POSACONAZOLE STADA

Non-Interchangeability between posaconazole tablets and posaconazole oral suspension The tablet and oral suspension are not to be used interchangeably due to the differences between these two formulations in frequency of dosing, administration with food and plasma drug concentration achieved.

Therefore, follow the specific dosage recommendations for each formulation. 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 as 40 mg/mL oral suspension and 300 mg concentrate for solution for infusion. Posaconazole tablets are the preferred formulation to optimize plasma concentrations and generally provide higher plasma drug exposures than posaconazole oral suspension.

Recommended dose is shown in Table 1. Table 1. 2) Refractory invasive fungal infections (IFI)/patients with IFI intolerant to 1st line therapy Loading dose of 300 mg (three 100 mg tablets) twice a day on the first day, then 300 mg (three 100 mg tablets) once a day thereafter.

Each dose may be taken without regard to food intake. Duration of therapy should be based on the severity of the underlying disease, recovery from immunosuppression, and clinical response. Prophylaxis of invasive fungal infections Loading dose of 300 mg (three 100 mg tablets) twice a day on the first day, then 300 mg (three 100 mg tablets) once a day thereafter.

Each dose may be taken without regard to food intake. Duration of therapy is based on recovery from neutropenia or immunosuppression. For patients with acute myelogenous leukemia or myelodysplastic syndromes, prophylaxis with posaconazole 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.

2). 2). It is recommended to exercise caution due to the potential for higher plasma exposure. Paediatric population The safety and efficacy of posaconazole in children aged below 18 years have not been established. 2, but no recommendation on a posology can be made.

No data are available for the tablet formulation. 2). The tablets should be swallowed whole with water and should not be crushed, chewed or broken.

Safety data mainly derive from studies with the oral suspension. The tablet formulation was investigated in AML and MDS patients and those after HSCT with or at risk for Graft versus Host Disease (GvHD) only. Maximum duration of exposure to the tablet formulation was shorter than with the oral suspension.

Plasma exposure resulting from the tablet formulation was higher than observed with the oral suspension. A higher incidence of adverse reactions cannot be ruled out. Summary of the safety profile Posaconazole tablets The safety of posaconazole tablets has been assessed in 230 patients enrolled in the pivotal clinical study.

Patients were enrolled in a non-comparative pharmacokinetic and safety trial of posaconazole tablets when given as antifungal prophylaxis. Patients were immunocompromised with underlying conditions including haematological malignancy, neutropenia post-chemotherapy, GVHD, and post HSCT.

Posaconazole therapy was given for a median duration of 28 days. Twenty patients received 200 mg daily dose and 210 patients received 300 mg daily dose (following twice daily dosing on Day 1 in each cohort). Posaconazole tablet and oral suspension safety The safety of posaconazole oral suspension has been assessed in > 2,400 patients and healthy volunteers enrolled in clinical trials and from post-marketing experience.

The most frequently reported serious related adverse reactions included nausea, vomiting, diarrhoea, pyrexia, and increased bilirubin. The safety of posaconazole tablet has been assessed in 336 patients and healthy volunteers enrolled in clinical trials.

The safety profile of tablets was similar to that of the oral suspension. Tabulated list of adverse reactions Within the organ system classes, adverse reactions are listed under headings of frequency using the following categories: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥ 1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).

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

5). g. midazolam, triazolam, alprazolam) should only be considered if clearly necessary. 5). Vincristine toxicity Concomitant administration of azole antifungals, including posaconazole, 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.

1. 5). 5). 5).