:
VM-26, PTG
VUMON(r)
:
Miscellaneous
Special pediatric considerations are noted when applicable, otherwise adult provisions apply.
:
[1]
Podophyllin resin derivatives have been used as medicaments for over 250 years. In 1861 Bentley reported cytotoxic activity for podophyllin, which in a later report (1942) was useful as a topical solution in oil for treating condyloma acuminatum. Teniposide is a semisynthetic podophyllotoxin derived from the root of Podophyllum peltatum (the May apple or mandrake). It is known to cause single-strand breaks in DNA. Teniposide also causes DNA damage through inhibition of the enzyme topoisomerase II and activation of oxidation-reduction reactions to produce derivatives that bind directly to DNA. Topoisomerase II carries out breakage and reunion reactions of DNA which are necessary for normal cellular function. Teniposide is cell cycle phase-specific with predominant activity occurring in late S phase and G2.
:
[2,3,4,5,6,7,8,9,10,11,12,13]
| Oral Absorption | not studied | |
| Distribution | high concentrations in liver, kidneys, small intestines and adrenals; found in ascitic fluid | |
| cross blood brain barrier? | yes (CSF: plasma ratio 1-3%) | |
| Vd | 28.45% of body weight adults: 7.5-30 L/m 2 children: 3-10 L/m 2 | |
| PPB | 99.4% | |
| Metabolism | primary route of elimination is by hepatic metabolism (86%) | |
| active metabolite(s) | yes | |
| inactive metabolite(s) | yes | |
| Excretion | 0-10% excreted in feces within 3 days | |
| urine | 44.5% within 72 hours, 21.3% unchanged | |
| t1/2 a | 45 minutes | |
| t1/2 b | 2.8-4 hours | |
| t1/2 g | 6.1-21.2 hours | |
| Cl | 7-17 mL/min/m 2 | |
:
[1,7]
Acute lymphocytic leukemia Neuroblastoma
Non-Hodgkin's lymphoma
Less frequent uses include: Hodgkin's disease Lung cancer, small cell Retinoblastoma Health Protection Branch approved indication.
:
[7]
Teniposide is contraindicated in patients who have a history of severe hypersensitivity reactions to teniposide or other drugs formulated in Cremophor EL (polyethoxylated castor oil). Animal studies have shown that teniposide is potentially carcinogenic. Its safe use in pregnancy and its effect on fertility have not been established. Breast feeding is not recommended due to the potential secretion into breast milk.
:
[7,14,15,16,17,18]
| ORGAN SITE | SIDE EFFECT | ONSET | |||
| cardiovascular | hypotension (with rapid IV infusion, rare if given over >= 30 minutes) | I | |||
| dermatologic | alopecia (31%, mild) | E | |||
| extravasation hazard (refer to Appendix 2) | IRRITANT | I | |||
| gastrointestinal | nausea and vomiting (4-11%, mild) | I | |||
| diarrhea (1%) | E | ||||
| anorexia (1%) | E | ||||
| stomatitis (3%, dose-limiting with 72 hour continuous infusion) | E | ||||
| hematologic | myelosuppression nadir 5-14 days, recovery 22-28 days | E | |||
| hepatic | elevated liver function tests (2%) | E | |||
| hypersensitivity | Type I (anaphylactoid), (5% overall, 15% neuroblastoma) | I | |||
| Type II (hemolytic anemia, rare) | I | ||||
| injection site | chemical phlebitis | I | |||
| neoplastic | acute myelogenous leukemia | L | |||
| ORGAN SITE | SIDE EFFECT | ONSET | |||
| neurologic | peripheral neuropathy (rare, more common and severe with previous vincristine) | E | |||
| renal/metabolic | nephrotoxicity (2%) | E | |||
Dose-limiting side effects are underlined. I = immediate (onset in hours to days); E = early (days to weeks); D = delayed (weeks to months); L = late (months to years) The incidence of Type 1 hypersensitivity reactions varies from 2-11%. No fatalities have been reported but hypotension and bronchospasm can occur with the first dose. There is a significant risk of hypersensitivity reactions in children treated with epipodophyllotoxins. One investigator reported a frequency of 3.6-6.5% with teniposide. Teniposide appears to cause more reactions than etoposide, possibly due to the presence of the surfactant Cremophor EL in the teniposide preparation. The most common symptoms of hypersensitivity have been flushing and chills. More severe reactions may produce bronchospasm, cyanosis and/or hypotension. Other symptoms described include urticaria, chest pain, sweating and pallor. Most symptoms can be relieved by discontinuing the teniposide infusion and administering an antihistamine. Pretreatment with an antihistamine and a corticosteroid may allow those patients who have reacted to tolerate a rechallenge. The use of teniposide in children has been associated with the development of secondary acute myelogenous leukemia (AML). This secondary AML typically presents 2 to 4 years after the primary diagnosis of acute lymphocytic leukemia or other malignancies in children treated with epipodophyllotoxins. The risk for development of secondary AML is approximately 6% and appears to be related to treatment frequency; once weekly or twice weekly dosing schedules show a higher risk than doses given less frequently.
:
[19]
| AGENT | EFFECT | MECHANISM | MANAGEMENT |
| phenytoin, phenobarbital | increased teniposide clearance by 2 to 3 fold, possibly resulting in decreased antineoplastic effect | possibly by induction of hepatic microsomal enzyme oxidation system | higher doses of teniposide may be required |
:
[9,20,21,22,23,24]
For basic information on solution preparation and compatibility, see Chemotherapy Chart in Appendix.
:
[7,25]
| BCCA administration guideline noted in bold, italics | |
| Subcutaneous | not used due to corrosive nature |
| Intramuscular | not used due to corrosive nature |
| Direct intravenous | not recommended, hypotension |
| Intermittent infusion | Start infusion slowly and stay with the patient for the first 10 minutes to observe for reactions. 0.2 mg/mL in D5W or NS over 30-60 minutes. In children, dilute to 1 mg/mL (D5W or NS) and infuse over 30-45 minutes. |
| Continuous infusion | in appropriate volume usually 3-5 days |
| Intraperitoneal | investigational, late peritonitis |
| Intrapleural | not recommended, avoid extravasation |
| Intrathecal | no information available on this route |
| Intra-arterial | no information available on this route |
| Intravesical | investigational, severe chemical cystitis |
:
[7,10,11,25,26,27]
Refer to protocol by which patient is being treated. Numerous dosing schedules exist and depend on disease, response and concomitant therapy. Guidelines for dosing also include consideration of white blood cell count. Dosage may be reduced and/or delayed in patients with bone marrow depression due to cytotoxic/radiation therapy.
Adults: Intravenous: twice weekly (biw): 150-200 mg/m2 q1w: 50-180 mg/m2 q3w: 100 mg/m2 q3w: 45-160 mg/m2/day x 2-5 days q4w: 30 mg/m2/day x 5-10 days 300-750 mg/m2 over 72 hours
Dosage in myelosuppression:
modify according to protocol by which patient is being treated; if no guidelines
available, refer to Appendix 6 "Dosage Modification for Myelosuppression"
Dosage in renal failure:
adjustment required, no details found
Dosage in hepatic failure: Bilirubin umol/L % usual dose
25-51 50% >51 25% Children: q7-10w: 150-165 mg/m2/dose twice weekly (biw)
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