topotecan

High Alert

IV: Metastatic ovarian cancer that has not responded to previous chemotherapy.
Small cell lung cancer unresponsive to first line therapy.
Stage IV-B persistent or recurrent cervical cancer not amenable to treatment with surgery or radiation (with cisplatin).
PO: Relapsed small cell lung cancer in patients with a complete or partial prior response and who are at least 45 days from the end of first-line chemotherapy.

Action ⬆ ⬇

Interferes with DNA synthesis by inhibiting the enzyme topoisomerase.

Therapeutic effects:

Death of rapidly replicating cells, particularly malignant ones.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability. 40% absorbed following oral administration.

Distribution: Well distributed to tissues.

Metabolism/Excretion: Small amounts metabolized by the liver. 18–33% excreted in feces and 20–50% excreted in urine (primarily as metabolites).

Half-Life: PO: 3–6 hr; IV: 2–3 hr.

Time/Action Profile ⬆ ⬇

(effects on WBCs)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1–2 hr	24 hr
IV	within days	11 days	7 days

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Renal impairment (↓ dose if CCr <40 mL/min);
Platelet count <25,000 cells/mm³ (↓ dose);
History of interstitial lung disease (ILD), pulmonary fibrosis, lung cancer, thoracic radiation, or use of pneumotoxic drugs or colony stimulating factors;
Rep: Women of reproductive potential;
Geri: Older adults may require dose due to age-related in renal function.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: alopecia

GI: abdominal pain, diarrhea, nausea, vomiting, ↑liver enzymes, anorexia, constipation, stomatitis

Hemat: anemia, leukopenia, thrombocytopenia

MS: arthralgia

Neuro: headache, fatigue, weakness

Resp: dyspnea, ILD

Interactions ⬆ ⬇

Drug-drug:

P-glycoprotein inhibitors, including amiodarone, azithromycin, captopril, carvedilol, clarithromycin, conivaptan, cyclosporine, diltiazem, dronedarone, erythromycin, felodipine, itraconazole, ketoconazole, lopinavir, ritonavir, quinidine, ranolazine, ticagrelor, or verapamil may ↑ levels and the risk of toxicity; avoid concurrent use
Neutropenia is prolonged by concurrent use of filgrastim (do not use filgrastim until day 6; 24 hr following completion of topotecan).
↑myelosuppression with other antineoplastics (especially cisplatin) or radiation therapy.
May ↓ antibody response to and ↑ risk of adverse reactions from live virus vaccines.

Route/Dosage ⬆ ⬇

PO (Adults ): 2.3 mg/m²/day for 5 days starting on day 1 of a 21-day course (round calculated oral dose to nearest 0.25 mg and prescribe the minimum number of 1 mg and 0.25 mg capsules with the same number of capsules prescribed for each of the 5 days).
IV (Adults ): Ovarian and Small Cell Lung Cancer: 1.5 mg/m²/day for 5 days starting on day 1 of a 21-day course; Cervical Cancer: 75 mg/m² on Days 1, 2, and 3 followed by cisplatin on Day 1 and repeated every 21 days.

Renal Impairment

PO (Adults ): CCr 30–49 mL/min: 1.5 mg/m²/day for 5 days starting on day 1 of a 21-day course; dose may be ↑ after first course by 0.4 mg/m²/day if no severe hematologic or GI toxicities occur; CCr <30 mL/min: 0.6 mg/m²/day for 5 days starting on day 1 of a 21-day course; dose may be ↑ after first course by 0.4 mg/m²/day if no severe hematologic or GI toxicities occur.

Renal Impairment

IV (Adults ): CCr 20–39 mL/min: 0.75 mg/m²/day for 5 days starting on day 1 of a 21-day course. Cervical Cancer: Administer at standard doses only if serum creatinine ≤1.5 mg/dL. Do not administer if serum creatinine >1.5 mg/dL.

Availability ⬆ ⬇

(Generic available)

Capsules: 0.25 mg; 1 mg
Powder for injection: 4 mg/vial
Solution for injection: 1 mg/mL

Assessment ⬆ ⬇

Monitor vital signs frequently during administration.
Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae; guaiac stools, urine, and emesis) and avoid IM injections and taking rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension.
Nausea and vomiting are common. Pretreatment with antiemetics should be considered.
Assess IV site frequently for extravasation, which causes mild local erythema and bruising.
Monitor for signs and symptoms of ILD (cough, fever, dyspnea, hypoxia). Discontinue topotecan if ILD is confirmed.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.Monitor CBC with differential and platelet count prior to administration and frequently during therapy. Baseline neutrophil count of ≥1500 cells/mm³ and platelet count of ≥100,000 cells/mm³ are required before first dose. The nadir of neutropenia occurs in 11 days, with a duration of 7 days. The nadir of thrombocytopenia occurs in 15 days, with a duration of 5 days. The nadir of anemia occurs in 15 days. Subsequent doses should not be administered until neutrophils recover to >1000 cells/mm³, platelets recover to >100,000 cells/mm³, and hemoglobin levels recover to 9 g/dL. When topotecan used as a single agent,↓ dose to 1.25 mg/m² if neutrophil <500 cells/mm³, or administer granulocyte-colony stimulating factor (G-CSF) starting no sooner than 24 hr following the last dose or platelet counts <25,000 cells/mm³ during previous cycle. When topotecan used with cisplatin,↓dose to 0.6 mg/m² (and to 0.45 mg/m² if necessary) for febrile neutropenia (neutrophil counts <1,000 cells/mm³ with temperature of ≥38°C (100.4°F), or administer G-CSF starting no sooner than 24 hr following the last dose or platelet counts <25,000 cells/mm³ during previous cycle.
- Monitor liver function. May cause transient ↑ in AST, ALT, and bilirubin concentrations.

Implementation ⬆ ⬇

Check dose carefully before administration.
PO: May be taken without regard to food. DNC: Capsules must be swallowed whole; do not open, crush, or chew. If patient vomits after taking dose, do not replace dose.
- Do not administer capsules to patients with Grade 3 or 4 diarrhea. When recovered to ≤Grade 1, resume with dose ↓ by 0.4 mg/m²/day for subsequent courses

IV Administration:

Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling IV medication. Discard IV equipment in specially designated containers.
Intermittent Infusion: Reconstitution: Reconstitute each vial with 4 mL of sterile water for injection.Diluent: Dilute further in D5W or 0.9% NaCl. Infusion is stable for 24 hr at room temperature or up to 7 days if refrigerated. Solution is yellow to yellow-green.Concentration: 10–50 mcg/mL.
Rate: Infuse over 30 min.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take as directed. If patient vomits after taking, do not replace dose; notify health care professional. Do not take missed doses; take next scheduled dose and notify health care professional. If any capsules are broken or leaking, do not touch with bare hands; dispose of capsules and wash hands with soap and water. Patient should be instructed to read the Patient Information guide prior to first dose and with each Rx refill in case of changes.
May cause drowsiness or sleepiness during and for several days after therapy. Caution patient to avoid driving and other activities requiring alertness until response to medication is known.
Instruct patient to notify health care professional if fever; chills; sore throat; signs of infection; bleeding gums; bruising; petechiae; blood in urine, stool; emesis; or signs and symptoms of interstitial lung disease occur. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor. Patient should be cautioned not to drink alcoholic beverages or take products containing aspirin or NSAIDs.
May cause diarrhea. Advise patient to notify health care professional if diarrhea with fever or stomach pain or cramps or diarrhea that occurs more than 3 times/day.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Discuss with patient the possibility of hair loss. Explore methods of coping.
Instruct patient not to receive any vaccinations without advice of health care professional.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for 6 months after last dose of topotecan and to avoid breastfeeding during and for 1 wk after last dose. Advise males with female partners of reproductive potential to use effective contraception during and for 3 months after last dose. May impair fertility in females and males.
Emphasize the need for periodic lab tests to monitor for side effects.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇