Adverse reactions : תופעות לוואי

4.8      Undesirable effects
The following adverse reactions are classified by system organ class and ranked under heading of frequency using the following convention: very common (≥ 10%), common (≥ 1% and < 10%); uncommon (≥ 0.1% and < 1%); rare (≥ 0.01% and < 0.1%), very rare (< 0.01%), not known (cannot be estimated from the available data).
Blood and lymphatic system disorders:

Very rare:
• haemolytic anaemia
• aplastic anaemia
• thrombocytopenia
In patients taking amiodarone there have been incidental findings of bone marrowgranulomas. The clinical significance of this is unknown

Not Known:
• neutropenia
• agranulocytosis

Cardiac disorders:
Common:
• bradycardia, generally moderate and dose-related.
Uncommon:
• onset or worsening of arrhythmia, sometimes followed by cardiac arrest (see sections 4.4and 4.5.) • conduction disturbances (sinoatrial block, AV block of various degrees) (see section 4.4) Very rare:
• marked bradycardia or sinus arrest in patients with sinus node dysfunction and/or inelderly patients.
Not known:
• Torsade de pointes (see section 4.4 and 4.5)

Injury, poisoning and procedural complications
Not known:
• Primary graft dysfunction post cardiac transplant (see section 4.4) 
Endocrine disorders (see section 4.4):
Common:
• hypothyroidism
• hyperthyroidism, sometimes fatal
Very rare:
• syndrome of inappropriate antidiuretic hormone secretion (SIADH)

Eye disorders:
Very common:
• corneal microdeposits usually limited to the area under the pupil, which are usually only discernable by slit-lamp examinations. They may be associated with colored halosin dazzling light or blurred vision. Corneal micro-deposits consist of complex lipid deposits and are reversible following discontinuation of treatment. The deposits are considered essentially benign and do not require discontinuation of amiodarone.
Very rare:
• optic neuropathy/neuritis that may progress to blindness (see section 4.4).

Gastrointestinal disorders:
Very common:
• benign gastrointestinal disorders (nausea, vomiting, dysgeusia) usually occurring withloading dosage and resolving with dose reduction.
Common:
• constipation
Uncommon:
• dry mouth
Not known:
• pancreatitis/acute pancreatitis

General Disorders:
Not known:
• Granuloma, including bone marrow granuloma

Hepato-biliary disorders: (see section 4.4):
Very common:
• isolated increase in serum transaminases, which is usually moderate (1.5 to 3 times normal range), occurring at the beginning of therapy. It may return to normal with dosereduction or even spontaneously.
Common:
• acute liver disorders with high serum transaminases and/or jaundice, including hepaticfailure, which are sometimes fatal
Very rare:
• chronic liver disease (pseudo alcoholic hepatitis, cirrhosis), sometimes fatal.

Immune system disorders:
Not known:
• Angioneurotic oedema (Quincke’s Oedema)
• Anaphylactic shock/anaphylactoid reaction including shock

Investigations:
Very rare:
• increase in blood creatinine.
Metabolism and nutrition disorders:
Not known:
• decreased appetite

Musculoskeletal and connective tissue disorders:
Not known:
• lupus like syndrome

Nervous system disorders:
Common:
• extrapyramidal tremor, for which regression usually occurs after reduction of dose or withdrawal
• nightmares
• sleep disorders.
Uncommon:
• peripheral sensorimotor neuropathy and/or myopathy, usually reversible on withdrawalof the drug (see section 4.4).
Very rare:
• cerebellar ataxia, for which regression usually occurs after reduction of dose orwithdrawal • benign intracranial hypertension (pseudo-tumor cerebri)
• headache
• vertigo
Not known:
• parkinsonism
• parosmia


Psychiatric disorders:
Common:
• libido decreased
Not known:
• confusional state/delirium
• hallucination
Reproductive system and breast disorders:
Very rare:
• epididymo-orchitis
• impotence.

Respiratory, thoracic and mediastinal disorders:
Common:
• pulmonary toxicity [hypersensitivity pneumonitis, alveolar/interstitial pneumonitis or fibrosis, pleuritis, bronchiolitis obliterans organising pneumonia (BOOP)], sometimes fatal (see section     4.4).
Very rare:
• bronchospasm in patients with severe respiratory failure and especially in asthmatic patients • surgery (possible interaction with a high oxygen concentration) (see sections 4.4 and4.5).
Pulmonary haemorrhage (there have been some reports of pulmonary haemorrhage, although exact frequencies are not known)

Skin and subcutaneous tissue disorders:
Very common:
• photosensitivity (see section 4.4).
Common:
• slate grey or bluish pigmentations of light-exposed skin, particularly the face, in case of prolonged treatment with high daily dosages; such pigmentations slowly disappear following treatment discontinuation.
• Eczema
Very rare:
• erythema during the course of radiotherapy
• skin rashes, usually non- specific
• exfoliative dermatitis
• alopecia
Not known:
• urticaria
• severe skin reactions sometimes fatal including toxic epidermal
• necrolysis/Stevens-Johnson syndrome
• bullous dermatitis and drug reaction with eosinophilia and systematic symptoms 
Vascular disorders:
Very rare:
• vasculitis.

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.