Noxafil Special Precautions

Hypersensitivity: There is no information regarding cross-sensitivity between NOXAFIL and other azole antifungal agents. Caution should be used when prescribing NOXAFIL to patients with hypersensitivity to other azoles.
Hepatic Toxicity: In clinical trials, there were infrequent cases of hepatic reactions (e.g., mild to moderate elevations in ALT, AST, alkaline phosphatase, total bilirubin, and/or clinical hepatitis). The elevations in liver function tests were generally reversible on discontinuation of therapy, and in some instances these tests normalized without drug interruption and rarely required drug discontinuation. Rarely, more severe hepatic reactions including cholestasis or hepatic failure were reported in patients with serious underlying medical conditions (e.g., hematologic malignancy) during treatment with NOXAFIL. NOXAFIL should be used with caution in patient with severe hepatic impairment. In these patients, the prolonged elimination half-life may lead to increased exposure.
Monitoring of hepatic function: Liver function tests should be evaluated at the start and during the course of NOXAFIL therapy. Patients who develop abnormal liver function test during NOXAFIL therapy should be monitored for the development of more severe hepatic function (particularly liver function tests and bilirubin). Discontinuation of NOXAFIL must be considered if clinical signs and symptoms consistent with liver disease develop that may be attributable to NOXAFIL.
QT Prolongation: Some azoles have been associated with prolongation of the QT interval. Results from a multiple time-matched ECG analysis in healthy volunteers did not show any increase in the mean of the QTc interval. Nevertheless, NOXAFIL should not be administered with drugs that are known to prolong the QTc interval and are metabolized through CYP3A4. NOXAFIL should be administered with caution to patient with potentially proarrhythmic conditions and should not be administered with medicines that are known to prolong QTc interval and are metabolized through CYP3A4.
Electrolyte Disturbances: Especially those involving potassium, magnesium or calcium levels, should be monitored and corrected as necessary before and during NOXAFIL therapy.
Vincristine Toxicity: Concomitant administration of azole antifungals, including NOXAFIL, with vincristine has been associated with neurotoxicity and other serious adverse reactions, including seizures, peripheral neuropathy, syndrome of inappropriate antidiuretic hormone secretion, and paralytic ileus. Reserve azole antifungals, including NOXAFIL, for patients receiving a vinca alkaloid, including vincristine, who have no alternative antifungal treatment options (see Interactions).
Venetoclax Toxicity: Concomitant administration of NOXAFIL with venetoclax (a CYP3A4 substrate) may increase venetoclax toxicities, including the risk of tumor lysis syndrome (TLS) and neutropenia (see Interactions). Refer to the venetoclax prescribing information for detailed guidance.
Gastrointestinal dysfunction: There are limited pharmacokinetic data in patients with severe gastrointestinal dysfunction (such as severe diarrhoea). Patients who have severe diarrhoea or vomiting should be monitored closely for breakthrough fungal infections.
Plasma exposure: Posaconazole plasma concentrations following administration of posaconazole tablets are generally higher than those obtained with posaconazole oral suspension. Posaconazole plasma concentrations following administration of posaconazole tablets may increase over time in some patients. Safety data at higher exposure levels achieved with posaconazole tablets are at present limited.