Topotecan

Hycamtin

0.25MG BASE, 1MG BASE capsuleVereinigte StaatenIm HandelZugelassen am 11. Okt. 2007

Inhalt auf Englisch

Anwendungsgebiete

HYCAMTIN ® capsules are indicated for the treatment of relapsed small cell lung cancer (SCLC) in patients with a prior complete or partial response and who are at least 45 days from the end of first-line chemotherapy. HYCAMTIN capsules is a topoisomerase inhibitor indicated for treatment of patients with relapsed small cell lung cancer (SCLC). ( 1 )

Gegenanzeigen

HYCAMTIN is contraindicated in patients who have a history of severe hypersensitivity reactions to topotecan. Reactions have included anaphylactoid reactions [see Adverse Reactions (6.2)] .

History of severe hypersensitivity reactions to topotecan ( 4 )

Warnhinweise und Vorsichtsmaßnahmen

Diarrhea: Severe diarrhea can occur. Withhold and reduce dose as recommended. ( 2.2 , 5.2 )
Interstitial Lung Disease (ILD): Fatal cases have occurred. Permanently discontinue if confirmed ILD. ( 5.3 )
Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of potential risk to the fetus and to use effective contraception. ( 5.4 , 8.1 , 8.3 )

5.1Myelosuppression

HYCAMTIN can cause severe myelosuppression. The following safety data are based on an integrated safety database from four trials in patients with lung cancer (N = 682) who received HYCAMTIN capsules at a dose of 2.3 mg/m 2 orally once daily for 5 consecutive days, starting on Day 1 of a 21-day cycle. The median day for neutrophil and platelet nadirs occurred on Day 15. Grade 4 neutropenia occurred in 32% of the 682 patients, with a median duration of 7 days.

Grade 4 neutropenia most commonly occurred during cycle 1 (20% of patients). Clinical sequelae of neutropenia included infection (17%), febrile neutropenia (4%), sepsis (2%), and septic death (1%). Grade 4 thrombocytopenia occurred in 6%, with a median duration of 3 days. Grade 3 or 4 anemia occurred in 25%. HYCAMTIN can cause fatal typhlitis (neutropenic enterocolitis). Consider the possibility of typhlitis in patients presenting with fever, neutropenia, and abdominal pain.

Anwendungsgebiete

Warnhinweise und Vorsichtsmaßnahmen

Diarrhea: Severe diarrhea can occur. Withhold and reduce dose as recommended. ( 2.2 , 5.2 )
Interstitial Lung Disease (ILD): Fatal cases have occurred. Permanently discontinue if confirmed ILD. ( 5.3 )
Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of potential risk to the fetus and to use effective contraception. ( 5.4 , 8.1 , 8.3 )

5.1Myelosuppression

Nebenwirkungen

The following serious adverse reactions are described elsewhere in the labeling:

Myelosuppression [see Warnings and Precautions (5.1)]
Diarrhea [see Warnings and Precautions (5.2)]
Interstitial Lung Disease (ILD) [see Warnings and Precautions (5.3)]
The most common Grade 3 or 4 hematologic adverse reactions (incidence > 20%) were neutropenia, anemia, and thrombocytopenia.
The most common (incidence > 10%) non-hematologic adverse reactions (all Grades) were nausea, diarrhea, vomiting, alopecia, fatigue, and anorexia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data in the Warnings and Precautions and below reflects exposure to HYCAMTIN capsules in 682 patients with recurrent lung cancer enrolled in four randomized, open label trials, including 275 patients with small lung cell lung cancer (SCLC) (Studies 478, 065 and 396), and 407 patients with non-small cell lung cancer (NSCLC) (Study 387), who received at least one dose of HYCAMTIN capsules.

Patients in these trials had advanced lung cancer and received prior chemotherapy in the first-line setting. Patients received HYCAMTIN capsules 2.3 mg/m 2 orally once daily for 5 consecutive days, starting on Day 1 of a 21-day cycle. The median number of cycles was 3 (range: 1 to 20). The safety of HYCAMTIN capsules was evaluated in a randomized trial (Study 478) conducted in 70 patients with recurrent SCLC [see Clinical Studies (14)] .

In the 682 patients who received HYCAMTIN capsules in the four lung cancer trials, 39 deaths (6%) occurred within 30 days after the last dose for a reason other than progressive disease: 13 due to hematologic toxicity, 5 due to non-hematologic toxicity (2 from diarrhea), and 21 due to other causes. Table 1 describes the hematologic and non-hematologic adverse reactions that occurred in greater than 5% of patients treated with HYCAMTIN capsules in these trials.

Table 1. Adverse Reactions Occurring in Greater than or Equal to 5% of Patients With Lung Cancer Adverse Reactions Adverse reactions were graded using National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Version 2.0. HYCAMTIN Capsules With Best Supportive Care (Study 478) HYCAMTIN Capsules Lung Cancer Population (Studies 478, 065, 396 and 387) N = 70 N = 682 All Grades (%) Grade 3 (%) Grade 4 (%) All Grades (%) Grade 3 (%) Grade 4 (%) Hematologic Anemia 94 15 10 98 18 7 Neutropenia 91 28 33 83 24 32 Thrombocytopenia 81 30 7 81 29 6 Non-hematologic Nausea 27 1 0 33 3 0 Vomiting 19 1 0 21 3

0.4 Diarrhea 14 4 1 22 4

0.4 Fatigue 11 0 0 19 4

0.1 Alopecia 10 0 0 20 0.1 0 Pyrexia 7 1 0 5 1 1 Anorexia 7 0 0 14 2 0 Asthenia 3 0 0 7 2 0

6.2Postmarketing Experience

The following reactions have been identified during post approval use of HYCAMTIN. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Gastrointestinal: Gastrointestinal perforation General and Administration Site Conditions: Mucosal inflammation Hypersensitivity: Allergic manifestations, anaphylactoid reactions, angioedema

Packung	Code	Status
TOPOTECAN HYDROCHLORIDE EQ 0.25MG BASE	NDA020981-001	Prescription
TOPOTECAN HYDROCHLORIDE EQ 1MG BASE	NDA020981-002	Prescription

Hycamtin

Anwendungsgebiete

Gegenanzeigen

Warnhinweise und Vorsichtsmaßnahmen

5.1Myelosuppression

Zwei Arzneimittel in einer Frage?

Hycamtin

Anwendungsgebiete

Gegenanzeigen

Warnhinweise und Vorsichtsmaßnahmen

5.1Myelosuppression

Zwei Arzneimittel in einer Frage?

5.2Diarrhea

5.3Interstitial Lung Disease

5.4Embryo-Fetal Toxicity Based

Wechselwirkungen

7.1Effect of Other Drugs on

Schwangerschaft und Stillzeit

8.1Pregnancy Risk Summary Based

Nebenwirkungen

6.1Clinical Trials Experience

6.2Postmarketing Experience

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