Adverse reactions : תופעות לוואי

4.8 Undesirable effects

Summary of the safety profile
The most frequently reported adverse drug reactions (ADRs) with itraconazole capsules treatment identified from clinical trials and/or from spontaneous reporting were headache, abdominal pain, and nausea. 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 open-label and double-blind clinical trials with Itranol Capsules involving 8499 patients in the treatment of dermatomycoses or onychomycosis, 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).


Adverse Drug Reactions
Infections and infestations

Uncommon                      Sinusitis, Upper respiratory tract infection, Rhinitis 
Blood and lymphatic system disorders

Rare                          Leukopenia
Immune system disorders

Uncommon                      Hypersensitivity*

Rare                          Serum sickness, Angioneurotic oedema, Anaphylactic reaction 
Endocrine disorders

Not known                     Pseudoaldosteronism
Metabolism and nutrition disorders

Rare                          Hypertriglyceridaemia

Nervous system disorders
Common                        Headache

Rare                          Tremor, Paraesthesia, Hypoaesthesia, Dysgeusia 
Eye disorders

Rare                          Visual disturbance (including diplopia and blurred vision) 
Ear and labyrinth disorder

Rare                          Transient or permanent hearing loss*, Tinnitus 
Cardiac disorders

Rare                          Congestive heart failure*
Respiratory, thoracic and mediastinal disorders

Rare                          Dyspnoea

Gastrointestinal disorders

  Adverse Drug Reactions

Common                    Abdominal pain, Nausea
Uncommon                  Diarrhoea, Vomiting, Constipation, Dyspepsia, Flatulence 
Rare                      Pancreatitis

Hepatobiliary disorders
Uncommon                  Hepatic function abnormal

Rare                      Serious hepatotoxicity (including some cases of fatal acute liver failure)*, Hyperbilirubinaemia

Skin and subcutaneous tissue disorders

Uncommon                  Urticaria, Rash, Pruritus
Rare                      Toxic     epidermal       necrolysis,      Stevens-Johnson      syndrome,        Acute generalised exanthematous pustulosis, Erythema multiforme, Exfoliative dermatitis, Leukocytoclastic vasculitis, Alopecia, Photosensitivity



Renal and urinary disorders

Rare                      Pollakiuria
Reproductive system and breast disorders

Uncommon                  Menstrual disorder

Rare                      Erectile dysfunction
General disorders and administration site conditions

Rare                      Oedema

Investigations
Rare                      Blood creatine phosphokinase increased


*see section 4.4


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

Blood and lymphatic system disorders: Granulocytopenia, Thrombocytopenia 
Immune system disorders: Anaphylactoid reaction

Metabolism and nutrition disorders: Hyperglycaemia, Hyperkalaemia, Hypokalaemia, Hypomagnesaemia

Psychiatric disorders: Confusional state

Nervous system disorders: Peripheral neuropathy*, Dizziness, Somnolence 
Cardiac disorders: Cardiac failure, Left ventricular failure, Tachycardia 
Vascular disorders: Hypertension, Hypotension

Respiratory, thoracic and mediastinal disorders: Pulmonary oedema, Dysphonia, Cough 
Gastrointestinal disorders: Gastrointestinal disorder

Hepatobiliary disorders: Hepatic failure*, Hepatitis, Jaundice
Skin and subcutaneous tissue disorders: Rash erythematous,
Hyperhidrosis
Musculoskeletal and connective tissue disorders: Myalgia, Arthralgia
Renal and urinary disorders: Renal impairment, Urinary incontinence
General disorders and administration site conditions: Generalised oedema, Face oedema, Chest pain, Pyrexia, Pain, Fatigue, Chills

Investigations: Alanine aminotransferase increased, Aspartate aminotransferase increased, Blood alkaline phosphatase increased, Blood lactate dehydrogenase increased, Blood urea increased, Gamma-glutamyltransferase increased, Hepatic enzyme increased, Urine analysis abnormal

Pediatric population

The safety of itraconazole capsules was evaluated in 165 pediatric patients aged 1 to 17 years who participated in 14 clinical trials (4 double-blind, placebo controlled trials; 9 open-label trials; and 1 trial had an open-label phase followed by a double-blind phase). These patients received at least one dose of itraconazole capsules for the treatment of fungal infections and provided safety data.


Based on pooled safety data from these clinical trials, the commonly reported adverse drug reactions (ADRs) in pediatric patients were Headache (3.0%), Vomiting (3.0%), Abdominal pain (2.4%), Diarrhoea (2.4%), Hepatic function abnormal (1.2%), Hypotension (1.2%), Nausea (1.2%), and Urticaria (1.2%). In general, the nature of ADRs in pediatric patients is similar to that observed in adult subjects, but the incidence is higher in the pediatric 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/