topotecan

toe-poe-TEE-kan

Therapeutic Classification: antineoplastics

Pharmacologic Classification: enzyme inhibitors

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 ≥45 days from the end of first-line chemotherapy.

Interferes with DNA synthesis by inhibiting the enzyme topoisomerase.

Therapeutic effects:

Death of rapidly replicating cells, particularly malignant ones.

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; 20–50% excreted in urine (primarily as metabolites).

Half-Life: PO: 3–6 hr; IV: 2–3 hr.

(effects on WBCs)

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

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.

Derm: alopecia

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

Hemat: anemia, neutropenia, thrombocytopenia

MS: arthralgia

Neuro: headache, fatigue, weakness

Resp: dyspnea, ILD

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 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.

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; may ↑ dose after 1st 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; may ↑ dose after 1st 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.

(Generic available)

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

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 ↑ fatigue, dyspnea, and orthostatic hypotension.
Nausea and vomiting are common. Pretreatment with antiemetics should be considered.
Monitor for signs/symptoms of ILD (cough, fever, dyspnea, hypoxia). If ILD confirmed, discontinue topotecan.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy. Monitor CBC with differential and platelet count before administration and frequently during therapy. Baseline neutrophil count ≥1500 cells/mm³ and platelet count ≥100,000 cells/mm³ are required before 1st 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. Topotecan monotherapy: If neutrophils <500 cells/mm³ or platelets <25,000 cells/mm³,↓ dose to 1.25 mg/m² or administer granulocyte-colony stimulating factor (G-CSF) starting no sooner than 24 hr following the last dose (specifically for neutropenia). When topotecan used with cisplatin:If febrile neutropenia (neutrophils <1000 cells/mm³ with temperature of ≥100.4°F or platelets <25,000 cells/mm³, ↓dose to 0.6 mg/m² (and to 0.45 mg/m² if necessary) or administer G-CSF starting no sooner than 24 hr following the last dose (specifically for neutropenia).
- Monitor liver function. May ↑ AST, ALT, and bilirubin.

High Alert: Check dose carefully before administration.
PO: Administer with or without food.DNC: Swallow capsules whole; do not open, crush, or chew. If vomiting occurs 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:

Wear gloves, gown, and mask while handling IV medication. Discard IV equipment in specially designated containers.
Topotecan is an irritant. If extravasation occurs, immediately stop infusion. Leave needle/cannula in place temporarily but do not flush the line. Gently aspirate extravasated solution; then remove needle/cannula. Elevate patient's extremity and apply dry cold compresses for 20 min 4 times day for 1–2 days.
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/mLRate: Infuse over 30 min..
Y-Site Compatibility:
- alemtuzumab
- amikacin
- amiodarone
- anidulafungin
- argatroban
- aztreonam
- bivalirudin
- buprenorphine
- butorphanol
- calcium chloride
- carboplatin
- caspofungin
- cefazolin
- cefotaxime
- cefotetan
- cefoxitin
- ceftriaxone
- cefuroxime
- chloramphenicol
- chlorpromazine
- ciprofloxacin
- cisatracurium
- cisplatin
- cyclophosphamide
- cyclosporine
- dacarbazine
- dactinomycin
- daptomycin
- daunorubicin
- dexmedetomidine
- dexrazoxane
- diltiazem
- diphenhydramine
- dobutamine
- docetaxel
- dopamine
- doxorubicin hydrochloride
- doxorubicin liposomal
- doxycycline
- droperidol
- enalaprilat
- ephedrine
- epinephrine
- erythromycin
- esmolol
- etoposide
- etoposide phosphate
- famotidine
- fentanyl
- fluconazole
- fludarabine
- furosemide
- gemcitabine
- gemtuzumab ozogamicin
- gentamicin
- glycopyrrolate
- granisetron
- haloperidol
- heparin
- hetastarch
- hydralazine
- hydrocortisone
- hydromorphone
- idarubicin
- ifosfamide
- insulin regular
- isoproterenol
- labetalol
- leucovorin
- levofloxacin
- lidocaine
- linezolid
- lorazepam
- magnesium sulfate
- mannitol
- meperidine
- mesna
- methadone
- methylprednisolone
- metoclopramide
- metoprolol
- metronidazole
- midazolam
- milrinone
- minocycline
- mitoxantrone
- morphine
- moxifloxacin
- nalbuphine
- naloxone
- nitroglycerin
- nitroprusside
- norepinephrine
- octreotide
- ondansetron
- oxaliplatin
- paclitaxel
- palonosetron
- pamidronate
- pentamidine
- phenylephrine
- potassium chloride
- procainamide
- prochlorperazine
- promethazine
- propranolol
- remifentanil
- succinylcholine
- sufentanil
- tacrolimus
- theophylline
- thiotepa
- tigecycline
- tirofiban
- tobramycin
- vancomycin
- vasopressin
- vecuronium
- verapamil
- vinblastine
- vincristine
- vinorelbine
- voriconazole
- zidovudine
- zoledronic acid
Y-Site Incompatibility:
- acyclovir
- allopurinol
- aminophylline
- amphotericin B deoxycholate
- ampicillin
- ampicillin/sulbactam
- bumetanide
- calcium gluconate
- cefepime
- ceftazidime
- clindamycin
- dantrolene
- dexamethasone
- diazepam
- digoxin
- ertapenem
- fluorouracil
- foscarnet
- fosphenytoin
- ganciclovir
- hydrocortisone
- imipenem/cilastatin
- ketorolac
- meropenem
- methohexital
- mitomycin
- nafcillin
- pantoprazole
- pemetrexed
- pentobarbital
- phenobarbital
- phenytoin
- piperacillin/tazobactam
- potassium acetate
- potassium phosphates
- rituximab
- sodium bicarbonate
- sodium phosphates
- trastuzumab
- trimethoprim/sulfamethoxazole

Explain purpose and side effects of medication to patient. Advise to read Patient Information before starting therapy. Instruct patient to take as directed. If vomiting occurs after taking, do not replace dose; notify health care provider. Do not take missed doses; take next scheduled dose and notify health care provider. If any capsules are broken or leaking, do not touch with bare hands; dispose of capsules and wash hands with soap and water.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other medications.
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.
Advise patient to notify health care provider if fever; chills; sore throat; signs of infection; bleeding gums; bruising; petechiae; blood in urine, stool, or 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 provider if diarrhea with fever, stomach pain, or cramps or for diarrhea that occurs >3 times/day.
Discuss with patient the possibility of hair loss. Explore methods of coping.
Instruct patient not to receive any vaccinations without advice of health care provider.
Rep: May cause fetal harm. Advise women of reproductive potential to use effective contraception during therapy and for 6 mo after last dose and to avoid breastfeeding during therapy and for 1 wk after last dose. Advise men with female partners of reproductive potential to use effective contraception during therapy and for 3 mo after last dose. May impair fertility in men and women.

Death of rapidly replicating cells, particularly malignant ones.

Hycamtin

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US Brand Names ⬆