the newborn cannot be excluded, women should not breast-feed whilst receiving Advagraf.
Fertility
A negative effect of tacrolimus on male fertility in the form of reduced sperm counts and motility was observed in rats (see section 5.3).
4.7 Effects on ability to drive and use machines
Tacrolimus may cause visual and neurological disturbances. This effect may be enhanced if Advagraf is administered in association with alcohol.
No studies on the effects of tacrolimus (Advagraf) on the ability to drive and use machines have been performed.
4.8 Undesirable effects
The adverse reaction profile associated with immunosuppressive agents is often difficult to establish owing to the underlying disease and the concurrent use of multiple medicinal products.
The most commonly reported adverse drug reactions (occurring in > 10% of patients) are tremor, renal impairment, hyperglycaemic conditions, diabetes mellitus, hyperkalaemia, infections, hypertension and insomnia.
Many of the adverse reactions stated below are reversible and/or respond to dose reduction. The frequency of adverse reactions is defined as follows: 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). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness
Cardiac disorders
common:
ischaemic coronary artery disorders, tachycardia
uncommon:
heart failures, ventricular arrhythmias and cardiac arrest, supraventricular arrhythmias, cardiomyopathies, ECG investigations abnormal, ventricular hypertrophy, palpitations, heart rate and pulse investigations abnormal
rare:
pericardial effusion
very rare:
echocardiogram abnormal
Blood and lymphatic system disorders
common:
anaemia, thrombocytopenia, leukopenia, red blood cell analyses abnormal, leukocytosis
uncommon:
coagulopathies, pancytopenia, neutropenia, coagulation and bleeding analyses, abnormal
rare:
thrombotic thrombocytopenic purpura, hypoprothrombinaemia
not known:
pure red cell aplasi
Nervous system disorders
very common:
headache, tremor
common:
nervous system disorders seizures, disturbances in consciousness, peripheral neuropathies, dizziness, paraesthesias and dysaesthesias, writing impaired
uncommon:
encephalopathy, central nervous system haemorrhages and cerebrovascular accidents, coma, speech and language abnormalities, paralysis and paresis, amnesia
rare:
hypertonia
very rare:
myasthenia
Eye disorders
common:
eye disorders, vision blurred, photophobia
uncommon:
cataract
rare:
blindness
Ear and labyrinth disorders
common:
tinnitus
uncommon:
hypoacusis
rare:
deafness neurosensory
very rare:
hearing impaired
Respiratory, thoracic and mediastinal disorders
common:
parenchymal lung disorders, dyspnoea, pleural effusion, cough, pharyngitis, nasal congestion and inflammations
uncommon:
respiratory failures, respiratory tract disorders, asthma
rare:
acute respiratory distress syndrome
Gastrointe