Gratril®
Granisetron
3 mg/3ml Ampoule
Chemotherapy-associated nausea and vomiting: Prevention of nausea and vomiting associated with initial and repeat courses of emetogenic chemotherapy, including high-dose cisplatin (injection and tablets); prevention of nausea and vomiting associated with anthracycline/cyclophosphamide chemotherapy regimens; prevention of nausea and vomiting associated with moderately and/or highly emetogenic chemotherapy regimens.
Radiation-associated nausea and vomiting: Prevention of nausea and vomiting associated with radiation therapy, including total body radiation and fractionated abdominal radiation.
Prevention of postoperative nausea and vomiting (off lable)
Mechanism of Action:
Selective 5-HT -receptor antagonist, blocking serotonin, both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone
Method of Administration:
Prevention of chemotherapy-associated nausea and vomiting:
IV: 10 mcg/kg within 30 minutes prior to chemotherapy; only on the day(s) chemotherapy is administered.
Prophylaxis of radiation therapy-associated emesis:
IV: 1 mg or 10 mcg/kg once daily prior to each fraction of radiation; administer in combination with dexamethasone
Notes
Contraindications:
Hypersensitivity to granisetron or any component of the formulation or to other 5-HT3 receptor antagonists.
Interactions:
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk – Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Serotonergic Agents (High Risk): Antiemetics (5HT3 Antagonists) may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Pregnancy and Lactation:
Adverse events have not been observed in animal reproduction studies. In an ex vivo placental perfusion study, granisetron was shown to cross the placenta in a concentration (dose) dependent manner
It is not known if granisetron is excreted in breast milk. The decision to continue or discontinue breast-feeding during therapy should take into account the risk of infant exposure, the benefits of breast-feeding to the infant, benefits of treatment to the mother, and the underlying maternal condition.
Warning and Precaution:
- ECG effects: Selective 5-HT antagonists, including granisetron, have been associated with dose dependent increases in ECG intervals (eg, PR, QRS duration, QT/QTc, JT), usually occurring with IV formulations (compared to oral) and occurring 1 to 2 hours after IV administration. In general, these changes are not clinically relevant; however, when used in conjunction with other agents that prolong these intervals (eg, Class I and III antiarrhythmics), arrhythmia or clinically relevant QT interval prolongation may occur resulting in torsade de pointes. Use with caution in patients at risk of QT prolongation and/or ventricular arrhythmia; patients with cardiac disease, electrolyte abnormalities, or who are receiving concomitant cardiotoxic chemotherapy are at higher risk.
- GI effects: Constipation may occur with all formulations, although a higher incidence is observed with tablets and the ER SUBQ injection. Hospitalization due to constipation or fecal impaction has been reported with the ER SUBQ injection. Progressive ileus and/or gastric distention may be masked by the ER SUBQ injection and transdermal patch (assess risks/benefits in patients with recent abdominal surgery). Granisetron does not stimulate gastric or intestinal peristalsis; do not use it in place of nasogastric suction.
- Hypersensitivity: Hypersensitivity reactions (including anaphylaxis) have been reported with granisetron in patients who have experienced hypersensitivity to other 5-HT antagonists (crossreactivity has been reported). Due to the ER properties of the SUBQ formulation, granisetron exposure may continue for 5 to 7 days following administration; hypersensitivity reactions may occur up to 7 days or longer following administration and may have an extended course.
- Serotonin syndrome: Serotonin syndrome (SS) has been reported with 5-HT receptor antagonists, predominantly when used in combination with other serotonergic agents (eg, selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, monoamine oxidase inhibitors, mirtazapine, fentanyl, lithium, tramadol, methylene blue). Some of the cases have been fatal. The majority of SS reports due to 5-HT receptor antagonist have occurred in a postanesthesia setting or in an infusion center. SS has also been reported following overdose of another 5-HT receptor antagonist. Signs of SS include mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile BP, diaphoresis, dizziness, flushing, hyperthermia); neuromuscular changes (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination); GI symptoms (eg, nausea, vomiting, diarrhea); and/or seizures.
Adverse Reactions:
Gastrointestinal: Constipation, nausea, vomiting
Nervous system: Headache
Neuromuscular & skeletal: Asthenia
Storage:
Store below 30 and protect from freezing.