NOXAFIL POWDERMIX KIT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NOXAFIL POWDERMIX KIT (NOXAFIL POWDERMIX KIT).
Posaconazole inhibits fungal CYP450-dependent 14α-demethylase, blocking ergosterol synthesis and disrupting fungal cell membrane integrity.
| Metabolism | Primarily hepatic via UDP-glucuronidation (UGT1A4); minor CYP450 involvement (CYP3A4); substrate of P-glycoprotein. |
| Excretion | Posaconazole is primarily excreted in the feces (77%) as unchanged drug, with renal excretion accounting for 14% of the dose (primarily as glucuronide conjugates). Less than 0.2% is excreted unchanged in urine. |
| Half-life | The terminal elimination half-life is approximately 27 hours (range 20-66 hours) in healthy subjects, allowing for once-daily dosing after steady state. |
| Protein binding | Posaconazole is highly protein bound (98-99%), primarily to serum albumin. |
| Volume of Distribution | Volume of distribution at steady state (Vdss) is approximately 7 L/kg (range 3-10 L/kg), indicating extensive extravascular distribution into tissues. |
| Bioavailability | Oral bioavailability of the Powdermix for oral suspension is highly variable, with a mean relative bioavailability of approximately 50% compared to the intravenous formulation (fasting conditions). Taking with food (especially high-fat meals) increases bioavailability by 4-fold. Due to nonlinear absorption, bioavailability increases proportionally with dose, but not dose-proportionally due to saturable absorption. |
| Onset of Action | Intravenous: Not applicable (NOXAFIL Powdermix Kit is for oral suspension only). Oral: Peak plasma concentrations are achieved 3-5 hours after administration; antifungal effect begins within hours of achieving therapeutic levels. |
| Duration of Action | Dosing interval: After steady state, the drug maintains therapeutic concentrations throughout the 24-hour dosing period. Clinical duration of action: Continuous antifungal activity as long as plasma concentrations remain above the MIC. Treatment courses typically last weeks to months depending on indication. |
300 mg (one 300-mg vial) intravenously twice on day 1, then 300 mg intravenously once daily starting on day 2. Alternatively, oral suspension: 200 mg (10 mL) three times daily. For prophylaxis, IV: 300 mg twice on day 1, then 300 mg once daily; oral: 200 mg three times daily.
| Dosage form | FOR SUSPENSION, DELAYED RELEASE |
| Renal impairment | No dose adjustment required for mild to severe renal impairment (CrCl ≥15 mL/min). For end-stage renal disease (CrCl <15 mL/min) or on hemodialysis, use with caution; intravenous vehicle may accumulate. |
| Liver impairment | No dose adjustment recommended for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C); use with caution. |
| Pediatric use | For children ≥2 years: IV: based on weight: <40 kg: 6 mg/kg every 12 hours on day 1, then 6 mg/kg once daily; ≥40 kg: 300 mg every 12 hours on day 1, then 300 mg once daily. Oral suspension: 2-<8 years: 6 mg/kg (max 200 mg) three times daily; 8-<12 years: 6 mg/kg (max 200 mg) three times daily; 12-17 years: 200 mg (10 mL) three times daily. |
| Geriatric use | No specific dose adjustment required; select dose with caution due to greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NOXAFIL POWDERMIX KIT (NOXAFIL POWDERMIX KIT).
| Breastfeeding | Posaconazole is excreted in human milk. The milk-to-plasma (M/P) ratio is unknown. Due to potential for adverse effects in nursing infants, breastfeeding is not recommended during treatment and for 24 hours after the last dose. |
| Teratogenic Risk | Posaconazole is classified as Pregnancy Category C. In animal studies, skeletal malformations and embryotoxicity were observed at maternally toxic doses. There are no adequate and well-controlled studies in pregnant women. First trimester: Theoretical risk based on animal data; use only if benefit outweighs risk. Second and third trimesters: Limited data; potential for fetal harm cannot be excluded. |
■ FDA Black Box Warning
No black box warning.
| Common Effects | Headache Rash Decreased appetite Decreased white blood cell count neutrophils Dizziness Electrolyte imbalance Fatigue Fever Decreased potassium level in blood Increased liver enzymes Insomnia difficulty in sleeping Itching Sleepiness Taste change Weakness Decreased magnesium level in blood Paresthesia tingling or pricking sensation High blood pressure Anorectal discomfort Increased glucose level in blood Hypoglycemia low blood glucose level Hypotension low blood pressure Nausea Diarrhea Anemia low number of red blood cells Low blood platelets Petechiae red or purple spot caused by bleeding into the skin Vomiting Cough Abdominal pain Constipation Indigestion Nosebleeds Rigors Swelling of legs Breathlessness |
| Serious Effects |
["Hypersensitivity to posaconazole or any component","Concomitant use with CYP3A4 substrates that prolong QT interval (e.g., pimozide, quinidine)"]
| Precautions | ["Electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia) increase risk of QT prolongation","Hepatotoxicity (monitor liver enzymes)","Severe hypersensitivity reactions","Drug interactions with CYP3A4 substrates","Use caution in renal impairment (IV formulation contains beta-cyclodextrin)"] |
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| Fetal Monitoring | Monitor liver function tests (AST, ALT, bilirubin) periodically. Assess for signs of hepatotoxicity, electrolyte disturbances (especially hypokalemia, hypomagnesemia), and QT prolongation via ECG at baseline and during therapy. In pregnancy, monitor fetal growth and development with ultrasound as indicated. |
| Fertility Effects | In animal studies, posaconazole impaired fertility in male and female rats at doses below human therapeutic exposures. Reversible effects on spermatogenesis and estrous cycle were observed. Human data on fertility effects are lacking. |