POSACONAZOLE MILPHARM

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 Posaconazole Milpharm oral suspension and Posaconazole tablets or Posaconazole gastro-resistant powder and solvent for oral suspension Posaconazole Milpharm is indicated for the adult population (≥18 years old) only.

Another formulation (Posaconazole gastro-resistant powder and solvent for oral suspension) is available for paediatric patients from 2 years to less than 18 years of age. The oral suspension is not to be used interchangeably with either the tablet or 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, follow the specific dose recommendations for each formulation. Posology Posaconazole is also available as 100 mg gastro-resistant tablet, 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 over the oral suspension to optimize plasma concentrations.

Recommended dose is shown in Table 1. Table 1. 2) 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 of Posaconazole Milpharm 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 of Posaconazole Milpharm 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.

Summary of the safety profile 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.

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: abnormal dreams, confusional state, sleep disorder Rare: 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: hypertension Uncommon: hypotension, vasculitis Rare: pulmonary embolism, deep vein thrombosis Respiratory, thoracic and mediastinal disorders Uncommon: cough, epistaxis, hiccups, nasal congestion, pleuritic pain, tachypnoea Rare: pulmonary hypertension, interstitial pneumonia, pneumonitis Gastrointestinal disorders Very Common: nausea Common: 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: Stevens Johnson syndrome, vesicular rash Not known 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, and 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).