Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of the safety profile
The most frequently reported adverse drug reactions (ADRs) with SPORANOX Oral Solution treatment identified from clinical trials and/or from spontaneous reporting were dizziness, headache, dysgeusia, dyspnoea, cough, abdominal pain, diarrhoea, vomiting, nausea, dyspepsia, rash, and pyrexia. The most serious ADRs were serious allergic reactions, cardiac failure/congestive heart failure/pulmonary oedema, pancreatitis, serious hepatotoxicity (including some cases of fatal acute liver failure), and serious skin reactions. Refer to subsection Tabulated list of adverse reactions for the frequencies and for other observed ADRs. Refer to section 4.4 (Special warnings and precautions for use) for additional information on other serious effects.

Tabulated list of adverse reactions
The ADRs in the table below were derived from double-blind and open-label clinical trials with SPORANOX Oral Solution involving 889 patients for the treatment of oropharyngeal and oesophageal candidiasis, and from spontaneous reporting.

The table below presents ADRs by System Organ Class. Within each System Organ Class, the ADRs are presented by incidence, using the following convention:

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).

Adverse Drug Reactions
Blood and lymphatic system disorders
Uncommon        Leukopenia, Thrombocytopenia
Immune system disorders
Uncommon        Hypersensitivity*
Not Known       Serum sickness, Angioneurotic oedema, Anaphylactic reaction Metabolism and nutrition disorders
Uncommon        Hypokalaemia
Not Known       Hypertriglyceridaemia
Nervous system disorders
Common          Dizziness, Headache, Dysgeusia
Uncommon        Peripheral neuropathy*, Paraesthesia, Hypoaesthesia
Eye disorders
Uncommon        Visual disturbances (including diplopia and blurred vision) Ear and labyrinth disorders
Uncommon        Tinnitus
Not Known       Transient or permanent hearing loss*
Cardiac disorders
Uncommon        Cardiac failure
Not Known       Congestive heart failure*
Respiratory, thoracic and mediastinal disorders
Common          Dyspnoea, Cough
Gastrointestinal disorders
Common          Abdominal pain, Diarrhoea, Vomiting, Nausea, Dyspepsia Uncommon        Constipation
Not Known       Pancreatitis
Hepatobiliary disorders
Uncommon        Hepatic failure*, Hyperbilirubinaemia
Not Known       Serious hepatotoxicity (including some cases of fatal acute liver failure)* Skin and subcutaneous tissue disorders
Common          Rash

Uncommon        Urticaria, Pruritus
Not Known       Toxic epidermal necrolysis, Stevens-Johnson syndrome, Acute generalised exanthematous pustulosis, Erythema multiforme, Exfoliative dermatitis, Leukocytoclastic vasculitis, Alopecia, Photosensitivity
Musculoskeletal and connective tissue disorders
Uncommon        Myalgia, Arthralgia
Reproductive system and breast disorders
Uncommon        Menstrual disorders
General disorders and administration site conditions
Common          Pyrexia
Uncommon        Oedema
Investigations
Not Known       Blood creatine phosphokinase increased
* see section 4.4.

Description of selected adverse reactions
The following is a list of additional ADRs associated with itraconazole that have been reported in clinical trials of SPORANOX Capsules and SPORANOX IV, excluding the ADR term “Injection site inflammation”, which is specific to the injection route of administration.

Infections and infestations: Sinusitis, Upper respiratory tract infection, Rhinitis Blood and lymphatic system disorders: Granulocytopenia
Immune system disorders: Anaphylactoid reaction
Metabolism and nutrition disorders: Hyperglycaemia, Hyperkalaemia, Hypomagnesaemia Psychiatric disorders: Confusional state
Nervous system disorders: Somnolence, Tremor
Cardiac disorders: Left ventricular failure, Tachycardia
Vascular disorders: Hypertension, Hypotension
Respiratory, thoracic and mediastinal disorders: Pulmonary oedema, Dysphonia Gastrointestinal disorders: Gastrointestinal disorder, Flatulence
Hepatobiliary disorders: Hepatitis, Jaundice, Hepatic function abnormal Skin and subcutaneous tissue disorders: Rash erythematous, Hyperhidrosis Renal and urinary disorders: Renal impairment, Pollakiuria, Urinary incontinence Reproductive system and breast disorders: Erectile dysfunction
General disorders and administration site conditions: Generalised oedema, Face oedema, Chest pain, Pain, Fatigue, Chills
Investigations: Alanine aminotransferase increased, Aspartate aminotransferase increased, Blood alkaline phosphatase increased, Blood lactate dehydrogenase increased, Blood urea increased, Gamma-glutamyl transferase increased, Hepatic enzyme increased, Urine analysis abnormal 
Paediatric Population
The safety of SPORANOX oral solution was evaluated in 250 paediatric patients aged 6 months to 14 years who participated in five open-label clinical trials. These patients received at least one dose of SPORANOX oral solution for prophylaxis of fungal infections or for treatment of oral thrush or systemic fungal infections and provided safety data.
Based on pooled safety data from these clinical trials, the very common reported ADRs in paediatric patients were Vomiting (36.0%), Pyrexia (30.8%), Diarrhoea (28.4%), Mucosal inflammation (23.2%), Rash (22.8%), Abdominal pain (17.2%), Nausea (15.6%), Hypertension (14.0%), and Cough (11.2%). The nature of ADRs in paediatric patients is similar to that observed in adult subjects, but the incidence is higher in the paediatric patients.


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. Any suspected adverse events 

should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il/