Dosing & Uses
Dosage Forms & Strengths
tablet
- 50mg
oral suspension
- 20mg/mL
Acute Lymphatic Leukemia
Induction: 2.5 mg/kg PO qDay; usually 100-200 mg PO qDay in average adult (other agents preferred)
May increase by 5 mg/kg/day after 4 weeks
Maintenance: 1.5-2.5 mg/kg PO qDay
Reduce dose by 75% if concomitant allopurinol administration
Reduce dose in renal impairment
Crohn Disease (Off-label)
1-1.5 mg/kg PO qHS
Administration
Take on empty stomach to reduce risk of N/V
Other Information
Monitor: CBC, LFTs
Other Indications & Uses
AML
(Off-label): CML, Crohn's disease, ulcerative colitis, histiocytosis X
Dosage Forms & Strengths
tablet
- 50mg
oral suspension (Purixan)
- 20mg/mL
Acute Lymphatic Leukemia
Starting dose: 1.25-2.5 mg/kg (50-75 mg/m²) PO qDay
Maintenance: 1.5-2.5 mg/kg PO qDay in combination with methotrexate
Reduce dose by 75% if concomitant allopurinol administration
Reduce dose in renal impairment
Administration
Take on empty stomach to reduce risk of N/V
Other Information
Monitor: CBC, LFTs
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10%
Elevated LFT's (15%)
1-10%
Nausea (10%)
Vomiting (10%)
Stomatitis (3-10%)
Thrombocytopenia (3-10%)
Rash (1-3%)
Diarrhea (1-3%)
Dizziness (1-3%)
Alopecia (1-3%)
Leukopenia (1-3%)
Frequency Not Defined
Fatigue
Anorexia
Headache
Chills and fever
Chest pain
Mucositis
Upper respiratory infection
Cough
Ulceration of intestine
Ulcerative stomatitis
Myelosuppression
Decreased hematocrit
Hepatotoxicity
Decreased resistance to infections
Hyperuricemia
Nephrotoxicity
Increased risk of pancreatitis in pts with IBD
Hyperpigmentation of skin
Arthralgias
Eye discomfort
Tinnitus
Postmarketing Reports
Photosensitivity
Hypoglycemia
Portal hypertension
Macrophage activation syndrome
Urticaria
Hyperbilirubinemia
Bone marrow toxicity
Hyperuricemia and/or hyperuricosuria
Skin rashes and hyperpigmentation
Alopecia
Fever (rare)
Warnings
Black Box Warnings
The drug should not be used unless a diagnosis of acute lymphatic leukemia has been adequately established, and the patient’s physician is knowledgeable in assessing response to chemotherapy
Contraindications
Hypersensitivity; prior resistance to 6-MP or thioguanine
Not effective for CLL, lymphomas, CNS leukemia
Cautions
Renal impairment
Reduce dose by 75% (ie, give quarter dose) when used concurrently with allopurinol
Recommended that evaluation of hemoglobin or hematocrit, total white blood cell count and differential count, and quantitative platelet count be obtained weekly while patient is on therapy
Bone marrow examination may be useful for evaluation of marrow status; decision to increase, decrease, continue, or discontinue a given dosage must be based upon degree of severity and rapidity with which changes are occurring; in many instances, particularly during induction phase of acute leukemia, complete blood counts will need to be done more frequently than once weekly in order to evaluate effect of therapy
Increased risk of bone marrow toxicity; evaluate patients with repeated severe myelosuppression for thiopurine S-methyltransferase (TPMT) or nucleotide diphosphatase (NUDT15) deficiency; TPMT genotyping or phenotyping (red blood cell TPMT activity) and NUDT15 genotyping can identify patients who have reduced activity of these enzymes; patients with homozygous TPMT or NUDT15 deficiency require substantial dosage reductions of the drug
Increased risk of developing lymphoproliferative disorders and other malignancies, notably skin cancers (melanoma and non-melanoma), sarcomas (Kaposi's and non-Kaposi's) and uterine cervical cancer in situ; increased risk appears to be related to degree and duration of immunosuppression; discontinuation of immunosuppression reported to provide partial regression of lymphoproliferative disorder; a treatment regimen containing multiple immunosuppressants (including thiopurines) should be used with caution as this could lead to lymphoproliferative disorders, some with reported fatalities; a combination of multiple immunosuppressants, given concomitantly increases risk of Epstein-Barr virus (EBV)-associated lymphoproliferative disorders
Macrophage activation syndrome (MAS) (hemophagocytic lymphohistiocytosis) a life-threatening disorder, may develop in patients with autoimmune conditions, in particular with inflammatory bowel disease (IBD); there could potentially be an increased susceptibility for developing the condition with the use of mercaptopurine (an unapproved use); if MAS occurs, or is suspected, discontinue therapy; monitor for and promptly treat infections such as EBV and cytomegalovirus (CMV), as these are known triggers for MAS
Drug fever very rarely reported; before attributing fever to drug, make every attempt to exclude more common causes of pyrexia, such as sepsis, in patients with acute leukemia
Avoid pregnancy
Hepatosplenic T-cell lymphomas
- Rare postmarketing cases reported primarily in adolescent and young adult patients with Crohn disease and ulcerative colitis treated with TNF blockers
- Reports have also included a patient being treated for psoriasis and 2 patients being treated for rheumatoid arthritis
- HSTCL is an aggressive, rare type of T-cell lymphoma (usually fatal)
- Most reported cases with TNF blockers have occurred with concomitant treatment with azathioprine or 6-mercaptopurine, although there have been cases reported receiving azathioprine or mercaptopurine alone
- The following HSTCL cases have been identified in the FDA Adverse Event Reporting System (AERS) database, the literature, and the HSTCL Cancer Survivors' Network: infliximab (20), etanercept (1), adalimumab (2), infliximab/adalimumab (5), certolizumab (0), golimumab (0), azathioprine (12), and mercaptopurine (3)
Pregnancy & Lactation
Pregnancy Category: D
Lactation: not known if excreted in breast milk, do not nurse
Pregnancy Categories
A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA:Information not available.
Pharmacology
Mechanism of Action
Analog of naturally occurring purines hypoxanthine and guanine
Purine antagonist, antineoplastic
Absorption
Bioavailability: 5-37%
Peak Plasma Time: 2 hr
Onset: 2 hr
Duration: variable
Distribution
Protein Bound: 19%
Vd: 0.56-0.9 L/kg
Metabolism
GI mucosa, liver
Metabolites: 6-thiouric acid
Elimination
Half-Life: 21 minutes (children), 47 min (adult)
Clearance: 11 mL/min/kg
Excretion: urine
Dialyzable: no
Pharmacogenomics
6-mercaptopurine is activated by guanine phosphoribosyltransferase (HGPRT) to form thioinosine monophosphate (TIMP) and by kinase enzymatic pathways to form active 6-thioguanine nucleotides
Thiopurine S-methyltransferase (TPMT) inactivates 6-mercaptopurine
Although complete TPMT deficiency is rare in the general population (0.3%), TPMT screening should be performed prior to administration in all patients prescribed azathioprine or 6-mercaptopurine
With TPMT deficiency, a larger proportion of 6-mercaptopurine is converted to the cytotoxic 6-thioguanine nucleotide analogues, which can lead to bone marrow toxicity and myelosuppression
Alleles associated with decreased TPMT enzymatic activity are TPMT*2, TPMT*3A, and TPMT*3C
Genetic testing laboratories
- The following companies currently offer testing for TPMT variants
- Prometheus Labs (http://www.prometheuslabs.com/)
- Arup Laboratories (http://www.aruplab.com/)
Images
Patient Handout
Formulary
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