Thioguanine: 40 mg Tablets

By | April 21, 2016

Thioguanine

ANTINEOPLASTIC

Highlights of Prescribing Information

  • Oral purine analog antineoplastic that may be useful as adjunctive treatment for acute lymphocytic or granulocytic leukemia in dogs or cats
  • Contraindications: Hypersensitivity to thioguanine
  • Caution: Hepatic dysfunction, bone marrow depression, infection, renal function impairment (adjust dosage), or history of urate urinary stones
  • Potentially mutagenic & teratogenic; use milk replacer if nursing
  • Adverse Effects: GI effects, bone marrow suppression, hepatotoxicity, pancreatitis, GI (including oral) ulceration, & dermatologic reactions
  • Cats may be more susceptible than dogs to adverse effects
  • Low therapeutic index; monitoring mandatory

What Is Drug Used For?

Thioguanine may be useful as adjunctive therapy for acute lymphocytic or granulocytic leukemia in dogs or cats.

Pharmacology / Actions

Intracellularly, thioguanine is converted to ribonucleotides that cause the synthesis and utilization of purine nucleotides to be blocked. The drug’s cytotoxic effects are believed to occur when these substituted nucleotides are inserted into RNA and DNA. Thioguanine has limited immunosuppressive activity. Extensive cross-resistance usually occurs between thioguanine and mercaptopurine.

Pharmacokinetics

Thioguanine is administered orally, but absorption is variable. In humans, only about 30% of a dose is absorbed. Thioguanine is distributed into the DNA and RNA of bone marrow, but several doses may be necessary for this to occur. It does not apparently enter the CNS, but does cross the placenta. It is unknown whether it enters maternal milk.

Thioguanine is rapidly metabolized primarily in the liver to a methylate derivative that is less active (and toxic) than the parent compound. This and other metabolites are eliminated in the urine.

Before you take Drug

Contraindications / Precautions / Warnings

Thioguanine is contraindicated in patients hypersensitive to it. The drug should be used cautiously (risk versus benefit) in patients with hepatic dysfunction, bone marrow depression, infection, renal function impairment (adjust dosage) or with a history of urate urinary stones. Thioguanine has a very low therapeutic index and should only be used by clinicians with experience in the use of cytotoxic agents and able to monitor therapy appropriately.

Adverse Effects

At usual doses, GI effects (nausea, anorexia, vomiting, diarrhea) may occur in small animals. However, bone marrow suppression, hepatotoxicity, pancreatitis, GI (including oral) ulceration, and dermatologic reactions are potentially possible. Cats may be particularly susceptible to the hematologic effects of thioguanine.

Reproductive / Nursing Safety

Thioguanine is potentially mutagenic and teratogenic and not recommended for use during pregnancy. In humans, the FDA categorizes this drug as category D for use during pregnancy (There is evidence of human fetal risk, hut the potential benefits from the use of the drug in pregnant women may be acceptable despite its potential risks.)

Although it is unknown whether thioguanine enters milk, use of milk replacer is recommended for nursing bitches or queens.

Overdosage / Acute Toxicity

Toxicity may be acute (GI effects) or delayed (bone marrow depression, hepatotoxicity, gastroenteritis). It is suggested to use standard protocols to empty the GI tract if ingestion was recent and treat supportively.

Drug Interactions

The following drug interactions have either been reported or are theoretical in humans or animals receiving thioguanine and maybe of significance in veterinary patients:

■ HEPATOTOXIC DRUGS (e.g., halothane, ketoconazole, valproic acid, phenobarbital, primidone, etc.): Thioguanine should be used cautiously with other drugs that can cause hepatotoxicity

■ IMMUNOSUPPRESSIVE DRUGS (e.g., azathioprine, cyclophosphamide, corticosteroids): Use with other immunosuppressant drugs may increase the risk of infection

■ MYELOSUPPRESSIVE DRUGS (e.g., chloramphenicol, flucytosine, ampho-tericin B, or colchicine): Use extreme caution when used concurrently with other drugs that are also myelosuppressive, including many of the other antineoplastics and other bone marrow depressant drugs; bone marrow depression maybe additive

■ VACCINES, LIVE: Live virus vaccines should be used with caution during therapy, if at all

Laboratory Considerations

■ Thioguanine may increase serum uric acid levels in some patients

How to use Drug

Drug dosage for dogs:

  1. a) For acute lymphocytic and granulocytic leukemia: 40 mg/m2 PO once daily (q24 hours) for 4-5 days, then every 3rd day thereafter ()
  2. b) As part of protocols for treatment of acute myelogenous leukemias: Protocol 1: Cytarabine 100 mg/m2 SC daily for 2-6 days; Thioguanine 50 mg/m2 PO q24-48h. Protocol 2: Cytarabine 100 mg/m2 SC daily for 2-6 days; Thioguanine 50 mg/m2 PO q24-48h; Doxorubicin 10 mg/m2 IV once a week ()

Drug dosage for cats:

  1. a) For acute lymphocytic and granulocytic leukemia: 25 mg/m2 PO once daily (q24 hours) for 1-5 days, then every 30 days thereafter as necessary ()

Monitoring

■ Hemograms (including platelets) should be monitored closely; initially every 1-2 weeks and every 1-2 months once on maintenance therapy. It is recommended by some clinicians that if the WBC count drops to between 5,000-7,000 cells/mm3 the dose be reduced by 25%. If WBC count drops below 5,000 cells/mm3 treatment should be discontinued until leukopenia resolves

■ Liver function tests; serum amylase, if indicated

■ Efficacy

Client Information

■ Clients must be briefed on the possibilities of severe toxicity developing from this drug, including drug-related neoplasms or mortality.

■ Clients should contact veterinarian if the animal exhibits clinical signs of abnormal bleeding, bruising, anorexia, vomiting, jaundice, or infection.

■ Although, no special precautions are necessary with handling intact tablets, it is recommended to wash hands after administering the drug.

Chemistry / Synonyms

A purine analog antineoplastic agent, thioguanine occurs as a pale yellow, odorless or practically odorless, crystalline powder. It is insoluble in water or alcohol.

Thioguanine may also be known as: NSC-752, 6- thioguanine, TG, 6-TG, 2-Amino-6-mercaptopurine, WR-1141, Lanvis, Tabloid, or Tioguanina.

Storage / Stability

Store tablets in tight containers at room temperature.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products: None

Human-Labeled Products:

Thioguanine Tablets: 40 mg; Tabloid (GlaxoSmithKline); (Rx)

 

Selections from the book: “Plumb’s Veterinary Drug Handbook. Sixth Edition”. 2008