Drug information of Thioguanine

Thioguanine

Drug group:

An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia.

Mechanism of effect

Thioguanine competes with hypoxanthine and guanine for the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) and is itself converted to 6-thioguanilyic acid (TGMP), which reaches high intracellular concentrations at therapeutic doses.

TGMP interferes with the synthesis of guanine nucleotides by its inhibition of purine biosynthesis by pseudofeedback inhibition of glutamine-5-phosphoribosylpyrophosphate amidotransferase, the first enzyme unique to the de novo pathway of purine ribonucleotide synthesis.

TGMP also inhibits the conversion of inosinic acid (IMP) to xanthylic acid (XMP) by competition for the enzyme IMP dehydrogenase. Thioguanine nucleotides are incorporated into both the DNA and the RNA by phosphodiester linkages, and some studies have shown that incorporation of such false bases contributes to the cytotoxicity of thioguanine.

Pharmacodynamic

Thioguanine is an antineoplastic anti-metabolite used in the treatment of several forms of leukemia including acute nonlymphocytic leukemia. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division.

Thioguanine is a 6-thiopurine analogue of the naturally occurring purine bases hypoxanthine and guanine. Intracellular activation results in incorporation into DNA as a false purine base. An additional cytotoxic effect is related to its incorporation into RNA. Thioguanine is cross-resistant with mercaptopurine.

Pharmacokinetics

  • (Half-Life: 15 min (initial phase); 5-9 hr (terminal phase
  • Absorption: 30%
  • (Time to peak: 8hr (serum
  • Metabolism: Liver
  • Metabolites: 2-amino-6-methylthiopurine, inorganic sulfate, thiouric acid
  • Excretion: Urine
  • Dialyzable: No

Dosage

Adult and pediatric

2 mg/kg/day PO 

Cautiously increase to 3 mg/kg/day if no response after 4 weeks

Drug contraindications

Hypersensitivity

Side effects

nausea , vomiting , anorexia

Alerts

  • (Not for long-term use (risk of hepatotoxicity
  • Myelosuppression may occur
  • (Monitor for infections (leukopenia
  • (Monitor for bleeding (thrombocytopenia
  • Secondary malignancies may occur
  • Tumor lysis syndrome may occur
  • Although active in CML, busulfan is preferred
  • Avoid pregnancy

Points of recommendation

You may have more chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu.

You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.

Very bad and sometimes life-threatening blood and bone marrow problems like anemia, low platelet counts, or low white blood cell counts have happened with thioguanine. Change in dose or even stopping the drug may be needed if any of these side effects happen. Talk with the doctor.

If you have upset stomach, throwing up, loose stools (diarrhea), or are not hungry, talk with your doctor. There may be ways to lower these side effects.

This medicine may add to the chance of getting some types of cancer. Talk with the doctor.

Have blood work checked as you have been told by the doctor. Talk with the doctor.

If you have a thiopurine methyltransferase deficiency, talk with your doctor.

Talk with your doctor before getting any vaccines. Use with thioguanine may either raise the chance of an infection or make the vaccine not work as well.

Use birth control that you can trust to prevent pregnancy while taking thioguanine.

If you are pregnant or you get pregnant while taking thioguanine , call your doctor right away.

Take on empty stomach to reduce risk of nausea and vomiting

Pregnancy level

D


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