Mercaptopurine
Mechanism :
Mercaptopurine competes with hypoxanthine and guanine for the enzyme hypoxanthine-guanine phosphoribosyl transferase (HGPRTase) and is itself converted to thioinosinic acid (TIMP). This intracellular nucleotide inhibits several reactions involving inosinic acid (IMP). In addition, 6-methylthioinosinate (MTIMP) is formed by the methylation of TIMP. Both TIMP and MTIMP have been reported to inhibit glutamine-5-phosphoribosylpyrophosphate amidotransferase, the first enzyme unique to the de novo pathway for purine ribonucleotide synthesis.
Indication :
- Acute lymphoblastic leukemia
- Lymphoma
- Non-Hodgkin Lymphoma (NHL)
- Crohn’s disease - steroid dependent/intractable
- Acute myeloid Leukemia
- Ulcerative colitis
- Histiocytosis
Contraindications :
Should not be used unless a diagnosis of acute lymphatic leukemia has been adequately established. Contraindicated in patients whose disease has demonstrated prior resistance to this drug and in patients who have a hypersensitivity to mercaptopurine or any component of the formulation. There is usually complete cross-resistance between mercaptopurine and thioguanine.
Dosing :
Leukemia/lymphoma/NHL:
Induction: 2.5-5 mg/kg once daily orally. Maintenance: 1.5-2.5 mg/kg/day.
Crohn’s disease:
Above 2 years: 1-1.5 mg/kg once at night, Max dose: 75 mg/day.
Adverse Effect :
Myelosuppression, anemia, leukopenia, and thrombocytopenia, hyperuricemia and hyperuricosuria, nausea, vomiting, stomatitis, diarrhea, ulcer formation. Miscellaneous: skin rashes, alopecia and hyperpigmentation.
Interaction :
Allopurinol: Delayed catabolism of mercaptopurine and the strong likelihood of inducing severe toxicity.
Thioguanine: Usually complete cross-resistance between mercaptopurine and thioguanine.
trimethoprim-sulfamethoxazole: Enhanced marrow suppression has been noted in some patients also receiving trimethoprim-sulfamethoxazole.
Warfarin: Inhibition of the anticoagulant effect of warfarin, when given with mercaptopurine, has been reported.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Caution – reduce dose. |
| 10-20 | Caution – reduce dose. |
| <10 | Caution – reduce dose. |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Unknown dialysability. Dose as in GFR<10 mL/min |
| HD | Dialysed. Dose as in GFR<10 mL/ min |
| HDF/High flux | Dialysed. Dose as in GFR<10 mL/ min |
| CAV/VVHD | Unknown dialysability. Dose as in GFR=10–20 mL/min |
Hepatic Dose :
Start at the low end of the dosing range in patients with hepatic impairment.