topotecan (Hycamtin)

Dosing and uses of Hycamtin (topotecan)

• Adult
• Pediatric

 

Adult dosage forms and strengths

powder for injection

• 4mg/vial

capsule

• 0.25mg
• 1mg

 

Small Cell Lung Cancer

Indicated for SCLC sensitive disease after failure of first-line chemotherapy

IV Infusion

• Administer 1.5mg/m² IV infused over 30 min qDay x5 days; repeat at 21-day cycles
• Absence of tumor progresssion: ≥ 4 courses is recommended
• Severe neutropenia or thrombocytopenia (Plt <25K/mm³): reduce to 1.25 mg/m² for subsequent courses

Capsules

• Administer 2.3mg/m² PO QD x5days; repeat at 21-day cycles
• Severe febrile neutropenia (ANC <500/mm³ with fever x7 days)/neutropenia (ANC<1000/mm³ x21 days)/thrombocytopenia (Plt<25K/mm³): Reduce by 0.4 mg/m²/day
• Grade 3/4 diarrhea: reduce by 0.4 mg/m²/day

 

Dosage modifications (SCLC)

Renal impairment

• CrCl 30-49 mL/min: Decrease dose to 1.5 mg/m² PO qDay
• CrCl <30 mL/min: Decrease dose to 0.6 mg/m² PO qDay
• Renal impairment dosage modification: Dose can be increased after the first course by 0.4 mg/m²/day if no severe hematologic or GI toxicities occur

Hematologic toxicities

• Do not administer subsequent courses of until neutrophils recover to >1,000 cells/mm³, platelets recover to >100,000 cells/mm³, hemoglobin levels recover to ≥9.0 g/dL (with transfusion if necessary)
• Reduce dose by 0.4 mg/m²/day PO (0.25 mg/m² IV) if: - neutrophil counts <500 cells/mm³ with fever or infection or lasting for ≥7 days - neutrophil counts of 500-1,000 cells/mm³ lasting beyond day 21 of treatment cycle - platelet counts <25,000 cells/mm³
• Also, consider G-CSF for severe neutropenia

Diarrhea

• Do not administer to patients with Grade 3 or 4 diarrhea
• After recovery to ≤Grade 1, reduce the dose by 0.4 mg/m²/day PO for subsequent courses

 

Cervical Cancer

Indicated for combination therapy with cisplatin for stage IV-B, recurrent or persistent cervical carcinoma which cannot be treated with surgery and/or radiation therapy

Administer 0.75 mg/m² IV infused over 30 min on Days 1,2, & 3 (with cisplatin 50 mg/m² on Day 1); repeat at 21-day cycles

Severe febrile neutropenia (<1000 cells/mm³) or thrombocytopenia (Plt <25K/mm³)

• Reduce all subsequent doses to 0.6 mg/m²
• Alternatively, G-CSF may be administered for febrile neutropenia starting on Day 4 of the course (24 hours after toptecan administration has been completed)

 

Ovarian Cancer

Indicated for metastatic ovarian cancer after failure of initial or subsequent chemotherapy

Administer 1.5mg/m² IV infused over 30 min qDay x5 days; repeat at 21-day cycles

Absence of tumor progresssion: ≥4 courses is recommended

Severe neutropenia or thrombocytopenia (Plt <25K/mm³): Reduce to 1.25 mg/m² for subsequent courses

 

Dosing Considerations

Verify dose using body surface area prior to dispensing

Recommended dosage should generally not exceed 4 mg IV

Prior to administration of the first treatment course, baseline counts for neutrophils should be >1,500/mm³ and platelets >100,000/mm³

 

Other Information

Monitor: CBC

 

Pediatric dosage forms and strengths

Safety and effectiveness not established

 

Hycamtin (topotecan) adverse (side) effects

>10%

Neutropenia (97%)

Leukopenia (97%)

Anemia (89%)

Thrombocytopenia (69%)

Nausea (64%)

Alopecia (49%)

Sepsis or pyrexia/ infection with neutropenia (43%)

Vomiting (45%)

Diarrhea (32%)

Fatigue (29%)

Constipation (29%)

Fever (28%)

Asthenia (25%)

Body/ back/ skeletal pain (23%)

Abdominal pain (22%)

Dyspnea (22%)

Anorexia (19%)

Stomatitis (18%)

Headache (18%)

Rash (16%)

Cough (15%)

 

Warnings

Black box warnings

Administer only to patients with baseline neutrophil counts of 1500 cells/mm³or higher and a platelet count of 100,000 cells/mm³ or higher

To assess the occurrence of bone marrow suppression, blood cell counts should be monitored

 

Contraindications

Hypersensitivity reactions to drug or any components

 

Cautions

Administer to patients with bone marrow suppression only if patient has adequate bone marrow reserves; monitor peripheral blood counts and adjust dose as needed

PO: Do NOT redose if ANC <1500/mm³; Plt 100,000 <mm³; Hgb <9 g/dL

Avoid use in pregnancy; can cause fetal harm; advise women of potential risk to fetus

Neutropenia: pancytopenia has been reported

Fatal cases of interstitial lung disease have occurred; permanently discontinue for confirmed ILd

If extravasation occurs, immediately stop administration and institute recommended management procedures; severe cases reported

PO: If patient vomits after taking capsule, do NOT repeat dose

PO: If diarrhea occurs, treat aggressively, potentially life-threatening

Monitor patients presenting with neutropenia, fever and abdominal pain; fatal typhlitis reported in patients with neutropenic enterocolitisas

Monitor patients presenting with cough, fever, dyspnea and/or hypoxia and a histroy of lung disease as fatalities due to interstitial lung disease have been reported

 

Pregnancy and lactation

Pregnancy category: d

Lactation: not known if excreted in breast milk, do not breast feed

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Hycamtin (topotecan)

Mechanism of action

Binds to topoisomerase I to produce double-strand breaks in DNA

 

Absorption

Bioavailability: 40% (PO)

Peak plasma time: 1-2 hr (PO)

 

Distribution

Protein Bound: 35%

 

Metabolism

Hepatic

 

Excretion

Half-life, terminal: 2-3 hr (IV); 3-6 hr (PO)

Excretion, PO: 35% feces; 22% urine

Excretion, IV: 20% feces; 54% urine

 

Administration

IV Incompatibilities

Y-site: dexamethasone sodium phosphate, fluorouracil, mitomycin, ticarcillin-clavulanate(?)

 

IV Compatibilities

Solution: D5W, Ns

Y-site: carbopolatin, cisplatin, cimetidine, cyclophosphamide, doxorubicin, etoposide, gemcitabine, granisetron, ifosfamide, methylprednisolone Na-succinate, metoclopramide, ondansetro, paclitaxel, prochlorperazine, vincristine

 

IV Preparation

No preservatives-reconstitute immediately prior to use

Reconstitute in 4 mL SWI to obtain a 1 mg/mL solution

No preservatives-use immediately

Dilute in 50-250 mL NS or D5W; stability is pH dependent although topotecan may be further diluted in Ns

 

IV Administration

Infuse over 30 min

 

Storage

Store intact vials at room temp protected from light