NOXAFIL

Non-interchangeability between Noxafil gastro-resistant powder and solvent for oral suspension and Noxafil oral suspension Noxafil gastro-resistant powder and solvent for oral suspension is indicated for paediatric population (<18 years old) only.

Another formulation (Noxafil oral suspension) is available for adult patients ≥18 years old. The gastro-resistant powder and solvent for oral suspension is not to be used interchangeably with oral suspension due to the differences in the dosing of each formulation.

Therefore, follow the specific dose recommendations for each of the formulations. Treatment should be initiated by a physician experienced in the management of fungal infections or in the supportive care of high-risk patients for which posaconazole is indicated as prophylaxis.

Posology Noxafil is also available as 40 mg/mL oral suspension; 100 mg gastro-resistant tablet; and 300 mg concentrate for solution for infusion. Dosing for paediatric patients 2 years to less than 18 years of age is shown in Table 1.

, the recommended dose for patients weighing 40 kg). For paediatric patients weighing > 40 kg, it is recommended to use posaconazole tablets if the patient can swallow whole tablets. Refer to the tablet SmPC for additional dosing information.

Table 1. Recommended dose in paediatric patients (2 years to less than 18 years of age) and weighing 10 to 40 kg Weight (kg) Dose (volume) 10-<12 kg 90 mg (3 mL) 12-<17 kg 120 mg (4 mL) 17-<21 kg 150 mg (5 mL) 21-<26 kg 180 mg (6 mL) 26-<36 kg 210 mg (7 mL) 36-40 kg 240 mg (8 mL) On Day 1, the recommended dose is administered twice.

After Day 1, the recommended dose is administered once daily. Duration of therapy For patients with refractory invasive fungal infections (IFI) or patients with IFI intolerant to 1st line therapy, the duration of therapy should be based on the severity of the underlying disease, recovery from immunosuppression, and clinical response.

For patients with acute myelogenous leukaemia or myelodysplastic syndromes, prophylaxis of invasive fungal infections with Noxafil 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.

Duration of therapy is based on recovery from neutropenia or immunosuppression. 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 2 years have not been established.

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 gastro-resistant powder and solvent for oral suspension and concentrate for solution for infusion safety The safety of posaconazole gastro-resistant powder and solvent for oral suspension and concentrate for solution for infusion has been assessed in 115 paediatric patients aged 2 to less than 18 years for prophylaxis use.

6 %). 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).

Table 2. Adverse reactions by body system and frequency reported in clinical studies and/or post-marketing use* Blood and lymphatic system disorders Common: neutropenia Uncommon: thrombocytopenia, leukopenia, anaemia, eosinophilia, lymphadenopathy, splenic infarction Rare: haemolytic uraemic syndrome, thrombotic thrombocytopenic purpura, pancytopenia, coagulopathy, haemorrhage Immune system disorders Uncommon: allergic reaction Rare: hypersensitivity reaction Endocrine disorders Rare: adrenal insufficiency, blood gonadotropin decreased, pseudoaldosteronism Metabolism and nutrition disorders Common: electrolyte imbalance, anorexia, decreased appetite, hypokalaemia, hypomagnesaemia Uncommon: hyperglycaemia, hypoglycaemia Psychiatric disorders Uncommon: Rare: abnormal dreams, confusional state, sleep disorder psychotic disorder, depression Nervous system disorders Common: paraesthesia, dizziness, somnolence, headache, dysgeusia Uncommon: convulsions, neuropathy, hypoaesthesia, tremor, aphasia, insomnia Rare: cerebrovascular accident, encephalopathy, peripheral neuropathy, syncope Eye disorders Uncommon: blurred vision, photophobia, visual acuity reduced Rare: diplopia, scotoma Ear and labyrinth disorder Rare: hearing impairment Cardiac disorders Uncommon: long QT syndrome§, electrocardiogram abnormal§, palpitations, bradycardia, supraventricular extrasystoles, tachycardia Rare: torsade de pointes, sudden death, ventricular tachycardia, cardio-respiratory arrest, cardiac failure, myocardial infarction Vascular disorders Common: Uncommon: hypertension hypotension, vasculitis Rare: pulmonary embolism, deep vein thrombosis Respiratory, thoracic and mediastinal disorders Uncommon: Rare: cough, epistaxis, hiccups, nasal congestion, pleuritic pain, tachypnoea pulmonary hypertension, interstitial pneumonia, pneumonitis Gastrointestinal disorders Very Common: Common: nausea vomiting, abdominal pain, diarrhoea, dyspepsia, dry mouth, flatulence, constipation, anorectal discomfort Uncommon: pancreatitis, abdominal distension, enteritis, epigastric discomfort, eructation, gastroesophageal reflux disease, oedema mouth Rare: gastrointestinal haemorrhage, ileus Hepatobiliary disorders Common: liver function tests raised (ALT increased, AST increased, bilirubin increased, alkaline phosphatase increased, GGT increased) Uncommon: hepatocellular damage, hepatitis, jaundice, hepatomegaly, cholestasis, hepatic toxicity, hepatic function abnormal Rare: hepatic failure, hepatitis cholestatic, hepatosplenomegaly, liver tenderness, asterixis Skin and subcutaneous tissue disorders Common: rash, pruritis Uncommon: mouth ulceration, alopecia, dermatitis, erythema, petechiae Rare: Not known: Stevens Johnson syndrome, vesicular rash photosensitivity reaction§ Musculoskeletal and connective tissue disorders Uncommon: back pain, neck pain, musculoskeletal pain, pain in extremity Renal and urinary disorders Uncommon: acute renal failure, renal failure, blood creatinine increased Rare: renal tubular acidosis, interstitial nephritis Reproductive system and breast disorders Uncommon: menstrual disorder Rare: breast pain General disorders and administration site conditions Common: pyrexia (fever), asthenia, fatigue Uncommon: oedema, pain, chills, malaise, chest discomfort, drug intolerance, feeling jittery, mucosal inflammation Rare: tongue oedema, face oedema Investigations Uncommon: altered medicine levels, blood phosphorus decreased, chest x-ray abnormal * Based on adverse reactions observed with the oral suspension, gastro-resistant tablets, concentrate for solution for infusion, and gastro-resistant powder and solvent for oral suspension.

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). 5).