POSACONAZOLE MYLAN

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. Non-Interchangeability between posaconazole tablets and posaconazole oral suspension The tablet is not to be used interchangeably with the oral suspension 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. Posology Posaconazole is also available as 40 mg/mL oral suspension and 300 mg concentrate for solution for infusion, and 300 mg gastro-resistant powder and solvent for oral suspension.

Posaconazole tablets generally provide higher plasma drug exposures than posaconazole oral suspension under both fed and fasted conditions. Therefore, the tablets are the preferred formulation to optimize plasma concentrations. Recommended dose in paediatric patients from 2 years of age weighing more than 40 kg and in adults is shown in Table 1.

Posaconazole gastro-resistant powder and solvent for oral suspension is recommended for oral use in paediatric patients 2 years of age and older weighing 40 kg or less. Refer to the gastro-resistant powder and solvent for oral suspension SmPC for additional dosing information although not all presentations may be marketed.

Table 1. 2) Treatment of invasive aspergillosis (only for adults) Loading dose of 300 mg (three 100 mg tablets or 300 mg concentrate for solution for infusion) twice a day on the first day, then 300 mg (three 100 mg tablets or 300 mg concentrate for solution for infusion) 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 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.

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 trials and from post- marketing experience.

The most frequently reported serious related adverse reactions included nausea, vomiting, diarrhoea, pyrexia, and increased bilirubin. Posaconazole tablets The safety of posaconazole tablet has been assessed in 104 healthy volunteers and 230 patients enrolled in 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.

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. 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). The safety of posaconazole tablets and concentrate for solution for infusion were also investigated in a controlled study of treatment of invasive aspergillosis.

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.

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