PURIXAN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PURIXAN (PURIXAN).

How it works

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).

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PURIXAN (PURIXAN).

Breastfeeding	Mercaptopurine is excreted into breast milk in low concentrations; M/P ratio is approximately 0.6. The American Academy of Pediatrics considers use compatible with breastfeeding, but monitor infant for signs of immunosuppression or myelosuppression.
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.

Warnings & precautions

■ FDA Black Box Warning

WARNING: MYELOSUPPRESSION, TOXICITY WITH REDUCED THIOPURINE METHYLTRANSFERASE (TPMT) ACTIVITY, and HEPATOTOXICITY. See full prescribing information for complete boxed warning.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to mercaptopurine or any component of the formulation","Severe pre-existing bone marrow suppression","Concurrent use with allopurinol unless dose-adjusted"]

Clinical Precautions

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)"]

Clinical Tips & Counseling

Drug interactions

Loading safety data…

PURIXAN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PURIXAN (PURIXAN).

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PURIXAN (PURIXAN).

Breastfeeding	Mercaptopurine is excreted into breast milk in low concentrations; M/P ratio is approximately 0.6. The American Academy of Pediatrics considers use compatible with breastfeeding, but monitor infant for signs of immunosuppression or myelosuppression.
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.

Warnings & precautions

■ FDA Black Box Warning

WARNING: MYELOSUPPRESSION, TOXICITY WITH REDUCED THIOPURINE METHYLTRANSFERASE (TPMT) ACTIVITY, and HEPATOTOXICITY. See full prescribing information for complete boxed warning.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to mercaptopurine or any component of the formulation","Severe pre-existing bone marrow suppression","Concurrent use with allopurinol unless dose-adjusted"]