POSACONAZOLE

Treatment should be initiated by a physician experienced in the management of fungal infections or in the supportive care in the high risk patients for which posaconazole is indicated as prophylaxis. Posology Posaconazole is also available for oral administration (oral suspension, gastro-resistant tablet).

4). Recommended dose is shown in Table 1. Table 1. Recommended dose according to indication Indication Dose and duration of therapy Treatment of invasive aspergillosis (only for adults) Loading dose of 300 mg Posaconazole (300 mg concentrate for solution for infusion or three 100 mg tablets) twice a day on the first day, then 300 mg (300 mg concentrate for solution for infusion or three 100 mg tablets) once a day thereafter.

Each tablet dose may be taken without regard to food intake. Recommended total duration of therapy is 6-12 weeks. Switching between intravenous and oral administration is appropriate when clinically indicated. Refractory invasive fungal infections (IFI)/patients with IFI intolerant to 1st line therapy Adults: Loading dose of 300 mg Posaconazole twice a day on the first day, then 300 mg once a day thereafter.

Duration of therapy should be based on the severity of the underlying disease, recovery from immunosuppression, and clinical response.

Paediatric patients aged 2 to less than 18 years:

Loading dose of 6 mg/kg (to a maximum of 300 mg) twice a day on the first day, then 6 mg/kg (to a maximum of 300 mg) once a day thereafter. Duration of therapy should be based on the severity of the underlying disease, recovery from immunosuppression, and clinical response.

Prophylaxis of invasive fungal infections Adults:

Loading dose of 300 mg Posaconazole twice a day on the first day, then 300 mg once a day thereafter. Duration of therapy is based on recovery from neutropenia or immunosuppression. For patients with AML or MDS, prophylaxis with Posaconazole 300 mg should start several days before the anticipated onset of neutropenia and continue for 7 days after the neutrophil count rises above 500 cells per mm3.

Paediatric patients aged 2 to less than 18 years:

Loading dose of 6 mg/kg (to a maximum of 300 mg) twice a day on the first day, then 6 mg/kg (to a maximum of 300 mg) once a day thereafter. Duration of therapy is based on recovery from neutropenia or immunosuppression. For patients with acute myelogenous leukaemia or myelodysplastic syndromes, prophylaxis with Posaconazole 300 mg should start several days before the anticipated onset of neutropenia and continue Posaconazole 300 mg should be administered via a central venous line, including a central venous catheter or peripherally inserted central catheter (PICC) by slow intravenous infusion over approximately 90 minutes.

Summary of the safety profile Safety data mainly derive from studies with the oral suspension. The safety of posaconazole oral suspension has been assessed in > 2,400 patients and healthy volunteers enrolled in clinical studies and from post-marketing experience.

The most frequently reported serious related adverse reactions included nausea, vomiting, diarrhoea, pyrexia, and increased bilirubin. Posaconazole concentrate for solution for infusion The safety of posaconazole concentrate for solution for infusion has been assessed in 72 healthy volunteers and 268 patients enrolled in a clinical study of antifungal prophylaxis.

The safety of posaconazole concentrate for solution for infusion and posaconazole tablet has been assessed in 288 patients enrolled in a clinical study of aspergillosis of whom 161 patients received the concentrate for solution for infusion and 127 patients received the tablet formulation.

Posaconazole 300 mg concentrate for solution for infusion was investigated in AML and MDS patients and those after HSCT with or at risk for GVHD only. Maximum duration of exposure to the concentrate for solution for infusion was shorter than with the oral suspension.

Plasma exposure resulting from the solution for infusion was higher than observed with the oral suspension. A higher incidence of adverse reactions cannot be ruled out. In initial studies of healthy volunteers, administration of a single dose of posaconazole infused over 30 minutes via a peripheral venous catheter was associated with a 12 % incidence of infusion site reactions (4 % incidence of thrombophlebitis).

Multiple doses of posaconazole administered via a peripheral venous catheter were associated with thrombophlebitis (60 % incidence). Therefore, in subsequent studies posaconazole was administered via central venous catheter. If a central venous catheter was not readily available, patients could receive a single infusion over 30 minutes via a peripheral venous catheter.

Hypersensitivity There is no information regarding cross-sensitivity between posaconazole and other azole antifungal agents. Caution should be used when prescribing Posaconazole 300 mg to patients with hypersensitivity to other azoles.

g. elevations in ALT, AST, alkaline phosphatase, total bilirubin and/or clinical hepatitis) have been reported during treatment with posaconazole. Elevated liver function tests were generally reversible on discontinuation of therapy and in some instances these tests normalised without interruption of therapy.

Rarely, more severe hepatic reactions with fatal outcomes have been reported. 2). 2). Monitoring of hepatic function Liver function tests should be evaluated at the start of and during the course of posaconazole therapy. Patients who develop abnormal liver function tests during Posaconazole 300 mg therapy must be routinely monitored for the development of more severe hepatic injury.

Patient management should include laboratory evaluation of hepatic function (particularly liver function tests and bilirubin). Discontinuation of Posaconazole 300 mg should be considered if clinical signs and symptoms are consistent with development of liver disease.

QTc prolongation Some azoles have been associated with prolongation of the QTc interval. 5). 3). Electrolyte disturbances, especially those involving potassium, magnesium or calcium levels, should be monitored and corrected as necessary before and during posaconazole therapy.

In patients, mean maximum plasma concentrations (Cmax) after posaconazole concentrate for solution for infusion are 4-fold increased compared to administration of oral suspension. An increased effect on the QTc interval cannot be ruled out.

Particular caution is advised in such cases where posaconazole is administered peripherally, as the recommended infusion time of 30 minutes may further increase Cmax. 5). g. midazolam, triazolam, alprazolam) should only be considered if clearly necessary.

1. 5). 5). 5). 5).