LANVIS

What it is

LANVIS is a tablet formulation containing 40 mg of tioguanine . Tioguanine is a derivative of mercaptopurine and an antagonist to purine metabolism . Its tumour inhibitory effects may be due to incorporation into DNA and RNA; feedback inhibition of de novo purine synthesis; and inhibition of purine nucleotide interconversion .

Approved indications

— Acute myeloblastic leukaemia . — Chronic granulocytic leukaemia, less commonly .

Dosing overview

The usual initial dose is approximately 2 to 2.5 mg/kg bodyweight per day, orally, usually calculated to the nearest multiple of 20 mg . The total daily dose may be given at one time, although some regimens demand 12 hourly dosage . Patients with inherited little or no thiopurine S-methyltransferase (TPMT) activity are at increased risk for severe tioguanine toxicity from conventional doses and generally require substantial dose reduction . Patients with inherited mutated NUDT15 gene are at increased risk for severe thiopurine toxicity such as early leukopenia and alopecia from conventional doses and generally require substantial dose reduction, with patients of Asian ethnicity particularly at risk .

Key safety warnings

LANVIS is not recommended for maintenance therapy or similar long term continuous treatments due to high risk of liver toxicity associated with vascular endothelial damage, which has been observed in a high proportion of children receiving LANVIS as part of maintenance therapy for acute lymphoblastic leukaemia . Liver toxicity usually presents as 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) . LANVIS 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 . Treatment with LANVIS causes bone marrow suppression leading to leucopenia and thrombocytopenia, with anaemia reported less frequently, though bone marrow suppression is readily reversible if LANVIS is withdrawn early enough . Individuals with an inherited deficiency of thiopurine methyltransferase (TPMT) may be unusually sensitive to the myelosuppressive effect of LANVIS and prone to developing rapid bone marrow depression, with fatal cases of myelosuppression reported in patients with low or absent TPMT activity treated with thiopurines . 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, with infectious disease and complications potentially more severe in these patients than in non-treated patients .

Contraindications

LANVIS is contraindicated in patients with hypersensitivity to any component of the preparation . It should not be used during viraemic states, marrow aplasia, severe anaemia, leucopenia or in bleeding states, severe liver dysfunction, renal failure or intolerance to the drug .

PBS listing

The 40 mg tablet is listed on the PBS as a single item with unrestricted access at an ex-manufacturer price of A$165.02 .

Regulatory history

LANVIS tioguanine 40 mg tablet was first listed on the Australian Register of Therapeutic Goods on 2 August 1991 .