THIOTEPA

THIOTEPA
(thye-oh-tep'a)
Classifications: antineoplastic; alkylating agent;
Therapeutic:antineoplastic

Prototype: Cyclophosphamide
Pregnancy Category: D

Availability

15 mg, 30 mg injection

Action

Cell-cycle nonspecific alkylating agent that selectively reacts with DNA phosphate groups to produce chromosome cross-linkage and consequent blocking of nucleoprotein synthesis. Nonvesicant, highly toxic hematopoietic agent.

Therapeutic Effect

Myelosuppression is cumulative and unpredictable and may be delayed. Has some immunosuppressive activity.

Uses

To produce remissions in malignant lymphomas, including Hodgkin's disease, and adenocarcinoma of breast and ovary. Also in chronic granulocytic and lymphocytic leukemia, superficial papillary carcinoma of urinary bladder, bronchogenic carcinoma, and in malignant effusions secondary to neoplastic disease of serosal cavities.

Unlabeled Uses

Prevention of pterygium recurrences following postoperative beta-irradiation; leukemia, malignant meningeal neoplasms.

Contraindications

Hypersensitivity to drug; acute leukemia; acute infection; pregnancy (category D), lactation.

Cautious Use

Chronic lymphocytic leukemia; myelosuppression produced by radiation; with other antineoplastics; bone marrow invasion by tumor cells; impaired kidney or liver function.

Route & Dosage

Malignant Lymphomas
Adult: IV 0.3–0.4 mg/kg q1–4wk IM/SC 30–60 mg/m2 once weekly Intracavitary 0.6–0.8 mg/kg instilled through same tubing used for paracentesis at intervals of at least 1 wk Intravesicular 60 mg in 30–60 mL of distilled water instilled into bladder to be retained for 2 h once/wk for 4 wk Intrathecal 1–11.5 mg/m2 1–2 times/wk
Child: IV 25–65 mg/m2/dose every 21 d

Administration

Intravenous
  • Use only under constant supervision by physicians experienced in therapy with cytotoxic agents.
  • Avoid exposure of skin and respiratory tract to particles of thiotepa during solution preparation.

PREPARE: Direct: Reconstitute each 15 mg vial with 1.5 mL sterile water for injection (supplied) to yield 10 mg/mL. Filter solution through a 0.22 micron filter to eliminate haze. Use immediately.  

ADMINISTER: Direct: Give 60 mg or fraction thereof over 1 min.  

INCOMPATIBILITIES Solution/additive: Cisplatin. Y-site: Cisplatin, filgrastim, minocycline, vinorelbine.

  • Store powder for injection and reconstituted solutions at 2°–8° C (35°–46° F); protect from light.
  • Solutions reconstituted with sterile water only are stable for 8 h under refrigeration.

Adverse Effects (≥1%)

GI: Anorexia, nausea, vomiting, stomatitis, ulceration of intestinal mucosa. Hematologic: Leukopenia, thrombocytopenia, anemia, pancytopenia. Skin: Hives, rash, pruritus. Urogenital: Amenorrhea, interference with spermatogenesis. Body as a Whole: Headache, febrile reactions, pain and weeping of injection site, hyperuricemia, slowed or lessened response in heavily irradiated area, sensation of throat tightness. Other: Reported with intravesical administration (lower abdominal pain, hematuria, hemorrhagic chemical cystitis, vesical irritability).

Interactions

Drug: May prolong muscle paralysis with mivacurium; anticoagulants, nsaids, salicylates, antiplatelet agents may increase risk of bleeding.

Pharmacokinetics

Absorption: Rapidly cleared from plasma. Onset: Gradual response over several wk. Metabolism: In liver. Elimination: 60% in urine within 24–72 h.

Nursing Implications

Assessment & Drug Effects

  • Monitor closely because most patients will manifest some evidence of toxicity.
  • Be aware that because of cumulative effects, maximum myelosuppression may be delayed 3–4 wk after termination of therapy.
  • Discontinue therapy (per manufacturer) if leukocyte count falls to 3000/mm3 or below or if platelet count falls below 150,000/mm3.
  • Lab tests: Determine Hgb level, WBC with differential, and thrombocyte (i.e., platelet) counts at least weekly during therapy and for at least 3 wk after therapy is discontinued.
  • Monitor leukocyte and thrombocyte counts as indicators for adaptations in nursing and drug regimens.

Patient & Family Education

  • Be aware of possibility of amenorrhea (usually reversible in 6–8 mo).
  • Report onset of fever, bleeding, a cold or illness, no matter how mild to physician; medical supervision may be necessary.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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