Adverse reactions : תופעות לוואי

4.8     Undesirable Effects

For this product there is a lack of modern clinical documentation which can be used as support for determining the frequency of undesirable effects. Thioguanine is usually one component of combination chemotherapy and consequently it is not possible to ascribe the side effects unequivocally to this drug alone.

The following convention has been utilised for the classification of frequency of undesirable effects: Very common ≥1/10 (≥10%), Common ≥1/100 and < 1/10 (≥1% and <10%), Uncommon ≥ 1/1000 and <1/100 (≥0.1% and <1%), Rare ≥1/10,000 and <1/1000 (≥0.01% and <0.1%), Very rare <1/10,000 (<0.01%).


System Organ Class           Frequency             Side effects
Blood     and      lymphatic Very common           Bone marrow failure (see section 4.4).
system disorders
Gastrointestinal disorders   Common                Stomatitis, gastrointestinal disorder Rare                   Necrotising colitis
Hepatobiliary disordersa     Very common           Venoocclusive liver disease: hyperbilirubinaemia, hepatomegaly,
weight increased due to fluid retention and ascites.

Portal hypertension: splenomegaly,
varices oesophageal and

thrombocytopenia.
Hepatic enzyme increased, blood alkaline phosphatase increased and gamma glutamyltransferase increased,
jaundice, hepatoportalsclerosis, portal fibrosis, nodular regenerative hyperplasia, peliosis hepatitis.
Common              Venoocclusive liver disease in short- term cyclical therapy.
Rare                Hepatic necrosis.

Metabolism and Nutrition Common                    Hyperuricaemia disorders
Renal and urinary disorders Common                 Hyperuricosuria and urate nephropathy (see section 4.4).
Skin and subcutaneous Not Known                    Photosensitivity (see section 4.4) tissue disorders a see description of selected adverse reactions


Hepato-biliary disorders
The liver toxicity associated with vascular endothelial damage occurs at a frequency of very common when tioguanine is used in maintenance or similar long term continuous therapy which is not recommended (see sections 4.2 and 4.4).

Reversal of signs and symptoms of this liver toxicity has been reported upon withdrawal of short term or long term continuous therapy.

Rare: centrilobular hepatic necrosis has been reported in a few cases including patients receiving combination chemotherapy, oral contraceptives, high dose tioguanine and alcohol.

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

(http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic@moh.gov.il).
Additionally, you can also report to www.perrigo-pharma.co.il.