolites in urine and feces account for ~17% of the administered radiolabeled dose. |
| Distribution |
* 1774 L |
| Clearance |
* 32 L/hr
* 51 L/hr [Single-Dose Suspension Administration of 200 mg, fasted]
* 21 L/hr [Single-Dose Suspension Administration of 200 mg, nonfat meal]
* 14 L/hr [Single-Dose Suspension Administration of 200 mg, high fat meal]
* 91 L/hr [Single-Dose Suspension Administration of 400 mg, fasted]
* 43 L/hr [Single-Dose Suspension Administration of 400 mg with liquid nutritional supplement (14 g fat)] |
| References |
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Cornely OA, Maertens J, Winston DJ, Perfect J, Ullmann AJ, Walsh TJ, Helfgott D, Holowiecki J, Stockelberg D, Goh YT, Petrini M, Hardalo C, Suresh R, Angulo-Gonzalez D: Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med. 2007 Jan 25;356(4):348-59.
[Pubmed]
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Ullmann AJ, Lipton JH, Vesole DH, Chandrasekar P, Langston A, Tarantolo SR, Greinix H, Morais de Azevedo W, Reddy V, Boparai N, Pedicone L, Patino H, Durrant S: Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med. 2007 Jan 25;356(4):335-47.
[Pubmed]
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Bhattacharya M, Rajeshwari K, Dhingra B: Posaconazole. J Postgrad Med. 2010 Apr-Jun;56(2):163-7.
[Pubmed]
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Frampton JE, Scott LJ: Posaconazole : a review of its use in the prophylaxis of invasive fungal infections. Drugs. 2008;68(7):993-1016.
[Pubmed]
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Schiller DS, Fung HB: Posaconazole: an extended-spectrum triazole antifungal agent. Clin Ther. 2007 Sep;29(9):1862-86.
[Pubmed]
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Kwon DS, Mylonakis E: Posaconazole: a new broad-spectrum antifungal agent. Expert Opin Pharmacother. 2007 Jun;8(8):1167-78.
[Pubmed]
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Groll AH, Walsh TJ: Posaconazole: clinical pharmacology and potential for management of fungal infections. Expert Rev Anti Infect Ther. 2005 Aug;3(4):467-87.
[Pubmed]
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Rachwalski EJ, Wieczorkiewicz JT, Scheetz MH: Posaconazole: an oral triazole with an extended spectrum of activity. Ann Pharmacother. 2008 Oct;42(10):1429-38. Epub 2008 Aug 19.
[Pubmed]
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Li Y, Theuretzbacher U, Clancy CJ, Nguyen MH, Derendorf H: Pharmacokinetic/pharmacodynamic profile of posaconazole. Clin Pharmacokinet. 2010 Jun;49(6):379-96. doi: 10.2165/11319340-000000000-00000.
[Pubmed]
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