thioguanine

Absorption: Variable and incomplete (average, 30%) following oral administration.

Distribution: Probably does not enter the CSF. Crosses the placenta.

Metabolism/Excretion: Highly metabolized by the liver; undergoes methylation via thiopurine methyltransferase (TPMT).

Half-Life: 11 hr.

Time/Action Profile ⬆ ⬇

(effect on blood counts)

ROUTE	ONSET	PEAK	DURATION
PO	7–10 days	14 days	21 days

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Tumors with demonstrated resistance to thioguanine or mercaptopurine (usually complete cross-resistance);
OB: Pregnancy (may cause fetal harm);
Lactation: Lactation.

Use Cautiously in:

Patients with childbearing potential;
Infections;
↓bone marrow reserve;
Other chronic debilitating illnesses;
Patients with homozygous TPMT enzyme deficiency or nucleotide diphosphatase (NUDT15) deficiency (substantial dose ↓ are required to avoid hematologic adverse events).

Adv. Reactions/Side Effects ⬆ ⬇

Derm: dermatitis, rash

EENT: loss of vibratory sense

GI: anorexia, diarrhea, hepatic veno-occlusive disease, hepatotoxicity, jaundice, nausea, stomatitis, vomiting

GU: gonadal suppression

Hemat: anemia, leukopenia, pancytopenia, thrombocytopenia

Metab: hyperuricemia

Neuro: unsteady gait

Interactions ⬆ ⬇

Drug-drug:

↑bone marrow depression with other antineoplastics or radiation therapy.
Sulfasalazine, olsalazine and mesalamine may ↓ metabolism and ↑ effects.

Route/Dosage ⬆ ⬇

Many other protocols are used
PO (Adults and Children ): Induction: 2 mg/kg (75–100 mg/m²) per day, rounded off to nearest 20 mg given as single dose; after 4 wk may ↑ to 3 mg/kg.Maintenance: 2–3 mg/kg (100 mg/m²) per day.

Availability ⬆ ⬇

Assessment ⬆ ⬇

Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis) and avoid IM injections and rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension.
Monitor intake and output, appetite, and nutritional intake. Administration of an antiemetic and adjustment of diet as tolerated may help maintain fluid and electrolyte balance and nutritional status.
Monitor for symptoms of tumor lysis syndrome (increased uric acid, phosphorous, and potassium that may lead to organ failure). Encourage patient to drink at least 2 L of fluid/day. Allopurinol may be used to decrease uric acid levels.

Lab Test Considerations:

Monitor CBC and differential at least weekly, daily in patients with elevated leukocyte counts. Bone marrow suppression usually occurs in 2–4 wk, but rapid ↓ in leukocyte count may occur in 1–2 wk. Notify health care professional of any rapid or severe drop in blood counts; therapy may need to be withheld until values stabilize. Bone marrow aspiration may be required to detect thioguanine-induced hypoplasia.
- Monitor for ↑ uric acid, serum creatinine, and BUN.
- Monitor for hepatotoxicity evidenced by ↑ AST, ALT, LDH, serum bilirubin, and alkaline phosphatase.

Implementation ⬆ ⬇

Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double check single, daily, and course-of-therapy dose limits; have second practitioner independently double check original order and dose calculations.
Avoid administration of live-virus vaccines to immunocompromised patients.
PO: Administer daily dose at bedtime. May also be divided into 2 doses and given 12 hr apart.
- If patient has difficulty swallowing tablets, confer with pharmacist regarding preparation of syrup.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take thioguanine as directed, even if nausea and vomiting occur. If vomiting occurs shortly after dose is taken, consult health care professional. Take combinations of drugs at prescribed times. Omit missed doses.
Instruct patient to notify health care professional if decreased urine output; swelling of lower extremities; yellowing of skin; nausea; vomiting; severe diarrhea; mouth sores; fever; chills; sore throat; signs of infection; bleeding gums; bruising; petechiae; or blood in urine, stool, or emesis occurs.
Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor. Caution patient not to drink alcoholic beverages or take products containing aspirin or NSAIDs.
Instruct patient to inspect oral mucosa for redness and ulceration. If ulceration occurs, advise patient to use sponge brush and rinse mouth with water after eating and drinking. Topical agents may be used if pain interferes with eating. Stomatitis pain may require treatment with opioid analgesics.
Instruct patient not to receive any vaccinations without advice of health care professional.
Rep: May be teratogenic. Advise female patients of reproductive potential to use effective contraception and to avoid breastfeeding during therapy. Advise patient to inform health care professional immediately if pregnancy is suspected. May cause gonadal suppression; however, patient should still use birth control.
Advise patient of need for medical follow-up and frequent lab tests.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇