Name of the Topoisomerase II inhibitors (podophyllotoxins) Drugs
- Etoposide
- Teniposide
1.Etoposide
| ETOPOSIDE |
| Availability: Capsules: 50 mg; Injection: 20 mg/ml; Powder for injection (phosphate): 100 mg in single-dose vials. Injection Solution: (Toposar): 20 mg/mL (5 mL, 25 mL, 50 mL). |
| Administration/handling: Administer by slow IV infusion. Wear gloves when preparing solution. If powder or solution comes in contact with skin, wash immediately and thoroughly with soap, water. May be carcinogenic, mutagenic, teratogenic. Handle with extreme care during preparation, administration |
| IV : Reconstitution: Toposar • Dilute to a concentration of 0.2–0.4 mg/mL in D5W or 0.9% NaCl. Etopophos • Reconstitute each 100 mg with 5–10 mL Sterile Water for Injection, D5W, or 0.9% NaCl to provide concentration of 20 mg/mL or 10 mg/mL, respectively. • May give without further dilution or further dilute to concentration as low as 0.1 mg/mL with 0.9% NaCl or D5W. |
| Rate of administration • (Toposar) Infuse slowly, at least 30–60 min (rapid IV may produce marked hypotension) at a rate not to exceed 100 mg/m2/hr. • Monitor for anaphylactic reaction during infusion (chills, fever, dyspnea, diaphoresis, lacrimation, sneezing, throat, back, chest pain). • (Etopophos) May give over as little as 5 min up to 210 min |
| Storage : (Toposar) Store injection at room temperature before dilution. • Concentrate for injection is clear, yellow. Diluted solution is stable at room temperature for 96 hrs at 0.2 mg/mL, 24 hrs at 0.4 mg/mL. Discard if crystallization occurs. Refrigerate vials. • Stable at room temperature for 24 hrs or for 7 days if refrigerated after reconstitution. |
| PO: Storage • Refrigerate gelatin capsules |
| For I.V. concentrations above 0.4mg/ml, mix each 100 mg with 250 to 500 ml of dextrose 5% in water or normal saline solution, to help prevent crystallization. |
| Give I.V. infusion over 30 to 60 minutes. Don’t use in-line filter |
| Avoid rapid infusion, which may cause severe hypotension and bronchospasm. Administer with antiemetics, as prescribed. |
| Wear disposable gloves when handling. If drug comes into contact with skin, wash thoroughly with soap and water. Be aware that drug is given with other chemotherapeutic agents. |
| Dosage individualized based on clinical response, tolerance to adverse effects. Treatment repeated at 3- to 4-wk intervals. Refer to individual protocols. |
| Refractory Testicular Tumors IV: Adults: 50–100 mg/m2/day on days 1–5, or 100 mg/m2/day on days 1, 3, 5 (as combination therapy). Give q3–4wks for 3–4 courses. |
| Small-Cell Lung Carcinoma PO: Adults: Twice the IV dose rounded to nearest 50 mg. Give once daily for doses 200 mg or less, in divided doses for dosages greater than 200 mg. IV: ADULTS: 35 mg/m2/day for 4 consecutive days up to 50 mg/m2/day for 5 consecutive days q3–4wks (as combination therapy). |
Mechanism of Action:
Induces single- and double-stranded breaks in DNA. Cell cycle–dependent and phase-specific; most effective in S and G2 phases of cell division. Therapeutic Effect: Inhibits, alters DNA synthesis.
Indications:
- Treatment of refractory testicular tumors
- Small-cell lung carcinoma.
OFF-LABEL:
- Acute lymphocytic, acute nonlymphocytic leukemias; Ewing’s and Kaposi’s sarcoma; Hodgkin’s and non-Hodgkin’s lymphomas; endometrial, gastric, non– small-cell lung carcinomas; multiple myeloma; myelodysplastic syndromes; neuroblastoma; osteosarcoma; ovarian germ cell tumors; primary brain, gestational trophoblastic tumors; soft tissue sarcomas; Wilms tumor.
Cautions & Contraindications:
- Hypersensitivity to etoposide.
Cautions:
- Hepatic/renal impairment
- Myelosuppression
- Elderly
- Pts with low serum albumin
Metabolism and Half- Life:
- Variably absorbed from GI tract. Rapidly distributed, low concentrations in CSF.
- Protein binding: 97%.
- Metabolized in liver. Primarily excreted in urine. Not removed by hemodialysis.
- Half-life: 3–12 hrs.
Drug Interactions:
- Bone marrow depressants (e.g., cladribine) may increase myelosuppression.
- Live-virus vaccines may potentiate virus replication, increase vaccine side effects, decrease pt’s antibody response to vaccine.
- Strong CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampin) may decrease concentration/effect.
- Expected decrease of leukocytes, platelets, RBC, Hgb, Hct
Side – Effects:
- Frequent: Mild to moderate nausea/vomiting, alopecia.
- Occasional: Diarrhea, anorexia, stomatitis.
- Rare : Hypotension, peripheral neuropathy
Nursing Considerations
Baseline assessment
- Obtain CBC before and at frequent intervals during therapy.
- Antiemetics readily control nausea, vomiting.
- Offer emotional support.
Intervention/evaluation
- Monitor CBC, liver function tests, and blood urea nitrogen and creatinine levels. Report platelet count below 50,000/mm3 or neutrophil count below 500/mm3.
- Monitor daily pattern of bowel activity, stool consistency.
- Monitor for hematologic toxicity (fever, sore throat, signs of local infection, unusual bruising/bleeding from any site), symptoms of anemia (excessive fatigue, weakness).
- Assess for paresthesia (peripheral neuropathy).
- Monitor for stomatitis.
- Monitor blood pressure during and after infusion. Stop infusion if severe hypotension occurs.
- With I.V. use, monitor infusion rate closely to prevent infusion reactions.
- Throughout infusion, check I.V. site for extravasation, which may cause thrombophlebitis.
- Keep diphenhydramine, hydrocortisone, epinephrine, and artificial airway at hand in case anaphylaxis occurs.
- Assist patient during ambulation as needed.
- Monitor for signs and symptoms of bone marrow depression.
Patient/family teaching
- Hair loss is reversible, but new hair growth may have different color, texture.
- Do not have immunizations without physician’s approval (drug lowers resistance).
- Avoid contact with those who have recently received live virus vaccine.
- Promptly report fever, sore throat, signs of local infection, unusual bruising or bleeding from any site, burning or pain with urination, numbness in extremities, yellowing of skin or eyes.
- Instruct patient to inspect mouth daily for ulcers and bleeding gums.
- Tell patient to immediately report difficulty breathing or signs and symptoms of allergic reaction.
- Caution female of childbearing age to avoid pregnancy and breastfeeding during drug therapy.
- Instruct patient to move slowly when sitting up or standing, to avoid lightheadedness or dizziness from sudden blood pressure decrease.
2. Teniposide
| TENIPOSIDE |
| Availability: injectable solution: 10mg/mL |
| Administration and Handling: IV Preparation: Must be diluted with either D5W or NS to a final concentration of 0.1, 0.2, 0.4 or 1 mg/mL. To prevent extraction of the plasticizer DEHP, prepare solutions in non-DEHP-containing containers such as glass or polyolefin PVC is not recommended. Administer 1 mg/mL solutions within 4 hr of preparation to reduce potential for precipitation. Precipitation may occur at any concentration. |
| IV Administration: Irritant – Slow IV infusion over >30 min. Rapid infusion may cause hypotension or increase nausea & vomiting. Flush thoroughly before & after administration; Incompatible with heparin; Do not use in-line filter during IV infusion. Storage: Store ampules in refrigerator. |
| Acute Lymphoblastic Leukemia: 165 mg/m²/dose IV on days 1, 4, 8, and 11 |
| Non-Hodgkin Lymphoma (Off-label): 30 mg/m²/day IV for 10 days; alternatively, 50 to 100 mg/m² every week as single agent or 60 to 70 mg/m²/day every week in combination with other chemotherapeutic drugs |
Mechanism of Action:
Semisynthetic podophyllotoxin derivative
Inhibits topoisomerase II to cause DNA strand breaks, preventing mitosis
Indications:
- Acute Lymphoblastic Leukemia
- Non-Hodgkin Lymphoma (Off-label)
Cautions & Contraindications:
- Hypersensitivity to teniposide or castor oil
- Platelets below 50,000/mm³ or ANC below 500/mm³
Metabolism and Half- Life:
- Protein Bound: >99%;
- Peak Plasma: 14.3 mcg/mL
- Metabolized in liver(major).
- Elimination: Half-Life: 5 hr (children)
- Clearance: 7-17 mL/min/sq.meter
- Excretion: Urine (44%); feces (<10%)
Drug Interactions:
The enzyme inducers phenobarbital and phenytoin have been found to lower its blood plasma concentrations.
Side- Effects:
- Bone marrow suppression.
- Alopecia
- Nausea & Vomiting
- Neutropenia , Thrombocytopenia
- Infection
- Hypersensitivity
- Fever
- Bleeding
- Arrhythmia
- Headache
- Weakness
- Renal dysfunction
- Neuropathy Tissue necrosis
Nursing Considerations
Baseline assessment
- Obtain CBC before and at frequent intervals during therapy.
- Antiemetics readily control nausea, vomiting.
- Offer emotional support.
Intervention/evaluation
- Monitor CBC, liver function tests, and blood urea nitrogen and creatinine levels. Report platelet count below 50,000/mm3.
- Monitor daily pattern of bowel activity, stool consistency.
- Monitor for hematologic toxicity (fever, sore throat, signs of local infection, unusual bruising/bleeding from any site), symptoms of anemia (excessive fatigue, weakness).
- Monitor for stomatitis.
- Monitor blood pressure during and after infusion. Stop infusion if severe hypotension occurs.
- With I.V. use, monitor infusion rate closely to prevent infusion reactions.
- Throughout infusion, check I.V. site for extravasation, which may cause thrombophlebitis.
- Assist patient during ambulation as needed.
- Monitor for signs and symptoms of bone marrow suppression.
Patient/family teaching
- Hair loss is reversible, but new hair growth may have different color, texture.
- Do not have immunizations without physician’s approval (drug lowers resistance).
- Avoid contact with those who have recently received live virus vaccine.
- Promptly report fever, sore throat, signs of local infection, unusual bruising or bleeding from any site, burning or pain with urination, numbness in extremities, yellowing of skin or eyes.
- Instruct patient to inspect mouth daily for ulcers and bleeding gums.
- Tell patient to immediately report difficulty breathing or signs and symptoms of allergic reaction.
- Instruct patient to move slowly when sitting up or standing, to avoid lightheadedness or dizziness from sudden blood pressure decrease.
REFERENCES
- Robert Kizior, Keith Hodgson, Saunders Nursing Drug handbook,1st edition 2024, Elsevier Publications. ISBN-9780443116070
- McGraw Hill- Drug Handbook, Seventh Edition, 2013, McGraw Hill Education Publications,9780071799430.
- April Hazard, Cynthia Sanoski, Davi’s Drug Guide for Nurses -Sixteenth Edition 2019, FA Davis Company Publications,9780803669451.
- Jones and Bartlet, Pharmacology for Nurses, Second Edition, 2020, Jones and Bartlet Learning Publications, ISBN 9781284141986.
- Nursebro.com, Search – Nursebro
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