Teniposide Injection

Teniposide is used with other chemotherapy drugs to treat acute lymphocytic leukemia (ALL; a type of cancer of the white blood cells) in children that has not improved or that has worsened after treatment with other medications. Teniposide is in a class of medications known as podophyllotoxin derivatives. It works by slowing or stopping the growth of cancer cells in your body.

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

Before receiving teniposide,

• tell your doctor and pharmacist if you are allergic to teniposide, any other medications, polyoxyethylated castor oil (Cremophor EL), or any of the ingredients in teniposide injection. Ask your pharmacist for a list of the ingredients.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: medications for nausea and vomiting, methotrexate (Abitrexate, Folex, Rheumatrex, Trexall), or tolbutamide (Orinase). Other medications may also interact with teniposide, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
• tell your doctor if you have or have ever had kidney or liver disease or if you have Down syndrome (an inherited condition causing a range of developmental and physical problems).
• tell your doctor if you are pregnant, plan to become pregnant, if you are breast-feeding, or if you plan to father a child. You should know that teniposide may stop sperm production in men. You should not become pregnant or breast-feed while you are receiving teniposide injection. If you or your partner become pregnant while receiving teniposide injection, call your doctor. Teniposide may harm the fetus.

The table below presents the incidences of adverse reactions derived from an analysis of data contained within literature reports of 7 studies involving 303 pediatric patients in which teniposide was administered by injection as a single agent in a variety of doses and schedules for a variety of hematologic malignancies and solid tumors. The total number of patients evaluable for a given event was not 303 since the individual studies did not address the occurrence of each event listed. Five of these 7 studies assessed teniposide activity in hematologic malignancies, such as leukemia. Thus, many of these patients had abnormal hematologic status at start of therapy with teniposide and were expected to develop significant myelosuppression as an endpoint of treatment.

Single-Agent VUMON Summary of Toxicity for All Evaluable Pediatric Patients

Toxicity	Incidence in Evaluable Patients (%)
Hematologic Toxicity
Myelosuppression, nonspecified	75
Leukopenia (<3,000 WBC/mcL)	89
Neutropenia (<2,000 ANC/mcL)	95
Thrombocytopenia (<100,000 plt/mcL)	85
Anemia	88
Non-Hematologic Toxicity
Mucositis	76
Diarrhea	33
Nausea/vomiting	29
Infection	12
Alopecia	9
Bleeding	5
Hypersensitivity reactions	5
Rash	3
Fever	3
Hypotension/Cardiovascular	2
Neurotoxicity	<1
Hepatic dysfunction	<1
Renal dysfunction	<1
Metabolic abnormalities	<1

Hematologic Toxicity

Teniposide, when used with other chemotherapeutic agents for the treatment of ALL, results in severe myelosuppression. Sepsis, sometimes fatal, may be a consequence of severe myelosuppression. Early onset of profound myelosuppression with delayed recovery can be expected when using the doses and schedules of teniposide necessary for treatment of refractory ALL, since bone marrow hypoplasia is a desired endpoint of therapy. The occurrence of acute non-lymphocytic leukemia (ANLL), with or without a preleukemic phase, has been reported in patients treated with teniposide in combination with other antineoplastic agents. (See PRECAUTIONS: Carcinogenesis, Mutagenesis, Impairment of Fertility.)

Gastrointestinal Toxicity

Nausea and vomiting are the most common gastrointestinal toxicities, having occurred in 29% of evaluable pediatric patients. The severity of this nausea and vomiting is generally mild to moderate.

Hypotension

Transient hypotension following rapid intravenous administration has been reported in 2% of evaluable pediatric patients. One episode of sudden death, attributed to probable arrhythmia and intractable hypotension, has been reported in an elderly patient receiving teniposide combination therapy for a non-leukemic malignancy.

No other cardiac toxicity or electrocardiographic changes have been documented. No delayed hypotension has been noted.

Allergic Reactions

Hypersensitivity reactions characterized by chills, fever, tachycardia, flushing, bronchospasm, dyspnea, rash, and blood pressure changes (hypertension or hypotension) have been reported to occur in approximately 5% of evaluable pediatric patients receiving intravenous teniposide. The incidence of hypersensitivity reactions to teniposide appears to be increased in patients with brain tumors and in patients with neuroblastoma.

Central Nervous System

Neurotoxicity has been reported, including severe cases of neuropathy, in patients receiving vincristine sulfate and teniposide concomitantly.

Acute central nervous system depression and hypotension have been observed in patients receiving investigational infusions of high-dose teniposide who were pretreated with antiemetic drugs. 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.

Alopecia

Alopecia, sometimes progressing to total baldness, was observed in 9% of evaluable pediatric patients who received teniposide as single-agent therapy. It was usually reversible.

Other Adverse Reactions

The following adverse reactions have been reported: headache, confusion, and asthenia. Headache and confusion were associated with hypersensitivity reactions.

To report SUSPECTED ADVERSE REACTIONS, contact WG Critical Care, LLC at 1-866-562-4708 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Acute central nervous system depression, hypotension, and metabolic acidosis have been observed in patients who were receiving higher than recommended doses of teniposide, and who were also pretreated with antiemetic drugs.

There is no known antidote for teniposide overdosage. The anticipated complications of overdosage are secondary to bone marrow suppression. Treatment should consist of supportive care, including blood products and antibiotics as indicated.

1. NIOSH Alert: Preventing occupational exposures to antineoplastic and other hazardous drugs in healthcare settings. 2004. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2004-165. 2. OSHA Technical Manual, TED 1-0.15A, Section VI: Chapter 2. Controlling Occupational Exposure to Hazardous Drugs. OSHA, 1999. http://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html. 3. American Society of Health-System Pharmacists. ASHP guidelines on handling hazardous drugs. Am J Health-Syst Pharm. 2006;63:1172-1193. 4. Polovich M, White JM, Kelleher LO, eds. 2005. Chemotherapy and biotherapy guidelines and recommendations for practice. 2nd ed. Pittsburgh, PA: Oncology Nursing Society.

Manufactured for:

WG Critical Care, LLC

Paramus, NJ 07652

Made in Italy

Rev. 04/2015

3000502A1