Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of the safety profile

The most common treatment-related adverse reactions were elevated liver chemistry tests (7.9%), nausea (7.4%), vomiting (5.5%), dyspnoea (3.2%), abdominal pain (2.7%), diarrhoea (2.7%), injection site reaction (2.2%), headache (2.0%), hypokalaemia (1.7%) and rash (1.7%).

The adverse reactions which most often led to permanent discontinuation of CRESEMBA treatment were confusional state (0.7%), acute renal failure (0.7%), increased blood bilirubin (0.5%), convulsion (0.5%), dyspnoea (0.5%), epilepsy (0.5%), respiratory failure (0.5%) and vomiting (0.5%).

Tabulated list of adverse reactions

Table 2 presents adverse reactions with isavuconazole in the treatment of invasive fungal infections, by System Organ Class and frequency.

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 2 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^; 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
Uncommon        Oedema peripheral^ ; Malaise; Asthenia
^ Indicates that grouping of appropriate preferred terms into a single medical concept occurred.
* ADR identified post-marketing.
# See section Description of selected adverse reactions below.


Description of selected adverse reactions

Delirium includes reactions of confusional state.
Elevated liver chemistry tests includes events of alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased, blood bilirubin increased, blood lactate dehydrogenase increased, gamma-glutamyltransferase increased, hepatic enzyme increased, hepatic function abnormal, hyperbilirubinemia, liver function test abnormal, and transaminases increased.

Laboratory effects

In a double-blind, randomized, active-controlled clinical study of 516 patients with invasive fungal disease caused by Aspergillus species or other filamentous fungi, elevated liver transaminases (alanine aminotransferase or aspartate aminotransferase) > 3 × Upper Limit of Normal (ULN) were reported at the end of study treatment in 4.4% of patients who received CRESEMBA. Marked elevations of liver transaminases > 10 × ULN developed in 1.2% of patients on isavuconazole.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions by using an online form https://sideeffects.health.gov.il/