thioguanine

Action and Spectrum

Actions and Spectrum: 

• thioguanine is a chemotherapy medication used to treat various types of cancer, including acute lymphoblastic leukemia. The mechanism of action of thioguanine involves its conversion to active metabolites that interfere with DNA synthesis and repair. 
• thioguanine is a purine analog converted to 6-thioguanine nucleotides (6-TGN) inside the cells. 6-TGNs are incorporated into DNA and RNA, disrupting normal cellular processes such as replication and transcription. thioguanine can also inhibit enzymes involved in DNA repair, leading to increased DNA damage and apoptosis (programmed cell death) of cancer cells. 
• The spectrum of activity of thioguanine is primarily against rapidly dividing cells, including cancer cells. Still, it can also affect other rapidly dividing cells in the body, such as bone marrow and gastrointestinal cells. thioguanine is effective against various hematological malignancies, including acute lymphoblastic leukemia, chronic myeloid leukemia, and acute myeloid leukemia. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Stomatitis 

Nausea 

Myelosuppression 

Nephrotoxicity 

Anorexia 

Vomiting 

Hyperuricemia 

Hepatotoxicity 

Black Box Warning

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Hypersensitivity: thioguanine should not be used in individuals with known hypersensitivity to the medication. 
• Pregnancy and breastfeeding: thioguanine is not recommended in pregnant or breastfeeding women as it may harm the developing fetus or nursing baby. 
• Immunosuppression: thioguanine should not be used in individuals with a weakened immune system, as it may further suppress the immune system and increase the risk of infections. 
• Hepatic dysfunction: thioguanine is metabolized in the liver, and individuals with liver dysfunction may be at increased risk of toxicity. 
• Previous bone marrow suppression: thioguanine should not be used in individuals who have previously experienced bone marrow suppression, as it may exacerbate this condition. 
• Vaccination: thioguanine should not be administered during or shortly before vaccination, as it may interfere with the immune response. 

Caution: 

• Increased risk of infections: thioguanine can lower the number of white blood cells in the body, increasing the risk of infections. Individuals taking thioguanine should be monitored for signs of infection. They may need to take precautions to reduce risk, such as avoiding contact with sick individuals and practicing good hygiene. 
• Bone marrow suppression: thioguanine can cause bone marrow suppression, which can lead to a decrease in the production of red blood cells, white blood cells, and platelets. This can result in anemia, increased risk of infections, and bleeding. Individuals taking thioguanine should be monitored for signs of bone marrow suppression, such as fatigue, shortness of breath, bruising, and bleeding. 
• Risk of hepatotoxicity: thioguanine can cause liver damage, especially in individuals with pre-existing liver disease. Individuals taking thioguanine should be monitored for signs of liver damage, such as jaundice, abdominal pain, and nausea. 
• Increased risk of secondary cancers: thioguanine has been associated with an increased risk of developing secondary cancers, particularly myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Individuals taking thioguanine should be monitored for signs of these conditions. 
• Interactions with other medications: thioguanine can interact with other medications, such as allopurinol and azathioprine, increasing the risk of toxicity. Individuals taking thioguanine should inform their healthcare provider of all their medications. 

Pregnancy / Lactation

Pregnancy consideration: D 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.   

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

Several factors, including the dose, the rate of metabolism, and the sensitivity of the cancer cells to the drug, influence thioguanine activity. The dose of thioguanine is usually adjusted based on the patient’s body weight and individual response, and the sensitivity of the cancer cells to the drug can be assessed through laboratory testing. 

Pharmacodynamics: 

• The pharmacodynamics of thioguanine involves its interaction with cellular processes, including DNA synthesis and repair, leading to cell death in rapidly dividing cells such as cancer cells. 

• thioguanine is a purine analog incorporated into DNA and RNA, interfering with normal cellular processes such as replication and transcription. This incorporation of thioguanine into DNA and RNA leads to the formation of abnormal base pairs and the inhibition of DNA synthesis and repair, ultimately leading to cell death. 

• thioguanine can also inhibit enzymes involved in DNA repair, such as topoisomerases and DNA polymerases, further increasing the amount of DNA damage and apoptosis (programmed cell death) in cancer cells. 

Pharmacokinetics: 

Absorption 

thioguanine is administered orally as tablets and rapidly absorbed from the gastrointestinal tract. Peak plasma concentrations are usually reached within 1 to 2 hours after administration.  

Distribution 

thioguanine has a relatively small volume of distribution, and it primarily distributes into the blood and other rapidly dividing tissues. thioguanine is also known to cross the blood-brain barrier.  

Metabolism 

thioguanine is extensively metabolized in the liver to form active metabolites, including 6-thioguanine nucleotides (6-TGNs). 6-TGNs are responsible for the pharmacological effects of thioguanine. thioguanine is metabolized by the enzyme thiopurine S-methyltransferase (TPMT), and individuals with genetic variants of TPMT may have decreased metabolism of thioguanine and an increased risk of toxicity.  

Elimination and Excretion 

thioguanine and its metabolites are primarily eliminated from the body through urine and feces. The elimination half-life of thioguanine is relatively short, around 80 minutes. 

Adminstartion

Administration: 

• thioguanine is available as an oral tablet and is usually taken once daily. The tablets should be taken on an empty stomach, at least one hour before or two hours after a meal, to maximize absorption. The tablets should be swallowed whole with water, not chewed, crushed, or broken. 
• The dosage of thioguanine is typically based on body weight and individual response, and it is essential to follow the dosage instructions provided by the prescribing healthcare provider. The dosage may be adjusted based on the patient’s response to treatment, and regular monitoring of blood cell counts and liver function is essential during treatment. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: thioguanine 

Why do we use thioguanine? 

• thioguanine is a chemotherapy medication primarily used to treat acute lymphoblastic leukemia (ALL), cancer affecting white blood cells. 
• thioguanine may also be used to treat other types of cancer, such as acute myeloid leukemia (AML) and chronic myeloid leukemia (CML).