Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
The safety of posaconazole oral suspension has been assessed in > 2,400 patients and healthy volunteers enrolled in clinical trials and from post-marketing experience. The most frequently reported serious related adverse reactions included nausea, vomiting, diarrhoea, pyrexia, and increased bilirubin.
The safety of posaconazole tablet has been assessed in 336 patients and healthy volunteers enrolled in clinical trials. The safety profile of tablets was similar to that of the oral suspension.

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 trials 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 Not known:                   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:                      paresthesia, 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:                        torsades 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, gastrooesophageal 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 
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.
§ See section 4.4.

Description of selected adverse reactions
Hepatobiliary disorders
During post marketing surveillance of posaconazole oral suspension, severe hepatic injury with fatal outcome has been reported (see section 4.4).

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/