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TIOGUANINE is a brand name for Thioguanine (also known as Tioguanine). The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Tioguanine is indicated primarily for the treatment of acute leukaemias especially acute myelogenous leukaemia and acute lymphoblastic leukaemia.
Verbatim from this product's MHRA label. Tap a section to expand.
Posology The exact dose and duration of administration will depend on the nature and dosage of other cytotoxic drugs given in conjunction with tioguanine. Tioguanine is variably absorbed following oral administration and plasma levels may be reduced following emesis or intake of food.
Tioguanine can be used at various stages of treatment in short term cycles. 4). Adults The usual dosage of tioguanine is between 100 and 200 mg/m2 body surface area, per day. Paediatric population Similar dosages to those used in adults, with appropriate correction for body surface area, have been used.
Use in the elderly There are no specific dosage recommendations in elderly patients (see dosage in renal or hepatic impairment). Tioguanine has been used in various combination chemotherapy schedules in elderly patients with acute leukaemia at equivalent doses to those used in younger patients.
Special populations:
Dosage in renal or hepatic impairment Consideration should be given to reducing the dosage in patients with impaired hepatic or renal function. TPMT-deficient patients Patients with inherited little or no thiopurine S-methyltransferase (TPMT) activity are at increased risk for severe tioguanine toxicity from conventional doses of tioguanine and generally require substantial dose reduction.
2). Most patients with heterozygous TPMT deficiency can tolerate recommended tioguanine doses, but some may require dose reduction. 2). 4). 4). Genotypic testing of NUDT15 variants may be considered before initiating tioguanine therapy.
In any case, close monitoring of blood counts is necessary. Method of administration Oral.
For this product there is a lack of modern clinical documentation which can be used as support for determining the frequency of undesirable effects. Tioguanine is usually one component of combination chemotherapy and consequently it is not possible to ascribe the side effects unequivocally to this drug alone.
01%). 4). Common Stomatitis, gastrointestinal disorderGastrointestinal disorders Rare Necrotising colitis 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, portal fibrosis, nodular regenerative hyperplasia, peliosis hepatitis.
Common Venoocclusive liver disease in short- term cyclical therapy. Uncommon cholestasis of pregnancy Hepatobiliary disordersa Rare Hepatic necrosis. 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. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Tioguanine is an active cytotoxic agent for use only under the direction of physicians experienced in the administration of such agents. Immunisation using a live organism vaccine has the potential to cause infection in immunocompromised hosts.
Therefore, immunisations with live organism vaccines are not recommended. In all cases, patients in remission should not receive live organism vaccines until at least 3 months after their chemotherapy treatment has been completed. 8).
This liver toxicity has been observed in a high proportion of children receiving tioguanine as part of maintenance therapy for acute lymphoblastic leukaemia and in other conditions associated with continuous use of tioguanine. This liver toxicity is particularly prevalent in males.
Liver toxicity usually presents as the clinical syndrome of hepatic veno-occlusive disease (hyperbilirubinaemia, tender hepatomegaly, weight gain due to fluid retention and ascites) or with signs of portal hypertension (splenomegaly, thrombocytopenia and oesophageal varices).
Histopathological features associated with this toxicity include hepatoportal sclerosis, nodular regenerative hyperplasia, peliosis hepatis and periportal fibrosis. Tioguanine therapy should be discontinued in patients with evidence of liver toxicity as reversal of signs and symptoms of liver toxicity have been reported upon withdrawal.
Monitoring Patients must be carefully monitored during therapy including blood cell counts and weekly liver function tests. Early indications of liver toxicity are signs associated with portal hypertension such as thrombocytopenia out of proportion with neutropenia and splenomegaly.
Elevations of liver enzymes have also been reported in association with liver toxicity but do not always occur. Haematological Effects Treatment with tioguanine causes bone marrow suppression leading to leucopenia and thrombocytopenia (see Hepatic effects).
1. In view of the seriousness of the indications there are no absolute contra-indications.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Anaemia has been reported less frequently. Bone marrow suppression is readily reversible if tioguanine is withdrawn early enough. Thiopurine S-methyltransferase (TPMT) deficiency There are individuals with an inherited deficiency of the enzyme TPMT who may be unusually sensitive to the myelosuppressive effect of tioguanine and prone to developing rapid bone marrow depression following the initiation of treatment with tioguanine.
This problem could be exacerbated by coadministration with drugs that inhibit TPMT, such as olsalazine, mesalazine or sulphasalzine. Some laboratories offer testing for TPMT deficiency, although these tests have not been shown to identify all patients at risk of severe toxicity.
Therefore close monitoring of blood counts is still necessary. Patients with NUDT15 variant Patients with inherited mutated NUDT15 gene are at increased risk for severe tioguanine toxicity, such as early leukopenia and alopecia, from conventional doses of thiopurine therapy.
2). 2 % in Europeans and 0 % in Africans. In any case, close monitoring of blood counts is necessary. During remission indication in acute myelogenous leukaemia the patient may frequently have to survive a period of relative bone marrow aplasia and it is important that adequate supportive facilities are available.
Patients on myelosuppressive chemotherapy are particularly susceptible to a variety of infections. Patients treated with thioguanine in combination with other immunosuppressive or chemotherapeutic agents, have shown increased susceptibility to viral, fungal, and bacterial infections, including severe or atypical infection.
The infectious disease and complications may be more severe in these patients than in non-treated patients which may be life- threatening or fatal. Appropriate treatment and supportive care should be instigated to manage the risk of infections.
During remission induction, particularly when rapid cell lysis is occurring, adequate precautions should be taken to avoid hyperuricaemia and/or hyperuricosuria and the risk of uric acid nephropathy. Monitoring Since tioguanine is strongly myelosuppresive full blood counts must be carried out frequently during remission induction.
Patients must be carefully monitored during therapy. The leucocyte and platelet counts continue to fall after treatment is stopped, so at the first sign of an abnormally large fall in these counts, treatment should be temporarily discontinued.
6). If cholestasis of pregnancy occurs, case by case assessment is necessary considering the risk-benefit profile of the product (potential withdrawal/dose reduction). Mutagenicity and carcinogenicity In view of its action on cellular DNA, tioguanine is potentially mutagenic and carcinogenic.
Lesch-Nyhan syndrome Since the enzyme hypoxanthine guanine phosphoribosyl transferase is responsible for the conversion of tioguanine to its active metabolite, it is possible that patients deficient in this enzyme, such as those suffering from Lesch-Nyhan Syndrome, may be resistant to the drug.
Resistance to azathioprine (Imuran*) which has one of the same active metabolites as tioguanine, has been demonstrated in two children with Lesch-Nyhan Syndrome. UV exposure Patients treated with tioguanine are more sensitive to the sun.
Exposure to sunlight and UV light should be limited, and patients should be recommended to wear protective clothing and to use a sunscreen with a high protection factor. Patients with lactose intolerance should be advised that tioguanine contains a […]