warnings and cautions
5 WARNINGS AND PRECAUTIONS Serious or severe injection site reactions (ISRs): Infection, prolonged bleeding, bruising, hematomas, nodules, pain, and tenderness have been reported. Patients who are neutropenic or receiving antiplatelet agents or anticoagulants may be at greater risk. Monitor for ISRs during treatment with SUSTOL. Inform patients that some ISRs may occur 2 weeks or more after SUSTOL administration. For ongoing ISRs, administer SUSTOL at a site away from the affected area and consider discontinuing SUSTOL for severe or persistent ISRs. ( 5.1 ) Gastrointestinal disorders: Monitor for constipation and consider optimizing patients' current bowel regimens used for managing preexisting constipation. Also monitor for decreased bowel activity, particularly in patients with risk factors for gastrointestinal obstruction. Instruct patients to seek immediate medical care if signs and symptoms of ileus occur. ( 5.2 ) Hypersensitivity reactions: Serious reactions have been reported and may occur up to 7 days or longer following SUSTOL administration and may have an extended course. If a reaction occurs, administer appropriate treatment and monitor until signs and symptoms resolve. ( 5.3 ) Serotonin syndrome: Reported with 5-HT receptor antagonists alone but particularly with concomitant use of serotonergic drugs. If such symptoms occur, discontinue SUSTOL and initiate supportive treatment. If concomitant use of SUSTOL with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome. ( 5.4 , 7.1 ) 5.1 Serious Injection Site Reactions Serious or severe injection site reactions (ISRs), including infections (e.g., abscess, cellulitis with gangrene), prolonged bleeding, bruising, hematomas, nodules, pain, and tenderness have been reported in clinical trials [ see Adverse Reactions ( 6.1 ) ] and/or postmarketing. Some postmarketing cases required emergent medical attention, hospitalization, surgical debridement, intravenous antibiotics, and/or incision and drainage. Patients who are neutropenic or receiving concomitant anticoagulant and antiplatelet medications may be at greater risk. Monitor patients for development of ISRs during treatment with SUSTOL. Inform patients that some ISRs may occur up to 2 weeks or more after SUSTOL administration. For ongoing ISRs, administer SUSTOL at a site away from the affected area [see Dosage and Administration ( 2.1 )]. Consider discontinuing SUSTOL for severe or persistent ISRs. 5.2 Gastrointestinal Disorders Constipation In clinical trials, 224 of 1131 (20%) of patients treated with SUSTOL 10 mg reported constipation compared to 13% to 15% in the 5-HT 3 receptor antagonist control arms. Hospitalization due to constipation or fecal impaction was reported in 5 SUSTOL-treated patients (0.3%). Monitor patients for the development of constipation while receiving treatment with SUSTOL taking into consideration the extended-release properties of the SUSTOL polymer formulation over at least 5 to 7 days, particularly in patients receiving opioid medications. Consider optimizing bowel regimens in patients using SUSTOL. Progressive Ileus and Gastric Distention SUSTOL may mask a progressive ileus and/or gastric distention. This should be particularly considered before use of SUSTOL in patients who have had recent abdominal surgery. Monitor for decreased bowel activity, particularly in patients with risk factors for gastrointestinal obstruction. 5.3 Hypersensitivity Reactions Hypersensitivity reactions, including anaphylaxis, have been reported in granisetron-treated patients who have exhibited hypersensitivity to other 5-HT 3 receptor antagonists [see Contraindications ( 4 )] . Avoid SUSTOL in patients who have had hypersensitivity reactions to other 5-HT 3 receptor antagonists [see Contraindications ( 4 )] . Due to the extended-release properties of the SUSTOL polymer formulation, exposure to granisetron may continue for 5 to 7 days following administration. Hypersensitivity reactions may occur up to 7 days or longer following SUSTOL administration and may have an extended course. Inform patients of the signs and symptoms of anaphylaxis, and instruct them to seek immediate medical care should signs and symptoms occur. If hypersensitivity reactions occur, administer appropriate treatment and monitor patients until signs and symptoms resolve. 5.4 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 SUSTOL and other serotonergic drugs. If symptoms of serotonin syndrome occur, discontinue SUSTOL and initiate supportive treatment. Patients should be informed of the increased risk of serotonin syndrome, especially if SUSTOL is used concomitantly with other serotonergic drugs [see Drug Interactions ( 7.1 )] .