Hycamtin 1mg Information
Hycamtin 1mg (Topotecan (topotecan hydrochloride)) Warning: Bone Marrow Suppression
Do not give HYCAMTIN to patients with baseline neutrophil counts less than 1,500 cells/mm. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection and death, monitor peripheral blood counts frequently on all patients receiving HYCAMTIN
Hycamtin 1mg (Topotecan (topotecan hydrochloride)) Indications And Usage
HYCAMTIN is indicated for the treatment of:
HYCAMTIN in combination with cisplatin is indicated for the treatment of:
Hycamtin 1mg (Topotecan (topotecan hydrochloride)) Dosage And Administration
Prior to administration of the first course of HYCAMTIN, patients must have a baseline neutrophil count of >1,500 cells/mm and a platelet count of >100,000 cells/mm.
Hycamtin 1mg (Topotecan (topotecan hydrochloride)) Dosage Forms And Strengths
4-mg (free base) single-dose vial, light yellow to greenish powder.
Hycamtin 1mg (Topotecan (topotecan hydrochloride)) Contraindications
HYCAMTIN is contraindicated in patients who have a history of severe hypersensitivity reactions (e.g., anaphylactoid reactions) to topotecan or to any of its ingredients. HYCAMTIN should not be used in patients with severe bone marrow depression.
Hycamtin 1mg (Topotecan (topotecan hydrochloride)) Warnings And Precautions
Pregnancy Category D
HYCAMTIN can cause fetal harm when administered to a pregnant woman.
Topotecan caused embryolethality, fetotoxicity, and teratogenicity in rats and rabbits when administered during organogenesis. There are no adequate and well controlled studies of HYCAMTIN in pregnant women. If this drug is used during pregnancy, or if a patient becomes pregnant while receiving HYCAMTIN, the patient should be apprised of the potential hazard to the fetus.
Hycamtin 1mg (Topotecan (topotecan hydrochloride)) Drug Interactions
Greater myelosuppression is also likely to be seen when HYCAMTIN is used in combination with other cytotoxic agents, thereby necessitating a dose reduction. However, when combining HYCAMTIN with platinum agents (e.g., cisplatin or carboplatin), a distinct sequence-dependent interaction on myelosuppression has been reported. Coadministration of a platinum agent on day 1 of dosing with HYCAMTIN required lower doses of each agent compared to coadministration on day 5 of the dosing schedule for HYCAMTIN.
For information on the pharmacokinetics, efficacy, safety, and dosing of HYCAMTIN at a dose of 0.75 mg/m2/day on days 1, 2, and 3 in combination with cisplatin 50 mg/m2 on day 1 for cervical cancer, see Dosage and Administration (2), Adverse Reactions (6 ), Clinical Pharmacology (12.3), and Clinical Studies (14).
Hycamtin 1mg (Topotecan (topotecan hydrochloride)) Use In Specific Populations
Pregnancy Category D .
HYCAMTIN can cause fetal harm when administered to a pregnant woman. In rabbits, a dose of 0.10 mg/kg/day (about equal to the clinical dose on a mg/m basis) given on days 6 through 20 of gestation caused maternal toxicity, embryolethality, and reduced fetal body weight. In the rat, a dose of 0.23 mg/kg/day (about equal to the clinical dose on a mg/m basis) given for 14 days before mating through gestation day 6 caused fetal resorption, microphthalmia, pre-implant loss, and mild maternal toxicity. A dose of 0.10 mg/kg/day (about half the clinical dose on a mg/m basis) given to rats on days 6 through 17 of gestation caused an increase in post-implantation mortality. This dose also caused an increase in total fetal malformations. The most frequent malformations were of the eye (microphthalmia, anophthalmia, rosette formation of the retina, coloboma of the retina, ectopic orbit), brain (dilated lateral and third ventricles), skull, and vertebrae.
There are no adequate and well controlled studies of HYCAMTIN in pregnant women. If this drug is used during pregnancy, or if a patient becomes pregnant while receiving HYCAMTIN, the patient should be apprised of the potential hazard to the fetus.
Of the 879 patients with metastatic ovarian cancer or small cell lung cancer in clinical studies of HYCAMTIN, 32% (n = 281) were 65 years of age and older, while 3.8% (n = 33) were 75 years of age and older. Of the 140 patients with stage IV-B, relapsed, or refractory cervical cancer in clinical studies of HYCAMTIN who received HYCAMTIN plus cisplatin in the randomized clinical trial, 6% (n = 9) were 65 years of age and older, while 3% (n = 4) were 75 years of age and older. No overall differences in effectiveness or safety were observed between these patients and younger adult patients, and other reported clinical experience has not identified differences in responses between the elderly and younger adult patients, but greater sensitivity of some older individuals cannot be ruled out.
There were no apparent differences in the pharmacokinetics of topotecan in elderly patients, once the age-related decrease in renal function was considered .
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function .
Hycamtin 1mg (Topotecan (topotecan hydrochloride)) Overdosage
There is no known antidote for overdosage with HYCAMTIN. The primary anticipated complication of overdosage would consist of bone marrow suppression.
One patient on a single-dose regimen of 17.5 mg/m given on day 1 of a 21-day cycle had received a single dose of 35 mg/m. This patient experienced severe neutropenia (nadir of 320/mm) 14 days later but recovered without incident.
Observe patients closely for bone marrow suppression, and supportive measures (such as the prophylactic use of G-CSF and/or antibiotic therapy).
Hycamtin 1mg (Topotecan (topotecan hydrochloride)) Description
HYCAMTIN (topotecan hydrochloride) is a semi-synthetic derivative of camptothecin and is an anti-tumor drug with topoisomerase I-inhibitory activity.
HYCAMTIN for Injection is supplied as a sterile lyophilized, buffered, light yellow to greenish powder available in single-dose vials. Each vial contains topotecan hydrochloride equivalent to 4 mg of topotecan as free base. The reconstituted solution ranges in color from yellow to yellow-green and is intended for administration by intravenous infusion.
Inactive ingredients are mannitol, 48 mg, and tartaric acid, 20 mg. Hydrochloric acid and sodium hydroxide may be used to adjust the pH. The solution pH ranges from 2.5 to 3.5.
The chemical name for topotecan hydrochloride is ()-10-[(dimethylamino)methyl]-4-ethyl-4,9-dihydroxy-1-pyrano[3’,4’:6,7] indolizino [1,2-]quinoline-3,14-(4,12)-dione monohydrochloride. It has the molecular formula CHNO•HCl and a molecular weight of 457.9.
Topotecan hydrochloride has the following structural formula:
It is soluble in water and melts with decomposition at 213° to 218°C.
Hycamtin 1mg (Topotecan (topotecan hydrochloride)) Clinical Studies
HYCAMTIN was studied in 2 clinical trials of 223 patients given topotecan with metastatic ovarian carcinoma. All patients had disease that had recurred on, or was unresponsive to, a platinum-containing regimen. Patients in these 2 studies received an initial dose of 1.5 mg/m given by intravenous infusion over 30 minutes for 5 consecutive days, starting on day 1 of a 21-day course.
One study was a randomized trial of 112 patients treated with HYCAMTIN (1.5 mg/m/day × 5 days starting on day 1 of a 21-day course) and 114 patients treated with paclitaxel (175 mg/m over 3 hours on day 1 of a 21-day course). All patients had recurrent ovarian cancer after a platinum-containing regimen or had not responded to at least 1 prior platinum-containing regimen. Patients who did not respond to the study therapy, or who progressed, could be given the alternative treatment.
Response rates, response duration, and time to progression are shown in Table 7.
a
The median time to response was 7.6 weeks (range 3.1 to 21.7) with HYCAMTIN compared to 6.0 weeks (range 2.4 to 18.1) with paclitaxel. Consequently, the efficacy of HYCAMTIN may not be achieved if patients are withdrawn from treatment prematurely.
In the crossover phase, 8 of 61 (13%) patients who received HYCAMTIN after paclitaxel had a partial response and 5 of 49 (10%) patients who received paclitaxel after HYCAMTIN had a response (2 complete responses).
HYCAMTIN was active in ovarian cancer patients who had developed resistance to platinum-containing therapy, defined as tumor progression while on, or tumor relapse within 6 months after completion of, a platinum-containing regimen. One complete and 6 partial responses were seen in 60 patients, for a response rate of 12%. In the same study, there were no complete responders and 4 partial responders on the paclitaxel arm, for a response rate of 7%.
HYCAMTIN was also studied in an open-label, non-comparative trial in 111 patients with recurrent ovarian cancer after treatment with a platinum-containing regimen, or who had not responded to 1 prior platinum-containing regimen. The response rate was 14% (95% CI = 7% to 20%). The median duration of response was 22 weeks (range 4.6 to 41.9 weeks). The time to progression was 11.3 weeks (range 0.7 to 72.1 weeks). The median survival was 67.9 weeks (range 1.4 to 112.9 weeks).
In a comparative trial, 147 eligible women were randomized to HYCAMTIN (0.75 mg/m/day IV over 30 minutes × 3 consecutive days starting on day 1 of a 21-day course) plus cisplatin (50 mg/m on day 1) and 146 eligible women were randomized to cisplatin (50 mg/m IV on day 1 of a 21-day course). All patients had histologically confirmed Stage IV-B, recurrent, or persistent carcinoma of the cervix considered not amenable to curative treatment with surgery and/or radiation. Fifty-six percent (56%) of patients treated with HYCAMTIN plus cisplatin and 56% of patients treated with cisplatin had received prior cisplatin with or without other agents as first-line chemotherapy.
Median survival of eligible patients receiving HYCAMTIN plus cisplatin was 9.4 months (95% CI: 7.9 to 11.9) compared to 6.5 months (95% CI: 5.8 to 8.8) among patients randomized to cisplatin alone with a log rank -value of 0.033 (significance level was 0.044 after adjusting for the interim analysis). The unadjusted hazard ratio for overall survival was 0.76 (95% CI: 0.59 to 0.98).
Hycamtin 1mg (Topotecan (topotecan hydrochloride)) How Supplied/storage And Handling
HYCAMTIN for Injection is supplied in 4-mg (free base) single-dose vials.
NDC 0007-4201-01 (package of 1)
NDC 0007-4201-05 (package of 5)
Hycamtin 1mg (Topotecan (topotecan hydrochloride)) Patient Counseling Information
Inform patients that HYCAMTIN may cause asthenia or fatigue. If these symptoms occur, caution should be observed when driving or operating machinery.
HYCAMTIN is a registered trademark of GlaxoSmithKline.
GlaxoSmithKline
Research Triangle Park, NC 27709
©2010, GlaxoSmithKline. All rights reserved.
April 2010
HYJ:20PI
Hycamtin 1mg (Topotecan (topotecan hydrochloride))
