FDA label 2cc28bb5-040b-4f66-a19c-91def2866dfc

5 WARNINGS AND PRECAUTIONS Hypersensitivity reactions, including anaphylaxis and anaphylactic shock : reported in patients treated with intravenous palonosetron HCl with or without known hypersensitivity to other selective 5-HT 3 receptor antagonists. If symptoms occur, discontinue ALOXI and initiate appropriate medical treatment. ( 5.1 ) Serotonin syndrome : reported with 5-HT 3 receptor antagonists alone, but particularly with concomitant use of serotonergic drugs. ( 5.2 , 7.1 ) 5.1 Hypersensitivity Reactions Hypersensitivity reactions, including anaphylaxis and anaphylactic shock, have been reported with administration of intravenous palonosetron HCl [see Adverse Reactions ( 6.2 )]. These reactions occurred in patients with or without known hypersensitivity to other 5-HT 3 receptor antagonists. If hypersensitivity reactions occur, discontinue ALOXI and initiate appropriate medical treatment. Do not reinitiate ALOXI in patients who have previously experienced symptoms of hypersensitivity [see Contraindications ( 4 )]. 5.2 Serotonin Syndrome The development of serotonin syndrome has been reported with 5-HT 3 receptor antagonists. Most reports have been associated with concomitant use of serotonergic drugs (e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors, mirtazapine, fentanyl, lithium, tramadol, and intravenous methylene blue). Some of the reported cases were fatal. Serotonin syndrome occurring with overdose of another 5-HT 3 receptor antagonist alone has also been reported. The majority of reports of serotonin syndrome related to 5-HT 3 receptor antagonist use occurred in a post-anesthesia care unit or an infusion center. Symptoms associated with serotonin syndrome may include the following combination of signs and symptoms: mental status changes (e.g. agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, with or without gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients should be monitored for the emergence of serotonin syndrome, especially with concomitant use of ALOXI and other serotonergic drugs. If symptoms of serotonin syndrome occur, discontinue ALOXI and initiate supportive treatment. Patients should be informed of the increased risk of serotonin syndrome, especially if ALOXI is used concomitantly with other serotonergic drugs [see Drug Interactions ( 7.1 )].

6 ADVERSE REACTIONS Serious or otherwise clinically significant adverse reactions reported in other sections of labeling: Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )] Serotonin Syndrome [see Warnings and Precautions ( 5.2 )] Most common adverse reactions (≥1 %) are: headache, constipation and fatigue. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact HELSINN at 1-844-357-4668 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 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 practice. In clinical trials for the prevention of nausea and vomiting associated with moderately emetogenic chemotherapy, 161 adult patients received a single oral dose of ALOXI 0. 5 mg. The most common adverse reactions reported in at least 2% of patients in two clinical trials were headache (4%) and constipation (1%). In other clinical trials, fatigue was also reported in 1% of patients. Less common adverse reactions, reported in less than 1%, were: Blood and Lymphatic System: anemia. Cardiovascular: hypertension, transient arrhythmia, first degree atrioventricular block, second degree atrioventricular block, QTc prolongation. Hearing and Labyrinth: motion sickness. Eye: eye swelling. Gastrointestinal System: gastritis, nausea, vomiting. General: fatigue, chills, pyrexia. Infections: sinusitis. Liver: transient, asymptomatic increases in bilirubin. Nutrition: anorexia. Musculoskeletal: joint stiffness, myalgia, pain in extremity. Nervous System: postural dizziness, dysgeusia. Psychiatric: insomnia. Respiratory System: dyspnea, epistaxis. Skin: generalized pruritus, erythema, alopecia. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of palonosetron HCl. 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 drug exposure. Hypersensitivity reactions : including dyspnea, bronchospasm, swelling/edema, erythema, pruritus, rash, urticarial, anaphylaxis and anaphylactic shock with intravenous administration of palonosetron HCl [see Warnings and Precautions ( 5.1 )]