topotecan (Rx)

Brand and Other Names:Hycamtin
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Dosing & Uses

AdultPediatric

Dosage Forms & 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

  • 1.5mg/m² IV qDay x5 days; repeat at 21-day cycles  
  • See Administration

Capsules

  • 2.3mg/m² PO QD x5days; repeat at 21-day cycles  

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

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  

Ovarian Cancer

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

1.5mg/m² IV qDay x5 days; repeat at 21-day cycles  

Dosage Modifications

Renal impairment

  • IV infusion (monotherapy)
    • Mild (CrCl 40-60 mL/min): No dosage adjustment necessary
    • Moderate (CrCl 20-39 mL/min): Decrease dose to 0.75 mg/m² PO qDay
    • Severe (CrCl <20 mL/min): Safety and efficacy has not been established
  • Capsules
    • CrCl 30-49 mL/min: Decrease dose to 1.5 mg/m² PO day
    • CrCl <30 mL/min: 0.6 mg/m² PO Day
    • Dose may be increased after first course by 0.4 mg/m²/day if no severe hematologic or gastrointestinal 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)
  • IV infusion (monotherapy)
    • Neutrophil count <500 cells/mm³: Reduce dose to 1.25 mg/m² alternatively, granulocyte-colony stimulating factor (G-CSF) starting no sooner than 24 hours after topotecan administration has been completed
    • Platelet count < 25.000 cells/mm³ during previous cycle: Reduce dose to 1.25 mg/m²
  • Combination therapy with cisplatin
    • Severe neutropenia (neutrophil counts <1,000 cells/mm³ with temperature of ≥38.0°C (100.4°F)): Reduce dose to 0.60 mg/m² (and further to 0.45 mg/m² if necessary); alternatively, G-CSF starting no sooner than 24 hours after topotecan administration has been completed
    • Platelet count <25.000 cells/mm³: Reduce dose to 0.60 mg/m² (and further to 0.45 mg/m² if necessary)

Diarrhea (capsules only)

  • 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

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

Monitor: CBC

Safety and effectiveness not established

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Interactions

Interaction Checker

and topotecan

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            IV infusion

            • Ovarian cancer
              • Neutropenia, grade 4 (80%)
              • Anemia, grade 3 or 4 (41%)
              • Thrombocytopenia, grade 4 (27%)
              • Febrile neutropenia (23%)
            • Small cell lung cancer
              • Neutropenia, grade 4 (70%)
              • Anemia, grade 3 or 4 (42%)
              • Thrombocytopenia. grade 4 (29%)
            • Cervical cancer (Combination therapy with cisplatin)
              • Constitutional, grade 3 or 4 (69%)
              • Pain, grade 3 or 4 (59%)
              • Neutropenia, grade 4 (48%)
              • Vomiting, grade 3 or 4 (40%)
              • Anemia, grade 3 (34%)
              • Thrombocytopenia, grade 3 (26%)
              • Neutropenia, grade 3 (26%)

            Capsule

            • All grades
              • Anemia (98%)
              • Sepsis (43%)
              • Nausea (33%)
              • Thrombocytopenia (29%)
              • Neutropenia (24%)
            • Grade 3 or 4
              • Neutropenia (24-32%)
              • Thrombocytopenia (6-29%)
              • Anemia (7-18%)

            1-10%

            IV infusion

            • Ovarian cancer
              • Nausea, grade 3 or 4 (10%)
              • Vomiting, grade 3 or 4 (10%)
              • Fatigue, grade 3 or 4 (7%)
              • Dyspnea, grade 3 or 4 (6%)
              • Diarrhea, grade 3 or 4 (6%)
              • Sepsis, grade 3 or 4 (5%)
              • Abdominal pain, grade 3 or 4 (5%)
              • Constipation, grade 3 or 4 (5%)
              • Intestinal obstruction, grade 3 or 4 (5%)
              • Asthenia, grade 3 or 4 (5%)
              • Pain, grade 3 or 4 (5%)
            • Small cell lung cancer
              • Neutropenia, grade 4 (9%)
              • Asthenia, grade 3 or 4 (9%)
              • Pneumonia, grade 3 or 4 (8%)
              • Nausea, grade 3 or 4 (8%)
              • Abdominal pain, grade 3 or 4 (6%)
              • Fatigue, grade 3 or 4 (6%)
              • Sepsis, grade 3 or 4 (5%)
            • Cervical cancer (Combination therapy with cisplatin)
              • Thrombocytopenia, grade 4 (7%)
              • Stomatitis-pharyngitis, grade 3 or 4 (6%)

            Capsule

            • All grades
              • Pyrexia (5%)
              • Asthenia (7%)
            • Grade 3 or 4
              • Diarrhea (4%)
              • Fatigue (4%)
              • Nausea (3%)
              • Vomiting (3%)
              • Anorexia (2%)
              • Asthenia (2%)
              • Pyrexia (1%)

            <1%

            Oral

            • Diarrhea, grade 4 (0.4%)
            • Vomiting, grade 4 (0.4%)
            • Fatigue, grade 4 (0.1%)
            • Alopecia, grade 3 (0.1%)

            Postmarketing Reports

            Blood and lymphatic system disorders: Myelosuppression, severe bleeding (in association with thrombocytopenia

            Immune system disorders: Allergic manifestations, anaphylactoid reactions

            Gastrointestinal Disorders: Gastrointestinal perforation; mucosal inflammation, abdominal pain potentially associated with neutropenic enterocolitis

            Pulmonary disorders: Interstitial lung disease

            Skin and subcutaneous tissue disorders: Angioedema, severe dermatitis, severe pruritus

            General disorders and administration site conditions: Extravasation

            Hepatobiliary disorders: Grade 1 transient elevations in hepatic enzymes (8%); Grade 3/4 (4%); Grade 3/4 elevated bilirubin (<2%)

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            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; monitor blood cell counts

            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

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

            Neutropenia: pancytopenia has been reported

            Grade 4 thrombocytopenia and grade 3-4 anemia reported; withhold and reduce dose based on neutrophil counts, platelet counts and hemoglobin levels

            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 history of lung disease as fatalities due to interstitial lung disease have been reported

            Combination with cisplatin

            • Administer first cycle of topotecan for injection only to patients with a baseline neutrophil count ≥1,500/mm³ and a platelet count ≥100,000/mm³; monitor blood counts frequently during treatment; withhold and reduce dose based on neutrophil counts, platelet counts and hemoglobin levels
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            Pregnancy & Lactation

            Pregnancy

            Based on animal data and its mechanism of action, therapy can cause fetal harm when administered to a pregnant woman; there are no available clinical data on use of therapy in pregnancy; drug caused embryolethality, fetotoxicity, and teratogenicity in rats and rabbits when administered during organogenesis at doses similar to the clinical dose.); advise pregnant women of potential risk to fetus

            Verify pregnancy status of females of reproductive potential prior to initiating therapy

            Contraception

            • Advise females of reproductive potential to use effective contraception during treatment and for 6 months after last dose

            Infertility

            • Females: Therapy can have both acute and long-term effects on fertility
            • Males: Effects on spermatogenesis occurred in animals administered topotecan; therapy may damage spermatozoa, resulting in possible genetic and fetal abnormalities; advise males with a female partner of reproductive potential to use effective contraception during treatment and for 3 months after the last dose

            Lactation

            There are no data on presence of drug or its metabolites in human milk or their effects on breastfed infant or on milk production; lactating rats excrete high concentrations of drug in milk

            Because of potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment and for 1 week after last dose

            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.

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            Pharmacology

            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

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            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

            Injection

            • Unopened vials: Store at 20-25°C (68-77°F); protect from light in original carton; vials contain no preservative, contents should be used immediately after reconstitution
            • Reconstituted vials: Store at 20-25°C (68-77°F) and ambient lighting conditions for 24 hr
            • Diluted solutions: Store at 20-25°C (68-77°F) for ≤4 hr or under refrigerated at 2-8°C (36-46°F) for ≤12 hr

            Capsule

            • Store refrigerated 2-8ºC (36-46ºF); store bottles protected from light in original outer cartons
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            Formulary

            FormularyPatient Discounts

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            • Compare formulary status to other drugs in the same class.
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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
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            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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