Ethylenimines

Ethylenimines

Thiotepa, an ethylenimine derivative, is a multifunctional alkylating drug.

Pharmacokinetics

After I.V. administration, thiotepa is 100% bioavailable. Significant systemic absorption may occur when thiotepa is administered into pleural (around the lungs) or peritoneal (abdominal) spaces to treat malignant effusions or is instilled into the bladder.

Metabolism and excretion

Thiotepa crosses the blood-brain barrier and is metabolized extensively in the liver. Thiotepa and its metabolites are excreted in urine.

Pharmacodynamics

Thiotepa exerts its cytotoxic activity by interfering with DNA replication and RNA transcription. Ultimately, it disrupts nucleic acid function and causes cell death.

Pharmacotherapeutics

Thiotepa is used to treat bladder cancer. This alkylating drug is also prescribed for palliative (symptom-relief) treatment of lymphomas and ovarian or breast cancers.

 

Wait! There’s more

Thiotepa is used for the treatment of intracavitary effusions (accumulation of fluid in a body cavity). It may also prove useful in the treatment of lung cancer.

 

Drug interactions

Thiotepa may interact with other drugs.

• Concurrent use of thiotepa, anticoagulants, and aspirin may increase the risk of bleeding.
• Taking thiotepa with neuromuscular blocking drugs may prolong muscular paralysis.
• Concurrent use of thiotepa and other alkylating drugs or radiation therapy may intensify toxicity rather than enhance the therapeutic response.

It’ll take your breath away

When used with succinylcholine, thiotepa may cause prolonged respirations and apnea (periods of not breathing). Thiotepa appears to inhibit the activity of cholinesterase, the enzyme that deactivates succinylcholine.

Warning!

Adverse reactions to thiotepa

The major adverse reactions to thiotepa are blood-related and include leukopenia, anemia, thrombocytopenia, and pancytopenia (deficiency of all cellular elements of the blood), which may be fatal.

Other adverse reactions include:

• nausea and vomiting (commonly)
• stomatitis and ulceration of the intestinal mucosa (especially at bone marrow transplantation doses)
• hives, rash, and pruritus (occasionally).