Teniposide
Brand name: Vumon
Drug class: Antineoplastic Agents
VA class: AN900
Molecular formula: C32H32O13S
CAS number: 29767-20-2
Warning
-
Administer only under supervision of qualified clinicians experienced in the use of cytotoxic therapy.
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Possible severe myelosuppression with resulting infection and bleeding. (See Myelosuppression under Cautions.)
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Possible serious and potentially fatal hypersensitivity reactions. Epinephrine, with or without corticosteroids and antihistamines, has been used to alleviate signs and symptoms. (See Sensitivity Reactions under Cautions.)
Introduction
Antineoplastic agent; a semisynthetic podophyllotoxin-derivative that is structurally and pharmacologically related to etoposide.
Uses for Teniposide
Acute Lymphocytic Leukemia
Induction therapy (as a component of multiple-drug antineoplastic regimens) in childhood acute lymphocytic (lymphoblastic) leukemia (ALL) that is refractory to induction with other therapy or has relapsed despite such therapy (designated an orphan drug by FDA for this use).
May prolong remission; however, experience is limited, and only a minority of patients achieve long-term survival.
Teniposide Dosage and Administration
General
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Consult specialized references for procedures for proper handling and disposal of antineoplastics. (See IV Administration under Dosage and Administration.)
Administration
IV Administration
For solution and drug compatibility information, see Compatibility under Stability.
Administer diluted solution by slow IV infusion. Do not administer by rapid IV injection. (See Cardiovascular Effects under Cautions.)
To prevent leaching of diethylhexyl phthalate (DEHP) plasticizer, use IV administration sets that do not contain DEHP (e.g., lipid sets, low DEHP-containing nitroglycerin sets).
Ensure that IV catheter or needle is in proper position and functional prior to infusion to avoid extravasation. (See Local Effects under Cautions.)
Flush IV access site thoroughly with 5% dextrose or 0.9% sodium chloride injection prior to and following administration. Heparin should not be used due to potential for drug precipitation.
Observe carefully for possible occlusion of the IV access site, including central venous catheters, particularly during prolonged (e.g., 24-hour) infusions. (See Compatibility under Stability.)
Observe closely for possible hypotensive or hypersensitivity reactions during administration (i.e., for ≥60 minutes after initiation of infusion) and frequently thereafter. (See Cardiovascular Effects and also see Sensitivity Reactions under Cautions.)
Handle cautiously. Skin reactions may occur following accidental exposure; use protective equipment (e.g., gloves). If accidental contact occurs, wash skin thoroughly with soap and water or flush mucosa thoroughly with water.
Dilution
Must be diluted before IV infusion.
Plastic equipment or devices may soften or crack and possibly leak when used with undiluted teniposide injection.
To prevent leaching of DEHP plasticizer, prepare diluted solutions in containers that do not contain DEHP (e.g., glass or polyolefin plastic bags or containers). Use of PVC containers not recommended.
For IV infusion, dilute concentrate in 5% dextrose or 0.9% sodium chloride injection to a final concentration of 0.1, 0.2, 0.4, or 1 mg/mL.
Rate of Administration
Administer over at least 30–60 minutes to minimize risk of hypotension. (See Cardiovascular Effects under Cautions.) If hypotensive reaction occurs, use slower rate of infusion and monitor carefully if restarting after discontinuance and appropriate treatment.
Dosage
Pediatric Patients
Acute Lymphocytic Leukemia
Patients Who Failed Induction Therapy with a Cytarabine-containing Regimen
IV165 mg/m2 (in combination with cytarabine 300 mg/m2) twice weekly for 8 or 9 doses.
Patients Who Failed Induction Therapy with Vincristine/Prednisone-containing Regimens
IV250 mg/m2 (in combination with vincristine 1.5 mg/m2) weekly for 4–8 weeks with oral prednisone 40 mg/m2 daily for 28 days.
Special Populations
Hepatic Impairment
Use with caution; dosage adjustments may be necessary.
Renal Impairment
Dosage adjustments may be necessary.
Patients with Down’s Syndrome
Initially, give half the usual dose; subsequent doses may be increased depending on degree of myelosuppression and mucositis encountered with previous doses.
Cautions for Teniposide
Contraindications
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Known hypersensitivity to teniposide or polyoxyl 35 castor oil (Cremophor EL, polyoxyethylated castor oil). (See Sensitivity Reactions under Cautions.)
Warnings/Precautions
Warnings
Adequate Patient Evaluation and Monitoring
Administer only under supervision of qualified clinicians experienced in the use of cytotoxic therapy.
Perform CBCs and renal and hepatic function tests prior to, during, and after completion of therapy. (See Myelosuppression under Cautions.)
Myelosuppression
Risk of dose-limiting myelosuppression (e.g., neutropenia, leukopenia, thrombocytopenia, anemia). Severe myelosuppression with resulting infection or bleeding may occur.
Monitor for myelosuppression frequently during and after treatment. Perform CBCs (leukocyte count with differential, platelet count, hemoglobin) prior to initiation of therapy and before each subsequent dose. If severe myelosuppression occurs, consider supportive therapy, antibiotics for complicating infections, and blood product transfusions; repeat bone marrow examination before continuing therapy.
Cardiovascular Effects
Transient hypotension reported following rapid IV administration, possibly resulting from direct effect of polyoxyl 35 castor oil contained in preparation.
Administer over at least 30–60 minutes; observe patient closely during administration (i.e., for ≥60 minutes after initiation of infusion) and frequently thereafter.
If clinically important hypotension occurs, discontinue infusion. BP usually normalizes within hours in response to infusion discontinuance and administration of IV fluids and other supportive therapy as necessary. Use slower rate of infusion and monitor carefully if restarting after discontinuance and appropriate treatment.
Sudden death secondary to intractable hypotension and probable arrhythmia reported in at least 1 geriatric patient receiving teniposide in combination therapy for a nonleukemic malignancy. Hypertensive reactions, sometimes severe and accompanied by cardiac failure, reported rarely.
Nervous System Effects
Acute CNS depression (manifested as somnolence and lethargy) and hypotension, accompanied by metabolic acidosis, reported in patients pretreated with antiemetics and receiving high-dose† [off-label] regimens of teniposide. CNS depression possibly resulting from depressant effects of antiemetic agents and high alcohol content of teniposide formulation.
Fetal/Neonatal Morbidity and Mortality
May cause fetal harm. Teratogenicity and embryotoxicity demonstrated in animals. Avoid pregnancy during therapy. If used during pregnancy or if pregnancy occurs during therapy, apprise of potential fetal hazard.
Sensitivity Reactions
Hypersensitivity Reactions
Risk of hypersensitivity reactions, including anaphylaxis-like manifestations (e.g., chills, fever, urticaria, tachycardia, flushing, bronchospasm, dyspnea, hypotension or hypertension). Reaction may occur with initial dose or with repeated exposure and may be life-threatening if not treated promptly with antihistamines, corticosteroids, epinephrine, IV fluids, and other supportive measures as necessary. Etiology unknown, but reactions may result from polyoxyl 35 castor oil component or from teniposide itself. Frequency possibly increased in patients with neuroblastomas or brain tumors. Observe patients closely during administration (i.e., for ≥60 minutes after initiation of infusion) and frequently thereafter. If manifestations of anaphylaxis occur, discontinue infusion immediately and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, antihistamines, pressor agents, IV fluids).
Generally contraindicated in patients with known hypersensitivity to teniposide or polyoxyl 35 castor oil; however, may consider cautious administration when the antileukemic benefit already demonstrated clearly outweighs the possible risk. When reinitiating therapy in a patient who previously developed a hypersensitivity reaction, pretreat with a corticosteroid and antihistamine and observe patient carefully during and after infusion.
Appropriate equipment and agents (e.g., epinephrine, antihistamines, corticosteroids, IV fluids, oxygen) should be readily available.
No evidence of cross-sensitization between teniposide and etoposide.
General Precautions
Toxicity
Administer only under constant supervision by clinicians experienced in therapy with cytotoxic agents and only when the potential benefits outweigh the possible risks.
Most adverse effects are reversible if detected early.
Discontinue or reduce dosage and institute appropriate measures as necessary when severe adverse effects occur.
Reinstitute therapy with caution, considering further need for the drug and possible toxicity recurrence.
Local Effects
Extravasation may result in local tissue necrosis and/or thrombophlebitis.
Dermatologic Effects
Alopecia reported; usually reversible but sometimes may progress to total baldness.
Carcinogenicity
Secondary acute myeloid (myelogenous, nonlymphocytic) leukemia (AML, ANLL), with or without a preleukemic phase, reported in patients receiving maintenance therapy with teniposide in combination with other antineoplastic agents. Assess potential benefit versus risks of therapy.
Animal studies to determine the carcinogenic potential of teniposide have not been performed to date; however, the drug should be considered a potential carcinogen.
Specific Populations
Pregnancy
Category D. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
Lactation
Not known whether teniposide is distributed into milk. Discontinue nursing or the drug.
Pediatric Use
Safety and efficacy established only for combination therapy of refractory childhood ALL. In an analysis of data from 7 studies involving 303 patients ranging in age from 0.5 months to 20 years who received teniposide as a single agent for a variety of hematologic malignancies and solid tumors, no age-related difference in tolerance was reported.
Each mL of teniposide concentrate for injection contains 30 mg of benzyl alcohol. Although a causal relationship has not been established, injections preserved with benzyl alcohol have been associated with toxicity in neonates.
Hepatic Impairment
Use with caution. (See Elimination: Special Populations, under Pharmacokinetics.)
Patients with Down’s Syndrome
Possible increased sensitivity to myelosuppressive chemotherapy. Dosage adjustments necessary. (See Down's Syndrome under Dosage and Administration.)
Patients with Hypoalbuminemia
Careful monitoring recommended. (See Distribution: Special Populations, under Pharmacokinetics.)
Common Adverse Effects
Neutropenia, leukopenia, anemia, thrombocytopenia, myelosuppression (nonspecified), mucositis, diarrhea, nausea, vomiting, infection, alopecia, bleeding, hypersensitivity reactions, rash, fever, hypotension.
Interactions for Teniposide
Specific Drugs
Drug |
Interaction |
Comments |
---|---|---|
Antiemetic agents |
Possible CNS depression when used concomitantly with higher than recommended dosages of teniposide |
|
Methotrexate |
Possible increased methotrexate clearance |
|
Sodium salicylate |
Possibility of substantially increased plasma teniposide concentrations and potential for increased toxicity |
Use concomitantly with caution |
Sulfamethizole |
Possibility of substantially increased plasma teniposide concentrations and potential for increased toxicity |
Use concomitantly with caution |
Tolbutamide |
Possibility of substantially increased plasma teniposide concentrations and potential for increased toxicity |
Use concomitantly with caution |
Teniposide Pharmacokinetics
Distribution
Extent
Limited distribution throughout the body because of extensive protein binding. Limited distribution into the brain; however, CSF concentrations are higher in patients with brain tumors.
Concentrations in saliva, CSF, and malignant ascites fluid are low relative to those in plasma.
Plasma Protein Binding
>99%.
Special Populations
Volume of distribution increases with decreasing albumin concentrations. (See Patients with Hypoalbuminemia under Cautions.)
Elimination
Elimination Route
44% of dose is excreted in urine within 120 hours after dosing (with only 4–12% excreted as unchanged drug); 0–10% of dose is excreted in feces within 72 hours.
Half-life
5 hours.
Special Populations
Possible association between increased concentrations of serum alkaline phosphatase or γ-glutamyltransferase (γ-glutamyltranspeptidase, GT, GGTP) and a decrease in plasma teniposide clearance. (See Hepatic Impairment under Cautions.)
Stability
Storage
Parenteral
Injection
2–8°C; protect from light.
Store diluted solutions at room temperature; do not refrigerate. Diluted solutions at concentrations of 0.1, 0.2, or 0.4 mg/mL are stable for up to 24 hours at room temperature. Diluted solutions at concentration of 1 mg/mL should be administered within 4 hours to reduce potential for precipitation. Stability and use times are identical for solutions prepared in glass or plastic containers.
Compatibility
For information on systemic interactions resulting from concomitant use, see Interactions.
Parenteral
Possible precipitation of diluted solutions. Precipitation reported during 24-hour infusions of teniposide diluted to concentrations of 0.1–0.2 mg/mL, resulting in occlusion of central venous access catheters. (See IV Administration under Dosage and Administration.) To minimize precipitation, avoid agitation, decrease storage time prior to administration, and avoid contact with other drugs or fluids.
Solution CompatibilityHID
Compatible |
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Dextrose 5% in water |
Ringer’s injection, lactated |
Sodium chloride 0.9% |
Drug Compatibility
Compatible |
---|
Acyclovir sodium |
Allopurinol |
Amifostine |
Amikacin sulfate |
Aminophylline |
Amphotericin B |
Ampicillin sodium |
Ampicillin sodium–sulbactam sodium |
Aztreonam |
Bleomycin sulfate |
Bumetanide |
Buprenorphine HCl |
Butorphanol tartrate |
Calcium gluconate |
Carboplatin |
Carmustine |
Cefazolin sodium |
Cefotaxime sodium |
Cefoxitin sodium |
Ceftazidime |
Ceftizoxime sodium |
Ceftriaxone sodium |
Cefuroxime sodium |
Chlorpromazine HCl |
Cimetidine HCl |
Ciprofloxacin |
Cisplatin |
Cladribine |
Clindamycin phosphate |
Co-trimoxazole |
Cyclophosphamide |
Cytarabine |
Dacarbazine |
Dactinomycin |
Daunorubicin HCl |
Dexamethasone sodium phosphate |
Diphenhydramine HCl |
Doxorubicin HCl |
Doxycycline hyclate |
Droperidol |
Enalaprilat |
Etoposide |
Etoposide phosphate |
Famotidine |
Floxuridine |
Fluconazole |
Fludarabine phosphate |
Fluorouracil |
Furosemide |
Gallium nitrate |
Ganciclovir sodium |
Gemcitabine HCl |
Gentamicin sulfate |
Granisetron HCl |
Haloperidol lactate |
Hydrocortisone sodium phosphate |
Hydrocortisone sodium succinate |
Hydromorphone HCl |
Hydroxyzine HCl |
Ifosfamide |
Imipenem–cilastatin sodium |
Leucovorin calcium |
Lorazepam |
Mannitol |
Mechlorethamine HCl |
Melphalan HCl |
Meperidine HCl |
Mesna |
Methotrexate sodium |
Methylprednisolone sodium succinate |
Metoclopramide HCl |
Metronidazole |
Minocycline HCl |
Mitomycin |
Mitoxantrone HCl |
Morphine sulfate |
Nalbuphine HCl |
Netilmicin sulfate |
Ondansetron HCl |
Potassium chloride |
Prochlorperazine edisylate |
Promethazine HCl |
Ranitidine HCl |
Sargramostim |
Sodium bicarbonate |
Streptozocin |
Thiotepa |
Ticarcillin disodium |
Ticarcillin disodium–clavulanate potassium |
Tobramycin sulfate |
Vancomycin HCl |
Vinblastine sulfate |
Vincristine sulfate |
Vinorelbine tartrate |
Zidovudine |
Incompatible |
Heparin |
Idarubicin HCl |
Actions
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Exact mechanism(s) of action not known; apparently produces cytotoxic effects by damaging DNA and thereby inhibiting or altering DNA synthesis.
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Induces single- and double-stranded DNA breaks and also induces DNA-protein cross-links, possibly through inhibition of type II topoisomerase.
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Cell-cycle specific, inducing G2-phase arrest and preferentially killing cells in the G2 and late S phases.
Advice to Patients
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Importance of advising patients and/or their parents or guardians of adverse effects and associated manifestations.
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Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
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Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed; necessity for clinicians to advise women to avoid pregnancy during therapy and to advise pregnant women of risk to the fetus.
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Importance of informing patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Parenteral |
For injection concentrate, for IV infusion only |
10 mg/mL |
Vumon (with dehydrated alcohol 42.7% and benzyl alcohol 30 mg and polyoxyl 35 castor oil 500 mg per mL) |
Bristol-Myers Squibb |
AHFS DI Essentials™. © Copyright 2023, Selected Revisions June 1, 2007. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.
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