thiotepa

High Alert

Bladder Instillation

Treatment of superficial papillary carcinoma of the urinary bladder.
IV: Treatment of breast or ovarian adenocarcinoma.

Intracavitary Instillation

Prevention of recurrent malignant effusions in pleura, pericardium, or peritoneum.Reduction in 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) in patients with class 3 beta-thalassemia.

Action ⬆ ⬇

Disrupts protein, DNA, and RNA synthesis by cross-linking strands of DNA and RNA (cell-cycle phase–nonspecific).

Therapeutic effects:

Death of rapidly replicating cells, particularly malignant ones.
Reduced graft rejection.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability. Variably absorbed following instillation (10–100%).

Distribution: Unknown.

Metabolism/Excretion: Extensively metabolized (primarily to active metabolite, TEPA). Excreted through skin when given in high doses (for allogeneic HSCT)

Half-Life: Thiotepa, 1.4–3.7 hr; TEPA, 4–17.6 hr.

Time/Action Profile ⬆ ⬇

(noted as effects on blood counts; effects after intracavitary administration are highly variable)

ROUTE	ONSET	PEAK	DURATION
IV	10 days (up to 30 days)	14 days	21 days

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Concurrent use of live or attenuated vaccines;
OB: May cause fetal harm;
Lactation: Avoid breastfeeding.

Use Cautiously in:

Rep: Women and men of childbearing potential (use effective contraception);
Active infections;
Decreased bone marrow reserve;
Moderate or severe hepatic or renal impairment.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: alopecia, blistering, pruritus, rash, skin discoloration, skin peeling

EENT: blurred vision

GI: ↑liver enzymes, anorexia, diarrhea, HEPATIC VENO-OCCLUSIVE DISEASE, mucositis, nausea, vomiting

GU: ↓fertility, dysuria, urinary retention

Hemat: anemia, leukopenia, thrombocytopenia, BLEEDING

Local: pain at IV site, pain at site of intracavitary instillation

Neuro: amnesia, apathy, confusion, disorientation, dizziness, drowsiness, ENCEPHALOPATHY, hallucinations, headache, SEIZURES

Misc: fatigue, fever, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), INFECTION, weakness

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inhibitors, including clarithromycin, itraconazole, or ritonavir may ↑ levels; avoid concurrent use.
Strong CYP3A4 inducers, including phenytoin or rifampinmay ↓ levels; avoid concurrent use.
May ↓ efficacy of cyclophosphamide when administered prior to cyclophosphamide; administer thiotepa after cyclophosphamide.
↑bone marrow depression with other antineoplastics or radiation therapy.
May prolong apnea after succinylcholine.

Route/Dosage ⬆ ⬇

Bladder Instillation

Intravesical
(Adults ): 60 mg retained for 2 hr once weekly for 4 wk; course may be cautiously repeated 1–2 times (bone marrow depression may occur).

Breast or Ovarian Adenocarcinoma

IV (Adults ): 0.3–0.4 mg/kg every 1–4 wk.

Malignant Effusions

Intracavitary
(Adults ): 0.6–0.8 mg/kg every 1–4 wk.

Class 3 Beta-Thalassemia

IV (Children ): 5 mg/kg every 12 hr for a total of 2 doses, given on Day -6 before allogeneic HSCT.

Availability ⬆ ⬇

(Generic available)

Lyophilized powder for injection: 15 mg/vial; 100 mg/vial

Assessment ⬆ ⬇

Monitor vital signs prior to and periodically during therapy.
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. Assess for nausea, vomiting, and anorexia. 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 fluids/day. Allopurinol may be used to decrease uric acid levels.

Lab Test Considerations:

Determine negative pregnancy status prior to starting therapy.
- Monitor CBC and differential prior to and weekly during therapy and for at least 3 wk after therapy. The nadir of leukopenia occurs after 10–14 days, although it may be delayed up to 1 mo. To prevent irreversible bone marrow depression, therapy should be discontinued if leukocyte count falls to ≤3000/mm³ or thrombocyte count falls to 150,000/mm³.
- Monitor for ↑ AST, ALT, LDH, serum bilirubin, uric acid, creatinine, and BUN.

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, dose calculations, and infusion pump settings.
Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard equipment in designated containers.
- Reconstitute 15 mg of powder with 1.5 mL of sterile water for injection for a concentration of 10 mg/mL. This concentration is suitable for intratumoral injection. May be further diluted for other routes. Solution is clear to slightly opaque. Do not use solution that is cloudy or that contains precipitate. Stable for 8 hr if refrigerated after reconstitution.
- May be administered by physician via several routes.
- Administration of live-virus vaccines to immunocompromised patients should be avoided.
Intracavitary: Reconstitute solution. Thiotepa is instilled via tube that was used to drain the effusion.
Bladder Instillation: Limit fluids per physician’s order for 8–12 hr prior to treatment. Reconstitute solution. Mix 60 mg with 30–60 mL of sterile water and instill in bladder via Foley catheter. Reposition patient every 15 min to allow maximal contact of solution with tumors. Solution should be retained for 2 hr. The lesser amount of solution (30 mL) is usually reserved for patients unable to hold 60 mL.

IV Administration:

Diluent: Following reconstitution, may be administered undiluted To eliminate haze, filter solution through a 0.22-micron filter prior to administration.
Rate: Administer by rapid injection over 1–3 min.
Intermittent Infusion: Diluent: Dilute further in 50–100 mL of 0.9% NaCl, D5W, dextrose/saline combinations, Ringer’s or LR. Use diluted solutions immediately.

Patient/Family Teaching ⬆ ⬇

Instruct patient receiving thiotepa via Foley catheter to notify health care professional if hematuria or dysuria occurs.
Instruct patient to notify health care professional if 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.
This drug may cause gonadal suppression; however, patient should still use birth control. Advise patient to inform health care professional immediately if pregnancy is suspected.
Discuss possibility of hair loss with patient. Explore methods of coping.
Instruct patient not to receive any vaccinations without advice of health care professional.
Rep: Advise women of reproductive potential to use effective contraception for at least 6 mo after final dose. Advise men of with partners of reproductive potential to use effective contraception for at least 1 yr after final dose. May impair male and female fertility.
Advise patient of need for medical follow-up and frequent lab tests.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇