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Teniposide

Pronunciation

(ten i POE side)

Index Terms

  • EPT
  • PTG
  • VM-26

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous:

Vumon: 10 mg/mL (5 mL [DSC]) [contains alcohol, usp, benzyl alcohol, cremophor el, dimethylacetamide]

Generic: 10 mg/mL (5 mL)

Brand Names: U.S.

  • Vumon [DSC]

Pharmacologic Category

  • Antineoplastic Agent, Podophyllotoxin Derivative
  • Antineoplastic Agent, Topoisomerase II Inhibitor

Pharmacology

Teniposide does not inhibit microtubular assembly; it has been shown to delay transit of cells through the S phase and arrest cells in late S or early G2 phase, preventing cells from entering mitosis. Teniposide is a topoisomerase II inhibitor, and appears to cause DNA strand breaks by inhibition of strand-passing and DNA ligase action.

Distribution

Vdss: Children: 3 to 11 L/m2; Adults: 8 to 44 L/m2; mainly into liver, kidneys, small intestine, and adrenals; limited distribution into CSF <1%

Metabolism

Extensively hepatic

Excretion

Urine (44%, 4% to 12% as unchanged drug); feces (≤10%)

Clearance: Renal: 10% of total body clearance

Half-Life Elimination

Children: 5 hours

Protein Binding

>99%; primarily albumin

Special Populations: Hepatic Function Impairment

There appears to be an association between an increase in serum alkaline phosphatase or gamma glutamyl-transpeptidase and a decrease in plasma clearance of teniposide.

Use: Labeled Indications

Acute lymphoblastic leukemia, refractory: Treatment of refractory childhood acute lymphoblastic leukemia (ALL) in combination with other chemotherapy

Use: Unlabeled

Treatment of refractory acute lymphoblastic leukemia (ALL) in adults

Contraindications

Hypersensitivity to teniposide, polyoxyl 35/polyoxyethylated castor oil (Cremophor EL), or any component of the formulation

Dosing: Adult

Note: Patients with Down syndrome and leukemia may be more sensitive to the myelosuppressive effects; administer the first course at half the usual dose and adjust dose in subsequent cycles upward based on degree of toxicities (myelosuppression and mucositis) in the previous course(s).

Acute lymphoblastic leukemia (ALL) consolidation treatment (off-label use; combination chemotherapy): IV: 165 mg/m2/dose days 1, 4, 8, and 11 of alternating consolidation cycles (Linker, 1991)

Dosing: Pediatric

Note: Patients with Down syndrome and leukemia may be more sensitive to the myelosuppressive effects; administer the first course at half the usual dose and adjust dose in subsequent cycles upward based on degree of toxicities (myelosuppression and mucositis) in the previous course(s).

Acute lymphoblastic leukemia (ALL), refractory (combination chemotherapy): IV: 165 mg/m2 twice weekly for 8 to 9 doses (in combination with cytarabine) or 250 mg/m2 weekly for 4 to 8 weeks (in combination with vincristine and prednisone)

Dosing: Renal Impairment

There are no specific dosage adjustments provided in the manufacturer’s labeling (has not been studied). However, dosage adjustment may be necessary in patients with significant renal impairment.

Dosing: Hepatic Impairment

There are no specific dosage adjustments provided in the manufacturer’s labeling (has not been studied). However, dosage adjustment may be necessary in patients with significant hepatic impairment.

Reconstitution

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]). Precipitation may occur at any concentration. Teniposide must be diluted with either D5W or 0.9% sodium chloride solutions to a final concentration of 0.1, 0.2, 0.4, or 1 mg/mL. Solutions should be prepared in non-DEHP-containing containers such as glass or polyolefin containers. The use of polyvinyl chloride (PVC) containers is not recommended. Because precipitation may occur at any concentration, the manufacturer recommends administrating as soon as possible after preparation. Teniposide contains N,N-dimethylacetamide, which is incompatible with many closed system transfer devices (CSTDs); the plastic components of CSTDs may dissolve and result in subsequent leakage and potential infusion of dissolved plastic into the patient (ISMP [Smetzer 2015]).

Administration

IV; must be administered slowly (over at least 30-60 minutes); do not administer by rapid IV injection. Administer through non-DEHP-containing administration sets. Incompatible with heparin; flush infusion line with D5W or NS before and after infusion. Precipitation may occur at any concentration; administer as soon as possible after preparation; inspect solution prior to administration. Observe patient continuously for at least the first 60 minutes after the start of the infusion, observe frequently thereafter. Stop infusion for signs of anaphylaxis (may require treatment with epinephrine, corticosteroids, antihistamines, pressors, or volume expanders); discontinue for clinically significant hypotension during infusion; if infusion is restarted after being withheld for hypotension, reinitiate at a slower infusion rate.

Teniposide contains N, N-dimethylacetamide, which is incompatible with many closed system transfer devices (CSTDs); the plastic components of CSTDs may dissolve and result in subsequent leakage and potential infusion of dissolved plastic into the patient (ISMP [Smetzer 2015]).

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).

Compatibility

Stable in D5W, LR, NS.

Y-site administration: Incompatible with idarubicin, heparin.

Storage

Store ampuls in refrigerator at 2°C to 8°C (36°F to 46°F). Protect from light. Solutions diluted for infusion to a concentration of 0.1, 0.2, or 0.4 mg/mL are stable at room temperature for up to 24 hours after preparation; solutions diluted to 1 mg/mL should be used within 4 hours of preparation. Because precipitation may occur at any concentration, the manufacturer recommends administrating as soon as possible after preparation. Use appropriate precautions for handling and disposal. Do not refrigerate solutions prepared for infusion.

Drug Interactions

Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Barbiturates: May decrease the serum concentration of Teniposide. Management: Consider alternatives to combined treatment with barbiturates and teniposide due to the potential for decreased teniposide concentrations. If the combination cannot be avoided, monitor teniposide response closely. Consider therapy modification

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Fosphenytoin: May decrease the serum concentration of Teniposide. Management: Consider alternatives to combined treatment with phenytoin and teniposide due to the potential for decreased teniposide concentrations. If the combination cannot be avoided, monitor teniposide response closely. Consider therapy modification

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Consider therapy modification

Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

Phenytoin: May decrease the serum concentration of Teniposide. Management: Consider alternatives to combined treatment with phenytoin and teniposide due to the potential for decreased teniposide concentrations. If the combination cannot be avoided, monitor teniposide response closely. Consider therapy modification

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

St John's Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Avoid combination

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination

VinCRIStine: Teniposide may enhance the neurotoxic effect of VinCRIStine. Monitor therapy

VinCRIStine (Liposomal): Teniposide may enhance the neurotoxic effect of VinCRIStine (Liposomal). Monitor therapy

Adverse Reactions

>10%:

Gastrointestinal: Mucositis (76%), diarrhea (33%), nausea/vomiting (29%; mild to moderate)

Hematologic: Neutropenia (95%), leukopenia (89%), anemia (88%), thrombocytopenia (85%), myelosuppression (75%)

Miscellaneous: Infection (12%)

1% to 10%:

Cardiovascular: Hypotension (2%; associated with rapid [<30 minutes] infusions)

Central nervous system: Fever (3%)

Dermatologic: Alopecia (9%; usually reversible), rash (3%)

Hematologic: Bleeding (5%)

Miscellaneous: Hypersensitivity reactions (5%; includes bronchospasm, chills, dyspnea, fever, flushing, hyper-/hypotension, tachycardia, or urticaria)

1%, postmarketing, and/or case reports: Arrhythmia, CNS depression, confusion, headache, hepatic dysfunction, intractable hypotension, metabolic abnormality, metabolic acidosis, neuropathy (severe), neurotoxicity, renal dysfunction, thrombophlebitis, tissue necrosis (upon extravasation), weakness

ALERT: U.S. Boxed Warning

Experienced physician:

Teniposide is a cytotoxic drug. Administer under the supervision of a qualified health care provider experienced in the use of cancer chemotherapeutic agents. Appropriate management of therapy and complications is possible only when adequate treatment facilities are readily available.

Bone marrow suppression:

Severe myelosuppression with resulting infection or bleeding may occur.

Hypersensitivity reactions:

Hypersensitivity reactions, including anaphylaxis-like symptoms, may occur with initial dosing or with repeated exposure to teniposide. Epinephrine, with or without corticosteroids and antihistamines, has been employed to alleviate hypersensitivity reaction symptoms.

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: [US Boxed Warning]: Severe myelosuppression resulting in infection or bleeding may occur; may be dose-limiting; monitor blood counts during and after treatment.

• Extravasation: Teniposide is considered an irritant (Pérez Fidalgo, 2012). For IV use only; ensure proper catheter/needle position prior to infusion; monitor infusion site; may cause local tissue necrosis and/or thrombophlebitis if extravasation occurs.

• Hypersensitivity reactions: [US Boxed Warning]: Hypersensitivity reactions, including anaphylaxis-like reactions, have been reported; may occur with initial dosing or with repeated exposure to teniposide. Epinephrine, with or without corticosteroids and antihistamines, has been employed to alleviate hypersensitivity reaction symptoms. Hypersensitivity reactions may include bronchospasm, dyspnea, hypertension, hypotension, tachycardia, flushing, chills, fever, or urticaria. Monitor closely during infusion (observe continuously for first 60 minutes, frequently thereafter). Stop infusion for signs of anaphylaxis; immediate treatment for anaphylactic reaction should be available during administration (may require treatment with epinephrine, corticosteroids, antihistamines, pressors, or volume expanders). Patients experiencing prior hypersensitivity are at risk for recurrence; re-treat only if the potential benefit outweighs the risk of hypersensitivity; premedication (with corticosteroids and antihistamines) is recommended for re-treatment.

• Hypotension: Hypotension may occur with rapid infusion; infuse slowly over at least 30 to 60 minutes; discontinue for clinically significant hypotension. If infusion is restarted after being withheld for hypotension, reinitiate at a slower infusion rate.

• Toxicity with high doses: Acute CNS depression, hypotension and metabolic acidosis have been reported; these events occurred in patients who received high-dose teniposide (investigation protocol) and were premedicated with antiemetics, which along with the alcohol content of teniposide, may have contributed to the CNS depression.

Disease-related concerns:

• Hepatic impairment: Use with caution; may require dosage reduction in patients with significant impairment.

• Renal impairment: Use with caution; may require dosage reduction in patients with significant impairment.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Down syndrome: Patients with Down syndrome and leukemia may be more sensitive to the myelosuppressive effects; reduced initial doses are recommended.

• Hypoalbuminemia: Since teniposide is highly bound to plasma proteins, carefully monitor patients with hypoalbuminemia.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors, 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.

• Dehydrated alcohol: Product contains about 43% alcohol.

• Dimethylacetamide (DMA): Teniposide contains N,N-dimethylacetamide, which is incompatible with many closed system transfer devices (CSTDs); the plastic components of CSTDs may dissolve and result in subsequent leakage and potential infusion of dissolved plastic into the patient (ISMP [Smetzer 2015]).

• Polyoxyl 35/polyoxyethylated castor oil: Contains polyoxyl 35/polyoxyethylated castor oil (Cremophor EL), which is associated with hypersensitivity reactions.

Special handling:

• Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).

Other warnings/precautions:

• Experienced physician: [US Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician. Appropriate management of therapy and complications is possible only when adequate treatment facilities are readily available.

Monitoring Parameters

CBC with differential and platelet count, renal and hepatic function tests; blood pressure; monitor for hypersensitivity reaction (observe continuously for first 60 minutes of infusion, frequently thereafter)

Pregnancy Risk Factor

D

Pregnancy Considerations

Adverse effects were observed in animal reproduction studies. May cause fetal harm if administered during pregnancy. Women of childbearing potential should avoid becoming pregnant during teniposide treatment.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience mouth sores or hair loss. Have patient report immediately to prescriber signs of infection, signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, weight gain), tachycardia, arrhythmia, shortness of breath, severe headache, severe dizziness, passing out, flushing, severe abdominal pain, severe nausea, vomiting, severe diarrhea, bruising, bleeding, loss of strength and energy, burning or numbness feeling, severe injection site pain or irritation, or confusion (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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