Campto Adverse Reactions

Clinical studies: Adverse reactions data has been extensively collected and analyzed for the clinical studies program in metastatic colorectal cancer that recurred or progressed following 5-FU-based therapy (second-line) and are presented as follows (patient population described as follows). The adverse reactions for other indications are expected to be similar to those for second-line colorectal cancer.
Clinical studies of the 100- to 125-mg/m² single-agent weekly dosage schedule: The weekly dosage schedule of irinotecan was evaluated in three clinical studies of 304 patients with metastatic carcinoma of the colon or rectum that had recurred or progressed following 5-FU-based therapy. Five (1.6%) deaths were potentially drug-related. These five patients experienced a constellation of medical events (myelosuppression, neutropenic sepsis without fever, small bowel obstruction, fluid accumulation, stomatitis, nausea, vomiting, diarrhea, and dehydration) that are known effects of irinotecan.
Neutropenic fever, defined as NCI Grade 4 neutropenia and Grade 2 or greater fever, occurred in nine other patients; these patients recovered with supportive care.
Eighty-one (26.6%) patients were hospitalized for events judged to be related to administration of irinotecan. The primary reasons for drug-related hospitalization were diarrhea, with or without nausea and/or vomiting; neutropenia/leukopenia, with or without diarrhea and/or fever; and nausea and/or vomiting.
Adjustments in the dose of irinotecan were made during the cycle of treatment and for subsequent cycles based on individual patient tolerance. The most common reasons for dose reduction were late diarrhea, neutropenia, and leukopenia. Thirteen (4.3%) patients discontinued treatment with irinotecan because of adverse events.
Clinical studies of the 300- to 350-mg/m² once-every-3-week single-agent dosage schedule: A total of 316 patients with metastatic colorectal cancer whose disease had progressed following prior 5-FU therapy received irinotecan in two studies involving once-every-3-week administration. Three (1%) deaths were potentially related to irinotecan treatment and were attributed to neutropenic infection, Grade 4 diarrhea, and asthenia, respectively. Hospitalizations due to serious adverse events, whether or not related to irinotecan administration, occurred at least once in 60% of patients who received irinotecan and, 8% of patients treated with irinotecan discontinued treatment due to adverse events.
Listing of adverse events: The drug-related adverse events (NCI Grades 1-4) as judged by the investigator that were reported in greater than 10% of the 304 patients enrolled in the three studies of the weekly dosage schedule are listed by body system in descending order of frequency in Table 6. (See Table 6.)

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NCI Grade 3 or 4 adverse events reported in the clinical studies of the weekly and once-every-3-week-dosage schedules (N = 620) are listed in Table 7, Table 8 and Table 9. (See Tables 7, 8 and 9.)

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The following additional drug-related events have been reported in clinical studies with irinotecan, but do not meet the criteria as defined previously as either >10% drug-related NCI Grades 1-4 or as a NCI Grade 3 or 4 drug-related event: rhinitis, increased salivation, miosis, lacrimation, diaphoresis, flushing, bradycardia, dizziness, extravasation, tumor lysis syndrome, and colonic ulceration.
Post-marketing surveillance: Cardiac disorders: Myocardial ischemic events have been observed following irinotecan therapy predominantly in patients with underlying cardiac disease, other known risk factors for cardiac disease or previous cytotoxic chemotherapy (see also Table 6, thromboembolic events).
Gastrointestinal disorders: Infrequent cases of intestinal obstruction, ileus, megacolon, or gastrointestinal hemorrhage, and rare cases of colitis, including typhlitis, ischemic and ulcerative colitis were reported. In some cases, colitis was complicated by ulceration, bleeding, ileus, or infection. Cases of ileus without preceding colitis have also been reported. Rare cases of intestinal perforation were reported.
Rare cases of symptomatic pancreatitis or asymptomatic elevated pancreatic enzymes have been observed.
Hypovolemia: There have been rare cases of renal impairment and acute renal failure, generally in patients who became infected and/or volume depleted from severe gastrointestinal toxicities.
Infrequent cases of renal insufficiency, hypotension or circulatory failure have been observed in patients who experienced episodes of dehydration associated with diarrhea and/or vomiting, or sepsis.
Infections and infestations: Bacterial, fungal and viral infections have been reported.
Immune system disorders: Hypersensitivity reactions including severe anaphylactic or anaphylactoid reactions have been reported (see Precautions).
Musculoskeletal and connective tissue disorders: Early effects, such as muscular contraction or cramps and paresthesia have been reported.
Nervous system disorders: Speech disorders, generally transient in nature, have been reported in patients treated with irinotecan; in some cases, the event was attributed to the cholinergic syndrome observed during or shortly after infusion of irinotecan.
Respiratory, thoracic and mediastinal disorders: Interstitial pulmonary disease presenting as pulmonary infiltrates is uncommon during irinotecan therapy. Early effects, such as dyspnea have been reported (see Precautions). Hiccups have also been reported.
Investigations: Rare cases of hyponatremia mostly related with diarrhea and vomiting have been reported. Increases in serum levels of transaminases (i.e., AST and ALT) in the absence of progressive liver metastasis have been very rarely reported.