Breast-feeding

Human data demonstrate that tacrolimus is excreted in breast milk. As detrimental effects on 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)

Go to top of the page4.7 Effects on ability to drive and use machines
 Tacrolimus may cause visual and neurological disturbances. This effect may be enhanced if tacrolimus 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

Go to top of the page4.8 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 reactions (occurring in > 10% of patients) are tremor, renal impairment, hyperglycaemic conditions, diabetes mellitus, hyperkalaemia, infections, hypertension and insomnia.

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.

Infections and infestations

As is well known for other potent immunosuppressive agents, patients receiving tacrolimus are frequently at increased risk for infections (viral, bacterial, fungal, protozoal). The course of pre-existing infections may be aggravated. Both generalised and localised infections can occur.

Cases of BK virus associated nephropathy, as well as cases of JC virus associated progressive multifocal leukoencephalopathy (PML), have been reported in patients treated with immunosuppressants, including Advagraf.

Neoplasms benign, malignant and unspecified

Patients receiving immunosuppressive therapy are at increased risk of developing malignancies. Benign as well as malignant neoplasms including EBV-associated lymphoproliferative disorders and skin malignancies have been reported in association with tacrolimus treatment.

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 aplasia, agranulocytosis, haemolytic anaemia
 
Immune system disorders
 
Allergic and anaphylactoid reactions have been observed in patients receiving tacrolimus (see section 4.4).
 
Endocrine disorders
 
rare:
 hirsutism
 
Metabolism and nutrition disorders
 
very common:
 diabetes mellitus, hyperglycaemic conditions, hyperkalaemia
 
common:
 anorexia, metabolic acidoses, other electrolyte abnormalities, hyponatraemia, fluid overload, hyperuricaemia