thiotepa

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, fatigue, hallucinations, headache, SEIZURES, weakness

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

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inhibitors, including clarithromycin, itraconazole, or ritonavir, may ↑ levels and risk of toxicity; avoid concurrent use.
Strong CYP3A4 inducers, including phenytoin or rifampin, may ↓ levels and effectiveness; 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.
May ↓ antibody response to live-virus vaccine and ↑ risk of adverse reactions; do not administer concurrently.

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)

Solution for injection (Tepylute): 10 mg/mL
Lyophilized powder for injection (Tepadina): 15 mg/vial; 100 mg/vial

Assessment ⬆ ⬇

Monitor vital signs prior to and periodically during therapy.
Monitor for bone marrow suppression. 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 and anemia. Provide supportive care for infection, bleeding and symptomatic anemia.
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.
Assess for hypersensitivity reactions, including anaphylaxis. If clinically significant allergic reactions occur, discontinue thiotepa and initiate appropriate medical treatment.
Monitor for signs and symptoms of cutaneous toxicity (skin discoloration, pruritus, blisters, desquamation, peeling) especially in the groin, axillae, skin folds, and under dressings.
Monitor for CNS toxicity (headache, apathy, psychomotor retardation, change in metal status, seizures, coma) during and shortly after therapy. If severe CNS toxicity occurs, discontinue administration and provide supportive care.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
- Monitor CBC and differential prior to and weekly during therapy and for ≥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 WBC count falls to ≤3000/mm³ or platelet count falls to 150,000/mm³.
- May ↑ AST, ALT, LDH, serum bilirubin, uric acid, BUN, and creatinine. Provide supportive care if hepatic veno-occlusive disease occurs.

Implementation ⬆ ⬇

High Alert: 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.
Thiotepa is hazardous. Follow applicable special handling and disposal procedures.
- May be administered by physician via several routes.
Intracavitary: Instill via tube that was used to drain the effusion.
Bladder Instillation: Limit fluids per medical order for 8–12 hr prior to treatment. Reconstitute solution. Mix 60 mg in 60 mL 0.9% NaCl and instill in urinary bladder via catheter. Reposition patient every 15 min to allow maximal contact of solution with tumors. Solution should be retained for 2 hr. The dose may be given in a volume of 30 mL for patients unable to retain 60 mL for 2 hr.

IV Administration:

Intermittent Infusion: Single-dose vial: Remove vial from refrigerator 1 hr prior to dilution. Diluent: Using a 16G needle with Leur-lock syringe, dilute solution of vial in bag of 0.9% NaCl for injection with a volume appropriate to obtain correct dose and concentration. Concentration: 0.5–1 mg/mL. After dilution, use immediately or refrigerate 24 hr or keep at room temperature 4 hr. Use only if free of particulates. Filter using a 0.2-micron filter prior to administration via central venous catheter. Discard any unused portion.
Lyophilized powder: Reconstitution: Reconstitute 15 mg vial with 1.5 mL sterile water for injection. Reconstitute 100 mg vial with 10 mL sterile water for injection. Invert repeatedly to mix. Solution is free of particulates as may be opalescent. Stable when refrigerated for 8 hr after reconstituted.Diluent: Using infusion bag of 0.9% NaCl solution for injection, dilute reconstituted solution to obtain appropriate dose and concentration. Concentration: 0.5–1 mg/mL. After dilution, use immediately or refrigerate 24 hr or keep at room temperature 4 hr. Use only if free of particulates. Filter using a 0.2-micron filter prior to administration.
Y-Site Compatibility:
- acyclovir
- allopurinol
- amifostine
- amikacin
- aminocaproic acid
- aminophylline
- amphotericin B deoxycholate
- amphotericin B lipid complex
- amphotericin B liposomal
- ampicillin
- ampicillin/sulbactam
- anidulafungin
- argatroban
- atracurium
- azithromycin
- aztreonam
- bivalirudin
- bleomycin
- bumetanide
- buprenorphine
- butorphanol
- calcium acetate
- calcium chloride
- calcium gluconate
- carboplatin
- carmustine
- caspofungin
- cefazolin
- cefepime
- cefotaxime
- cefotetan
- cefoxitin
- ceftazidime
- ceftriaxone
- cefuroxime
- chloramphenicol
- chlorpromazine
- ciprofloxacin
- cisatracurium
- clindamycin
- cyclophosphamide
- cyclosporine
- cytarabine
- dacarbazine
- dactinomycin
- daptomycin
- daunorubicin
- dexamethasone
- dexmedetomidine
- dexrazoxane
- digoxin
- diltiazem
- diphenhydramine
- dobutamine
- docetaxel
- dopamine
- doxorubicin hydrochloride
- doxycycline
- droperidol
- enalaprilat
- epinephrine
- epirubicin
- ertapenem
- erythromycin
- esmolol
- etoposide
- etoposide phosphate
- famotidine
- fentanyl
- floxuridine
- fluconazole
- fludarabine
- fluorouracil
- foscarnet
- fosphenytoin
- furosemide
- ganciclovir
- gemcitabine
- gentamicin
- glycopyrrolate
- granisetron
- haloperidol
- heparin
- hydralazine
- hydrocortisone sodium succinate
- hydromorphone
- hydroxyzine
- idarubicin
- ifosfamide
- imipenem/cilastatin
- insulin, regular
- irinotecan
- isoproterenol
- ketorolac
- labetalol
- leucovorin calcium
- levofloxacin
- lidocaine
- linezolid
- lorazepam
- magnesium sulfate
- mannitol
- melphalan
- meperidine
- meropenem
- mesna
- methadone
- methotrexate
- methylprednisolone
- metoclopramide
- metoprolol
- metronidazole
- midazolam
- milrinone
- mitomycin
- mitoxantrone
- morphine
- moxifloxacin
- nafcillin
- nalbuphine
- nitroglycerin
- norepinephrine
- octreotide
- ondansetron
- oxaliplatin
- paclitaxel
- palonosetron
- pamidronate
- pemetrexed
- pentamidine
- pentobarbital
- phenobarbital
- phentolamine
- phenylephrine
- piperacillin/tazobactam
- potassium acetate
- potassium chloride
- potassium phosphates
- procainamide
- prochlorperazine
- promethazine
- propranolol
- remifentanil
- rituximab
- rocuronium
- sodium acetate
- sodium bicarbonate
- sodium phosphates
- succinylcholine
- sufentanil
- tacrolimus
- theophylline
- thiopental
- tigecycline
- tirofiban
- tobramycin
- topotecan
- trastuzumab
- trimethoprim/sulfamethoxazole
- vancomycin
- vasopressin
- vecuronium
- vinblastine
- vincristine
- voriconazole
- zidovudine
- zoledronic acid
Y-Site Incompatibility:
- alemtuzumab
- amiodarone
- busulfan
- cisplatin
- dantrolene
- diazepam
- filgrastim
- gemtuzumab ozogamicin
- minocycline
- naloxone
- nicardipine
- nitroprusside
- pantoprazole
- phenytoin
- verapamil

Patient/Family Teaching ⬆ ⬇

Instruct patient to bathe with water at least twice daily through 48 hr after administration and change sheets daily during therapy with thiotepa to ↓ cutaneous toxicity.
Instruct patient receiving thiotepa via urinary bladder 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.
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 ≥6 mo after final dose. Advise men with female partners of reproductive potential to use effective contraception for ≥1 yr after final dose. May impair male and female fertility. Advise patient to inform health care professional immediately if pregnancy is suspected and to avoid breastfeeding.
Advise patient of need for medical follow-up and frequent lab tests.

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

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇