Irinotel Adverse Reactions

Blood: Neutropenia is a frequent and dose-limiting toxicity of irinotecan. Neutropenia is observed in most patients, and is grade 3 or 4 in up to 33% treated with 100 mg/m² weekly.
Thrombocytopenia and anemia are generally less frequent and not severe. However, blood transfusions were given in approximately 10% of 304 patients during phase II trials. Leukocyte nadirs have occurred on days 21 to 29 during weekly intravenous administration, and recovery is evident by days 27 to 34.
Eosinophilia is observed in up to one-third of patients during therapy.
Gastrointestinal: Diarrhea is a dose-limiting toxicity during irinotecan therapy. It can induce both early and late forms of diarrhea. Abdominal cramps, nausea, vomiting, diaphoresis and anorexia may precede the onset of diarrhea. Pretreatment with ondansetron plus diphenhydramine may be useful in preventing gastrointestinal symptoms. Early diarrhea may be mediated by a cholinergic mechanism. Increased formation of its active metabolite SN-38 may also contribute to or cause diarrhea. Early diarrhea can be severe but is usually transient, may be ameliorated by administration of atropine. Data suggests that the late-onset diarrhea (can be prolonged, may lead to dehydration and electrolyte imbalance, and can be life threatening) is due to a secretory mechanism, possibly related to drug related alteration of intestinal epithelial cells. Fluid electrolyte replacement is essential. It should be carefully monitored, treated promptly with loperamide as it blocks major secretory mechanisms. If grade III or IV late diarrhea as per NCl criteria occurs, irinotecan injections should be delayed until recovery and subsequent doses have to be reduced.
Cardiovascular System: Flushing is reported but does not generally require treatment.
Central Nervous System: Insomnia and dizziness is reported. Dizziness may represent orthostatic hypotension secondary to dehydration.
Kidney/Genitourinary: Renal failure related to diarrhea-induced renal hypoperfusion has occurred occasionally.
Liver: Elevation of serum transaminases and bilirubin has been observed in up to 25% of patients.
Liver enzyme elevations to NCl grade 3 or 4 is usually seen in < 10% and typically in patients with hepatic metastases.
Respiratory: Pulmonary toxicity, frequently described as pneumonitis, has been reported infrequently in patients with SCLC or NSCLC. Symptoms of dyspnea on exertion may occur.
Corticosteroid therapy has produced equivocal results.
Eosinophilia has preceded the occurrence of pulmonary toxicity in several patients.
General: Alopecia has been observed in 12% to 70% of patients.
Skin rashes and pain are reported at the infusion site.
A constellation of symptoms resembling a cholinergic syndrome has been described in patients treated with irinotecan. Most or all symptoms respond to subcutaneous atropine (0.25 to 0.5mg).
Asthenia, fever & abdominal pain may occur.