Drug information of Imatinib

Mechanism of effect

Imatinib inhibits proliferation and induces apoptosis in Bcr-Abl–positive cell lines, as well as fresh leukemic cells from Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia (CML)

Pharmacodynamic

Imatinib inhibits proliferation and induces apoptosis in Bcr-Abl–positive cell lines, as well as fresh leukemic cells from Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia (CML)

Pharmacokinetics

T max is 2 to 4 h. Mean absolute bioavailability is 98%.Approximately 95% is protein bound. In the liver, primarily via CYP3A4 isoenzyme, but also via CYP1A2, 2D6, 2C9, and 2C19. Major metabolite is N-demethylated piperazine derivative (active). The half-life is approximately 18 h (parent drug) and 40 h (major active metabolite); 68% is excreted in the feces and 13% in the urine, primarily as metabolites

Drug indications

Ph+ CML , Ph+ acute lymphoblastic leukaemia, , gastrointestinal stromal tumors , myelodysplastic/myeloproliferative diseases

Dosage

--Hypereosinophilic Syndrome and/or Chronic Eosinophilic Leukemia: Adults: PO 400 mg/d. For patients with demonstrated FIP1L1-PDGFR alpha fusion kinase, start with 100 mg/d. Dose increase from 100 to 400 mg may be considered in the absence of adverse drug reactions if assessments demonstrate an insufficient response to therapy. --Myelodysplastic/Myeloproliferative Diseases: Adults: PO 400 mg/d. --Ph+ ALL: Adults: PO 600 mg/d. --Children 2 y and older: PO 340 mg/m 2 /d (max, 600 mg).

Drug contraindications

None well documented

Side effects

nausea , Headache , chest pain , Dermatit , dry mouth , constipation , abdominal pain , vomiting , fatigue , Blurred vision , rash , flushing , Diarrhea , asthenia , Chills , Night sweats , pruritus , thrombocytopenia , neutropenia , lymphopenia , leukopenia , anemia , palpitations , Rhinitis , dyspepsia , edema , Peripheral edema , anxiety , Alopecia , Infections , malaise , conjunctivitis , gastritis , fluid retention , pain in the extremities , Pain , CNS hemorrhage , hemorrhage , stomatitis , dry eyes , Nasopharyngitis , Anaphylactic reaction , superficial edema

Interactions

Acetaminophen , Ipratropium bromide , Ifosfamide , Aprepitant , Erythromycin , Itraconazole , Tadalafil , Tamsulosin , Trazodone , Venlafaxine , Voriconazole , Vinorelbine , Clarithromycin , Quinidine , Metoprolol , Midazolam , Nifedipine , Vardenafil , Warfarin , Verapamil , Cyclosporine , Phenobarbital , Phenytoin , Phenytoin phenobarbital , Lovastatin , Levothyroxine , Trimipramine , Topotecan , Tolterodine , Ginseng , Zonisamide , Simvastatin , Budesonide , Posaconazole , Trastuzumab , Nilotinib , Clozapine , Disulfiram , Bisoprolol , fentanyl , Axitinib , Phenindione , Butalbital and Acetaminophen , Ivacaftor , brigatinib , Copanlisib , Dabrafenib , Acalabrutinib , Cabazitaxel , Halofantrine , Palbociclib , Ixazomib , Pimavanserin , Tasimelteon , Flibanserin , Avanafil , Estazolam , Entrectinib , Abemaciclib , Eliglustat , Suvorexant , Ruxolitinib , riociguat , Gefitinib , Remdesivir , Cannabidiol , Sarecycline , talazoparib , vemurafenib , Meningococcal conjugate vaccine , Artesunate , Avapritinib

Alerts

Monitor patients for GI symptoms at the start of therapy. Weigh and monitor patients regularly for signs and symptoms of fluid retention. Carefully investigate unexpected rapid weight gain and provide appropriate treatment. Perform CBC weekly for first month, biweekly for second month, and periodically thereafter as clinically indicated. Monitor liver function (alkaline phosphatase, bilirubin, transaminases) prior to therapy, then monthly or as clinically indicated during treatment. Monitor TSH levels in thyroidectomy patients receiving levothyroxine replacement therapy. Closely monitor the growth of children under treatment. Carefully monitor patients with cardiac disease, risk factors for cardiac failure, or a history of renal failure, and evaluate and treat any patient with signs and symptoms consistent with cardiac failure. Perform an echocardiogram and determine serum troponin levels in patients with hypereosinophilic syndrome and/or chronic eosinophilic leukemia and in patients with myelodysplastic/myeloproliferative diseases or aggressive systemic mastocytosis associated with high eosinophil levels. Closely monitor patients at risk for tumor lysis syndrome (eg, patients with tumors having a high proliferative rateor a high tumor burden prior to treatment)

Points of recommendation

• Administer doses of 400 or 600 mg once daily; administer dose of 800 mg as 400 mg twice daily. Use 400 mg tablets for daily doses of 800 mg and higher to reduce exposure to iron. • Treatment may be continued as long as there is no evidence of progressive disease or unacceptable toxicity. • Administer pediatric doses as a single dose once daily or split dose twice daily. • Administer each dose with a meal and a large glass of water to reduce GI irritation. • If patient is unable to swallow film-coated tablets, the tablets may be dispersed in a glass of water or apple juice. Place required number of tablets in a glass with appropriate volume of beverage (50 mL for 100 mg tablet, 200 mL for 400 mg tablet) and stir with a spoon until the tablets have disintegrated. Immediately administer suspension after complete disintegration of the tablets. • Do not crush imatinib tablets. Direct contact of crushed tablets with the skin or mucous membranes should be avoided. If contact occurs, wash thoroughly. Personnel should avoid exposure to crushed tablets

Pregnancy level

D

Related drugs

bosutinib , zanubrutinib , Avapritinib , tucatinib