Teniposide is a chemotherapeutic medicine (anti-cancer medicine) that is classified as a "Topoisomerase inhibitor".
Indications of Teniposide:
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Acute lymphoblastic leukemia that is refractory to treatment:
It is used to treat childhood ALL (acute lymphoblastic leukemia) in combination with other drugs that is refractory to treatment.
Teniposide Dose in Adults
Note: First cycle should be given at half the actual dose to patients with Down syndrome and leukemia due to an increased incidence of myelosuppression.
Teniposide dose in the treatment of ALL (consolidation phase):
- 165 mg/m² intravenous on days 1, 4, 8, and 11 of alternating consolidation cycle.
Teniposide Dose in Children
Teniposide dose in the treatment of ALL as a part of combination therapy in children older than 6 months of age:
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165 mg/m² intravenous two times per week (for a total of 8 to 9 doses), or
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250 mg/m² IV once a week for 4 to 8 weeks
Teniposide dose in the treatment of high-risk Neuroblastoma in children:
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100 mg/m² administered intravenously (48 hours after a 6-hour cisplatin infusion dose is completed every 3 weeks)
Pregnancy Risk Category: D
- Teniposide is toxic to the fetus and may harm the fetus. It is best to avoid this during pregnancy.
Use while breastfeeding
- Data is limited and it is not known whether the drug enters breast milk when injected into lactating mothers or not.
- Deciding the treatment for lactating mothers depend on the condition of the mother. When necessary, breastfeeding may then be discontinued.
Teniposide Dose Adjustment in renal disease:
- Dosage adjustment is required in patients with significant renal impairment.
Dose adjustment in liver disease:
- Dosage adjustment is required with significant hepatic impairment.
Common Side Effects of Teniposide:
-
Gastrointestinal:
- Mucositis
- Diarrhea
- Nausea And Vomiting
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Hematologic & Oncologic:
- Neutropenia
- Leukopenia
- Anemia
- Thrombocytopenia
- Bone Marrow Depression
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Infection:
- Infection
Less Common Side Effects of Teniposide Include:
-
Cardiovascular:
- Hypotension
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Dermatologic:
- Hair loss
- Rashes
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Hematologic & Oncologic:
- Bleeding
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Hypersensitivity:
- Allergic reactions
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Miscellaneous:
- Fever
Contraindications to Teniposide:
Hypersensitivity to teniposide, Cremophor® EL (polyoxyethylated castor oil), or any other component of the formulation
Warnings and precautions
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Bone marrow suppression: [US Boxed Warning]
It can lead to severe myelosuppression, which can result in fatal infections or bleeding. Therefore, it is important to monitor blood counts.
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Extravasation
It is an irritant. It is important to position the catheter/needle correctly as it can cause tissue necrosis when it leaks out of the blood vessel or thrombophlebitis.
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Hypersensitivity [US Boxed Warning]
Allergic reactions can occur. These may include anaphylaxis and bronchospasm as well as dyspnea.
It is important to stop the infusion immediately and give treatment with Epinephrine with or without antihistamines and corticosteroids.
If there is a history of hypersensitivity in the past, recurrences are common. Premedication with antihistamines and corticosteroids is advised.
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Hypotension
Hypotension can result. The infusion should be administered slowly over at least 30-60 minutes.
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High doses can cause toxicities
CNS depression and metabolic acidosis are more common when the drug is administered in high doses or combined with antiemetics.
Teniposide: Drug Interactions:
Risk Factor C (Need to monitor the therapy) |
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Increase levels of CYP3A4 substrate |
Decrease levels of CYP3A4 substrates |
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Risk Factor C (Need to monitor the therapy) |
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Increased risk of marrow suppression |
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Increased risk of infections |
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Others |
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Risk Factor D Drugs: Consider alternative Drugs
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Risk Factor D Drugs |
Effect |
Management |
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Barbiturates |
Decrease the serum concentration of Teniposide |
Consider alternatives to combined treatment, monitor response |
|
Baricitinib |
Enhance the immunosuppressive effect of immunosuppressants |
Avoid use with potent immunosuppressants, permitted with antirheumatic doses |
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CYP3A4 Inducers (Strong) |
Increase the metabolism of CYP3A4 Substrates (High risk with Inducers) |
Consider an alternative, consult labeling |
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CYP3A4 Inhibitors (Strong) |
Decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors) |
- |
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Dabrafenib |
Decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers) |
Seek alternatives, monitor clinical effects |
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Deferiprone |
Enhance the neutropenic effect of Myelosuppressive Agents |
Avoid concomitant use, monitor neutrophil count |
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Echinacea |
Diminish the therapeutic effect of Immunosuppressants |
- |
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Enzalutamide |
Decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers) |
Avoid concurrent use with narrow therapeutic index substrates, use with caution |
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Fingolimod |
Enhance the immunosuppressive effect of Immunosuppressants |
Avoid concomitant use, monitor for additive effects |
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Fosphenytoin |
Decrease the serum concentration of Teniposide |
Consider alternatives to combined treatment, monitor response |
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Leflunomide |
Enhance the adverse/toxic effect of Immunosuppressants |
Consider not using loading dose, monitor for bone marrow suppression |
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Lenograstim |
Diminish the therapeutic effect of Antineoplastic Agents |
Avoid use before/after myelosuppressive chemotherapy |
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Lipegfilgrastim |
Diminish the therapeutic effect of Antineoplastic Agents |
Avoid concomitant use with myelosuppressive chemotherapy |
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Lorlatinib |
Decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers) |
Avoid concurrent use with substrates with minimal decrease in serum concentrations |
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Mifepristone |
Increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors) |
Minimize doses of substrates, monitor for increased concentrations/toxicity |
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Mitotane |
Decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers) |
Adjust doses of substrates substantially |
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Nivolumab |
Diminish the therapeutic effect of Immunosuppressants |
- |
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Palifermin |
Enhance the adverse/toxic effect of Antineoplastic Agents |
Do not administer within 24 hours of myelotoxic chemotherapy |
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Phenytoin and Teniposide |
Decreased teniposide concentrations |
Consider alternatives to combined treatment. Monitor teniposide response closely if combination cannot be avoided. |
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Roflumilast and Immunosuppressants |
Enhanced immunosuppressive effect |
Evaluate if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating roflumilast therapy. |
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Sipuleucel-T and Immunosuppressants |
Diminished therapeutic effect |
Evaluate if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. |
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St John's Wort and CYP3A4 Substrates |
Decreased serum concentration of CYP3A4 Substrates |
Consider alternative for one of the interacting drugs. Consult appropriate manufacturer labeling. |
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Stiripentol and CYP3A4 Substrates |
Increased serum concentration of CYP3A4 Substrates |
Use of stiripentol with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Any CYP3A4 substrate used with stiripentol requires closer monitoring. |
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Tofacitinib and Immunosuppressants |
Enhanced immunosuppressive effect |
Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease-modifying antirheumatic drugs (DMARDs) is permitted. |
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Inactivated Vaccines and Immunosuppressants |
Reduced vaccine efficacy |
Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. Revaccinate at least 3 months after immunosuppressant discontinuation if vaccinated during immunosuppressant therapy. |
Risk Factor X Drugs: Avoid concomitant use with Teniposide
Risk Factor X Drugs |
Effect |
Management |
|
BCG (Intravesical) |
Diminished therapeutic effect |
Avoid combination with Immunosuppressants, Myelosuppressive Agents |
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Cladribine |
Enhanced immunosuppressive and myelosuppressive effect |
Use with caution with Immunosuppressants, Myelosuppressive Agents |
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Conivaptan |
Increased serum concentration of CYP3A4 Substrates (High risk with Inhibitors) |
Minimize doses of substrates, monitor for increased concentrations/toxicity |
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Dipyrone |
Enhanced adverse/toxic effect of Myelosuppressive Agents |
Use with caution, monitor for agranulocytosis and pancytopenia |
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Fusidic Acid (Systemic) |
Increased serum concentration of CYP3A4 Substrates (High risk with Inhibitors) |
Minimize doses of substrates, monitor for increased concentrations/toxicity |
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Idelalisib |
Increased serum concentration of CYP3A4 Substrates (High risk with Inhibitors) |
Minimize doses of substrates, monitor for increased concentrations/toxicity |
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Natalizumab |
Enhanced adverse/toxic effect |
Use with caution with Immunosuppressants, monitor for concurrent infection risk |
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Pimecrolimus |
Enhanced adverse/toxic effect of Immunosuppressants |
Use with caution, monitor for increased toxicity |
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Tacrolimus (Topical) |
Enhanced adverse/toxic effect of Immunosuppressants |
Use with caution, monitor for increased toxicity |
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Vaccines (Live) |
Diminished therapeutic effect, enhanced adverse/toxic effect |
Avoid combination with Immunosuppressants, avoid live-organism vaccines for at least 3 months after immunosuppressants |
Monitoring parameters:
- Blood pressure
- CBC
- Renal function tests
- Hepatic function tests
- Monitor for hypersensitivity reaction
How to administer Teniposide?
- Before and after each infusion, the infusion line should always be cleaned with normal saline.
- You should administer it by slow intravenous injection over half an hour to one hour using non-DEHP-containing sets. To prevent precipitation, it should be administered immediately after preparation.
- Close monitoring for hypotension should be performed.
- In case of anaphylaxis, the infusion should be stopped immediately and treated with Epinephrine or corticosteroids.
- It contains N, N–dimethylacetamide. This may make it incompatible with closed-system transfer devices whose plastic content may dissolve, resulting in leakage or possible infusion of dissolved material into the patient.
Mechanism of action of Teniposide:
- It acts as a topoisomerase-2 inhibitor. It works by delaying the transit of cells through the S phase and arrests cells in the late S/early G phase to prevent them from entering mitosis.
- It prevents DNA ligase and strand passing, resulting in DNA strand breakage.
Protein binding (primarily albumin): More than 99%
Metabolism: Extensively in the liver.
Half-life elimination: Children: 5 hours
Excretion: Urine (44%); feces (≤10%)
International Brands of Teniposide:
- VM 26-Bristol
- Vumon
Teniposide Brand Names in Pakistan:
No Brands are Available in Pakistan. It is not available readily in the markets.
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