Posaconazole Oral Suspension (Noxafil)
Manufacturer: Schering-Plough Corporation, Kenil-worth, NJ
Indication: Posaconazole is indicated for the treatment of oropharyngeal candidiasis, including infections refractory ((PriCara) and/or fluconazole (Diflucan, Pfizer). Oral candidiasis is a fungal infection of the mouth and throat caused by the yeast Candida.
This agent is also indicated for the prophylaxis of invasive Aspergillus and Candida infections in patients 13 years of age and older who are at high risk for the development of infection because of their severely immunocompromised status. Examples include recipients of hematopoietic stem cell transplants, patients with graft-versus-host disease, and patients with hema-tological malignancies with prolonged neutropenia arising from chemotherapy.
Drug Class: This novel lipophilic triazole antifungal agent has a molecular formula of C37H42F2N8O4, yielding a molecular weight of 700.8. Posaconazole blocks the synthesis of ergosterol, a key component of the fungal cell membrane, through the inhibition of the enzyme lanosterol 14a-demethy-lase and by the accumulation of methylated sterol precursors. Posaconazole inhibits cytochrome P450 (CYP 450)-dependent 14a-demethylase in the biosynthetic pathway of ergosterol. Inhibition of this enzyme leads to an accumulation of toxic 14a-methylsterols and a depletion of ergosterol. This results in impairment of the integrity of the fungal cell membrane and blockage of cell growth and division. kamagra soft tablets
Uniqueness of Product: Posaconazole is the first anti-fungal agent approved by the Food and Drug Administration for the prevention of invasive fungal infections caused by Aspergillus species. Posaconazole can help prevent these life-threatening infections while patients are being treated for serious conditions such as acute leukemia and graft-versus-host disease.
Hypersensitivity: There is no information regarding cross-sensitivity between posaconazole and other azole antifungal agents. Caution should be used when prescribing posacona-zole to patients with hypersensitivity to other azoles.
Hepatic Toxicity: In clinical trials, there were infrequent cases of hepatic reactions, including mild-to-moderate elevations in alanine and aspartate transaminases (ALT, AST), alkaline phosphatase, total bilirubin, and clinical hepatitis. The elevated liver enzyme levels were generally reversible when therapy was discontinued; in some instances, liver function test results returned to normal without drug interruption. Discontinuation of therapy was rarely required.
In rare instances, more severe hepatic reactions (e.g., cholestasis, hepatic failure, including fatalities) were reported in patients with serious underlying medical conditions (e.g., hematological malignancy) during treatment with posaconazole. These severe hepatic events were seen primarily in patients receiving 800 mg daily (400 mg twice daily or 200 mg four times daily) for another indication. Monitoring of Hepatic Function: Liver function findings should be evaluated at the start of and during the course of posaconazole therapy. Patients whose liver enzyme concentrations become abnormal during posaconazole therapy should be monitored for the development of more severe hepatic injury.
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Patient management should include laboratory evaluation of hepatic function (particularly liver enzymes and bilirubin). Discontinuation of posaconazole must be considered if clinical signs and symptoms consistent with liver disease develop that may be attributable to this agent.
Drug Interactions with Cyclosporine: Cases of elevated cyclosporine levels resulting in rare serious adverse events (nephrotoxicity and leukoencephalopathy) and death were reported in clinical efficacy studies. Dose reduction and more frequent clinical monitoring of cyclosporine, tacrolimus (e.g., Prograf, Fujisawa), and sirolimus (Rapamune, Wyeth) should be performed when posaconazole therapy is initiated.
Arrhythmias and QT Prolongation: Some azoles, including posaconazole, have been associated with prolongation of the QT interval on the electrocardiogram (ECG). Results from a multiple time-matched ECG analysis in healthy volunteers did not show any increase in the mean of the corrected QT (QTc) interval. During clinical development, torsades de pointes occurred in one patient taking posacona-zole. This patient was seriously ill with multiple confounding risk factors, including a history of cardiotoxic chemotherapy, hypokalemia, and concomitant medications that might have contributed to the problem.
Posaconazole should be administered with caution to patients with potentially proarrhythmic conditions. It should not be taken with drugs that are known to prolong the QTc interval and that are metabolized through CYP 3A4. Rigorous attempts to correct potassium, magnesium, and calcium levels should be made before posaconazole therapy is started.
Dosage and Administration. Posaconazole Oral Suspension 200 mg/5 ml should be administered three times a day. A measured dosing spoon is provided, marked for doses of 2.5 ml and 5 ml. The duration of therapy is based on recovery from neutropenia or immunosuppression.
To enhance the oral absorption of posaconazole and optimize plasma concentrations:
Commentary: During the last two decades, systemic fungal infections have been recognized as a major cause of morbidity and mortality. Only a few therapeutic options are available for these infections. Posaconazole was developed to meet the increasing need for a new antifungal therapy and to address the rising incidence of invasive fungal infections and the emergence of fungal resistance. It has a broad spectrum of anti-fungal activity and may be beneficial for both systemic and superficial infections. kamagra oral jelly uk
Posaconazole has shown promising clinical efficacy against life-threatening fungal infections that are often refractory to currently available antifungal therapies for invasive asper-gillosis, fusariosis, and an emerging infection, zygomycosis. This agent can help prevent the development of life-threatening invasive fungal infections during therapy for serious conditions, such as acute leukemia and graft-versus-host disease.