PURIXAN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PURIXAN (PURIXAN).
Purixan (mercaptopurine) is a purine analog that inhibits de novo purine synthesis by interfering with nucleotide interconversion and incorporation into DNA and RNA. It requires intracellular activation to 6-mercaptopurine ribonucleotide (6-MP ribonucleotide) via hypoxanthine-guanine phosphoribosyltransferase (HGPRT).
| Metabolism | Primarily hepatic metabolism via thiopurine methyltransferase (TPMT) and xanthine oxidase (XO). Aldehyde oxidase contributes to minor metabolism. |
| Excretion | Renal excretion of unchanged drug and metabolites; approximately 50% as unchanged drug, 20% as 6-thiouric acid, and minor amounts as other metabolites. Biliary/fecal elimination accounts for less than 10%. |
| Half-life | Terminal elimination half-life is approximately 3-4 hours in adults with normal renal function; prolonged to 20-50 hours in renal impairment. Clinically, monitoring for myelosuppression is essential due to accumulation. |
| Protein binding | Approximately 30% bound, primarily to albumin. |
| Volume of Distribution | Vd is approximately 0.5-0.9 L/kg, indicating moderate distribution into total body water; extensive distribution into cells and tissues. |
| Bioavailability | Oral bioavailability is highly variable, ranging from 5% to 37%, due to extensive first-pass metabolism; administration with food may alter absorption. |
| Onset of Action | Oral: Clinical effect (remission induction) typically observed within 2-4 weeks; time to response may be longer in some patients. |
| Duration of Action | Duration of action is variable; sustained immunosuppression or antileukemic effect persists for days to weeks after discontinuation, with myelosuppression often lasting 1-2 weeks. |
| Molecular Weight | 152.2 |
75 mg/kg once weekly orally; may be increased by 25 mg/kg every 2-4 weeks to a maximum of 150 mg/kg once weekly.
| Dosage form | SUSPENSION |
| Renal impairment | No specific dose adjustment required; use with caution in severe renal impairment (GFR <30 mL/min) due to limited data. |
| Liver impairment | Child-Pugh A: No adjustment; Child-Pugh B: Reduce dose by 25%; Child-Pugh C: Reduce dose by 50%. |
| Pediatric use | 75 mg/kg once weekly orally; may be increased by 25 mg/kg every 2-4 weeks to a maximum of 150 mg/kg once weekly. Safety and efficacy not established in children <2 years. |
| Geriatric use | No specific adjustment; monitor renal function and for increased sensitivity due to age-related decline in renal function. |
| 1st trimester | Contraindicated due to teratogenicity; associated with fetal malformations. |
| 2nd trimester | Contraindicated; risk of fetal growth restriction and prematurity. |
| 3rd trimester | Contraindicated; may cause neonatal myelosuppression and immunosuppression. |
Clinical note
Comprehensive clinical and safety monograph for PURIXAN (PURIXAN).
| Placental transfer | Mercaptopurine crosses the placenta; fetal exposure has been documented. |
| Breastfeeding | Mercaptopurine (PURIXAN) is excreted into breast milk in low amounts; however, due to potential for adverse effects (e.g., myelosuppression, immunosuppression) in the nursing infant, caution is advised. Manufacturer recommends discontinuing breastfeeding during therapy. |
| Lactation Rating |
■ FDA Black Box Warning
WARNING: MYELOSUPPRESSION, TOXICITY WITH REDUCED THIOPURINE METHYLTRANSFERASE (TPMT) ACTIVITY, and HEPATOTOXICITY. See full prescribing information for complete boxed warning.
| Serious Effects |
Hypersensitivity to mercaptopurine or any component of the formulationSevere hepatic impairmentPregnancy (especially first trimester)Concurrent use with allopurinol (unless dose adjusted)
| Precautions | Bone marrow suppression (leukopenia, thrombocytopenia, anemia), Hepatotoxicity (elevated transaminases, cholestasis, hepatic necrosis), Increased toxicity in patients with genetic deficiency of TPMT, Immunosuppression leading to increased infection risk, Carcinogenicity (secondary malignancies) |
| Food/Dietary | No specific food-drug interactions are known for mercaptopurine. However, mercaptopurine absorption may be slightly reduced by food, but taking with food is recommended to alleviate GI intolerance. Avoid grapefruit juice if also receiving vincristine as part of chemotherapy regimen (grapefruit juice inhibits CYP3A4 and may increase vincristine toxicity). |
Loading safety data…
| L4 (Possibly hazardous) |
| Teratogenic Risk | PURIXAN (mercaptopurine) is teratogenic in animals. In humans, first trimester exposure is associated with increased risk of congenital malformations, including craniofacial, cardiac, and CNS defects. Second and third trimester exposure may cause intrauterine growth restriction, premature birth, and fetal myelosuppression. |
| Fetal Monitoring | Monitor maternal complete blood count and liver function tests weekly during first month, then at least monthly. Monitor fetal growth via serial ultrasound. Consider amniocentesis for chromosomal analysis if first trimester exposure occurs. |
| Fertility Effects | Mercaptopurine may cause oligospermia or azoospermia in males, and amenorrhea or ovulatory dysfunction in females. Effects are generally reversible upon discontinuation. |
| Clinical Pearls | Mercaptopurine (PURIXAN) is a prodrug activated via hypoxanthine-guanine phosphoribosyltransferase (HGPRT). Dose reduce by 25-50% when coadministered with allopurinol due to inhibition of xanthine oxidase, the main metabolic pathway. Monitor thiopurine methyltransferase (TPMT) and NUDT15 genotypes prior to initiation to identify poor metabolizers at risk for severe myelosuppression. Administer with food to reduce GI upset; avoid concurrent use with warfarin (increases INR) and olsalazine/mesalamine (may inhibit TPMT). |
| Patient Advice | Take this medication exactly as prescribed, usually once daily with food to decrease stomach upset. · Do not crush or chew the tablets; swallow whole. · Avoid live vaccines (e.g., MMR, varicella, intranasal flu) while taking this drug. · Report any signs of infection (fever, sore throat, easy bruising/bleeding) immediately. · Your doctor will order regular blood tests to monitor blood counts and liver function. · Tell your doctor if you are pregnant, planning to become pregnant, or breastfeeding. |