Box 8 Prescribing guidelines for imatinib

Imatinib is administered at a dosage of 100–400 mg/day (to be adjusted in children) depending on the molecular abnormality involved (100 mg/day for PDGFRA rearrangement, 400 mg/day for PDGFRB rearrangement), taken as a single oral dose with a meal (to improve gastrointestinal tolerability).

In case of specific cardiac involvement related to eosinophilic heart disease, as some cases of paradoxical worsening have been reported at the initial phase of treatment (tumor lysis syndrome), a short course of oral corticosteroids (e.g., 1 mg/kg/day for 5–7 days) may also be prescribed jointly initially. Because of its potential teratogenic effects, contraception (in both female and male) is mandatory for all patients of childbearing potential receiving imatinib, as is adequate photoprotection (risk of photosensitivity).

Imatinib is generally well tolerated, likely since the dosages are lower than those used for the treatment of chronic myeloid leukemia. The main potential adverse reactions are musculoskeletal pain, gastrointestinal disorders, photosensitivity, cytopenia, edema, abnormal liver function tests and growth retardation in children. These adverse reactions should be screened for at each follow-up visit and call for require regular laboratory monitoring (e.g., every 2 weeks for the first 2 months, and then every 3 months thereafter). In case of laboratory abnormalities suggestive of imatinib toxicity (e.g., severe neutropenia < 1.0 × 10⁹/L, thrombocytopenia < 50 × 10⁹/L, cytolysis >5ULN, etc.), temporary cessation of therapy is recommended. Finally, since cases of viral reactivation (sometimes with fulminant hepatitis) have been reported in HBV-positive patients treated with imatinib, HBV viral load monitoring is recommended at the start of treatment and semiannually thereafter in patients with anti-HBc antibodies.

When imatinib is co-administered with other drugs, drug interactions may occur. In particular, imatinib is a substrate for s-glycoprotein and is metabolized by cytochrome 3A4 (CYP3A4); caution should therefore be exercised when imatinib is prescribed in combination with CYP3A4 inducers (including rifampicin, phenobarbital, carbamazepine and phenytoin), CYP3A4 inhibitors (protease inhibitors, azole drugs, macrolides, amiodarone, diltiazem, vancomycin, etc., risk of decreased effectiveness of imatinib), CYP3A4 inhibitors (protease inhibitors, azole drugs, macrolides, amiodarone, diltiazem, verapamil, etc., increased risk of adverse reactions from imatinib), or with other CYP3A4 substrates with a narrow therapeutic margin (e.g., anticalcineurins, sirolimus, warfarin and other coumarin derivatives, and digoxin).