CAMPTOSAR PACKAGE INSERT PDF
Irinotecan hydrochloride 20 mg/ml concentrate for solution for infusion capecitabine, please make sure that you also read the package insert for these. CATALOG SHEET · PACKAGE INSERT · SDS SHEET · BAR CODES · WHOLESALER ITEM NUMBERS · STORAGE REQUIREMENTS · RETURN GOODS. In depth information on Camptosar (irinotecan) for treatment of colorectal cancer. spacer. Camptosar (irinotecan) Product Information For Health Care Professionals CAMPTOSAR – Package Insert.
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Appropriate management of complications is possible camptosra when adequate diagnostic and treatment facilities are readily available.
Both forms of diarrhea may be severe. Early diarrhea occurring during or shortly after infusion of CAMPTOSAR may be accompanied by cholinergic symptoms of rhinitis, increased salivation, miosis, lacrimation, diaphoresis, flushing, and intestinal hyperperistalsis that can cause abdominal cramping.
Late diarrhea generally occurring more than 24 hours after administration of CAMPTOSAR can be prolonged, may lead to dehydration and electrolyte imbalance, and can be life threatening.
Late diarrhea should be treated promptly ihsert loperamide; patients with severe diarrhea should be carefully monitored and given fluid and electrolyte replacement if they become dehydrated see WARNINGS section.
Oackage hydrochloride was clinically investigated as CPT It is available in two single-dose sizes: The pH of the solution has been adjusted to 3. Irinotecan hydrochloride is a semisynthetic derivative of camptothecin, an alkaloid extract from plants such as Camptotheca acuminata. The chemical name is 4S -4,diethylhydroxy[ 4-piperidino-piperidino carbonyloxy]-1H-pyrano[3′,4′: Its structural formula is as follows:.
It is slightly soluble in water and organic solvents. Irinotecan is a derivative of camptothecin. Camptothecins interact specifically with the enzyme topoisomerase I which relieves torsional strain in DNA by packsge reversible single-strand breaks. Irinotecan and pacakge active metabolite SN bind to the topoisomerase I-DNA complex and prevent religation of these single-strand breaks.
Current research suggests that the cytotoxicity of irinotecan is due to double-strand DNA damage produced during DNA synthesis when replication enzymes interact with the ternary complex formed by topoisomerase I, DNA, and either irinotecan or SN Damptosar cells cannot efficiently repair these double-strand breaks. Irinotecan serves as a water-soluble precursor of the lipophilic metabolite SN SN is formed from irinotecan by carboxylesterase-mediated cleavage of the carbamate bond between the camptothecin moiety and the dipiperidino side chain.
In vitro cytotoxicity assays show that the potency of SN relative to irinotecan varies from 2- to fold.
Both irinotecan and SN exist in an active lactone form and an inactive hydroxy acid anion form. A pH-dependent equilibrium exists between the two forms such that an acid pH promotes the formation of the lactone, while a more basic pH favors the hydroxy acid anion form.
Administration of irinotecan has resulted in antitumor activity in mice bearing cancers of rodent origin and in human carcinoma xenografts of various histological types. After intravenous infusion of irinotecan in humans, irinotecan plasma concentrations decline in a multiexponential manner, with a mean terminal elimination half-life of about 6 to 12 hours. The half-lives of the lactone active forms of irinotecan and SN are similar to those of total irinotecan and SN, as the lactone and hydroxy acid forms are in equilibrium.
Maximum concentrations of the active metabolite SN are generally seen within 1 hour following the end of a minute infusion of irinotecan.
Because of the longer collection period, these values provide a more accurate reflection of the terminal elimination half-lives of irinotecan and SN The plasma protein to which irinotecan and SN predominantly binds is albumin.
The metabolic conversion of irinotecan to the active metabolite SN is mediated by carboxylesterase enzymes and primarily occurs in the liver.
SN subsequently undergoes conjugation insrrt form a glucuronide metabolite. The disposition of irinotecan has not been fully elucidated in humans.
HIGHLIGHTS OF PRESCRIBING INFORMATION
In studies using the weekly schedule, the terminal half-life of irinotecan was 6. No change in the starting dose is recommended for geriatric patients receiving the weekly dosage schedule of irinotecan. The influence of hepatic insufficiency on the pharmacokinetic characteristics of irinotecan and its metabolites has not been formally studied.
The influence of renal insufficiency on the pharmacokinetics of irinotecan has not been evaluated. Clinical studies using these two dosage schedules are described below.
Data from three open-label, single-agent, clinical studies, involving a total of patients in 59 centers, support the use of CAMPTOSAR in the treatment of patients with metastatic cancer of the colon or rectum that has recurred or progressed following treatment with fluorouracil 5-FU -based therapy.
These studies were designed to evaluate tumor response rate and do not provide information on actual clinical benefit, such as effects on survival and disease-related symptoms. In each study, CAMPTOSAR was administered in repeated 6-week courses consisting of a minute intravenous infusion once weekly for 4 weeks, followed by a 2-week rest period. Study 1 enrolled 48 patients and was conducted by a single investigator at several regional hospitals.
All patients in these studies had metastatic colorectal cancer, and the majority had disease that recurred or progressed following a 5-FU-based regimen administered for metastatic disease. Packagw these patients, 2 complete and 27 partial responses were observed, for an overall response rate of The majority of responses were observed within the first two courses of therapy, but responses did occur in later courses of treatment one response was observed after the eighth course.
Rates were also similar in patients with cancer of the colon or cancer of the rectum and in patients with single and multiple metastatic sites. The response rate was Patients with a performance czmptosar of 3 or 4 have not been studied.
Patients who had received previous irradiation to the pelvis responded to CAMPTOSAR at approximately the same rate as those who had not previously received irradiation. Data from an open-label, single-agent, single arm, multicenter, clinical study involving a total of patients support a once everyweek dosage schedule of irinotecan in the treatment of patients with metastatic cancer of the colon or rectum that recurred or progressed following treatment with 5-FU.
Among the previously treated patients in this trial, the intent-to-treat response rate was Two multicenter, randomized, clinical studies further support the use of irinotecan given by the once-everyweek dosage schedule in patients with metastatic colorectal cancer whose disease has recurred or progressed following prior 5-FU therapy. In the first study, second-line irinotecan therapy plus best supportive care was compared with best supportive care alone.
In the second study, second-line irinotecan therapy camposar compared with infusional 5-FU-based therapy. The highest total dose permitted was mg. Best supportive care was provided to patients in both arms of Study 1 and included antibiotics, analgesics, corticosteroids, transfusions, psychotherapy, or any other symptomatic therapy as clinically indicated. If late diarrhea persisted for greater than 24 hours despite loperamide, a 7-day course of fluoroquinolone antibiotic prophylaxis was given.
Patients in the control arm of the second study received one of the following 5-FU regimens: Patients were to be followed every camptosad to 6 weeks for 1 year. A total of patients were randomized in the two studies at 94 centers in Europe, the Middle East, and South Africa.
The primary endpoint in both studies was survival. In Study 1, median survival for patients treated with irinotecan was 9. In Study 2, median survival for patients treated with irinotecan was Multiple regression analyses determined that patients’ baseline characteristics also had a significant effect on survival.
The overall results of the two phase 3 studies are shown in Table packagee. Measurements of innsert, performance status, and weight loss were collected prospectively in the two studies; however, the plan for the analysis of these data was defined retrospectively. When comparing irinotecan with best supportive care in Study 1, this analysis showed a statistically significant advantage for irinotecan, with longer time to development of pain 6.
Because of the inclusion of patients with non-measurable disease, intent-to-treat response rates could not be assessed.
At each visit, patients completed a questionnaire consisting of 30 questions, such as “Did pain interfere with daily activities?
The answers from the 30 questions were converted into 15 subscales, that were scored from 0 to The global health status subscale was derived from two questions about the patient’s sense of general well being in the past week.
The results as summarized in Table 4 are based on patients’ worst post-baseline scores. In Study 1, a multivariate analysis and univariate analyses of the individual subscales were performed and corrected for multivariate testing. Patients receiving irinotecan reported significantly better caamptosar for the global health status, on two of five functional subscales, and on four of nine symptom subscales.
As expected, patients receiving irinotecan noted significantly more diarrhea than those receiving best supportive care. Packave Study 2, the multivariate analysis on all 15 subscales did not indicate a statistically significant difference between irinotecan and infusional 5-FU.
The subscale scores of each patient were collected at each visit until the patient dropped out of the study. It is usually transient and only infrequently is severe. It may be accompanied by symptoms of rhinitis, increased salivation, miosis, lacrimation, diaphoresis, flushing, and intestinal hyperperistalsis that can cause abdominal cramping.
Patients with severe diarrhea should cam;tosar carefully monitored and given fluid and electrolyte replacement if they become dehydrated. Routine administration of a colony-stimulating factor CSF is not necessary, but physicians may wish to consider CSF use in individual patients experiencing significant neutropenia. Irinotecan was teratogenic in rats at doses greater than 1. Teratogenic effects included a variety of external, visceral, and insett abnormalities.
There are no adequate and well-controlled studies of irinotecan in pregnant women. If the insertt is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus.
Care of Intravenous Site: Care should be taken to avoid canptosar, and the infusion site should be monitored for signs of inflammation. Should extravasation occur, flushing the site with sterile water and applications of ice are recommended. It is recommended that patients receive premedication with antiemetic agents. Physicians should also consider providing patients with an antiemetic regimen packge. Treatment of Cholinergic Symptoms: Prophylactic or therapeutic administration of 0.
These symptoms are expected to occur more frequently with higher irinotecan doses.
Camptosar® (Irinotecan) – GlobalRPH
Patients at Particular Risk: However in clinical trials of the weekly dosage schedule, it has been noted that patients with modestly elevated baseline serum total bilirubin levels 1. An association between baseline bilirubin elevations and an increased risk of late diarrhea has not been observed in studies of the weekly dosage schedule.
Patients and patients’ caregivers should be informed of the expected toxic effects of CAMPTOSAR, particularly of its gastrointestinal manifestations, such as nausea, vomiting, and diarrhea. Each patient should be instructed to have loperamide readily available and to begin treatment for late diarrhea generally occurring more than 24 hours after administration of CAMPTOSAR at the first episode of poorly formed or loose stools or the earliest onset of bowel movements more frequent than normally expected for the patient.
One dosage regimen for loperamide used in clinical trials consisted of the following Note: This dosage regimen exceeds the usual dosage recommendations for loperamide. During the night, the patient may take 4 mg of loperamide every 4 hours.