Noxafil

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. Non-interchangeability between Noxafil oral suspension and Noxafil tablets or Noxafil gastro-resistant powder and solvent for oral suspension Noxafil oral suspension is not to be used interchangeably with either Noxafil gastro-resistant tablet or the gastro-resistant powder and solvent for oral suspension due to the differences in frequency of dosing, administration with food and plasma drug concentration achieved.

Therefore, the specific dose recommendations for each formulation should be followed. Noxafil tablets generally provide higher plasma drug exposures than Noxafil oral suspension under both fed and fasted conditions. To optimise plasma concentrations, Noxafil tablets are preferred over the oral suspension.

Posology Noxafil oral suspension is only indicated for adult patients. Dosing recommendations are shown in Table 1. Table 1. Recommended dose in adults Indication Dose and duration of therapy Refractory invasive fungal infections (IFI)/patients with IFI intolerant to 1st line therapy 200 mg (5 mL) four times a day.

Alternatively, patients who can tolerate food or a nutritional supplement may take 400 mg (10 mL) twice a day during or immediately following a meal or nutritional supplement. Duration of therapy should be based on the severity of the underlying disease, recovery from immunosuppression, and clinical response.

5 mL) once a day for 13 days. Each dose should be administered during or immediately after a meal, or a nutritional supplement in patients who cannot tolerate food to enhance the oral absorption and to ensure adequate exposure. Prophylaxis of invasive fungal infections 200 mg (5 mL) three times a day.

Each dose should be administered during or immediately after a meal, or a nutritional supplement in patients who cannot tolerate food to enhance the oral absorption and to ensure adequate exposure. The duration of therapy is based on recovery from neutropenia or immunosuppression.

For patients with acute myelogenous leukaemia or myelodysplastic syndromes, prophylaxis 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.

Summary of the safety profile Safety data derive from clinical trials in adults with the oral suspension, intravenous, and tablet formulations, and in paediatric participants with the intravenous, tablet, and powder for suspension formulations.

The most frequently reported serious related adverse reactions included nausea, vomiting, diarrhoea, pyrexia, and increased bilirubin. 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* System organ class Adverse reactions Frequency Blood and lymphatic system disorders neutropenia Common thrombocytopenia, leukopenia, anaemia, eosinophilia, lymphadenopathy, splenic infarction Uncommon haemolytic uraemic syndrome, thrombotic thrombocytopenic purpura, pancytopenia, coagulopathy, haemorrhage Rare Immune system disorders allergic reaction Uncommon hypersensitivity reaction Rare Endocrine disorders adrenal insufficiency, blood gonadotropin decreased, pseudoaldosteronism Rare 11 System organ class Adverse reactions Frequency Metabolism and nutrition disorders electrolyte imbalance, anorexia, decreased appetite, hypokalaemia, hypomagnesaemia Common hyperglycaemia, hypoglycaemia Uncommon Psychiatric disorders abnormal dreams, confusional state, sleep disorder Uncommon psychotic disorder, depression Rare Nervous system disorders paraesthesia, dizziness, somnolence, headache, dysgeusia Common convulsions, neuropathy, hypoaesthesia, tremor, aphasia, insomnia Uncommon cerebrovascular accident, encephalopathy, peripheral neuropathy, syncope Rare Eye disorders blurred vision, photophobia, visual acuity reduced Uncommon diplopia, scotoma Rare Ear and labyrinth disorder hearing impairment Rare Cardiac disorders long QT syndrome§, electrocardiogram abnormal§, palpitations, bradycardia, supraventricular extrasystoles, tachycardia Uncommon torsade de pointes, sudden death, ventricular tachycardia, cardio-respiratory arrest, cardiac failure, myocardial infarction Rare Vascular disorders hypertension Common hypotension, vasculitis Uncommon pulmonary embolism, deep vein thrombosis Rare Respiratory, thoracic and mediastinal disorders cough, epistaxis, hiccups, nasal congestion, pleuritic pain, tachypnoea Uncommon pulmonary hypertension, interstitial pneumonia, pneumonitis Rare Gastrointestinal disorders nausea Very Common vomiting, abdominal pain, diarrhoea, dyspepsia, dry mouth, flatulence, constipation, anorectal discomfort Common pancreatitis, abdominal distension, enteritis, epigastric discomfort, eructation, gastroesophageal reflux disease, oedema mouth Uncommon gastrointestinal haemorrhage, ileus Rare Hepatobiliary disorders liver function tests raised (ALT increased, AST increased, bilirubin increased, alkaline phosphatase increased, GGT increased) Common hepatocellular damage, hepatitis, jaundice, hepatomegaly, cholestasis, hepatic toxicity, hepatic function abnormal Uncommon hepatic failure§, hepatitis cholestatic, hepatosplenomegaly, liver tenderness, asterixis Rare 12 System organ class Adverse reactions Frequency Skin and subcutaneous tissue disorders rash, pruritus Common mouth ulceration, alopecia, dermatitis, erythema, petechiae Uncommon Stevens Johnson syndrome, vesicular rash Rare photosensitivity reaction§ Not known Musculoskeletal and connective tissue disorders back pain, neck pain, musculoskeletal pain, pain in extremity Uncommon Renal and urinary disorders acute renal failure, renal failure, blood creatinine increased Uncommon renal tubular acidosis, interstitial nephritis Rare Reproductive system and breast disorders menstrual disorder Uncommon breast pain Rare General disorders and administration site conditions : pyrexia (fever), asthenia, fatigue Common oedema, pain, chills, malaise, chest discomfort, drug intolerance, feeling jittery, mucosal inflammation Uncommon tongue oedema, face oedema Rare Investigations altered medicine levels, blood phosphorus decreased, chest x-ray abnormal Uncommon * 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. 8). Monitoring of hepatic function 5 Liver function tests should be evaluated prior to 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. Discontinuation of posaconazole should be considered if clinical signs and symptoms are consistent with development of liver disease.

2). 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.

5). 5). Refer to the venetoclax SmPC for detailed guidance. 5). 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.

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