Teniposide (Systemic)


VA CLASSIFICATION
Primary: AN900

Commonly used brand name(s): Vumon.

Another commonly used name is
VM-26.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antineoplastic—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Leukemia, acute lymphocytic (treatment)—Teniposide is indicated, in combination with other approved anticancer agents, for induction therapy of refractory childhood acute lymphocytic (lymphoblastic) leukemia.{01}

[Lymphoma, non-Hodgkin's (treatment)]—Teniposide is indicated as a single agent or in combination for therapy of refractory non-Hodgkin's lymphoma.{02}

[Neuroblastoma (treatment)]—Teniposide is indicated as a single agent or in combination for therapy of refractory neuroblastoma.{02}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Source—
    Semisynthetic derivative of podophyllotoxin{01}{02}{03}

Chemical group—
    Podophyllotoxin{01}
Molecular weight—
    656.66{01}{03}


pH
    Approximately 5 (adjusted with maleic acid){01}


Other characteristics
    Lipophilic{01}

Solubility
    Insoluble in water and ether; slightly soluble in methanol and very soluble in acetone and dimethylformamide{01}

Partition coefficient
    Octanol/water: Approximately 100{01}

Mechanism of action/Effect:

Teniposide is a topoisomerase II inhibitor. Topoisomerase II creates and reseals double-stranded DNA breaks and is therefore likely to be involved in DNA replication and repair. Teniposide is able to to induce the stabilization of a DNA-topoisomerase II complex such that the strand-rejoining activity of the enzyme is impaired.{03}

Teniposide acts at the premitotic stage of cell division to prevent cells from entering mitosis by causing dose-dependent single- and double-stranded breaks in DNA and DNA-protein cross-links. It does not intercalate into or bind strongly to DNA. It is cell phase–specific, acting in the late S or early G2 phase of cell division.{01}{03}

Distribution:

Limited, probably because of very high plasma protein binding. Mean steady-state volumes of distribution range from 8 to 44 liters per square meter of body surface area (L/m 2) in adults and 3 to 11 L/m2 in children. The steady-state volume of distribution is inversely related to plasma albumin concentrations. Teniposide crosses the blood-brain barrier to only a limited extent, although one study found higher concentrations of teniposide in the cerebrospinal fluid (CSF) of patients with brain tumors than in the CSF of patients who did not have brain tumors. Concentrations in saliva, CSF, and malignant ascites fluid are low compared to simultaneous plasma concentrations.{01}

Protein binding:

Very high (greater than 99%).{01}

Half-life:


Terminal:

5 hours.{01}

Note: Plasma teniposide concentrations decline biexponentially following intravenous infusion.{01}



Peak plasma concentration

Greater than 40 micrograms per mL (mcg/mL) after intravenous infusions of 137 to 203 mg per square meter of body surface area over a period of 1 to 2 hours in pediatric patients. Concentrations generally declined to less than 2 mcg/mL by 20 to 24 hours after the infusion.{01}

Elimination:
    Renal, 4 to 12% of a dose as unchanged teniposide. In a study of tritium-labeled teniposide in adults, 44% of the radiolabel (parent compound and metabolites) was recovered in urine within 120 hours after dosing.{01}
    Fecal, 0 to 10% of a dose.{01}


Precautions to Consider

Carcinogenicity

Children with acute lymphocytic leukemia (ALL) in remission who were given maintenance therapy with teniposide once or twice a week (in combination with other antineoplastics) were found to have an approximately twelvefold increase in relative risk of developing secondary acute nonlymphocytic leukemia (ANLL), compared to patients treated with less intensive schedules.{01}

No association was found between a short course of teniposide for induction of remission or consolidation and an increased risk of secondary ANLL, but the number of patients studied was small.{01}

Studies in animals have not been done.{01}

Mutagenicity

Teniposide has been found to be mutagenic in bacterial and mammalian tests including Ames/Salmonella and B. subtilis bacterial mutagenicity assays. It caused gene mutations in both Chinese hamster ovary cells and mouse lymphoma cells and DNA damage (as measured by alkaline elution) in human lung carcinoma–derived cell lines. Teniposide also caused aberrations in chromosome structure in primary cultures of human lymphocytes in vitro and in L5178y/TK +/- mouse lymphoma cells in vitro. Chromosome aberrations were observed in vivo in the embryonic tissue of pregnant Swiss albino mice. Teniposide also caused a dose-related increase in sister chromatid exchanges in Chinese hamster ovary cells.{01}

Pregnancy/Reproduction

Pregnancy—
Adequate and well-controlled studies in humans have not been done.{01}Use in pregnancy is not recommended.{02}

In general, it is recommended that women of childbearing age be advised to avoid becoming pregnant during therapy with teniposide. If a woman becomes pregnant during treatment with teniposide, it is recommended that she be informed of the potential risk to the fetus.{01}

Intravenous administration of teniposide to pregnant rats in doses between 1 and 3 mg per kg of body weight (mg/kg) per day on alternate days from day 6 to day 16 post coitum (during organogenesis) caused retarded embryonic development, prenatal mortality, and teratogenicity (including spinal and rib defects, deformed extremities, anophthalmia, and celosomia).{01}

FDA Pregnancy Category D.{01}

Breast-feeding

It is not known whether teniposide is distributed into breast milk. However, it is recommended that any decision regarding breast-feeding during teniposide therapy should take into account the potential risk to the infant.{01}

Pediatrics

Children with Down syndrome may be more sensitive to the effects of this medicine compared to other children.{01}


Geriatrics


One case of sudden death attributed to probable arrhythmia and intractable hypotension has been reported in an elderly patient treated with teniposide for a nonleukemic malignancy.{01}


Dental

The bone marrow depressant effects of teniposide may result in an increased incidence of microbial infection, delayed healing, and gingival bleeding. Dental work, whenever possible, should be completed prior to initiation of therapy or deferred until blood counts have returned to normal. Patients should be instructed in proper oral hygiene, including caution in use of regular toothbrushes, dental floss, and toothpicks.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Antiemetics    (the risk of acute central nervous system depression and hypotension may be increased during concurrent use, especially with higher-than-recommended doses of teniposide, probably because of the depressant effects of both the antiemetic and the alcohol present in the teniposide injection{01})


» Blood dyscrasia–causing medications (see Appendix II )    (leukopenic and/or thrombocytopenic effects of teniposide may be increased with concurrent or recent therapy if these medications cause the same effects; dosage adjustment of teniposide, if necessary, should be based on blood counts )


» Bone marrow depressants, other (see Appendix II) or
» Radiation therapy    (additive bone marrow depression, including severe dermatitis and/or mucositis, may occur; dosage reduction may be required when two or more bone marrow depressants, including radiation, are used concurrently or consecutively)


Methotrexate    (concurrent use with teniposide may slightly increase the plasma clearance of methotrexate; an increase in intracellular concentrations of methotrexate has been observed in the presence of teniposide in vitro{01})


Phenobarbital or
Phenytoin    (decreased teniposide effectiveness due to increased clearance{04})


» Sodium salicylate or
» Sulfamethizole or
» Tolbutamide    (therapeutic concentrations of sodium salicylate, sulfamethizole, or tolbutamide have been shown to cause small but significant displacement of teniposide from plasma protein binding sites, which could lead to substantial increases in free plasma teniposide concentrations and, possibly, increased toxicity{01})


Vaccines, killed virus    (because normal defense mechanisms may be suppressed by teniposide therapy, the patient's antibody response to the vaccine may be decreased. The interval between discontinuation of medications that cause immunosuppression and restoration of the patient's ability to respond to the vaccine depends on the intensity and type of immunosuppression-causing medication used, the underlying disease, and other factors; estimates vary from 3 months to 1 year)


» Vaccines, live virus    (because normal defense mechanisms may be suppressed by teniposide therapy, concurrent use with a live virus vaccine may potentiate the replication of the vaccine virus, may increase the side/adverse effects of the vaccine virus, and/or may decrease the patient's antibody response to the vaccine; immunization of these patients should be undertaken only with extreme caution after careful review of the patient's hematologic status and only with the knowledge and consent of the physician managing the teniposide therapy. The interval between discontinuation of medications that cause immunosuppression and restoration of the patient's ability to respond to the vaccine depends on the intensity and type of immunosuppression-causing medication used, the underlying disease, and other factors; estimates vary from 3 months to 1 year. Patients with leukemia in remission should not receive live virus vaccine until at least 3 months after their last chemotherapy. In addition, immunization with oral poliovirus vaccine should be postponed in persons in close contact with the patient, especially family members)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Leukopenia, severe or
» Thrombocytopenia, severe    (bone marrow depression occurs 7 to 10 days after treatment and may increase risk of infection{02})


Risk-benefit should be considered when the following medical problems exist
» Chickenpox, existing or recent (including recent exposure) or
» Herpes zoster    (risk of severe, generalized disease)


» Down syndrome    (patients may be especially sensitive to the myelosuppressive effects of teniposide; a 50% reduction in initial dosage is recommended{01})


Hepatic function impairment or
Renal function impairment    (caution is recommended, since increases in serum alkaline phosphatase or gamma-glutamyl transpeptidase have been associated with a decrease in the plasma clearance of teniposide and approximately 10% of a dose is eliminated unchanged in the urine; dosage adjustment may be necessary in patients with significant hepatic or renal function impairment{01})


» Hypoalbuminemia    (the steady-state volume of distribution of teniposide increases with a decrease in plasma albumin concentrations; careful monitoring is recommended{01})


» Infection, pre-existing    (recovery may be impaired; needs to be brought under control before initiation of teniposide treatment due to risk of septicemia{02})


» Sensitivity to teniposide or to castor oil    (hypersensitivity reactions to teniposide injection may be caused by the medication itself or by the polyoxyethylated castor oil present in the injection; patients who are known to be sensitive to castor oil, or who have experienced a previous hypersensitivity reaction to teniposide, should be treated with teniposide only if the benefit clearly outweighs the risk of a probable hypersensitivity reaction{01})



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

» Hemoglobin concentration, {01}
» Leukocyte count, total and, if appropriate, differential{01} and
» Platelet count{01}    (determinations recommended prior to initiation of therapy and at periodic intervals during therapy{01})


Hepatic function {01} and
Renal function{01}    (determinations recommended prior to initiation of therapy and at periodic intervals during therapy{01})


» Vital signs    (continuous monitoring recommended for at least the first 60 minutes after the start of a teniposide infusion and at periodic intervals thereafter, to detect possible signs of a hypersensitivity reaction, including anaphylaxis{01})




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Anemia{01} (unusual tiredness)—usually asymptomatic
    
hypersensitivity reaction{01} (chills; fever; flushing of the face; hives; hypertension or hypotension; rapid heartbeat; shortness of breath, troubled breathing, tightness in chest, or wheezing)
    
leukopenia{01} or neutropenia{01} (fever or chills; cough or hoarseness; lower back or side pain; painful or difficult urination)—symptomatic only if neutropenic fever occurs
    
mucositis{01} (sores in mouth and on lips)
    
thrombocytopenia{01} (unusual bleeding or bruising; black, tarry stools; blood in urine or stools; pinpoint red spots on skin)—usually asymptomatic

Note: Bone marrow depression ( leukopenia or thrombocytopenia) may be severe. {01} It is characterized by an early onset and delayed recovery. {01} Bone marrow hypoplasia is a desired end point of therapy in refractory acute lymphocytic leukemia. {01}
The occurrence of hypersensitivity reactions appears to be increased in patients with brain tumors or neuroblastoma. {01} Hypersensitivity reactions, including anaphylaxis-like symptoms, may occur on initial or after repeated exposure to teniposide, and may be life-threatening if not treated promptly. {01}


Incidence less frequent
    
Hypotension{01} —usually asymptomatic
    
skin rash{01}

Note: Transient hypotension has been reported following rapid intravenous administration. {01}


Incidence rare
    
Hepatic function impairment{01} (yellow eyes or skin)—usually asymptomatic
    
neurotoxicity{01}
    
renal function impairment{01} (decreased urination; swelling of face, fingers, feet, or lower legs)



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Nausea or vomiting —usually mild to moderate{01}
    
diarrhea{01}



Those not indicating need for medical attention
Incidence more frequent
    
Loss of hair{01}


Note: Alopecia, sometimes progressing to total baldness, is usually reversible. {01}





Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Acute and chronic
    
Bone marrow suppression{01} (fever; chills; cough or hoarseness; lower back or side pain; painful or difficult urination; unusual bleeding or bruising; black, tarry stools; blood in urine or stools; pinpoint red spots on skin)


Treatment of overdose
Supportive blood product and antibiotic therapy, as indicated, is recommended. There is no known antidote. {01}


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Teniposide (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to teniposide or castor oil



Carcinogenicity—
Secondary acute nonlymphocytic leukemia (ANLL) reported

Pregnancy—Use not recommended because of embryotoxic and teratogenic effects in animal studies; notifying physician immediately if pregnancy is suspected





Breast-feeding—Potential risks to the infant should be considered





Use in children—Children with Down syndrome may be more sensitive to the effects of this medication

Other medications, especially blood dyscrasia–causing medications, bone marrow depressants, live virus vaccines, previous cytotoxic drug or radiation therapy, sodium salicylate, sulfamethizole, or tolbutamide
Other medical problems, especially especially Down syndrome, existing or recent chickenpox or herpes zoster infection, hypoalbuminemia, leukopenia, preexisting infection, or thrombocytopenia

Proper use of this medication
Importance of continuing treatment even if nausea or vomiting occurs

» Proper dosing

Precautions while using this medication
» Importance of close monitoring by the physician, especially blood counts, and liver and renal function tests

Possibility of local tissue injury and scarring if infiltration occurs; telling physician or nurse right away if redness, pain, swelling, or lump under the skin occurs at injection site

» Avoiding immunizations unless approved by physician; other persons in patient's household should avoid immunizations with oral poliovirus vaccine; avoiding persons who have taken oral poliovirus vaccine, or wearing a protective mask that covers nose and mouth

Caution if bone marrow depression occurs
» Avoiding exposure to persons with bacterial infections, especially during periods of low blood counts; checking with physician immediately if fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination occurs

» Checking with physician immediately if unusual bleeding or bruising; black, tarry stools; blood in urine or stools; or pinpoint red spots on skin occur

Caution in use of regular toothbrush, dental floss, or toothpick; physician, dentist, or nurse may suggest alternatives; checking with physician before having dental work done

Not touching eyes or inside of nose unless hands washed immediately before

Using caution to avoid accidental cuts with use of sharp objects such as safety razor or fingernail or toenail cutters

Avoiding contact sports or other situations where bruising or injury may occur


Side/adverse effects
Informing physician or nurse immediately if symptoms of a hypersensitivity reaction occur during an injection

Signs of other potential side effects, especially anemia, leukopenia or neutropenia, mucositis, thrombocytopenia, skin rash, hepatic function impairment, neurotoxicity, and renal function impairment

Possibility of hair loss


General Dosing Information
Patients receiving teniposide should be under the supervision of a physician experienced in cancer chemotherapy.{01}

Teniposide injection must be diluted prior to use. It should be administered by slow intravenous infusion over a period of at least 30 to 60 minutes to prevent hypotension.{01}

Care must be taken to avoid extravasation during intravenous administration, which can result in tissue necrosis and/or thrombophlebitis.{01}

Equipment and medications (including epinephrine and oxygen) necessary for treatment of a possible anaphylactic reaction should be immediately available during each administration of teniposide.{01}

If treatment is reinstituted in a patient who has previously had a hypersensitivity reaction to teniposide, pretreatment with corticosteroids and antihistamines, along with careful clinical observation during and after the infusion, are recommended.{01}

Since occlusion of central venous access devices has occurred during 24-hour teniposide infusions in concentrations of 0.1 to 0.2 mg per mL, frequent observation is recommended to minimize the risk.{01}

Safety considerations for handling this medication
There is limited but increasing evidence and concern that personnel involved in preparation and administration of parenteral antineoplastic agents may be at some risk because of the potential mutagenicity, teratogenicity, and/or carcinogenicity of these agents, although the actual risk is unknown. USP advisory panels recommend cautious handling both in preparation and disposal of antineoplastic agents. Precautions that have been suggested include:    • Use of a biological containment cabinet during reconstitution and dilution of parenteral medications and wearing of disposable surgical gloves, goggles, gowns, and masks.
   • Pregnant personnel should not come in contact with antineoplastic medication containers or mixing supplies.
   • Use of proper technique to prevent contamination of the medication, work area, and operator during transfer between containers (including proper training of personnel in this technique).
   • Cautious and proper disposal of needles, syringes, vials, ampules, and unused medication.
   • Use of proper technique in handling spills, including the use of dilute sodium hypochlorite solution (1% active chlorine) and water, and proper disposal of waste.
A number of medical centers have developed detailed guidelines for handling of antineoplastic agents.

The procedure for the preparation, handling, and disposal of teniposide should be the same as that used with other antineoplastic agents.{01}

Direct contact of skin or mucosa with teniposide requires immediate washing with soap and water or thoroughly flushing with water, respectively.{01}


Combination chemotherapy
Teniposide may be used in combination with other agents in various regimens. As a result, the incidence and/or severity of side effects may be altered and different dosages (usually reduced) may be used. For example, teniposide is part of the following chemotherapeutic combinations:

• —teniposide and cytarabine.{01}


• —teniposide and vincristine and prednisone.{01}
For specific dosages and schedules, consult the literature. For information regarding each agent, consult the individual monographs.

For treatment of adverse effects
It is recommended that the teniposide infusion be discontinued if significant hypotension develops, and administration of fluids or other supportive therapy be instituted as appropriate. Blood pressure usually returns to normal within hours. If the infusion is then re-started, the administration rate should be reduced and the patient carefully monitored.{01}

It is recommended that anaphylaxis be treated by stopping the infusion immediately and administering antihistamines, corticosteroids, epinephrine, intravenous fluids, and other supportive measures as indicated.{01}


Parenteral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

TENIPOSIDE INJECTION

Usual adult dose
[Lymphoma, non-Hodgkin's (treatment)]
Intravenous infusion (over a minimum of 30 minutes), 30 mg per square meter of body surface area per day for 10 days, as a single agent,{02} or

Intravenous infusion (over a minimum of 30 minutes), 30 mg per square meter of body surface area per day every five days, as a single agent,{02} or

Intravenous infusion (over a minimum of 30 minutes), 50 to 100 mg per square meter of body surface area once per week, as a single agent,{02} or

Intravenous infusion (over a minimum of 30 minutes), 60 to 70 mg per square meter of body surface area once per week, given in combination with other chemotherapeutic agents.{02}


Usual pediatric dose
Leukemia, acute lymphocytic
Intravenous infusion (over at least 30 to 60 minutes), 165 mg per square meter of body surface area two times per week for eight or nine doses, given in combination with intravenous cytarabine (300 mg per square meter of body surface area two times a week for eight or nine doses){01} or

Intravenous infusion (over at least 30 to 60 minutes), 250 mg per square meter of body surface area once a week for four to eight weeks, given in combination with intravenous vincristine (1.5 mg per square meter of body surface area once a week for four to eight weeks) and oral prednisone (40 mg per square meter of body surface area per day for twenty-eight days).{01}

[Neuroblastoma (treatment)]
Intravenous infusion (over a minimum of 30 minutes), 130 to 180 milligrams per square meter of body surface area once per week, as a single agent,{02} or

Intravenous infusion (over a minimum of 30 minutes), 100 mg per square meter of body surface area every 21 days, given in combination with other chemotherapeutic agents.{02}


Note: It is recommended that the first course of teniposide in patients with Down syndrome be given at one half the usual dose.{01} Subsequent courses may utilize higher doses, depending on the degree of myelosuppression and mucositis occurring in previous courses.{01}


Strength(s) usually available
U.S.—


10 mg per mL (50 mg per 5-mL ampul) (Rx) [Vumon ( benzyl alcohol) (N,N-dimethylacetamide) (polyoxyethylated castor oil) (dehydrated alcohol) (maleic acid. )]

Canada—


10 mg per mL (50 mg per 5-mL ampul) (Rx) [Vumon ( benzyl alcohol) (ethanol) ( maleic acid) (N,N-dimethylacetamide) (polyoxyethylated castor oil. )]
{02}
Packaging and storage:
Store between 2 and 8 °C (36 and 46 °F). The injection is not adversely affected by freezing.{01}

Preparation of dosage form:
Teniposide injection is prepared for intravenous infusion by dilution with 5% dextrose injection or 0.9% sodium chloride injection to produce a final concentration of 100, 200, or 400 mcg (0.1, 0.2, or 0.3 mg, respectively) or 1 mg of teniposide per mL.{01}

Use of polyvinyl chloride (PVC) containers is not recommended, because of possible leaching of diethylhexylphthalate (DEHP) from PVC bags into the medication.{01} Use of non–DEHP-containing containers, such as glass or polyolefin plastic bags or containers, is recommended instead.{01} Also, non–DEHP intravenous administrations sets, such as lipid administration sets or low DEHP-containing nitroglycerin sets, are recommended.{01} Contact of undiluted (but not diluted) teniposide injection with plastic equipment or devices used to prepare an infusion may result in softening or cracking and possible product leakage.{01}

Caution—Use of products containing benzyl alcohol is generally not recommended for preparation of medications for use in neonates. A fatal toxic syndrome consisting of metabolic acidosis, central nervous system depression, respiratory problems, renal failure, hypotension, and possibly seizures and intracranial hemorrhages has been associated with this use.

Stability:
Solution of teniposide is stable for 4 hours at room temperature between 15 and 30 °C (59 and 86 °F) at concentrations of 0.1 to 0.2 mg per mL.{02}

It is recommended that teniposide infusions containing 1 mg per mL be administered within 4 hours of preparation to reduce the possibility of precipitation.{01} Teniposide injections that have been diluted to concentrations of 0.1 to 1 mg per mL are chemically stable for up to 24 hours at ambient room temperature and lighting conditions.{01} After dilution, the injection should not be refrigerated.{01}{01} The type of container in which the medication is kept (glass or plastic) does not affect stability.{01}

Avoid contact with buffered solutions above pH 8.{02}

Precipitation has been reported during 24-hour intravenous infusions of teniposide in concentrations of 0.1 to 0.2 mg per mL, leading to occlusion of central venous access catheters.{01} Precipitation may also occur if the diluted solution is subjected to excessive agitation during preparation.{01} Storage time prior to administration should be kept to a minimum.{01}

Incompatibilities:
Heparin can cause precipitation of teniposide; therefore, the administration set should be flushed thoroughly with 5% dextrose injection or 0.9% sodium chloride injection before and after administration of teniposide.{01}



Developed: 09/30/1997
Revised: 05/25/2000



References
  1. Vumon package insert (Bristol—US), New 2/94, Rec 7/97.
  1. Product Information: Vumon®, teniposide. Bristol Canada. In: Welbanks L (ed): Compendium of Pharmaceuticals and Specialties, 35th ed. Canadian Pharmaceutical Association, Ottawa, Ontario, Canada, 2000: p. 1729-1730.
  1. Clark PI & Slevin ML: The clinical pharmacology of etoposide and teniposide. Clin Pharmacokinet 1987; 12:223-252.
  1. Baker DK, Relling MV, Pui C-H et al: Increased teniposide clearance with concomitant anticonvulsant therapy. J Clin Oncol 1992; 10:311-315.
Hide
(web4)