Thiotepa

TEPADINA (thiotepa) is an alkylating drug indicated: To reduce the risk of graft rejection when used in conjunction with high-dose busulfan and cyclophosphamide as a preparative regimen for allogeneic hematopoietic progenitor (stem) cell transplantation (HSCT) for pediatric patients with class 3 beta-thalassemia. For treatment of adenocarcinoma of the breast or ovary. For controlling intracavitary effusions secondary to diffuse or localized neoplastic diseases of various serosal cavities. For treatment of superficial papillary carcinoma of the urinary bladder.

Thiotepa is a cytotoxic agent of the polyfunctional type, related chemically and pharmacologically to the nitrogen mustard. The radiomimetic action of thiotepa is believed to occur through the release of ethyleneimine radicals which, like irradiation, disrupt the bonds of DNA. One of the principle bond disruptions is initiated by alkylation of guanine at the N-7 position, which severs the linkage between the purine base and the sugar and liberates alkylated guanines.

The recommended dosage of TEPADINA for class 3 beta-thalassemia is two administrations of 5 mg/kg given by intravenous infusion approximately 12 hours apart on Day -6 before allogeneic HSCT in conjunction with high-dose busulfan and cyclophosphamide. The recommended dosage of TEPADINA for treatment of adenocarcinoma of the breast or ovary is 0.3 mg/kg to 0.4 mg/kg by intravenous infusion. The recommended dosage of TEPADINA for treatment of malignant effusions is 0.6 mg/kg to 0.8 mg/kg intracavitary. The recommended dosage of TEPADINA for treatment of superficial papillary carcinoma of the urinary bladder is 60 mg in 30 mL to 60 mL of 0.9% Sodium Chloride Injection into the bladder by catheter. See Full Prescribing Information for preparation and administration instructions.

TEPADINA is contraindicated in: Patients with severe hypersensitivity to thiotepa Concomitant use with live or attenuated vaccines Hypersensitivity to the active substance. Concomitant use with live or attenuated vaccines.

Boxed warning (severe myelosuppression and carcinogenicity tepadina): may cause severe marrow suppression, and high doses may cause marrow ablation with resulting infection or bleeding. Monitor hematologic laboratory parameters. Cutaneous toxicity: Cleanse skin at least twice daily through 48 hours after the last dose of TEPADINA. Embryo-Fetal toxicity: Can cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential of the potential risk to a fetus and to use effective contraception.

The following clinically significant adverse reactions are described elsewhere in the labeling: Myelosuppression Infection Hypersensitivity Cutaneous Toxicity Hepatic Veno-Occlusive Disease Central Nervous System Toxicity Carcinogenicity The most common adverse reactions (incidence greater than 10%) are neutropenia, anemia, thrombocytopenia, elevated alanine aminotransferase, elevated aspartate aminotransferase, elevated bilirubin, mucositis, cytomegalovirus infection, hemorrhage, diarrhea, hematuria and rash.

Effect of Cytochrome CYP3A Inhibitors and Inducers In vitro studies suggest that thiotepa is metabolized by CYP3A4 and CYP2B6 to its active metabolite TEPA. Avoid co-administration of strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin, ritonavir) and strong CYP3A4 inducers (e.g., rifampin, phenytoin) with TEPADINA due to the potential effects on efficacy and toxicity. Consider alternative medications with no or minimal potential to inhibit or induce CYP3A4. If concomitant use of strong CYP3A4 modulators cannot be avoided, closely monitor for adverse drug reactions.

TEPADINA multichamber flexible bag and vials must be stored and transported refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze.