Hycamtin

topotecan hydrochloride

Hycamtin

Pharmacologic class: DNA topoisomerase inhibitor

Therapeutic class: Antineoplastic

Pregnancy risk category D

FDA Box Warning

Give under supervision of physician experienced in cancer chemotherapy, in facility with adequate diagnostic and treatment resources.

Don't administer to patients with baseline neutrophil counts below 1,500 cells/mm3. Obtain frequent peripheral blood cell counts on all patients to monitor for bone marrow depression.

Action

Regulates DNA replication and repair of broken DNA strands, relieving torsional strain; exerts cytotoxic effects during DNA synthesis

Availability

Capsules: 0.25 mg, 1 mg

Injection: 4 mg in 4-ml single-dose vials

Injection (powder for solution): 4 mg in single-dose vials

Indications and dosages

Metastatic ovarian cancer or small-cell lung cancer after first-line chemotherapy fails

Adults: 1.5 mg/m2 daily by I.V. infusion given over 30 minutes for 5 consecutive days, starting on day 1 of 21-day cycle

Relapsed small-cell lung cancer

Adults: 2.3 mg/m2 P.O. daily for 5 consecutive days; repeat every 21 days

Stage IV-B, recurrent, or persistent cervical carcinoma not amenable to curative treatment with surgery or radiation therapy (in combination with cisplatin)

Adults: 0.75 mg/m2 I.V. daily over 30 minutes on days 1, 2, and 3; followed by cisplatin 50 mg/m2 by I.V. infusion on day 1, repeated every 21 days

Dosage adjustment

• Renal impairment

• Neutropenia

• Grade 3 or 4 diarrhea (capsules)

Contraindications

• History of severe hypersensitivity to drug or its components

• Severe bone marrow depression

Precautions

Use cautiously in:

• pregnant or breastfeeding patients

• children (safety and efficacy not established).

Administration

Before starting therapy, check blood counts. Patient must have baseline neutrophil count above 1,500 cells/mm3 and platelet count above 100,000 cells/mm3 to receive drug.

Prepare drug under vertical laminar-flow hood, wearing gloves and protective clothing. Follow facility policy for discarding used drug containers and I.V. equipment.

• If skin contacts drug, wash immediately with soap and water.

• To reconstitute, add 4 ml of sterile water to 4-mg vial. Dilute further in normal saline solution or dextrose 5% in water. Give immediately over 30 minutes using infusion pump.

• Round calculated oral daily dose to nearest 0.25 mg, and administer minimum number of 1-mg and 0.25-mg capsules. Know that the same number of capsules should be prescribed for each of the 5 dosing days.

Adverse reactions

CNS: asthenia, fatigue, paresthesia

GI: nausea, diarrhea, constipation, abdominal pain, stomatitis, anorexia, severe diarrhea, neutropenic colitis

Hematologic: anemia, leukopenia, thrombocytopenia, neutropenia

Musculoskeletal: back pain, skeletal pain

Respiratory: coughing, dyspnea, interstitial lung disease

Skin: erythematous or maculopapular rash, pruritus, urticaria, dermatitis, bullous eruption, alopecia

Other: fever, body pain, sepsis

Interactions

Drug-drug. Cisplatin: severe bone marrow depression

Granulocyte colony-stimulating factor: prolonged neutropenia

Live-virus vaccines: increased risk of infection from vaccine

Drug-diagnostic tests. Alanine aminotransferase, aspartate aminotransferase, bilirubin: increased levels

Patient monitoring

• Closely monitor CBC with white cell differential.

Assess for signs and symptoms of bleeding tendency, severe diarrhea (with capsule use), and neutropenic colitis (fever, neutropenia, and compatible pattern of abdominal pain).

Monitor patient for signs and symptoms of interstitial lung disease (cough, fever, dyspnea, or hypoxia); discontinue drug if diagnosis is confirmed.

• Monitor closely for sepsis, other infections, and increased hepatic enzyme levels.

Patient teaching

• Tell patient to take capsules whole with or without food and not to break, divide, chew, or crush them.

Advise patient to immediately report unusual bleeding or bruising, diarrhea, abdominal pain, cough, difficulty breathing, sore throat, fever, or chills.

• Teach patient safety measures to avoid bruising and bleeding.

• Tell patient to minimize GI upset by eating small, frequent servings of food and drinking plenty of fluids.

Advise female patient to notify prescriber of suspected pregnancy. Caution her not to breastfeed during therapy.

• Inform patient that drug may cause hair loss.

• Tell patient he'll undergo regular blood testing during therapy.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

topotecan

(toe-poe-tee-kan) ,

Hycamtin

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: enzyme inhibitors
Pregnancy Category: D

Indications

Intravenous: Metastatic ovarian cancer that has not responded to previous chemotherapy.Small cell lung cancer unresponsive to first line therapy. Oral: 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.Stage IV-B persistent or recurrent cervical cancer not amenable to treatment with surgery or radiation (with cisplatin).

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.
Distribution: Unknown.
Metabolism and Excretion: 30% excreted in urine; small amounts metabolized by the liver.
Half-life: PO—3–6 hr; IV—2–3 hr.

Time/action profile (effects on WBCs)

ROUTEONSETPEAKDURATION
POunknown1–2 hr24 hr
IVwithin days11 days7 days

Contraindications/Precautions

Contraindicated in: Hypersensitivity;Pre-existing severe myelosuppression; Obstetric / Lactation: Pregnancy or lactation.
Use Cautiously in: Impaired renal function (↓ dose if CCr <40 mL/min);Platelet count <25,000 cells/mm3 (↓ dose);History of interstitial lung disease, pulmonary fibrosis, lung cancer, thoracic radiation, or use of pneumotoxic drugs or colony stimulating factors; Geriatric: May require dose ↓ due to age-related ↓ in renal function.

Adverse Reactions/Side Effects

Central nervous system

  • headache (most frequent)
  • fatigue
  • weakness

Respiratory

  • interstitial lung disease (life-threatening)
  • dyspnea (most frequent)

Gastrointestinal

  • abdominal pain (most frequent)
  • diarrhea (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)
  • anorexia
  • constipation
  • ↑ liver enzymes
  • stomatitis

Dermatologic

  • alopecia (most frequent)

Hematologic

  • anemia (most frequent)
  • leukopenia (most frequent)
  • thrombocytopenia (most frequent)

Musculoskeletal

  • arthralgia

Interactions

Drug-Drug interaction

Neutropenia is prolonged by concurrent use of filgrastim (do not use 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

Oral (Adults) 2.3 mg/m2/day for 5 days repeated every 21 days (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).
Intravenous (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

Oral (Adults) Ovarian and Small Cell Lung Cancer—CCr 30–49 mL/min—1.8 mg/m2/day starting on day 1 of a 21-day course.
Intravenous (Adults) CCr 20–39 mL/min—0.75mg/m2/day for 5 days starting on day 1 of a 21-day course. Cervical Cancer—Administer at standard doses only if serum creatinine is ≤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

Nursing implications

Nursing 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 interstitial lung disease (cough, fever, dyspnea, hypoxia). Discontinue topotecan if interstitial lung disease is confirmed.
  • Lab Test Considerations: 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 9.0 mg/dL. If severe neutropenia occurs during any course, subsequent doses should be reduced by 0.25 mg/m2 or filgrastim may be administered following the subsequent course of therapy starting on day 6, 24 hr after the completion of topotecan.
    • Monitor liver function. May cause transient ↑ in AST, ALT, and bilirubin concentrations.

Potential Nursing Diagnoses

Risk for infection (Adverse Reactions)

Implementation

  • high alert: Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double check single, daily, and course-of-therapy dose limits; have second practitioner independently double check original order, dose calculations and infusion pump settings.
  • Oral: May be taken without regard to food. Capsules must be swallowed whole; do not open, crush, or chew. If patient vomits after taking dose, do not replace dose.
  • Intravenous Administration
  • pH: 2.5–3.5.
  • 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: 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.
  • Y-Site Compatibility: alemtuzumab, anidulafungin, argatroban, bivalirudin, carboplatin, caspofungin, cisplatin, cyclophosphamide, dactinomycin, daptomycin, dexmedetomidine, doxorubicin, etoposide, fenoldopam, gemcitabine, granisetron, ifosfamide, levofloxacin, meperidine, methylprednisolone, metoclopramide, nesiritide, octreotide, ondansetron, oxaliplatin, paclitaxel, palonosetron, pamidronate, prochlorperazine, teniposide, thiotepa, tigecycline, tirofiban, vincristine, voriconazole, zoledronic acid
  • Y-Site Incompatibility: amphotericin B lipid complex, dexamethasone sodium phosphate, ertapenem, fluorouracil, mitomycin, pantoprazole, pemetrexed, rituximab, trastuzumab

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 refill; new information may be available.
  • 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.
  • Advise patient that this medication may have teratogenic effects. Contraception should be used during therapy and breast feeding avoided.
  • Emphasize the need for periodic lab tests to monitor for side effects.

Evaluation/Desired Outcomes

  • Decrease in size and spread of malignancy.

topotecan

A water-soluble derivative of camptothecin, obtained from the Chinese tree Camptotheca accuminata. It is a topoisomerase inhibitor which is FDA-approved for treating ovarian, cervical and small cell carcinoma of the lung.

Hycamtin

A brand name for TOPOTECAN.
References in periodicals archive ?
Two synthetic forms, marketed as Camptosar and Hycamtin, are used in chemotherapy treatments today.
It has also introduced Hycamtin, a GSK product having its patent in the name of SmithKline Beecham.
Topoisomerase inhibitor-based cancer drugs at present in clinical use include Irinotecan for colorectal cancer (Wiseman and Markham 1996), Hycamtin for lung cancer (Riemsma et al.
Topotecan is AP-bioequivalent to Hycamtin (GlaxoSmithKline PLC).
In The Journal North 40 portfolio, drug giant GlaxoSmithKline, was in focus as the UK's National Institute for Health and Clinical Excellence (NICE) said that it would recommend the use of its drug Hycamtin.
IV Hycamtin is the first specific lung cancer drug that has ever been approved by the EU.
Hospitals can treat patients with Hycamtin only if it is paid for from the general hospital budget.
Other big sellers among recently launched drugs were the Kredex heart treatment, Hycamtin for cancer and Requip for Parkinson's disease.
Hycamtin is one of the first of a relatively new kind of anticancer drugs that kills cancer cells by inhibiting an enzyme essential to the replication of human DNA.
Topotecan Eagle is a hybrid of GlaxoSmithKline's (LON:GSK) Hycamtin, which has been approved in the EU since November 1996.
Topotecan hydrochloride for injection, Hycamtin for