Home » Drug Information » FDA Approved Drugs » 2006
Medical Areas: Immunology | Family Medicine | Infections and Infectious Diseases
View By:YearCompanyConditionsTherapeutic AreasDrug Names
The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Approval Status: Approved in September 2006
Treatment Area: Fungal infections
Noxafil (posaconazole) is a triazole antifungal agent. It blocks
the synthesis of ergosterol, a key component of the fungal cell
membrane, through the inhibition of the enzyme lanosterol
14a-demethylase and accumulation of methylated sterol
Noxafil is specifically indicated for the prophylaxis of
invasive Aspergillus and Candida infections in subjects, 13 years
of age and older, who are at high risk of developing these
infections due to being severely immunocompromised.
Noxafil is supplied as a 4-ounce (123 mL) suspension designed
for oral administration. The recommended initial dose of the drug
is 200 mg (5 mL) three times a day with a full meal.
FDA approval of Noxafil was based on the results of two clinical
Study 1 This randomized, double-blind trial compared
200 mg of posaconazole oral suspension, given three times a day,
with 400 mg of fluconazole, given once a day, as prophylaxis
against invasive fungal infections in allogeneic hematopoietic stem
cell transplant (HSCT) recipients with Graft versus Host Disease
(GVHD). Treatment duration was 80 days for posaconazole and 77 days
for fluconazole. The primary endpoint was efficacy, evaluated using
a composite endpoint of proven/probable invasive fungal infections,
death, or treatment with systemic anti-fungal therapy. In this
study the clinical failure rate of posaconazole (33%) was similar
to fluconazole (37%). Cause mortality was similar at 16 weeks for
the posaconazole group (19%) and the fluconazole group (20%).
Study 2 This was a randomized, open-label study that
compared 200 mg of posaconazole oral suspension (three times a
day), with 400 mg of fluconazole suspension (once daily) or 200 mg
itraconazole oral solution (twice a day), as prophylaxis against
IFIs in neutropenic patients who were receiving cytotoxic
chemotherapy for acute myelogenous leukemia or myelodysplastic
syndromes. Subjects were assessed for 107 days post-treatment. The
primary endpoint was the same as study 1. In this study clinical
failure was lower for patients treated with posaconazole (27%) when
compared to patients treated with fluconazole or itraconazole
(42%). Cause mortality was lower at 100 days for the posaconazole
treated group (14%) versus the fluconazole and itraconazole groups
In both study groups subjects receiving posaconazole prophylaxis
experienced substantially lower breakthrough infections caused by
Aspergillus species when compared to subjects receiving fluconazole
Ongoing Study Commitments
- Schering has agreed to a deferred pediatric study under PREA
for prophylaxis of invasive fungal infections in pediatric patients
ages zero months to twelve years of age who are at high risk for
developing these infections.
Final Report Submission: September 15, 2011
- Schering has agreed to a post approval study to be conducted
among patients receiving antifungal prophylaxis. The study will
enroll patients who are at risk for low absorption. Different
dosing strategies including the use of therapeutic drug monitoring
to increase plasma concentrations will be explored.
Protocol Submission: by January 2007
Study Start: by January 2008
Final Report Submission: by March 2011
Adverse reactions associated with the use of Noxafil may
include, but are not limited to, the following:
- abdominal pain
In addition, Noxafil has been associated with prolongation of
the QT interval on the electrocardiogram. It should be administered
with caution to patients with potentially proarrhythmic conditions
and should not be administered with drugs that are known to prolong
the QTc interval and are metabolized through CYP3A4.
Mechanism of Action
Noxafil is a triazole antifungal agent. It blocks the synthesis
of ergosterol, a key component of the fungal cell membrane, through
the inhibition of the enzyme lanosterol 14a-demethylase and
accumulation of methylated sterol precursors.
Notheis G, Tarani L, Costantino F, Jansson A, Rosenecker
J, Friederici D, Belohradsky BH, Reinhardt D, Seger R, Schweinitz
DV, Wintergerst U Posaconazole for treatment of refractory
invasive fungal disease. Mycoses 2006;49 Suppl
Groll AH, Walsh TJ Antifungal efficacy and
pharmacodynamics of posaconazole in experimental models of invasive
fungal infections. Mycoses 2006;49 Suppl 1:7-16.
Dodds Ashley ES, Alexander BD Posaconazole.
Drugs of today 2005 Jun;41(6):393-400.
Carrillo-Munoz AJ, Quindos G, Ruesga M, Alonso R, del
Valle O, Hernandez-Molina JM, McNicholas P, Loebenberg D, Santos
P Antifungal activity of posaconazole compared with
fluconazole and amphotericin B against yeasts from oropharyngeal
candidiasis and other infections. The Journal of antimicrobial
chemotherapy 2005 Mar;55(3):317-9. Epub 2005 Feb 10.
Courtney R, Pai S, Laughlin M, Lim J, Batra V
Pharmacokinetics, safety, and tolerability of oral posaconazole
administered in single and multiple doses in healthy adults.
Antimicrobial Agents and Chemotherapy 2003
For additional information regarding Noxafil or fungal
infections, please vist the Schering web page.