Cresemba

Posology Early targeted therapy (pre-emptive or diagnostic-driven therapy) may be instituted pending confirmation of the disease from specific diagnostic tests. However, once these results become available, antifungal therapy should be adjusted accordingly.

4 mg/kg isavuconazole 1 Six administrations in total. 2 Maintenance dose: Starting 12 to 24 hours after the last loading dose. 3 After reconstitution and dilution. The maximum of any individual loading or daily maintenance dose to be administered to any paediatric patient is 200 mg isavuconazole.

1). 3). Switch to oral isavuconazole CRESEMBA is available as 100 mg and 40 mg hard capsules. 2), switching between intravenous and oral administration is appropriate when clinically indicated. 2 of the Summary of Product Characteristics for CRESEMBA 40 mg and 100 mg hard capsules.

Elderly No dose adjustment is necessary for elderly patients; however, the clinical experience in elderly patients is limited. 2). No dose recommendation can be made for paediatric patients with renal impairment, as no relevant data are available.

2). Isavuconazole has not been studied in adult patients with severe hepatic impairment (Child-Pugh Class C). 2). No dose recommendation can be made for paediatric patients with hepatic impairment, as no relevant data are available. Paediatric population The safety and efficacy of isavuconazole in paediatric patients aged less than 1 year has not been established.

Method of administration Intravenous use. 8 mg/mL isavuconazole prior to administration by intravenous infusion over a minimum of 1 hour to reduce the risk of infusion-related reactions. Higher concentrations should be avoided as these may cause local irritation at the site of infusion.

2 μm. CRESEMBA must only be given as an intravenous infusion. 6.

7%). 5%). Tabulated list of adverse reactions Table 3 presents adverse reactions with isavuconazole in the treatment of invasive fungal infections in adults, by System Organ Class and frequency. 14 The frequency of adverse reactions is defined as follows: very common (≥1/10); common (≥1/100 to <1/10); and uncommon (≥1/1,000 to <1/100); not known (frequency cannot be estimated from available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Table 3 Summary of adverse reactions by MedDRA System Organ Class and frequency System Organ Class Adverse Drug Reactions Blood and lymphatic system disorders Uncommon Neutropenia; Thrombocytopenia^; Pancytopenia; Leukopenia^; Anaemia^ Immune system disorders Uncommon Hypersensitivity^ Not known Anaphylactic reaction* Metabolism and nutrition disorders Common Hypokalaemia; Decreased appetite Uncommon Hypomagnesaemia; Hypoglycaemia; Hypoalbuminaemia; Malnutrition^; Hyponatraemia Psychiatric disorders Common Delirium^# Uncommon Depression; Insomnia^ Nervous system disorders Common Headache; Somnolence Uncommon Convulsion^; Syncope; Dizziness; Paraesthesia^; Encephalopathy; Presyncope; Neuropathy peripheral; Dysgeusia Ear and labyrinth disorders Uncommon Vertigo Cardiac disorders Uncommon Atrial fibrillation; Tachycardia; Bradycardia^; Palpitations; Atrial flutter; Electrocardiogram QT shortened; Supraventricular tachycardia; Ventricular extrasystoles; Supraventricular extrasystoles Vascular disorders Common Thrombophlebitis^ Uncommon Circulatory collapse; Hypotension Respiratory, thoracic and mediastinal disorders Common Dyspnoea^; Acute respiratory failure^ Uncommon Bronchospasm; Tachypnoea; Haemoptysis; Epistaxis Gastrointestinal disorders Common Vomiting; Diarrhoea; Nausea; Abdominal pain^ Uncommon Dyspepsia; Constipation; Abdominal distension Hepatobiliary disorders Common Elevated liver chemistry tests^# Uncommon Hepatomegaly; Hepatitis Skin and subcutaneous tissue disorders Common Rash^; Pruritus Uncommon Petechiae; Alopecia; Drug eruption; Dermatitis^ Musculoskeletal and connective tissue disorders Uncommon Back pain Renal and urinary disorders Common Renal failure General disorders and administration site conditions Common Chest pain^; Fatigue; Injection site reaction^ Uncommon Oedema peripheral^; Malaise; Asthenia 15 ^ Indicates that grouping of appropriate preferred terms into a single medical concept occurred.

8). In case of anaphylactic reaction, isavuconazole should be discontinued immediately and appropriate medical treatment should be initiated. Caution should be used in prescribing isavuconazole to patients with hypersensitivity to other azole antifungal agents.

8). The infusion should be stopped if these reactions occur. Severe cutaneous adverse reactions Severe cutaneous adverse reactions, such as Stevens-Johnson syndrome, have been reported during treatment with azole antifungal agents. If a patient develops a severe cutaneous adverse reaction, CRESEMBA should be discontinued.

3). In a QT study in healthy human subjects, isavuconazole shortened the QTc interval in a concentration-related manner. 1 ms]. 4 ms]. Caution is warranted when prescribing isavuconazole to patients taking other medicinal products known to decrease the QT interval, such as rufinamide.

8). The elevations in liver transaminases rarely required discontinuation of isavuconazole. Monitoring of hepatic enzymes should be considered, as clinically indicated. Hepatitis has been reported with azole antifungal agents including isavuconazole.

Severe hepatic impairment Isavuconazole has not been studied in patients with severe hepatic impairment (Child-Pugh Class C). Use in these patients is not recommended unless the potential benefit is considered to outweigh the 5 risks.

2). 3). For the strong CYP3A4 inhibitor lopinavir/ritonavir, a two-fold increase in isavuconazole exposure was observed. For other strong CYP3A4/5 inhibitors, a less pronounced effect can be expected. 5). 5). CYP3A4/5 substrates including immunosuppressants Isavuconazole can be considered a moderate inhibitor of CYP3A4/5, and systemic exposure to medicinal products metabolised by CYP3A4 may be increased when co-administered with isavuconazole.

Concomitant use of isavuconazole with CYP3A4 substrates such as the immunosuppressants tacrolimus, sirolimus or ciclosporin may increase the systemic exposure to these medicinal products. 5). CYP2B6 substrates Isavuconazole is an inducer of CYP2B6.

1. 5). 5). g. phenobarbital), phenytoin and St. 5). 4).