topotecan hydrochloride

topotecan hydrochloride

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.

References in periodicals archive ?
is pleased to announce the addition of Topotecan Hydrochloride for Injection, 4 mg (base)/vial to its diverse portfolio.
Bedford Laboratories Topotecan Hydrochloride for Injection, 4 mg (base)/vial is sold individually and is latex free, UPC bar coded and preservative free.
FDA approval and launch of its topotecan hydrochloride for injection, a chemotherapy agent, in conjunction with the innovator's patent expiry.
INEX and GSK entered into an agreement in November 2001 to develop GSK's anticancer drug, topotecan hydrochloride, with INEX's proprietary liposomal drug delivery technology.
The drug is comprised of GSK's approved anticancer agent topotecan hydrochloride encapsulated in INEX's TCS.
Topotecan hydrochloride is marketed by GSK as Hycamtin(R).
Topotecan TCS is a combination of INEX's technology with GSK's approved chemotherapy drug topotecan hydrochloride, marketed with the trade name Hycamtin(R).
The first drug to be developed under the agreement is the combination of INEX's drug delivery technology and the GSK camptothecin compound topotecan hydrochloride, marketed by GSK as Hycamtin(R).