Mirtazapine is NOT contraindicated with dasatinib in leukemia patients
Mirtazapine can be safely used in patients with leukemia receiving dasatinib, as there is no pharmacokinetic interaction between these medications and mirtazapine is not listed among the drugs that should be avoided with dasatinib. 1
Pharmacokinetic Rationale
Mirtazapine does not interact with dasatinib's metabolism:
Dasatinib is a CYP3A4 substrate, and the NCCN guidelines specifically list drugs that should be avoided due to CYP3A4 inhibition (ketoconazole, itraconazole, erythromycin, clarithromycin, ritonavir, atazanavir, indinavir, nefazodone, nelfinavir, saquinavir, telithromycin) 1
Mirtazapine is notably absent from this list of contraindicated CYP3A4 inhibitors 1
Mirtazapine is primarily metabolized by CYP1A2, CYP2D6, and CYP3A4, but it is not a significant inhibitor of CYP3A4 at therapeutic doses
Drugs Actually Contraindicated with Dasatinib
The following categories should be avoided or used with extreme caution:
Strong CYP3A4 inhibitors that increase dasatinib exposure and should be avoided: ketoconazole, itraconazole, erythromycin, clarithromycin, ritonavir, atazanavir, indinavir, nefazodone, nelfinavir, saquinavir, telithromycin 1
CYP3A4 inducers that decrease dasatinib concentrations: dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarbital, St. John's wort 1
Gastric acid suppressors: H2 blockers and proton pump inhibitors (famotidine, omeprazole) are not recommended as they reduce dasatinib absorption due to its pH-dependent solubility 1, 2
Narrow therapeutic index CYP3A4 substrates should be used with caution: alfentanil, astemizole, terfenadine, cisapride, cyclosporine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, ergot alkaloids 1
Clinical Monitoring Considerations
When using mirtazapine in dasatinib-treated leukemia patients, monitor for:
Hematologic toxicity from dasatinib: Grade 3-4 neutropenia (ANC < 500/mm³), thrombocytopenia (platelet count < 50,000/mm³), and anemia require dose interruption and adjustment 1
Dasatinib-specific adverse effects: pleural effusion (occurs in 28-33% of patients), pulmonary arterial hypertension (5% incidence), and bleeding due to platelet dysfunction 1, 3, 4
QT prolongation risk: While dasatinib can cause QT prolongation, mirtazapine has minimal QT effects and is not listed among drugs that prolong QT interval that should be avoided 1
Important Caveats
Depression management in leukemia patients requires consideration of:
Mirtazapine's sedating and appetite-stimulating properties may actually be beneficial in leukemia patients experiencing treatment-related anorexia and insomnia
The primary concern with dasatinib remains its significant myelosuppression, pleural effusion risk (especially in older patients), and pulmonary toxicity—none of which are exacerbated by mirtazapine 1, 3, 4
If antacid therapy is needed for mirtazapine-related gastrointestinal symptoms, administer antacids at least 2 hours before or after dasatinib to avoid reducing dasatinib absorption 1