. 2022 May 2;22:483. doi: 10.1186/s12885-022-09522-3

Table 2.

Formulation, administration and toxicity of investigational drugs

Drug	Formulation	Administration	Toxicity
Methotrexate (MTX)	Tablets	Orally, once weekly.	Bone-marrow suppression leading to leucopenia, thrombocytopenia, and anemia. MTX is also hepatotoxic.
6-mercaptopurine (6MP)	Tablets and liquid formulation	Orally, daily. Doses are to be taken once a day at a regular schedule.	Bone-marrow suppression leading to leucopenia, thrombocytopenia, and anemia. 6MP is also hepatotoxic. The incidence of hepatotoxicity varies considerably and can occur with any dose, but more frequently when a dose of 75 mg/m² body surface area per day is exceeded, and most frequent in TPMT wild type patients. In general, the incidence and severity of side effects are considered to be dose-related.
6-thioguanine (6TG)	5 mg/mL oral suspension^a	Orally, daily. Doses are to be taken once a day at a regular schedule.	Bone-marrow suppression leading to leucopenia, thrombocytopenia, and anemia. 6TG is also hepatotoxic. At doses higher than those used in TEAM (40–60 mg/m²) 6TG has been related to an increased risk of sinusoidal obstruction syndrome and nodular regenerative hyperplasia.

Drug

Formulation

Administration

Toxicity

Methotrexate

(MTX)

Tablets

Orally, once weekly.

Bone-marrow suppression leading to leucopenia, thrombocytopenia, and anemia. MTX is also hepatotoxic.

6-mercaptopurine

(6MP)

Tablets and liquid formulation

Orally, daily. Doses are to be taken once a day at a regular schedule.

Bone-marrow suppression leading to leucopenia, thrombocytopenia, and anemia. 6MP is also hepatotoxic. The incidence of hepatotoxicity varies considerably and can occur with any dose, but more frequently when a dose of 75 mg/m² body surface area per day is exceeded, and most frequent in TPMT wild type patients. In general, the incidence and severity of side effects are considered to be dose-related.

6-thioguanine

(6TG)

5 mg/mL oral suspension^a

Orally, daily. Doses are to be taken once a day at a regular schedule.

Bone-marrow suppression leading to leucopenia, thrombocytopenia, and anemia. 6TG is also hepatotoxic. At doses higher than those used in TEAM (40–60 mg/m²) 6TG has been related to an increased risk of sinusoidal obstruction syndrome and nodular regenerative hyperplasia.

^aThe oral suspension is provided by Nova Laboratories Ltd. to the TEAM study. The liquid preparation has a limited shelf life (see package). Only 40 mg 6-thioguanine tablets are presently marketed, making accurate dosing difficult to achieve, especially for treatments using doses of less than 20 mg. Although the currently approved tablet formulation can be halved or quartered to derive an intermediate dose, in most cases this still requires rounding doses up or down. Moreover, young children, many adolescents and some adults find taking tablets very difficult. Acceptability of the formulation is of paramount importance, especially in diseases where adherence can significantly impact on outcomes. Suspension administered using an oral syringe will allow the dose of 6-thioguanine to be tailored to patient requirements, both accurately and safely. Moreover, improved ease of administration for children is expected to enhance medication acceptability and adherence