Vumon

Podophyllotoxin Derivatives

Hazardous Drugs Classification
NIOSH 2016 List: Group 1
NIOSH (Draft) 2020 List: Table 1
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
Extravasation Risk
Irritant

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Teniposide is available as a 10-mg/mL solution ampule.
Dilution:
Prepare diluted solutions in non-di (2-ethylhexyl) phthalate (DEHP) containing large volume parenteral containers such as glass or polyolefin plastic bags or containers.
Dilute the calculated teniposide dose/volume in 5% Dextrose injection or 0.9% Sodium Chloride injection to a final concentration of 0.1 mg/mL, 0.2 mg/mL, 0.4 mg/mL, or 1 mg/mL.
Precipitation of teniposide may occur at the recommended concentrations; excessive agitation during the preparation of the diluted admixture may increase the risk of precipitation.
Storage following dilution: Diluted admixtures at concentrations of 0.1 mg/mL, 0.2 mg/mL, or 0.4 mg/mL are stable at room temperature for at least 24 hours after preparation; due to the potential for precipitation, diluted admixtures at concentrations of 1 mg/mL should be stored at room temperature and administered within 4 hours of preparation. Do not refrigerate.
Intravenous (IV) Infusion:
Administer the diluted admixture over at least 30 to 60 minutes using a non-DEHP containing IV administration set; do NOT give via rapid IV injection.
Ensure the IV catheter or needed is properly placed and functional prior to the infusion; monitor during the infusion for signs of extravasation.
Flush the administration apparatus thoroughly with 5% Dextrose injection or 0.9% Sodium Chloride injection before and after teniposide administration; heparin solutions may cause precipitation.
Monitor patients for hypersensitivity reactions; stop the infusion immediately for hypotension or anaphylaxis and administer appropriate supportive care.

nephrotoxicity / Delayed / 0-1.0
hepatotoxicity / Delayed / 0-1.0
new primary malignancy / Delayed / Incidence not known
leukemia / Delayed / Incidence not known
serious hypersensitivity reactions or anaphylaxis / Rapid / Incidence not known
bronchospasm / Rapid / Incidence not known
tissue necrosis / Early / Incidence not known

neutropenia / Delayed / 95.0-95.0
leukopenia / Delayed / 89.0-89.0
anemia / Delayed / 88.0-88.0
thrombocytopenia / Delayed / 85.0-85.0
bone marrow suppression / Delayed / 75.0-75.0
bleeding / Early / 5.0-5.0
hypotension / Rapid / 2.0-2.0
neurotoxicity / Early / 0-1.0
sinus tachycardia / Rapid / Incidence not known
hypertension / Early / Incidence not known
dyspnea / Early / Incidence not known
confusion / Early / Incidence not known
phlebitis / Rapid / Incidence not known
peripheral neuropathy / Delayed / Incidence not known
hypoalbuminemia / Delayed / Incidence not known

diarrhea / Early / 33.0-33.0
vomiting / Early / 29.0-29.0
nausea / Early / 29.0-29.0
infection / Delayed / 12.0-12.0
alopecia / Delayed / 9.0-9.0
fever / Early / 3.0-3.0
rash / Early / 3.0-3.0
flushing / Rapid / Incidence not known
headache / Early / Incidence not known
urticaria / Rapid / Incidence not known
chills / Rapid / Incidence not known
asthenia / Delayed / Incidence not known

Severe bone marrow suppression/myelosuppression (e.g., anemia, neutropenia, and thrombocytopenia) resulting in bleeding and infection may occur with teniposide therapy; therefore, administration requires an experienced clinician knowledgeable in the use of cancer chemotherapeutic agents and requires a specialized care setting (e.g., facilities equipped with adequate laboratory and supportive medical services to monitor for and treat drug-related complications). Obtain complete blood counts prior to starting teniposide, prior to each subsequent dose, and after therapy at clinically appropriate intervals. Perform a bone marrow examination prior to continuing therapy in patients who develop severe myelosuppression.[60884]

Vumon

Rx

Topoisomerase II inhibitor
Used with other chemotherapy for induction therapy in patients with refractory acute lymphocytic leukemia
Severe myelosuppression and hypersensitivity reactions have occurred

165 mg/m2 IV in combination with cytarabine 300 mg/m2 IV twice weekly for 8 to 9 doses was evaluated in a clinical study. Alternatively, teniposide 250 mg/m2 IV once weekly and vincristine 1.5 mg/m2 IV once weekly for 4 to 8 weeks plus prednisone 40 mg daily for 28 days was studied in another clinical trial. A dosage reduction or therapy discontinuation may be necessary in patients who develop severe toxicity.[60884]

165 mg/m2 IV in combination with cytarabine 300 mg/m2 IV twice weekly for 8 to 9 doses was evaluated in a clinical study. Alternatively, teniposide 250 mg/m2 IV once weekly and vincristine 1.5 mg/m2 IV once weekly for 4 to 8 weeks plus prednisone 40 mg orally daily for 28 days was studied in another clinical trial. A dosage reduction or therapy discontinuation may be necessary in patients who develop severe toxicity.

100 mg/m2 IV plus cisplatin repeated every 3 weeks has been studied. Complete remission (CR) rates following induction therapy (22% vs 13%) and overall remission rates (ORR) following induction therapy and surgery (73% vs 59%) were not significantly improved with 5 cycles of cisplatin 90 mg/m2 IV on day 1 followed 48 hr later by teniposide 100 mg/m2 IV repeated every 3 weeks compared with 5 cycles of cyclophosphamide plus doxorubicin in a randomized, phase II study in 140 patients (age range, 1 to 25.2 years) with newly diagnosed disseminated neuroblastoma; additionally, event-free survival (EFS) and overall survival (OS) were not significantly different between the 2 treatment arms. Etoposide 200 mg/m2 was substituted for teniposide in 29 patients (42%) due to an allergic reaction. In a nonrandomized study in patients (age range, > 1 to < 16 years) with newly diagnosed stage III (n=33) and IV (n=60) neuroblastoma, treatment with cyclophosphamide plus doxorubicin alternating with cisplatin plus teniposide (3 cycles each) resulted in ORR of 88% (CR, 47%) and 69% (CR, 33%), respectively, and median OS times of 60 and 26 months, respectively. Some responding patients in this study received multi-agent maintenance chemotherapy (n=57) or an autologous bone marrow transplant (n=13).

The teniposide dosage has not been established for the treatment of advanced bladder cancer. Treatment with single-agent teniposide 100 mg/m2 IV over 45 minutes weekly for 4 weeks repeated every 6 weeks produced 1 partial response (PR) (4%) in 23 patients with advanced transitional cell carcinoma (TCC) of the bladder in a nonrandomized study; additionally, single-agent teniposide 30 mg/m2/day IV over 1 hour for 5 days repeated every 3 weeks resulted in 2 PR (5%) in 40 patients with disseminated TCC of the urinary tract in a phase II study. First-line chemotherapy with teniposide 100 mg/m2 IV on days 1 and 8 in combination with cisplatin, doxorubicin, and 5-fluorouracil repeated every 3 weeks led to an overall response rate (ORR) of 52.7% and a median overall survival time of 44 weeks in 36 evaluable patients with locally advanced or metastatic TCC of the urinary tract. The ORR was 51% when teniposide 100 mg/m2 IV over 30 min on days 1 and 2 plus cisplatin repeated every 3 weeks was given as first-line systemic chemotherapy in 41 patients with metastatic TCC of the bladder in a phase II study. In another small phase II study in 27 patients with metastatic TCC of the bladder, the ORR was 19% following treatment with teniposide 60 mg/m2 IV on days 1 and 2 plus doxorubicin repeated every 21 days.

60 mg/m2 IV on day 1 of CHVmP/BP has been studied. The addition of mid-cycle bleomycin (10 mg IV on day 15) and vincristine (1.4 mg/m2 (Max of 2 mg) on day 15) to teniposide (60 mg/m2 IV on day 1), cyclophosphamide (600 mg/m2 IV on day 1), doxorubicin (50 mg/m2 IV on day 1), and prednisone (40 mg/m2 orally on days 1-5) (CHVmP/BP) repeated every 3 weeks for 3 cycles resulted in significantly improved 5-year freedom from progression (FFP) (43% vs 26%; p = 0.006) and overall survival (OS) (48% vs 28%; p = 0.014) rates compared with CHVmP alone in 141 previously untreated patients with intermediate- or high-grade non-Hodgkin lymphoma (NHL) in a randomized study; additionally, 10-year FFP (34% vs 23%; p = 0.024) and OS (34% vs 22%; p = 0.024) rates remained significantly improved with CHVmP/BV in a long-term analysis. In a randomized, phase III study in 346 previously untreated intermediate- or high-grade NHL patients, the 5-year FFP (49% vs 47%), relapse-free survival (54% vs 59%), and OS (55% vs 49%) rates were not significantly different with 8 cycles of CHVmP/BV compared with methotrexate (with leucovorin rescue), doxorubicin, cyclophosphamide, etoposide, mechlorethamine, vincristine, procarbazine, and prednisone (ProMACE-MOPP). In another multicenter, randomized, phase III study in 194 patients with aggressive NHL who responded to 3 initial cycles of CHVmP/BV, the median time to disease progression and OS time were not significantly different with 5 additional cycles of CHVmP/BV compared with 3 additional cycles of CHVmP/BV followed by high-dose chemotherapy and autologous bone marrow transplant; additionally, the 5-year FFP (56% vs 61%) and OS (77% vs 68%) rates were not significantly different in the 2 treatment arms.

60 mg/m2 IV on day 1 in combination with cyclophosphamide (600 mg/m2 on day 1), doxorubicin (25 mg/m2 on day 1), and prednisolone or prednisone (40 mg/m2 orally on days 1 to 5) repeated monthly for 6 cycles then every other month for one year (CHVP) plus interferon alfa-2b (5 million units SC 3 times/week for 18 months) (CHVP+INF) has been studied as first-line therapy in patients with follicular non-Hodgkin lymphoma (NHL) in randomized clinical trials. At a median follow-up of 6 years, the median progression-free survival (2.9 vs 1.5 years; p = 0.0002) and overall survival (OS) (not reached vs 5.6 years; p = 0.0084) times were significantly improved with CHVP+INF compared with CHVP alone in 242 previously untreated patients with follicular NHL in a multicenter, randomized, phase III study. First-line treatment with CHVP+INF significantly prolonged median time to disease progression and the OS time compared with single-agent fludarabine in 131 elderly patients with follicular lymphoma in a multicenter, randomized study; additionally, the 2-year failure-free survival rate (63% vs 49%, respectively; p < 0.05) and OS rate (77% vs 62%) were improved with CHVP+INF. Grade 3 or 4 neutropenia was reported in significantly more patients treated with CHVP+INF compared with fludarabine; however, grade 3 or 4 infection was reported in less than 1% of patients in both treatment arms. First-line treatment with CHVP+INF resulted in a lower 5-year event-free survival rate (48% vs 60%; p = 0.05) compared with high-dose chemotherapy followed by autologous stem-cell transplant in a randomized trial in 166 patients with follicular NHL; however, the 5-year OS rate (84% vs 78%, respectively; p = 0.49) was not significantly different between study arms. There were no secondary cancers after CHVP+INF therapy compared with 10 secondary malignancies (7 resulting in death) following ASCT.

100 or 120 mg/m2 IV over 1 hour on days 1, 3, and 5 in combination with cisplatin 80 mg/m2 IV on day 1 repeated every 3 weeks for up to 6 cycles has been administered in patients with inoperable, locally advanced or metastatic non-small cell lung cancer in randomized clinical studies. In a 4-arm, randomized trial in 225 patients that evaluated 2 teniposide dosage regimens with or without cisplatin, combination therapy with teniposide plus cisplatin led to a significantly improved overall response rate (22% vs 6%; p < 0.001), median overall survival (OS) time (7.2 vs 5.9 months; p = 0.008), and median progression-free survival time (4.3 vs 2.2 months; p = 0.003) compared with single-agent teniposide; however, combination therapy resulted in significantly higher rates of grade 3 and 4 hematologic toxicity, nausea and vomiting, and infection and 5 toxic deaths due to sepsis. In a randomized, phase III trial in 317 patients, there were no significant differences in the median OS time (9.9 vs 9.7 months), 1-year OS rate (41% vs 43%), or 2-year OS rate (18% vs 19%) in patients who received teniposide plus cisplatin compared with paclitaxel plus cisplatin. Grade 3 and 4 hematologic toxicity (including neutropenia, thrombocytopenia, and anemia), febrile neutropenia, and infection were reported significantly more often with teniposide plus cisplatin compared with paclitaxel plus cisplatin; additionally, there were 6 toxic deaths (3.6%) in the teniposide plus cisplatin arm and 3 toxic deaths (1.9%) in the paclitaxel plus cisplatin arm.

Various regimens have been studied. 60 or 80 mg/m2 IV for 5 days every 3 weeks or 60 mg/m2 IV on days 2 to 4 in combination with CAV have been studied. In a randomized, phase III trial in 140 patients with limited disease (LD)- or extensive disease (ED)-small cell lung cancer (SCLC), the median overall survival (OS) time was nonsignificantly lower in patients who received cyclophosphamide, doxorubicin, and vincristine (CAV) plus teniposide 60 mg/m2 IV on days 2 to 4 (CAV-T) (10 months; range, 0.2 to 68.2 months) compared with CAV plus etoposide (CAV-E) (12 months; range, 0.6 to 62.5 months). More grade 3 and 4 hematologic (27% vs 20%) and gastrointestinal (15% vs 11%) toxicity was reported with CAV-T compared with CAV-E; additionally, death due to myelosuppression was reported in 5 patients and 1 patient in the CAV-T and CAV-E arms, respectively. In a 3-arm, randomized study in 135 patients with ED-SCLC, the overall response rate (ORR) was significantly lower with single-agent teniposide (60 mg/m2/day IV on days 1 to 5 repeated every 3 weeks) compared with cyclophosphamide, etoposide, and cisplatin (43% vs 56%; p = 0.02). In a randomized trial in 94 elderly patients with previously untreated LD- or ED-SCLC, the ORR (71% vs 65%) and median OS time (11.5 vs 8.5 months) were not significantly different with teniposide 80 mg/m2 IV on days 1 to 5 repeated every 3 weeks compared with etoposide; however, hematologic toxicity was more common in patients who received teniposide.

†Indicates off-label use

Specific guidelines for dosage adjustments in hepatic impairment are not available; dose adjustments may be necessary for patients with significant hepatic impairment.

Specific guidelines for dosage adjustments in renal impairment are not available; dose adjustments may be necessary for patients with significant renal impairment.

Acetaminophen; Ibuprofen: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Amlodipine; Celecoxib: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Apalutamide: (Moderate) Monitor patients for reduced efficacy of teniposide if coadministration with apalutamide is necessary. Teniposide is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Coadministration with other strong CYP3A4 inducers reduced plasma concentrations of teniposide.
Aprepitant, Fosaprepitant: (Moderate) Use caution if teniposide and aprepitant, fosaprepitant are used concurrently and monitor for an increase in teniposide-related adverse effects for several days after administration of a multi-day aprepitant regimen. Teniposide is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of teniposide. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Atazanavir: (Major) The plasma concentrations of teniposide may be significantly elevated when administered concurrently with atazanavir. Clinical monitoring for adverse effects, such as myelosuppression, is recommended during coadministration. Atazanavir is an inhibitor of CYP3A4. Teniposide is a CYP3A4 substrate.
Atazanavir; Cobicistat: (Major) The plasma concentrations of teniposide may be significantly elevated when administered concurrently with atazanavir. Clinical monitoring for adverse effects, such as myelosuppression, is recommended during coadministration. Atazanavir is an inhibitor of CYP3A4. Teniposide is a CYP3A4 substrate. (Major) The plasma concentrations of teniposide may be significantly elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as myelosuppression, is recommended during coadministration. Cobicistat is a CYP3A4 and P-glycoprotein (P-gp) inhibitor, while teniposide is a CYP3A4 and P-gp substrate.
Bupivacaine; Meloxicam: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Carbamazepine: (Moderate) Monitor for reduced teniposide efficacy if coadministration with carbamazepine is necessary; the concomitant use of teniposide and carbamazepine may increase the clearance of teniposide resulting in reduced teniposide efficacy. Teniposide is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration of teniposide and enzyme-inducing antiepileptic drugs resulted in teniposide clearance values that were 2- to 3-times higher than values with teniposide alone.
Carvedilol: (Moderate) Increased concentrations of teniposide may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and teniposide is a P-gp substrate.
Celecoxib: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Celecoxib; Tramadol: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Cobicistat: (Major) The plasma concentrations of teniposide may be significantly elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as myelosuppression, is recommended during coadministration. Cobicistat is a CYP3A4 and P-glycoprotein (P-gp) inhibitor, while teniposide is a CYP3A4 and P-gp substrate.
Codeine; Phenylephrine; Promethazine: (Moderate) Acute central nervous system (CNS) depression, hypotension, and metabolic acidosis have been observed in patients receiving investigational infusions of high-dose teniposide who were pretreated with antiemetics with CNS-depressant activities (e.g., phenothiazine and related antiemetics). The depressant effects of the antiemetic agents and the alcohol content of the teniposide formulation may place patients receiving higher than recommended doses of teniposide at risk for central nervous system depression.
Codeine; Promethazine: (Moderate) Acute central nervous system (CNS) depression, hypotension, and metabolic acidosis have been observed in patients receiving investigational infusions of high-dose teniposide who were pretreated with antiemetics with CNS-depressant activities (e.g., phenothiazine and related antiemetics). The depressant effects of the antiemetic agents and the alcohol content of the teniposide formulation may place patients receiving higher than recommended doses of teniposide at risk for central nervous system depression.
Conivaptan: (Major) Avoid coadministration of conivaptan, a CYP3A4/P-glycoprotein (P-gp) inhibitor and teniposide, a CYP3A4/P-gp substrate. Concurrent use may result in elevated teniposide serum concentrations. According to the manufacturer, concomitant use of conivaptan, a strong CYP3A4 inhibitor, and CYP3A substrates, such as teniposide, should be avoided. Coadministration of conivaptan with other CYP3A substrates has resulted in increased mean AUC values (2 to 3 times). Theoretically, similar pharmacokinetic effects could be seen with teniposide. Treatment with teniposide may be initiated no sooner than 1 week after completion of conivaptan therapy.
Cyclizine: (Moderate) Acute central nervous system (CNS) depression, hypotension, and metabolic acidosis have been observed in patients receiving investigational infusions of high-dose teniposide who were pretreated with antiemetics with CNS-depressant activities (e.g., phenothiazine and related antiemetics). The depressant effects of the antiemetic agents and the alcohol content of the teniposide formulation may place patients receiving higher than recommended doses of teniposide at risk for central nervous system depression.
Cyclosporine: (Minor) Concurrent use of teniposide or etoposide with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Daclatasvir: (Moderate) Systemic exposure of teniposide, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of teniposide; monitor patients for potential adverse effects.
Darunavir: (Major) The plasma concentrations of teniposide may be significantly elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects, such as myelosuppression, is recommended during coadministration. Darunavir is an inhibitor of CYP3A4. Teniposide is a CYP3A4 substrate.
Darunavir; Cobicistat: (Major) The plasma concentrations of teniposide may be significantly elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as myelosuppression, is recommended during coadministration. Cobicistat is a CYP3A4 and P-glycoprotein (P-gp) inhibitor, while teniposide is a CYP3A4 and P-gp substrate. (Major) The plasma concentrations of teniposide may be significantly elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects, such as myelosuppression, is recommended during coadministration. Darunavir is an inhibitor of CYP3A4. Teniposide is a CYP3A4 substrate.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) The plasma concentrations of teniposide may be significantly elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as myelosuppression, is recommended during coadministration. Cobicistat is a CYP3A4 and P-glycoprotein (P-gp) inhibitor, while teniposide is a CYP3A4 and P-gp substrate. (Major) The plasma concentrations of teniposide may be significantly elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects, such as myelosuppression, is recommended during coadministration. Darunavir is an inhibitor of CYP3A4. Teniposide is a CYP3A4 substrate.
Dichlorphenamide: (Moderate) Use dichlorphenamide and teniposide together with caution. Metabolic acidosis is associated with the use of dichlorphenamide and has been reported with teniposide in patients who received higher than recommended doses. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Diclofenac: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Diclofenac; Misoprostol: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Diflunisal: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Dimenhydrinate: (Moderate) Acute central nervous system (CNS) depression, hypotension, and metabolic acidosis have been observed in patients receiving investigational infusions of high-dose teniposide who were pretreated with antiemetics with CNS-depressant activities (e.g., phenothiazine and related antiemetics). The depressant effects of the antiemetic agents and the alcohol content of the teniposide formulation may place patients receiving higher than recommended doses of teniposide at risk for central nervous system depression.
Diphenhydramine; Ibuprofen: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Diphenhydramine; Naproxen: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Dronabinol: (Moderate) Acute central nervous system (CNS) depression, hypotension, and metabolic acidosis have been observed in patients receiving investigational infusions of high-dose teniposide who were pretreated with antiemetics with CNS-depressant activities (e.g., phenothiazine and related antiemetics). The depressant effects of the antiemetic agents and the alcohol content of the teniposide formulation may place patients receiving higher than recommended doses of teniposide at risk for central nervous system depression.
Dronedarone: (Moderate) Dronedarone is metabolized by and is an inhibitor of CYP3A; dronedarone also inhibits P-gp. Teniposide is a substrate for CYP3A4 and P-gp. Coadministration of dronedarone with CYP3A4 and P-gp substrates may result in increased exposure of the substrate and should, therefore, be undertaken with caution.
Droperidol: (Moderate) Acute central nervous system (CNS) depression, hypotension, and metabolic acidosis have been observed in patients receiving investigational infusions of high-dose teniposide who were pretreated with antiemetics with CNS-depressant activities (e.g., phenothiazine and related antiemetics). The depressant effects of the antiemetic agents and the alcohol content of the teniposide formulation may place patients receiving higher than recommended doses of teniposide at risk for central nervous system depression.
Elbasvir; Grazoprevir: (Moderate) Administering teniposide with elbasvir; grazoprevir may result in elevated teniposide plasma concentrations. Teniposide is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Eliglustat: (Major) Coadministration of teniposide and eliglustat may result in increased plasma concentrations of teniposide. If coadministration is necessary, use caution and monitor closely. Teniposide is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) The plasma concentrations of teniposide may be significantly elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as myelosuppression, is recommended during coadministration. Cobicistat is a CYP3A4 and P-glycoprotein (P-gp) inhibitor, while teniposide is a CYP3A4 and P-gp substrate.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) The plasma concentrations of teniposide may be significantly elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as myelosuppression, is recommended during coadministration. Cobicistat is a CYP3A4 and P-glycoprotein (P-gp) inhibitor, while teniposide is a CYP3A4 and P-gp substrate.
Enzalutamide: (Moderate) Monitor patients for reduced efficacy of teniposide if coadministration with enzalutamide is necessary. Teniposide is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Coadministration with other strong CYP3A4 inducers reduced plasma concentrations of teniposide.
Etodolac: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Etravirine: (Moderate) Etravirine is a CYP3A4 inducer/substrate and a P-glycoprotein (PGP) inhibitor and teniposide is a CYP3A4 and PGP substrate. Caution is warranted if these drugs are coadministered.
Fenoprofen: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Flurbiprofen: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Fosamprenavir: (Major) Concomitant use of teniposide and fosamprenavir may result in altered teniposide plasma concentrations. Teniposide is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is an inducer of P-gp and a potent inhibitor and moderate inducer of CYP3A4.
Fosphenytoin: (Moderate) Monitor for reduced teniposide efficacy if coadministration with fosphenytoin is necessary; the concomitant use of teniposide and fosphenytoin may increase the clearance of teniposide resulting in reduced teniposide efficacy. Teniposide is a CYP3A4 substrate. Fosphenytoin is converted to phenytoin in vivo; phenytoin is a strong CYP3A4 inducer. Coadministration of teniposide and enzyme-inducing antiepileptic drugs resulted in teniposide clearance values that were 2- to 3-times higher than values with teniposide alone.
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and teniposide as coadministration may increase serum concentrations of teniposide and increase the risk of adverse effects. Teniposide is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and teniposide as coadministration may increase serum concentrations of teniposide and increase the risk of adverse effects. Teniposide is a substrate of P-glycoprotein (P-gp); pibrentasvir is a P-gp inhibitor.
Hydrocodone; Ibuprofen: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Ibuprofen: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Ibuprofen; Famotidine: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Ibuprofen; Oxycodone: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Ibuprofen; Pseudoephedrine: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with teniposide, a CYP3A substrate, as teniposide toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Indomethacin: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Isavuconazonium: (Major) Concomitant use of isavuconazonium with teniposide may result in increased serum concentrations of teniposide. Teniposide is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring for adverse effects, such as myelosuppression, are advised if these drugs are used together.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Monitor patients for reduced efficacy of teniposide if coadministration with rifampin is necessary. Teniposide is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with other strong CYP3A4 inducers reduced plasma concentrations of teniposide.
Isoniazid, INH; Rifampin: (Moderate) Monitor patients for reduced efficacy of teniposide if coadministration with rifampin is necessary. Teniposide is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with other strong CYP3A4 inducers reduced plasma concentrations of teniposide.
Ketoprofen: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Ketorolac: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Ledipasvir; Sofosbuvir: (Major) Caution and close monitoring of teniposide-associated adverse reactions is advised with concomitant administration of ledipasvir. Teniposide is a substrate of the drug transporter P-glycoprotein (P-gp); ledipasvir is a P-gp inhibitor. Taking these drugs together may increase teniposide plasma concentrations.
Lopinavir; Ritonavir: (Moderate) Concurrent administration of teniposide with ritonavir may result in elevated teniposide plasma concentrations. Teniposide is a substrate for CYP3A4 and P-glycoprotein (P-gp); ritonavir inhibits both CYP3A44 and P-gp. Caution and close monitoring are advised if these drugs are administered together.
Lumacaftor; Ivacaftor: (Moderate) Monitor patients for reduced efficacy of teniposide if coadministration with lumacaftor; ivacaftor is necessary. Teniposide is a CYP3A4 substrate and lumacaftor; ivacaftor is a strong CYP3A4 inducer. Coadministration with other strong CYP3A4 inducers reduced plasma concentrations of teniposide.
Meclizine: (Moderate) Acute central nervous system (CNS) depression, hypotension, and metabolic acidosis have been observed in patients receiving investigational infusions of high-dose teniposide who were pretreated with antiemetics with CNS-depressant activities (e.g., phenothiazine and related antiemetics). The depressant effects of the antiemetic agents and the alcohol content of the teniposide formulation may place patients receiving higher than recommended doses of teniposide at risk for central nervous system depression.
Meclofenamate Sodium: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Mefenamic Acid: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Meloxicam: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Methotrexate: (Moderate) Use methotrexate and teniposide together with caution; increased methotrexate levels and increased methotrexate toxicity may occur. The plasma clearance of methotrexate was slightly increased when these agents were co-administered in a pharmacokinetic study. Additionally, increased intracellular methotrexate levels were observed in vitro in the presence of teniposide.
Mitotane: (Moderate) Monitor patients for reduced efficacy of teniposide if coadministration with mitotane is necessary. Teniposide is a CYP3A4 substrate and mitotane is a strong CYP3A4 inducer. Coadministration with other strong CYP3A4 inducers reduced plasma concentrations of teniposide.
Nabumetone: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Naproxen: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Naproxen; Esomeprazole: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Naproxen; Pseudoephedrine: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Nilotinib: (Major) Concomitant use of nilotinib, a substrate and inhibitor of CYP3A4 and P-glycoprotein (P-gp), and teniposide, a P-gp and CYP3A4 substrate with a narrow therapeutic range, may result in increased teniposide levels. A teniposide dose reduction may be necessary if these drugs are used together.
Nirmatrelvir; Ritonavir: (Moderate) Concurrent administration of teniposide with ritonavir may result in elevated teniposide plasma concentrations. Teniposide is a substrate for CYP3A4 and P-glycoprotein (P-gp); ritonavir inhibits both CYP3A44 and P-gp. Caution and close monitoring are advised if these drugs are administered together.
Nonsteroidal antiinflammatory drugs: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Oritavancin: (Moderate) Teniposide is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of teniposide may be reduced if these drugs are administered concurrently.
Oxaprozin: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Pazopanib: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and teniposide, a CYP3A4 substrate, may cause an increase in systemic concentrations of teniposide. Use caution when administering these drugs concomitantly.
Phenobarbital: (Moderate) Monitor for reduced teniposide efficacy if coadministration with phenobarbital is necessary; the concomitant use of teniposide and phenobarbital may increase the clearance of teniposide resulting in reduced teniposide efficacy. Teniposide is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer. Coadministration of teniposide and enzyme-inducing antiepileptic drugs resulted in teniposide clearance values that were 2- to 3-times higher than values with teniposide alone.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Monitor for reduced teniposide efficacy if coadministration with phenobarbital is necessary; the concomitant use of teniposide and phenobarbital may increase the clearance of teniposide resulting in reduced teniposide efficacy. Teniposide is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer. Coadministration of teniposide and enzyme-inducing antiepileptic drugs resulted in teniposide clearance values that were 2- to 3-times higher than values with teniposide alone.
Phenytoin: (Moderate) Monitor for reduced teniposide efficacy if coadministration with phenytoin is necessary; the concomitant use of teniposide and phenytoin may increase the clearance of teniposide resulting in reduced teniposide efficacy. Teniposide is a CYP3A4 substrate and phenytoin is a strong CYP3A4 inducer. Coadministration of teniposide and enzyme-inducing antiepileptic drugs resulted in teniposide clearance values that were 2- to 3-times higher than values with teniposide alone.
Piroxicam: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Posaconazole: (Major) Posaconazole and teniposide should be coadministered with caution due to an increased potential for adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of teniposide. Further, both teniposide and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and teniposide, ultimately resulting in an increased risk of adverse events.
Primidone: (Moderate) Monitor for reduced teniposide efficacy if coadministration with primidone is necessary; the concomitant use of teniposide and primidone may increase the clearance of teniposide resulting in reduced teniposide efficacy. Teniposide is a CYP3A4 substrate and primidone is metabolized to phenobarbital, a strong CYP3A4 inducer. Coadministration of teniposide and enzyme-inducing antiepileptic drugs resulted in teniposide clearance values that were 2- to 3-times higher than values with teniposide alone.
Prochlorperazine: (Moderate) Acute central nervous system (CNS) depression, hypotension, and metabolic acidosis have been observed in patients receiving investigational infusions of high-dose teniposide who were pretreated with antiemetics with CNS-depressant activities (e.g., phenothiazine and related antiemetics). The depressant effects of the antiemetic agents and the alcohol content of the teniposide formulation may place patients receiving higher than recommended doses of teniposide at risk for central nervous system depression.
Promethazine: (Moderate) Acute central nervous system (CNS) depression, hypotension, and metabolic acidosis have been observed in patients receiving investigational infusions of high-dose teniposide who were pretreated with antiemetics with CNS-depressant activities (e.g., phenothiazine and related antiemetics). The depressant effects of the antiemetic agents and the alcohol content of the teniposide formulation may place patients receiving higher than recommended doses of teniposide at risk for central nervous system depression.
Promethazine; Dextromethorphan: (Moderate) Acute central nervous system (CNS) depression, hypotension, and metabolic acidosis have been observed in patients receiving investigational infusions of high-dose teniposide who were pretreated with antiemetics with CNS-depressant activities (e.g., phenothiazine and related antiemetics). The depressant effects of the antiemetic agents and the alcohol content of the teniposide formulation may place patients receiving higher than recommended doses of teniposide at risk for central nervous system depression.
Promethazine; Phenylephrine: (Moderate) Acute central nervous system (CNS) depression, hypotension, and metabolic acidosis have been observed in patients receiving investigational infusions of high-dose teniposide who were pretreated with antiemetics with CNS-depressant activities (e.g., phenothiazine and related antiemetics). The depressant effects of the antiemetic agents and the alcohol content of the teniposide formulation may place patients receiving higher than recommended doses of teniposide at risk for central nervous system depression.
Rifampin: (Moderate) Monitor patients for reduced efficacy of teniposide if coadministration with rifampin is necessary. Teniposide is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with other strong CYP3A4 inducers reduced plasma concentrations of teniposide.
Rifapentine: (Moderate) Monitor patients for reduced efficacy of teniposide if coadministration with rifapentine is necessary. Teniposide is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with other strong CYP3A4 inducers reduced plasma concentrations of teniposide.
Ritonavir: (Moderate) Concurrent administration of teniposide with ritonavir may result in elevated teniposide plasma concentrations. Teniposide is a substrate for CYP3A4 and P-glycoprotein (P-gp); ritonavir inhibits both CYP3A44 and P-gp. Caution and close monitoring are advised if these drugs are administered together.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Plasma concentrations of teniposide, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with voxilaprevir, a P-gp inhibitor. Monitor patients for increased side effects if these drugs are administered concurrently.
St. John's Wort, Hypericum perforatum: (Moderate) Monitor patients for reduced efficacy of teniposide if coadministration with St. John's Wort is necessary. Teniposide is a CYP3A4 substrate and St. John's Wort is a strong CYP3A4 inducer. Coadministration with other strong CYP3A4 inducers reduced plasma concentrations of teniposide.
Sulindac: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Sumatriptan; Naproxen: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Tolbutamide: (Moderate) Use tolbutamide and teniposide together with caution; increased teniposide levels and increased teniposide toxicity may occur. Teniposide is highly protein bound. In a study, therapeutically relevant concentrations of tolbutamide displaced protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Tolmetin: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Trimethobenzamide: (Moderate) Acute central nervous system (CNS) depression, hypotension, and metabolic acidosis have been observed in patients receiving investigational infusions of high-dose teniposide who were pretreated with antiemetics with CNS-depressant activities (e.g., phenothiazine and related antiemetics). The depressant effects of the antiemetic agents and the alcohol content of the teniposide formulation may place patients receiving higher than recommended doses of teniposide at risk for central nervous system depression.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Valdecoxib: (Major) Dose-limiting bone marrow suppression is the most significant toxicity associated with teniposide, and may include thrombocytopenia. An additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Salicylates also displace protein-bound teniposide in fresh human serum to a small but significant extent. Because of the extremely high binding of teniposide to plasma proteins, these small decreases in binding could cause substantial increases in plasma free drug concentrations that could result in potentiation of teniposide toxicity, including bone marrow suppression.
Vemurafenib: (Major) Concomitant use of vemurafenib and teniposide may result in altered concentrations of teniposide. Vemurafenib is an inhibitor of P-glycoprotein (PGP) and an inducer of CYP3A4. Teniposide is a substrate of PGP and CYP3A4. Use caution and monitor patients for toxicity and efficacy.
Vincristine Liposomal: (Moderate) Use teniposide and vincristine together with caution; neurotoxicity including cases of severe neuropathy have been reported.
Vincristine: (Moderate) Use teniposide and vincristine together with caution; neurotoxicity including cases of severe neuropathy have been reported.
Zonisamide: (Minor) Zonisamide is a weak inhibitor of P-glycoprotein (P-gp), and teniposide is a substrate of P-gp. There is theoretical potential for zonisamide to affect the pharmacokinetics of drugs that are P-gp substrates. Use caution when starting or stopping zonisamide or changing the zonisamide dosage in patients also receiving drugs which are P-gp substrates.

Teniposide/Vumon Intravenous Inj Sol: 1mL, 10mg

Less than 21 years: 250 mg/m2 IV per week or 165 mg/m2 IV twice weekly.21 years and older: Safety and efficacy not established.

Safety and efficacy not established.

250 mg/m2 IV per week or 165 mg/m2 IV twice weekly.

250 mg/m2 IV per week or 165 mg/m2 IV twice weekly.

250 mg/m2 IV per week or 165 mg/m2 IV twice weekly.

Mechanism of Action: Teniposide is active during the G2-phase of the cell cycle. Teniposide binds to a complex of DNA and topoisomerase II. Topoisomerase II is an enzyme that coils and uncoils DNA and also examines and repairs damaged pieces of DNA. When DNA and topoisomerase II are bound together, teniposide will stabilize this complex and prevent further progression in the cell cycle. DNA strand breaks develop, causing cell death.Although fluoroquinolone antibiotics also interact with topoisomerase enzymes, bactericidal concentrations do not affect the human enzyme.

Teniposide is administered intravenously. It is highly bound to plasma proteins (greater than 99%). Steady-state volume of distribution (Vd) increases with a decrease in plasma albumin levels. The mean steady-state Vd of teniposide ranges from 8 to 44 L/m2 in adults. The blood-brain barrier may limit diffusion of teniposide into the cerebral spinal fluid (CSF). Teniposide levels in saliva, CSF, and malignant ascites are lower relative to plasma levels. Renal clearance of the parent drug accounts for about 10% of total body clearance. Following a radiolabeled teniposide dose of 10 mg/kg or 67 mg/m2 IV, 44% of the dose was recovered in urine (parent drug, 4% to 12%) within 120 hours and 0% to 10% of the dose was excreted in feces within 72 hours.
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, P-gp
Teniposide is a substrate for CYP3A4 isoenzymes and P-glycoprotein (P-gp).

Plasma levels increased linearly following teniposide IV doses of 100 to 333 mg/m2 per day in adults. There was no drug accumulation in these patients after 3 days of teniposide administration.

Teniposide is classified by the FDA as pregnancy category D; it may cause fetal harm if administered during pregnancy. Females of reproductive potential should avoid becoming pregnant during teniposide therapy. Advice women who become pregnant during therapy of the potential hazard to the fetus. Major anomalies included spinal and rib defects, deformed extremities, anophthalmia, and celosomia were observed in the offspring of pregnant rats who received teniposide IV doses of 0.1 to 3 mg/kg (0.6 to 18 mg/m2) every second day from day 6 to day 16 post coitum.[60884]

It is not known if teniposide is secreted in human milk. Because there is a potential for adverse reactions in nursing infants from teniposide, a decision should be made to either discontinue breast-feeding or to discontinue teniposide, taking into account the importance of teniposide therapy to the mother.[60884]