"The U.S. Food and Drug Administration today expanded the approved uses of Abraxane (paclitaxel protein-bound particles for injectable suspension, albumin-bound) to treat patients with late-stage (metastatic) pancreatic cancer.
QT prolongation has been reported with KYTRIL [see WARNINGS AND PRECAUTIONS and DRUG INTERATIONS]
Clinical 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 to rates in the clinical trials of another drug and may not reflect the rates observed in patients.
Chemotherapy-Induced Nausea and Vomiting
The following have been reported during controlled clinical trials or in the routine management of patients. The percentage figures are based on clinical trial experience only. Table 1 gives the comparative frequencies of the two most commonly reported adverse reactions ( ≥ 3%) in patients receiving KYTRIL Injection, in single-day chemotherapy trials. These patients received chemotherapy, primarily cisplatin, and intravenous fluids during the 24-hour period following KYTRIL Injection administration. Reactions were generally recorded over seven days post-KYTRIL Injection administration.
Table 1: Principal Adverse Reactions in Clinical Trials —
|Percent of Patients With Reaction|
| KYTRIL Injection
|1 Metoclopramide/dexamethasone and phenothiazines/dexamethasone.|
In over 3,000 patients receiving KYTRIL Injection (2 to 160 mcg/kg) in single-day and multiple-day clinical trials with emetogenic cancer therapies, adverse events, other than those adverse reactions listed in Table 1, were observed; attribution of many of these events to KYTRIL is uncertain.
Hepatic: In comparative trials, mainly with cisplatin regimens, elevations of AST and ALT ( > 2 times the upper limit of normal) following administration of KYTRIL Injection occurred in 2.8% and 3.3% of patients, respectively. These frequencies were not significantly different from those seen with comparators (AST: 2.1%; ALT: 2.4%).
Cardiovascular: Hypertension (2%); hypotension, arrhythmias such as sinus bradycardia, atrial fibrillation, varying degrees of A-V block, ventricular ectopy including non-sustained tachycardia, and ECG abnormalities have been observed rarely.
Central Nervous System: Agitation, anxiety, CNS stimulation and insomnia were seen in less than 2% of patients. Extrapyramidal syndrome occurred rarely and only in the presence of other drugs associated with this syndrome.
Other: Fever (3%), taste disorder (2%), skin rashes (1%). In multiple-day comparative studies, fever occurred more frequently with KYTRIL Injection (8.6%) than with comparative drugs (3.4%, P < 0.014), which usually included dexamethasone.
Postoperative Nausea and Vomiting
The adverse reactions listed in Table 2 were reported in ≥ 2% of adults receiving KYTRIL Injection 1 mg during controlled clinical trials.
Table 2: Adverse Reactions in Controlled Clinical Trials
in Postoperative Nausea and Vomiting (Reported in ≥ 2% of Adults Receiving
KYTRIL Injection 1 mg)
|Percent of Patients With Reaction|
| KYTRIL Injection
|Hepatic Enzymes Increased||5.6||4.1|
In a clinical study conducted in Japan, the types of adverse events differed notably from those reported above in Table 2. The adverse events in the Japanese study that occurred in ≥ 2% of patients and were more frequent with KYTRIL 1 mg than with placebo were: fever (56% to 50%), sputum increased (2.7% to 1.7%), and dermatitis (2.7% to 0%).
The following adverse reactions have been identified during post approval use of KYTRIL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to KYTRIL exposure.
QT prolongation has been reported with KYTRIL [see WARNINGS AND PRECAUTIONS and DRUG INTERACTIONS]
Read the Kytril Injection (granisetron hydrochloride) Side Effects Center for a complete guide to possible side effects
Granisetron does not induce or inhibit the cytochrome P-450 drug-metabolizing enzyme system in vitro. There have been no definitive drug-drug interaction studies to examine pharmacokinetic or pharmacodynamic interaction with other drugs; however, in humans, KYTRIL Injection has been safely administered with drugs representing benzodiazepines, neuroleptics and anti-ulcer medications commonly prescribed with antiemetic treatments. KYTRIL Injection also does not appear to interact with emetogenic cancer chemotherapies. Because granisetron is metabolized by hepatic cytochrome P-450 drug-metabolizing enzymes, inducers or inhibitors of these enzymes may change the clearance and, hence, the half-life of granisetron. No specific interaction studies have been conducted in anesthetized patients. In addition, the activity of the cytochrome P-450 subfamily 3 A4 (involved in the metabolism of some of the main narcotic analgesic agents) is not modified by KYTRIL in vitro.
In in vitro human microsomal studies, ketoconazole inhibited ring oxidation of KYTRIL. However, the clinical significance of in vivo pharmacokinetic interactions with ketoconazole is not known. In a human pharmacokinetic study, hepatic enzyme induction with phenobarbital resulted in a 25% increase in total plasma clearance of intravenous KYTRIL. The clinical significance of this change is not known.
QT prolongation has been reported with KYTRIL. Use of KYTRIL in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic may result in clinical consequences.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 6/22/2011
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