POSACONAZOLE
| POSACONAZOLE (pos-a-con'a-zole) Noxafil Classifications: antibiotic; azole antifungal; Therapeutic:antifungal; antibiotic Prototype: Fluconazole Pregnancy Category: C |
Availability
200 mg/5 mL oral suspension
Action
Azole antifungals inhibit ergosterol synthesis, the principal sterol in the fungal cell membrane, thus interfering with the functions of fungal cell membrane. This results in increased membrane permeability causing leakage of cellular contents.
Therapeutic Effect
Azole antifungals have a broad spectrum of antifungal activity against common fungal pathogens, exerting their effect by altering fungal cell membranes.
Uses
Prophylactic treatment of invasive Aspergillus and Candida infections in patients 13 y of age and older who are at high risk due to immunosuppression (e.g., hematopoietic stem cell transplant recipients with graft versus host disease, or patients with hematologic malignancies with prolonged neutropenia from chemotherapy).
Unlabeled Uses
Treatment of febrile neutropenia or refractory invasive fungal infection; treatment of periorbital cellulitis due to Rhizopus sp.; treatment of refractory histoplasmosis; treatment of refractory coccidioidomycosis; treatment of fungal necrotizing fasciitis.
Contraindications
Hypersensitivity to posaconazole; coadministration with ergot alkaloids, or CYP3A4 substrates; history of QT prolongation; abnormal levels of potassium, magnesium, or calcium; pregnancy (category C); lactation; children <13 y.
Cautious Use
Hypersensitivity to other azole antifungal antibiotics; hepatic disease or hepatitis; cardiac arrhythmias; history of proarrhythmic conditions; CHF, myocardial ischemia, atrial fibrillation; AIDS.
Route & Dosage
| Prophylactic Treatment of Invasive Aspergillus and Candida Infections Adult: PO 200 mg t.i.d. |
Administration
Oral- Shake well before use. Give with a full meal or liquid nutritional supplement.
- Store at 15°–30° C (59°–86° F).
Adverse Effects (≥1%)
Body as a Whole: Anxiety, bacteremia, dizziness, edema, fatigue, fever, headache, infection, insomnia, rigors, weakness. CNS: QT/QTc prolongation, tremor. CV: Hypertension, hypotension, tachycardia. GI: Abdominal pain, anorexia constipation, diarrhea, dyspepsia, mucositis, nausea, vomiting. Hematologic: Anemia, febrile neutropenia, neutropenia, petechiae, thrombocytopenia. Metabolic: Bilirubinemia, creatinine levels increased, elevated liver enzymes, hypocalcemia, hyperglycemia, hypokalemia, hypomagnesemia. Musculoskeletal: Arthralgia, back pain, musculoskeletal pain. Respiratory: Cough, dyspnea, epistaxis, pharyngitis, upper respiratory tract infection. Skin: Pruritus, rash. Special Senses: Blurred vision, taste disturbances. Urogenital: Vaginal hemorrhage.Interactions
Drug: Rifabutin and phenytoin increase the metabolism of posaconazole resulting in decreased plasma levels. Cimetidine decreases the absorption of posaconazole. Posaconazole is known to increase the plasma levels of cyclosporine, tacrolimus, rifabutin, midazolam, and phenytoin. Coadministration with other drugs that cause QT prolongation (e.g., quinidine) can result in torsades de pointes. Posaconazole may increase the plasma levels of ergot alkaloids, vinca alkaloids, hmg coa reductase inhibitors, and calcium channel blockers. Food: Administration with food increases absorption of posaconazole.Pharmacokinetics
Peak: 3–5 h. Distribution: 98% protein bound. Metabolism: Conjugated to inactive metabolites. Elimination: Primarily fecal elimination (71%) with minor renal elimination. Half-Life: 35 h.Nursing Implications
Assessment & Drug Effects
- Monitor for and report S&S of breakthrough fungal infections, especially in those with severe renal impairment, or experiencing vomiting and diarrhea, or who cannot tolerate a full meal or supplement along with posaconazole.
- Monitor and report degree of improvement of oropharyngeal candidiasis.
- Monitor those with proarrhythmic conditions for development of arrhythmias.
- Lab tests: Baseline and periodic LFTs; baseline serum electrolytes.
- Withhold drug and notify physician of abnormal serum potassium, magnesium, or calcium levels.
- Monitor blood levels of phenytoin, cyclosporine, tacrolimus, and sirolimus with concurrent therapy. Monitor for adverse effects of concurrently administered statins or calcium channel blockers.
Patient & Family Education
- Follow directions for taking the drug (see Administration).
- Do not take and prescription or nonprescription drugs without informing your physician.
- Know parameters for withholding drug (i.e., inability to take with a full meal or nutritional supplement).
- Report immediately any of the following to your health care provider: vomiting, diarrhea, inability to eat, jaundice of skin, yellowing of eyes, itching, or skin rash.
Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; 
Canadian drug name; 
Prototype drug