Thioguanine (also known as 6-thioguanine or 6-TG) is a medication that belongs to a class of drugs called purine analogs. It is used primarily in the treatment of acute leukemias. The drug is an analog of the naturally occurring purine base guanine and becomes incorporated into DNA and RNA, causing disruptions in normal synthesis and function.

Thioguanine or 6-thioguanine is the generic name of Tabloid. It is an orally available anti-neoplastic antimetabolite drug that is used in various types of blood cancers.

Thioguanine (Tabloid) Uses:

• Acute myeloid leukemia:
  • Used in treatment (remission induction and consolidation) of acute myeloid (nonlymphocytic) leukemia (AML)
• Limitations of use:
  • Thioguanine use for AML maintenance therapy or other similar longterm continuous treatments is not recommended because of the high risk of hepatotoxicity.
• Off Label Use of Thioguanine in Adults:
  • Acute lymphoblastic leukemia

Thioguanine Dose in Adults

Note:

• Before taking thioguanine, some people should be tested for TPMT or NUDT15 deficiency.
• If they have these deficiencies, they might react badly to the usual dose of the drug.
• These patients usually need a lower dose to be safe.

Thioguanine Dose in the treatment of Acute myeloid leukemia (AML):

• Start with a dose of 2 mg for every kilogram of the patient's weight, taken once daily for 4 weeks.
• If there's no improvement after 4 weeks and blood tests show healthy counts of ANC and platelets, the dose can be raised to 3 mg for every kilogram of the patient's weight.
• But be sure to watch the patient closely when increasing the dose.

Thioguanine (Tabloid) Dose in the treatment of Acute lymphoblastic leukemia (ALL):

For a special phase called "late intensification":

• Take 60 mg of thioguanine for every square meter of the patient's body surface, once a day, from day 29 to 42.
• This is combined with other medicines like doxorubicin, vincristine, dexamethasone, cyclophosphamide, and cytarabine.

Thioguanine (Tabloid) Dosage adjustment for TPMT and/or NUDT15 deficiency:

• Heterozygous Deficiency (medium activity):
  • Some people with this type of deficiency can handle the usual dose, but some might need less.
  • If someone has both TPMT and NUDT15 deficiencies, they might need an even lower dose.
  • Guideline: Start with 30-50% less than the usual dose. Adjust the dose depending on blood count and the illness being treated. Wait 2-4 weeks after each adjustment.
• Homozygous Deficiency (low activity):
  • Start with just 10% of the usual dose.
  • Guideline: Give a really small dose (10 times less than usual) and instead of daily, give it just 3 times a week. Adjust depending on blood count and the illness. Wait 4-6 weeks after adjustments. If using for non-cancer reasons, think about using a different drug.
• Homozygous Wild Type (normal activity):
  • No need to change the dose.
  • Wait 2 weeks after adjustments. If taking other drugs with thioguanine, adjust doses evenly without focusing only on thioguanine.

Thioguanine Dose in Childrens

Note:

• Before giving thioguanine, test for TPMT and NUDT15 problems.
• People with these issues can get really sick with the usual dose and often need less.
• The dose depends on the person and is given in mg per square meter or mg per kilogram.
• Always be extra careful with the dosage.

Thioguanine (Tabloid) Dose in the treatment of Acute lymphoblastic leukemia (ALL):

For the "Delayed intensification" phase in kids older than 1 year and teenagers:

• Take 60 mg of thioguanine per square meter of body area, once a day, for 14 days.

Thioguanine (Tabloid) Dose in the treatment of Acute myeloid leukemia (AML):

Using the DCTER regimen:

• For babies and kids under 3:
  • Take 3.3 mg of thioguanine for each kilogram they weigh, every day for 4 days. This can be given all at once or split into two doses. This is combined with two other drugs: cytarabine and daunorubicin.
• For kids aged 3 and up, including teenagers:
  • Take 100 mg of thioguanine for each square meter of their body surface, every day for 4 days. This can be given all at once or split into two doses. This is also combined with cytarabine and daunorubicin.

Following the Manufacturer's instructions:

• For all kids and teenagers:
  • Take 2 mg of thioguanine for each kilogram they weigh, once a day for 4 weeks. If there's no improvement after 4 weeks and blood tests are good, the dose can be increased to 3 mg per kilogram. Be very careful when increasing the dose.

Thioguanine (Tabloid) Dose in the treatment of Acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) with Down syndrome:

Using the DCTER regimen:

• For babies and kids under 3:
  • Take 3.3 mg of thioguanine for each kilogram they weigh, every day for 4 days. This can be given all at once or split into two doses. This is combined with two other drugs: cytarabine and daunorubicin.
• For kids aged 3 and up, including teenagers:
  • Take 100 mg of thioguanine for each square meter of their body surface, every day for 4 days. This can be given all at once or split into two doses. This is also combined with cytarabine and daunorubicin.

Thioguanine (Tabloid) Dose in the treatment of low-grade gliomas CNS Tumors:

Using the TPCV regimen:

• For kids under 10 years old:
  • Take 30 mg of thioguanine for each square meter of their body surface. Give this dose every 6 hours and do this 11 times (from the start to 66 hours). Repeat this process every 42 days, and do it 8 times in total. While doing this, also give them other medicines: procarbazine, lomustine, and vincristine.

Thioguanine (Tabloid) Dose adjustment in TPMT and/or NUDT15 deficiency:

• Heterozygous Deficiency (medium activity):
  • Some might need a lower dose, but many can handle the usual dose.
  • If they have both TPMT and NUDT15 issues, they might need even less medicine.
  • Guideline: Start with 30-50% less than the usual dose. Adjust depending on how the patient reacts and the condition being treated. Wait 2-4 weeks after changing the dose.
• Homozygous Deficiency (low activity):
  • Start with just 10% of the normal dose.
  • Guideline: Give a very low dose (10 times less than usual) and not daily, but just 3 times a week. Adjust the dose based on the patient's reaction and the condition. Wait 4-6 weeks after changing the dose. If the medicine is not for cancer, think about using a different drug.
• Homozygous Wild Type (normal activity):
  • No need to change the starting dose.
  • Wait 2 weeks after changing any doses. If using other drugs too, adjust all drugs equally without focusing only on thioguanine.

Pregnancy Risk Factor D

• Tests on animals show that this drug can harm unborn babies.
• Women who can get pregnant should be very careful not to become pregnant while taking this medicine.

Use of thioguanine during breastfeeding

• We're not sure if thioguanine gets into breast milk.
• But because it might harm a baby who is breastfed, the maker of the drug advises either stopping the medicine or not breastfeeding while on it.
• This decision should consider how important the treatment is for the mother.

Thioguanine (Tabloid) Dose in Kidney Disease:

• The drug's maker hasn't given any special dosing instructions for people with kidney problems.

Tabloid Dose in Liver disease:

• Before Treatment: The drug's maker hasn't given special dosing instructions for people with liver problems.
• During Treatment: If there are signs of liver damage or issues (like higher liver enzyme levels, yellowing of the skin, or certain liver diseases), stop using the drug.

Side effects of Thioguanine (Tabloid):

• Cardiovascular:
  • Esophageal Varices
  • Portal Hypertension
• Endocrine & Metabolic:
  • Fluid Retention
  • Hyperuricemia (Common)
  • Increased Gamma Glutamyl Transferase
  • Weight Gain
• Gastrointestinal:
  • Anorexia
  • Intestinal Necrosis
  • Intestinal Perforation
  • Nausea
  • Stomatitis
  • Vomiting
• Hematologic & Oncologic:
  • Anemia (May Be Delayed)
  • Bone Marrow Depression
  • Granulocytopenia
  • Hemorrhage
  • Leukopenia (Common; May Be Delayed)
  • Pancytopenia
  • Splenomegaly
  • Thrombocytopenia (Common; May Be Delayed)
• Hepatic:
  • Ascites
  • Hepatic Disease (Hepatoportal Sclerosis)
  • Hepatic Focal Nodular Hyperplasia (Regenerative)
  • Hepatic Necrosis (Centrilobular)
  • Hepatic Sinusoidal Obstruction Syndrome
  • Hepatomegaly (Tender)
  • Hepatotoxicity
  • Hyperbilirubinemia
  • Increased Liver Enzymes
  • Increased Serum Alkaline Phosphatase
  • Jaundice
  • Peliosis Hepatitis
  • Periportal Fibrosis
• Infection:
  • Infection
• Neuromuscular & Skeletal:
  • Bone Hypoplasia

Contraindications to Thioguanine (Tabloid):

• If the patient didn't respond to thioguanine (or a similar drug called mercaptopurine) in the past, be cautious.
• In Canada (but not the US): Don't use thioguanine if the patient is allergic to it or any ingredient in the medicine.

Warnings and precautions

Suppression of bone marrow

• This drug can lower blood cell counts (like red cells, white cells, or platelets). This is a usual side effect and can be delayed.
• Lower white cells can increase infection risk, and lower platelets can increase bleeding risk.
• If blood counts drop too much, stop the treatment.
• Some people have genetic differences that make them more sensitive to this drug, leading to even lower blood cell counts. This can be due to their genes (TPMT or NUDT15) or if they're taking certain other drugs (like mesalazine). These people might need much smaller doses of thioguanine.

Hepatotoxicity

• Taking thioguanine for a long time or as an ongoing treatment can seriously harm the liver. There's a risk of liver damage, blockages in small liver blood vessels, and increased pressure in the liver's blood supply.
• Watch liver health closely. Stop the drug if there are signs of liver problems like yellow skin, a swollen liver, weight gain from fluid build-up, a swollen spleen, or bleeding veins in the esophagus.
• Liver damage might happen even if typical liver tests are okay. Specific signs of this damage include scar-like changes in the liver and other changes to liver tissue.
• Liver problems from this drug might be more common in men.
• It's not a good idea to use thioguanine as a long-term treatment.
• Tell patients to avoid alcohol, as it can make liver problems more likely.

Photosensitivity

• Thioguanine can make your skin sensitive to the sun, so it's a good idea to use sunscreen and wear protective clothing when you're outside to avoid getting sunburned.

Secondary malignancies

• Thioguanine has the potential to increase the risk of developing secondary cancers.

Tumor lysis syndrome

• When undergoing treatment with thioguanine, it's common to experience high levels of uric acid in the blood (hyperuricemia).
• To manage this, it's important to stay well-hydrated, and your doctor may recommend taking a medication called allopurinol as a preventive measure.

Genetic variation NUDT15:

• Some individuals carry a genetic variation in a gene called NUDT15, and these individuals may require significant dose reductions of thiopurine medications like thioguanine and mercaptopurine.
• Reduced NUDT15 activity is strongly associated with intolerance to mercaptopurine, especially in patients with acute lymphoblastic leukemia (ALL).
• Research has shown that patients with a specific TT genetic variant in NUDT15 are extremely sensitive to mercaptopurine, often requiring much lower doses (averaging only 8.3% of the standard dose).
• This genetic variant is most commonly found in East Asian and Hispanic populations.
• If patients experience severe bone marrow problems or repeated myelosuppressive episodes during treatment, it's advisable to consider testing for NUDT15 deficiency, along with testing for TPMT deficiency, to better tailor their medication dosages.

TPMT Deficiency

• Some individuals have a genetic deficiency in an enzyme called TPMT, which can make them particularly sensitive to the bone marrow-suppressing effects of certain medications.
• In such cases, significant dose reductions may be necessary.
• It is advisable to consider testing for TPMT deficiency, and guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC) recommend dose reductions for patients with either reduced TPMT activity (heterozygous) or complete TPMT deficiency (homozygous).
• These guidelines help ensure that medication dosages are adjusted appropriately to minimize adverse effects and optimize treatment outcomes (Relling 2011; Relling 2013).

Thioguanine: Drug Interaction

Monitoring parameters:

• CBC with Differential and Platelet Count: Frequently check your blood counts.
• Liver Function Tests: Initially weekly, then monthly (or more often if you have liver issues or take other liver-affecting drugs).
• Serum Uric Acid: Keep an eye on uric acid levels.
• Genetic Testing: Consider testing for TPMT and NUDT15 genes if you experience severe blood problems.

Watch for Liver and Blood Issues

• Hepatotoxicity Signs: Look for signs like liver problems.
• Portal Hypertension Signs: Check for symptoms like a swollen spleen, varicose veins in the esophagus, or low platelet counts.
• Sinusoidal Obstruction Syndrome: Be aware of signs like fluid buildup, belly swelling, tender liver, or jaundice.
• Tumor Lysis Syndrome: Keep an eye out for this complication.
• Adherence Monitoring: Make sure you're taking your medication as prescribed.

How to administer Thioguanine (Tabloid)?

• Take this medication by mouth.
• You can take the entire daily dose all at once.

Mechanism of action of Thioguanine (Tabloid):

• Thioguanine is similar to a natural compound called guanine.
• It gets incorporated into both DNA and RNA.
• This inclusion disrupts the creation and processing of purine molecules in the body.

Absorption:

• Around 30% of the medication is absorbed into the body.
• This absorption can vary greatly, ranging from 14% to 46%, depending on the person.

Distribution:

• Thioguanine doesn't reach the levels needed for therapy in the cerebrospinal fluid (CSF), which surrounds the brain and spinal cord.

Metabolism:

• The liver is responsible for breaking down thioguanine.
• Thiopurine methyltransferase (TPMT) plays a significant role in this process.
• TPMT converts thioguanine into active and inactive compounds.

Half-life Elimination:

• Thioguanine has a terminal elimination half-life of 5 to 9 hours.

Time to Peak in Serum:

• The highest concentration of the medication in the bloodstream is typically reached within 8 hours.
• Most of what's measured in the blood is actually the medication's metabolites, not the parent compound.

Excretion:

• Thioguanine and its breakdown products are primarily excreted in the urine.

International Brands of Thioguanine:

• 6-TG
• Lanvis
• Tabloid
• Thioguanin Glaxo Wellcome
• Thioguanine Wellcome

Thioguanine

 Brand Names in Pakistan: