Mercaptopurine

Mercaptopurine Uses, Dosage, Side Effects, Food Interaction and all others data.

Mercaptopurine is a purine antagonist which is converted intracellularly into its active nucleotides, including thioinosinic acid. The nucleotides inhibit several reactions which ultimately interferes with nucleic acid synthesis and prevents the formation of RNA and DNA.

Mercaptopurine is one of a large series of purine analogues which interfere with nucleic acid biosynthesis and has been found active against human leukemias. It is an analogue of the purine bases adenine and hypoxanthine. It is not known exactly which of any one or more of the biochemical effects of mercaptopurine and its metabolites are directly or predominantly responsible for cell death.

Mercaptopurine
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Mercaptopurine
Availability	Prescription only
Generic	Mercaptopurine
Mercaptopurine Other Names	Mercaptopurina, Mercaptopurine, Mercaptopurinum, Mercapurin
Related Drugs	methotrexate, doxorubicin, imatinib, Gleevec, Adriamycin, Sprycel
Weight	100mg/5ml, 50mg
Type	Oral suspension, oral tablet
Formula	C₅H₄N₄S
Weight	Average: 152.177 Monoisotopic: 152.015666838
Protein binding	Plasma protein binding averages 19% over the concentration range 10 to 50 µg/mL (a concentration only achieved by intravenous administration of mercaptopurine at doses exceeding 5 to 10 mg/kg).
Groups	Approved
Therapeutic Class	Cytotoxic Chemotherapy
Manufacturer	Aspen
Available Country	United Kingdom, United States
Last Updated:	September 19, 2023 at 7:00 am

Uses

Mercaptopurine is used for maintenance therapy of acute lymphatic (lymphocytic, lymphoblastic) leukemiaas part of a combination regimen. The response to this agent depends upon the particular subclassification of acute lymphatic leukemia and the age of the patient (pediatric or adult).

Mercaptopurine is not effective for prophylaxis or treatment of central nervous system leukemia. Mercaptopurine is not effective in acute myelogenous leukemia, chronic lymphatic leukemia, the lymphomas (including Hodgkins Disease), or solid tumors.

Mercaptopurine is also used to associated treatment for these conditions: Acute Lymphoblastic Leukaemias (ALL), Acute Promyelocytic Leukemia (APL), Crohn's Disease (CD), Hepatitis, Autoimmune, Lymphoma, Lymphoblastic, Ulcerative Colitis

How Mercaptopurine works

Mercaptopurine competes with hypoxanthine and guanine for the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) and is itself converted to thioinosinic acid (TIMP). TIMP inhibits several reactions that involve inosinic acid (IMP), such as the conversion of IMP to xanthylic acid (XMP) and the conversion of IMP to adenylic acid (AMP) via adenylosuccinate (SAMP). Upon methylation, TIMP forms 6-methylthioinosinate (MTIMP) which inhibits glutamine-5-phosphoribosylpyrophosphate amidotransferase in addition to TIMP. Glutamine-5-phosphoribosylpyrophosphate amidotransferase is the first enzyme unique to the de novo pathway for purine ribonucleotide synthesis. According to experimental findings using radiolabeled mercaptopurine, mercaptopurine may be recovered from the DNA in the form of deoxythioguanosine. In comparison, some mercaptopurine may be converted to nucleotide derivatives of 6-thioguanine (6-TG) via actions of inosinate (IMP) dehydrogenase and xanthylate (XMP) aminase that convert TIMP to thioguanylic acid (TGMP).

Dosage

Mercaptopurine dosage

Crohn's disease:

Adult: Initially 1-1.5 mg/kg daily, may increase to 125 mg daily.
Child: Initially 1-1.5 mg/kg daily increased to a max of 75 mg daily

Acute lymphocytic leukemia:

Adult: Usual maintenance dose: Initially, 1.5-2.5 mg/kg daily as a single dose, usually used in combination with methotrexate. Dose may vary individually based on response and tolerance. Monitor blood counts at least once wkly. Withdraw treatment immedietely if there is a sharp drop in the white cell count or severe bone-marrow depression. May resume treatment slowly and carefully if white cell count remains constant for 2-3 days or rises. Reduce dose when used with allopurinol.
Child: Usual maintenance dose: Initially, 1.5-2.5 mg/kg daily as a single dose, usually used in combination with methotrexate. Dose may vary individually based on response and tolerance. Monitor blood counts at least once wkly. Withdraw treatment immedietely if there is a sharp drop in the white cell count or severe bone-marrow depression. May resume treatment slowly and carefully if white cell count remains constant for 2-3 days or rises. Reduce dose when used with allopurinol.

Should be taken on an empty stomach. Best taken on an empty stomach 1 hr before or 2 hr after meals. Ensure adequate fluid intake.

Side Effects

Hyperuricaemia, bone marrow toxicity, hypoplasia, anorexia, diarrhoea, leukopenia, thrombocytopenia, intestinal ulceration, crystalluria with haematuria, immunosuppression, interstitial pneumonitis. Cutaneous hyperpigmentation, alopecia.

Toxicity

Signs and symptoms of overdosage may be immediate such as anorexia, nausea, vomiting, and diarrhea; or delayed such as myelosuppression, liver dysfunction, and gastroenteritis. The oral LD₅₀ of mercaptopurine was determined to be 480 mg/kg in the mouse and 425 mg/kg in the rat.

Precaution

Hepatic or renal dysfunction; monitor hepatic function periodically. Mercaptopurine is potentially carcinogenic. Thiopurine S-methyl transferase (TPMT) deficiency; porphyria.

Interaction

Anticoagulant action of warfarin may be inhibited by mercaptopurine. Enhanced toxicity with myelosuppressive drugs.

Food Interaction

Drink plenty of fluids.
Take on an empty stomach.

[Moderate] ADJUST DOSING INTERVAL: Limited data suggest that food may decrease the oral bioavailability of 6-mercaptopurine (6-MP).

In one study, the pharmacokinetics of 6-MP were studied on two separate occasions in seven patients.

A single dose of 6-MP was administered after an overnight fast on one occasion and 15 minutes after a standard breakfast on the other.

The authors reported that peak plasma levels of 6-MP were lower and took longer to reach following administration in the fed state.

In addition, plasma levels were undetectable (less than 20 ng
MANAGEMENT: Until more information is available regarding the effect of food on 6-MP absorption, it may be advisable to take 6-MP on an empty stomach 1 hour before or 2 hours after a meal.

Mercaptopurine Drug Interaction

Major: adalimumab, infliximabModerate: mesalamine, mesalamine, mesalamineUnknown: diphenhydramine, duloxetine, budesonide, omega-3 polyunsaturated fatty acids, escitalopram, pregabalin, metoprolol, metoprolol, esomeprazole, pantoprazole, acetaminophen, cyanocobalamin, ascorbic acid, cholecalciferol, alprazolam

Mercaptopurine Disease Interaction

Major: infections, hepatic dysfunction, myelosuppression, TMPT enzyme deficiencyModerate: renal dysfunction

Volume of Distribution

The volume of distribution exceeded that of the total body water.

Elimination Route

Clinical studies have shown that the absorption of an oral dose of mercaptopurine in humans is incomplete and variable, averaging approximately 50% of the administered dose. The factors influencing absorption are unknown.

Half Life

Triphasic: 45 minutes, 2.5 hours, and 10 hours.

Pregnancy & Breastfeeding use

Pregnancy category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).