Palonosetron is a highly selective 5-HT3 receptor antagonist indicated for the prevention of acute chemotherapy-induced nausea and vomiting (CINV) associated with initial and repeat courses of moderately or highly emetogenic chemotherapy and for the prevention of delayed emesis following moderately emetogenic chemotherapy. Palonosetron is also used for the prevention of post-operative nausea and vomiting (PONV). Palonosetron (Aloxi) is available in a parenteral formulation and as an oral capsule. Palonosetron has a long half-life (roughly 40 hours) which enhances efficacy in the treatment of delayed-CINV and allows for one-time dosing within a 7-day period. Palonosetron's superior efficacy in controlling delayed emesis has been demonstrated against both ondansetron and dolasetron. However, the superiority of palonosetron in acute-CINV, as compared to ondansetron or dolasetron, has not been consistently determined. Results from two pivotal phase III clinical trials for the prevention of PONV have demonstrated the safety and efficacy of palonosetron in producing a complete response (no emesis or use of rescue medication) for a 24-hour time period following surgery. The American Society of Clinical Oncology (ASCO) guidelines recommend that adult patients who are treated with moderate to high-emetic-risk chemotherapy agents should be offered a 3-drug combination of a 5-HT3 receptor antagonist, a neurokinin 1 (NK1) receptor antagonist, and dexamethasone; olanzapine is also added to the 3-drug combination during use of high-emetic-risk agents. Children receiving moderate to high-emetic-risk agents should be offered a 2-drug combination of a 5-HT3 receptor antagonist and dexamethasone; aprepitant is also added to the 2-drug combination during use of high-emetic-risk agents.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Take approximately 1 hour prior to beginning chemotherapy.
-May be taken with or without food.
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
-For chemotherapy-induced nausea and vomiting:-Adult patients: Give IV over 30 seconds approximately 30 minutes before the start of chemotherapy.
-Pediatric patients: Infuse IV over 15 minutes approximately 30 minutes before the start of chemotherapy.
-For post-operative nausea/vomiting: Give IV over 10 seconds immediately before the induction of anesthesia.
-Do not mix with other drugs.
-Flush the infusion line with normal saline before and after administration.
Vein discoloration and vein distention have been reported in less than 1% of adult patients who received IV palonosetron for the prevention of chemotherapy induced nausea and vomiting in clinical trials.
After IV administration of palonosetron for the prevention of chemotherapy induced nausea and vomiting (CINV) in clinical trials, headache (9%) and dizziness (1%) were reported in patients who received 0.25 mg (n = 633) and other central nervous system adverse events that occurred in < 1% of patients include drowsiness (somnolence), insomnia, hypersomnia, and paresthesias. Headache, dizziness, and dyskinesia were also reported in < 1% of pediatric patients (n = 163, age 2 months-17 years) receiving palonosetron for the prevention of chemotherapy induced nausea and vomiting. Dizziness occurred in < 1% of patients for the prevention of postoperative nausea and vomiting in clinical trials.
Constipation (5%) and diarrhea (1%) were reported in patients who received palonosetron 0.25 mg IV (n = 633) for the prevention of chemotherapy induced nausea and vomiting (CINV) in clinical trials. In other studies, 2 subjects experienced severe constipation following a single palonosetron injection dose of approximately 0.75 mg (3 times the recommended dose). Flatulence occurred in 1% of patients who received IV palonosetron for the prevention of postoperative nausea and vomiting (PONV) in clinical trials. Other gastrointestinal adverse events that occurred in less than 1% of patients who received IV palonosetron include dyspepsia, abdominal pain, xerostomia (dry mouth), hiccups, flatulence (CINV), hypersalivation, diarrhea (PONV), GI hypomotility, and anorexia.
Infusion site pain was reported in less than 1% of pediatric patients (n = 163, age 2 months to 17 years) receiving palonosetron for the prevention of chemotherapy-induced nausea and vomiting. Rarely, hypersensitivity such as anaphylactoid reactions or anaphylactic shock, dyspnea, bronchospasm, and also an injection site reaction (i.e., burning, induration, discomfort, and pain) have been reported with IV palonosetron use during postmarketing experience.
QT prolongation (on electrocardiogram) was reported in 5% of patients who received palonosetron 0.075 mg IV (n = 336) compared with 3% of patients who received placebo (n = 369) for the prevention of postoperative nausea and vomiting (PONV) in clinical trials. It was also reported in 1% of adult patients undergoing surgery and who received other concomitant perioperative and intraoperative medications in clinical trials and in less than 1% of patients during the prevention of chemotherapy-induced nausea and vomiting (CINV) in clinical trials. When palonosetron injection is given at a dose of 9 times the maximum recommended adult dose, it does not prolong the QT interval to any clinically relevant extent. Bradycardia, sinus bradycardia, tachycardia, and nonsustained tachycardia were reported in 1% of adult patients undergoing surgery and in CINV clinical trials. Hypotension was reported in 1% of adult patients during (CINV) clinical trials. Other cardiovascular adverse events that occurred in less than 1% of patients who received IV palonosetron include hypertension, myocardial ischemia, extrasystoles, sinus tachycardia, sinus arrhythmia, supraventricular extrasystole, decreased blood pressure, hypotension (PONV), ventricular extrasystoles, edema, and decreased T-wave amplitude.
Fatigue was reported in less than 1% of patients who received palonosetron 0.25 mg IV (n = 633) for the prevention of chemotherapy induced nausea and vomiting in clinical trials.
Pruritus occurred in 1% of adult patients undergoing surgery who received IV palonosetron and other concomitant perioperative and intraoperative medications in clinical trials. Contact dermatitis (allergic dermatitis), skin disorder, and rash (unspecified) were reported in less than 1% of adult and pediatric patients who received IV palonosetron for the prevention of chemotherapy induced nausea and vomiting in clinical trials. Erythema has been reported during postmarketing experience with IV palonosetron.
Tinnitus and motion sickness have been reported in less than 1% of adult patients who received IV palonosetron for the prevention of chemotherapy induced nausea and vomiting in clinical trials.
Amblyopia and ocular irritation have been reported in less than 1% of adult patients who received IV palonosetron for the prevention of chemotherapy induced nausea and vomiting in clinical trials.
Arthralgia has been reported in less than 1% of adult patients who received IV palonosetron for the prevention of chemotherapy induced nausea and vomiting in clinical trials.
Anxiety (1%) and euphoria (< 1%) have been reported in adult patients who received IV palonosetron for the prevention of chemotherapy induced nausea and vomiting in clinical trials.
Hyperkalemia has been reported in 1% of adult patients who received IV palonosetron for the prevention of chemotherapy induced nausea and vomiting in clinical trials. Other metabolic abnormalities that occurred in < 1% of patients who received IV palonosetron for prevention of CINV or postoperative nausea and vomiting include electrolyte fluctuations, hyperglycemia, metabolic acidosis, glycosuria, decreased appetite, and hypokalemia.
Urinary retention was reported with the use of IV palonosetron during clinical trials, occurring in < 1% of patients for prevention of chemotherapy induced nausea and vomiting and in 1% for prevention of postoperative nausea and vomiting.
Transient, asymptomatic elevations in AST and/or ALT levels and hyperbilirubinemia have been reported in less than 1% of adult patients who received IV palonosetron for the prevention of chemotherapy induced nausea and vomiting in clinical trials. Elevations in AST and/or ALT levels (1%) and elevated hepatic enzymes (< 1%) occurred in adult patients undergoing surgery who received IV palonosetron and other concomitant perioperative and intraoperative medications in clinical trials.
Hypoventilation and laryngospasm occurred in < 1% of adult patients undergoing surgery who received IV palonosetron and other concomitant perioperative and intraoperative medications in clinical trials.
Weakness was reported in 1% of patients who received IV palonosetron for the prevention of chemotherapy induced nausea and vomiting in clinical trials.
Hot flashes were reported in < 1% of patients who received IV palonosetron for the prevention of chemotherapy induced nausea and vomiting in clinical trials.
Fever and flu-like syndrome were reported < than 1% of patients who received IV palonosetron for the prevention of chemotherapy induced nausea and vomiting in clinical trials. Chills were reported in < 1% of patients who received IV palonosetron for the prevention of postoperative nausea and vomiting in clinical trials.
Decreased platelet counts (thrombocytopenia) were reported in < 1% of adult patients undergoing surgery who received IV palonosetron and other concomitant perioperative and intraoperative medications in clinical trials.
Serotonin syndrome has been reported with 5-HT3 receptor antagonists, such as palonosetron, during concurrent use of other medications known to increase CNS or peripheral serotonin levels or during overdose. Some of the reported cases were fatal; most occurred in a post-anesthesia care unit or infusion center. If serotonin syndrome becomes evident during treatment, discontinue palonosetron and any other serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is a range of signs and symptoms that can include mental status changes (e.g., agitation, hallucinations, delirium, coma), gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), and/or seizures. Cases consistent with serotonin syndrome have been reported in pediatric patients after inadvertent overdose of oral ondansetron (estimated ingestion > 5 mg/kg). Symptoms reported in these cases included somnolence, agitation, tachycardia, tachypnea, hypertension, flushing, mydriasis, diaphoresis, myoclonic movements, horizontal nystagmus, hyperreflexia, and seizures. Patients required supportive care, including intubation in some cases, with complete recovery in 1-2 days.
Hypersensitivity reactions to palonosetron, including anaphylaxis, have been reported with or without known hypersensitivity to other 5-HT3 receptor antagonists. Palonosetron should not be used in any patient with a known or suspected palonosetron hypersensitivity or hypersensitivity to any inactive ingredients of the product. Palonosetron should be used cautiously in patients with prior allergic reactions to other 5HT-3 receptor antagonists (e.g., granisetron hypersensitivity, dolasetron hypersensitivity, or ondansetron hypersensitivity); it is not known if a cross-sensitivity exists. Cross-sensitivity has been reported with some agents in the class. Furthermore, it has been hypothesized that antagonism at serotonin (5HT) receptors, and the subsequent increased concentrations of serotonin, increase the risk of developing bronchospasm and/or vasoconstriction. There have been several reports of anaphylactic/anaphylactoid reactions associated with the use of drugs in this class. It is not clear at this time if these reactions are due to the use of the serotonin antagonist alone or due to a drug interaction between the serotonin antagonist and a chemotherapeutic agent. Nevertheless, clinicians should not overlook this possibility. If hypersensitivity reactions occur, discontinue palonosetron injection and initiate appropriate medical treatment. Do not reinitiate palonosetron injection in patients who have previously experienced symptoms of hypersensitivity.
Safety and efficacy of palonosetron have not been established in neonates for any indication. The drug has been used for chemotherapy-induced nausea/vomiting (CINV) prophylaxis in children as young as 1 month. Palonosetron did not demonstrate non-inferiority to ondansetron in pediatric patients for the prevention of postoperative nausea and vomiting.
There are no available data on palonosetron use in pregnant women to inform a drug-associated risk. Animal-based teratology studies have not revealed evidence of harm to the fetus when palonosetron is given to rats and rabbits during organogenesis at doses up to 1,894 and 3,789 times the recommended human IV dose, respectively. The effects of palonosetron on labor and delivery are not known. Evidence is limited on the safety or efficacy of the serotonin 5-HT3 inhibitors for nausea and vomiting of pregnancy. Alternatives in this class to palonosetron exist for consideration for use during pregnancy, due to more published data in this population. The American College of Obstetricians and Gynecologists (ACOG) practice bulletin includes ondansetron as a third-line pharmacologic treatment option for nausea and vomiting of pregnancy in patients who have failed other therapies.
There are no data on the presence of palonosetron in human milk, the effects of palonosetron on the breastfed infant, or the effects of palonosetron on milk production. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.
For chemotherapy-induced nausea/vomiting prophylaxis (CINV prophylaxis):
-for acute chemotherapy-induced nausea/vomiting (CINV) prophylaxis associated with initial and repeat courses of highly emetogenic cancer chemotherapy:
Intravenous dosage:
Adults: 0.25 mg IV over 30 seconds, given as a single dose 30 minutes prior to chemotherapy.
Infants >= 1 month, Children, and Adolescents: 20 mcg/kg/dose IV (max: 1.5 mg/dose) infused over 15 minutes as a single dose 30 minutes prior to chemotherapy.
-for chemotherapy-induced nausea/vomiting (CINV) prophylaxis associated with initial and repeat courses of moderately emetogenic cancer chemotherapy:
Intravenous dosage:
Adults: 0.25 mg IV over 30 seconds, given as a single dose 30 minutes prior to chemotherapy. Intravenous dosing is effective for both acute and delayed CINV.
Infants >= 1 month, Children, and Adolescents: 20 mcg/kg/dose IV (max: 1.5 mg/dose) infused over 15 minutes as a single dose 30 minutes prior to chemotherapy.
Oral dosage:
Adults: 0.5 mg PO as a single dose approximately 60 minutes prior to chemotherapy.
For post-operative nausea/vomiting (PONV) prophylaxis for up to 24 hours after surgery:
NOTE: Efficacy beyond 24 hours has not been established.
Intravenous dosage:
Adults: 0.075 mg IV single dose administered over 10 seconds immediately before the induction of anesthesia.
Maximum Dosage Limits:
-Adults
0.25 mg IV or 0.5 mg PO as a single dose.
-Geriatric
0.25 mg IV or 0.5 mg PO as a single dose.
-Adolescents
20 mcg/kg/dose IV (Max: 1.5 mg/dose).
-Children
20 mcg/kg/dose IV (Max: 1.5 mg/dose).
-Infants
20 mcg/kg/dose IV.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Dosage adjustment is not required.
Patients with Renal Impairment Dosing
Dosage adjustment is not necessary in patients with any degree of renal impairment.
Intermittent hemodialysis
Dialysis studies have not been performed; however, due to the large volume of distribution it is unlikely that palonosetron clearance is affected by hemodialysis.
Continuous hemodialysis (CAVHD, CVVHD)
Dialysis studies have not been performed; however, due to the large volume of distribution it is unlikely that palonosetron clearance is affected by hemodialysis.
*non-FDA-approved indication
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dihydrocodeine with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Acetaminophen; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Acetaminophen; Hydrocodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Acetaminophen; Oxycodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering oxycodone with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Alfentanil: (Moderate) If concomitant use of alfentanil and palonosetron is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Alosetron: (Major) Theoretically, the coadministration of two potent and selective 5HT-3 antagonists, such as palonosetron and alosetron could lead to severe constipation. Constipation, reported individually with alosetron in roughly 25% of patients, could be worsened by the administration of palonosetron, which has a constipation rate of roughly 5% as well as a long half-life. Patients who are debilitated, elderly or taking medications that decrease GI motility may be at greater risk for constipation. Ischemic colitis has been reported in patients receiving alosetron during clinical trials and post-marketing. If a decision is made to co-prescribe palonosetron and alosetron, the patient should be informed of the potential for worsening constipation and should contact their health care provider immediately. If severe constipation or ischemic colitis develops while taking these two drugs, the alosetron should be discontinued immediately and not re-started.
Apomorphine: (Contraindicated) The concurrent use of apomorphine and serotonin-receptor antagonists is contraindicated due to the possibility of an excessive lowering of blood pressure and unconsciousness. Additionally, additive QT prolongation is possible during coadministration of apomorphine with dolasetron, granisetron, and ondansetron.
Aprepitant, Fosaprepitant: (Minor) Aprepitant, fosaprepitant is indicated for the prophylaxis of chemotherapy-induced nausea/vomiting in combination with a 5HT3 antagonist, one of which is palonosetron. Palonosetron is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and theoretically could increase plasma concentrations of palonosetron. The AUC of another CYP3A4 substrate, midazolam, was increased for several days after aprepitant dosing when the two drugs were coadministered; however, in clinical drug interaction studies, aprepitant did not have clinically important effects on the pharmacokinetics of ondansetron, granisetron, or dolasetron. The effects of aprepitant on palonosetron pharmacokinetics has not been evaluated. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction.
Artemether; Lumefantrine: (Major) Artemether; lumefantrine should be used with caution with netupitant; palonosetron. Lumefantrine is an inhibitor of CYP2D6, and palonosetron is a substrate of the CYP2D6 isoenzyme. Coadministration may lead to increased palonosetron concentrations and serotonin-related side effects.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Aspirin, ASA; Oxycodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering oxycodone with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Atazanavir: (Moderate) The plasma concentrations of palonosetron may be elevated when administered concurrently with atazanavir. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Atazanavir is a CYP3A4 inhibitor; palonosetron is a substrate of CYP3A4.
Atazanavir; Cobicistat: (Moderate) The plasma concentrations of palonosetron may be elevated when administered concurrently with atazanavir. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Atazanavir is a CYP3A4 inhibitor; palonosetron is a substrate of CYP3A4. (Moderate) The plasma concentrations of palonosetron may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Cobicistat is an inhibitor of CYP3A4 and CYP2D6; palonosetron is a substrate of both CYP3A4 and CYP2D6.
Benzhydrocodone; Acetaminophen: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering benzhydrocodone with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as methylene blue. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Buprenorphine: (Moderate) If concomitant use of buprenorphine and palonosetron is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Buprenorphine; Naloxone: (Moderate) If concomitant use of buprenorphine and palonosetron is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Capsaicin; Metaxalone: (Moderate) Concomitant use of metaxalone and serotonin-receptor antagonists (5HT-3 receptor antagonists) may increase the risk for serotonin syndrome. Monitor patients for serotonin syndrome if concomitant use is necessary.
Celecoxib; Tramadol: (Moderate) If concomitant use of tramadol and palonosetron is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Chlorpheniramine; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Chlorpheniramine; Hydrocodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Citalopram: (Major) Because of the potential risk and severity of serotonin syndrome, use caution and monitor closely when administering palonosetron with other drugs that have serotonergic properties, such as citalopram. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Cobicistat: (Moderate) The plasma concentrations of palonosetron may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Cobicistat is an inhibitor of CYP3A4 and CYP2D6; palonosetron is a substrate of both CYP3A4 and CYP2D6.
Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Codeine; Guaifenesin: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Codeine; Phenylephrine; Promethazine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Codeine; Promethazine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Darunavir: (Moderate) The plasma concentrations of palonosetron may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Darunavir is an inhibitor of CYP3A4 and CYP2D6; palonosetron is a substrate of both CYP3A4 and CYP2D6.
Darunavir; Cobicistat: (Moderate) The plasma concentrations of palonosetron may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Cobicistat is an inhibitor of CYP3A4 and CYP2D6; palonosetron is a substrate of both CYP3A4 and CYP2D6. (Moderate) The plasma concentrations of palonosetron may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Darunavir is an inhibitor of CYP3A4 and CYP2D6; palonosetron is a substrate of both CYP3A4 and CYP2D6.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) The plasma concentrations of palonosetron may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Cobicistat is an inhibitor of CYP3A4 and CYP2D6; palonosetron is a substrate of both CYP3A4 and CYP2D6. (Moderate) The plasma concentrations of palonosetron may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Darunavir is an inhibitor of CYP3A4 and CYP2D6; palonosetron is a substrate of both CYP3A4 and CYP2D6.
Desvenlafaxine: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as desvenlafaxine. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Although clinical studies have shown that desvenlafaxine does not have a clinically relevant effect on CYP2D6 inhibition at doses of 100 mg/day, the manufacturer recommends the dose reduction of CYP2D6 substrates, such as palonosetron,by up to one-half if co-administered with desvenlafaxine 400 mg/day.
Dextromethorphan; Quinidine: (Moderate) Coadminister with caution. Palonosetron is metabolized by CYP2D6, and quinidine is an inhibitor of this isoenzyme. Coadministration may result in elevated plasma concentrations of palonosetron, causing ain increased risk for serotonin-related adverse events.
Dichlorphenamide: (Moderate) Use dichlorphenamide and palonosetron together with caution as both drugs can cause metabolic acidosis. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Dronedarone: (Moderate) Coadminister dronedarone and palonosetron together with caution. Dronedarone is an inhibitor of CYP2D6 and CYP3A4. Palonsetron is a substrate for CYP2D6 and CYP3A4. Coadministration of dronedarone and palonosetron may result in elevated plasma concentrations of palonsetron.
Duloxetine: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as duloxetine. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Elbasvir; Grazoprevir: (Moderate) Administering palonosetron with elbasvir; grazoprevir may result in elevated palonosetron plasma concentrations. Palonosetron is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) The plasma concentrations of palonosetron may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Cobicistat is an inhibitor of CYP3A4 and CYP2D6; palonosetron is a substrate of both CYP3A4 and CYP2D6.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) The plasma concentrations of palonosetron may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as CNS effects, is recommended during coadministration. Cobicistat is an inhibitor of CYP3A4 and CYP2D6; palonosetron is a substrate of both CYP3A4 and CYP2D6.
Escitalopram: (Major) Because of the potential risk and severity of serotonin syndrome, use caution and monitor closely when administering palonosetron with other drugs that have serotonergic properties, such as escitalopram. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Fenfluramine: (Moderate) Monitor for decreased efficacy of fenfluramine if coadministered with serotonin receptor antagonists. Concurrent use may decrease the activity of fenfluramine. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Fentanyl: (Moderate) If concomitant use of fentanyl and palonosetron is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Fluoxetine: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as fluoxetine. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Fluvoxamine: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as fluvoxamine. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Homatropine; Hydrocodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Hydrocodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Hydrocodone; Ibuprofen: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Hydromorphone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydromorphone with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as methylene blue. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Ibuprofen; Oxycodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering oxycodone with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Ipecac: (Major) Ipecac has been shown to be effective in producing emesis in patients who have ingested antiemetics, provided ipecac is given promptly (usually within 1 hour of antiemetic consumption). If ipecac is administered after the antiemetic therapy has begun to exert therapeutic effects, ipecac may be less effective. The duration of the antiemetics action may need to be taken into account when selecting the appropriate clinical path for treating patients for overdosage. Patients on chronic or longer-acting antiemetic therapy, such as the 5HT-3 receptor antagonists, may be unresponsive to ipecac or other methods which induce vomiting.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with palonosetron may result in increased serum concentrations of palonosetron. Palonosetron is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Isocarboxazid: (Moderate) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as monoamine oxidase inhibitors (MAOIs). Serotonin syndrome has been described following the concomitant use of 5-HT3 receptor antagonists and other serotonergic drugs. Monitor for the emergence of serotonin syndrome. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment.
Lasmiditan: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and serotonin-receptor antagonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Levomilnacipran: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as levomilnacipran. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If serotonin syndrome is suspected, discontinue palonosetron and levomilnacipran and initiate appropriate medical treatment.
Levorphanol: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering levorphanol with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Linezolid: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as linezolid. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Lithium: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as lithium. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Meperidine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering meperidine with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Metaxalone: (Moderate) Concomitant use of metaxalone and serotonin-receptor antagonists (5HT-3 receptor antagonists) may increase the risk for serotonin syndrome. Monitor patients for serotonin syndrome if concomitant use is necessary.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as methylene blue. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Methylene Blue: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as methylene blue. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Milnacipran: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as milnacipran. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Mirabegron: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as palonosetron may be increased when co-administered with mirabegron. Palonosetron is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Mirtazapine: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as mirtazapine. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Mitotane: (Minor) Use caution if mitotane and palonosetron are used concomitantly, and monitor for decreased efficacy of palonosetron and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer. Palonosetron is metabolized via multiple CYP isoenzymes, including CYP3A4; coadministration may theoretically result in decreased plasma concentrations of palonosetron, however, the potential for clinically significant drug interactions appears to be low.
Monoamine oxidase inhibitors: (Moderate) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as monoamine oxidase inhibitors (MAOIs). Serotonin syndrome has been described following the concomitant use of 5-HT3 receptor antagonists and other serotonergic drugs. Monitor for the emergence of serotonin syndrome. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment.
Morphine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering morphine with serotonin-receptor antagonist. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Morphine; Naltrexone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering morphine with serotonin-receptor antagonist. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Nalbuphine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering nalbuphine with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Olanzapine; Fluoxetine: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as fluoxetine. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Oliceridine: (Moderate) If concomitant use of oliceridine and serotonin-receptor antagonists is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Oxycodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering oxycodone with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Oxymorphone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering oxymorphone with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Ozanimod: (Major) Coadministration of ozanimod with palonosetron is not recommended due to the potential for hypertensive crisis. If coadministration is necessary, closely monitor patients for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Palonosetron may increase blood pressure by increasing serotonin concentrations.
Paroxetine: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as paroxetine. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Peginterferon Alfa-2b: (Moderate) Monitor for adverse effects associated with increased exposure to palonosetron if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while palonosetron is a CYP2D6 substrate.
Phenelzine: (Moderate) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as monoamine oxidase inhibitors (MAOIs). Serotonin syndrome has been described following the concomitant use of 5-HT3 receptor antagonists and other serotonergic drugs. Monitor for the emergence of serotonin syndrome. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment.
Quinidine: (Moderate) Coadminister with caution. Palonosetron is metabolized by CYP2D6, and quinidine is an inhibitor of this isoenzyme. Coadministration may result in elevated plasma concentrations of palonosetron, causing ain increased risk for serotonin-related adverse events.
Remifentanil: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering remifentanil with serotonin-receptor antagonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Selegiline: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant selegiline and serotonin-receptor antagonist use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Sertraline: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as sertraline. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Sufentanil: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Tapentadol: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tapentadol with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Tramadol: (Moderate) If concomitant use of tramadol and palonosetron is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Tramadol; Acetaminophen: (Moderate) If concomitant use of tramadol and palonosetron is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Tranylcypromine: (Moderate) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as monoamine oxidase inhibitors (MAOIs). Serotonin syndrome has been described following the concomitant use of 5-HT3 receptor antagonists and other serotonergic drugs. Monitor for the emergence of serotonin syndrome. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment.
Venlafaxine: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as venlafaxine. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Vilazodone: (Major) Because of the potential risk and severity of serotonin syndrome, use caution and monitor closely when administering palonosetron with other drugs that have serotonergic properties, such as vilazodone. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Palonosetron selectively blocks serotonin 5-HT3 receptors to prevent emesis and appears to have little to no affinity for other serotonin receptors. 5-HT3 receptors are found centrally in the chemoreceptor trigger zone (CTZ) of the area postrema, and peripherally at vagal nerve terminals in the intestines. Emesis during chemotherapy appears to be associated with the release of serotonin from enterochromaffin cells in the small intestine. The released serotonin then activates the 5-HT3 receptors located on vagal afferent nerves to initiate the vomiting reflex. Palonosetron, by blocking the vagal nerve endings in the intestines, prevents signal transmission to the CTZ, and reduces the incidence of chemotherapy-induced nausea and vomiting (CINV).
Palonosetron is administered orally and intravenously. It has a long half-life (roughly 40 hours) that allows for one-time dosing in the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV). Palonosetron and metabolites are primarily eliminated renally via metabolic pathways. The parent drug represented 40% of the dose, while inactive metabolites accounted for roughly 50% of the dose. In healthy subjects, total body clearance was roughly 160 mL/hour/kg and renal clearance was 67 mL/hour/kg. Due to the long elimination half-life, the single dosage regimen should not be repeated within 7 days.
Affected cytochrome P450 isoenzymes and drug transporters: CYP2D6, CYP3A4, CYP1A2
The potential for clinically significant pharmacokinetic drug interactions with palonosetron appears to be low. In-vitro studies have suggested that CYP2D6, and to a lesser extent CYP3A4 and CYP1A2, are involved in the metabolism of palonosetron. Pharmacokinetically, palonosetron parameters do not differ between poor and extensive metabolizers of CYP2D6, suggesting that inhibition or induction of the CYP2D6 enzyme by other drugs would not affect palonosetron disposition. Palonosetron has not been shown to inhibit CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1, CYP34/5 nor does palonosetron induce CYP1A2, CYP2D6, or CYP3A4/5. CYP2C19 has not been investigated; other 5HT-3 antagonists have not been shown to have interactions via the CYP2C19 enzyme. In vitro, palonosetron was an inhibitor of MATE1, MATE2-k, OCT1, and OCT2, and OCT3 transporters. An in vivo interaction between palonosetron and transporter substrates is considered unlikely.
-Route-Specific Pharmacokinetics
Oral Route
After oral administration of palonosetron, the bioavailability is 97%. Plasma concentrations rise initially, then are followed by a slow elimination. Cmax and AUC are dose-proportional over the range of 0.3 to 90 mcg/kg in healthy subjects and cancer patients.
Intravenous Route
After a single dose of palonosetron at 3 mcg/kg IV to six cancer patients, mean (+/-SD) maximum plasma concentration (Cmax) was estimated to be 5.6 +/- 5.5 ng/mL and mean AUC was 35.8 +/- 20.9 ng x hour/mL. Palonosetron has a large volume of distribution of 8.3 +/- 2.5 L/kg; protein binding is not important clinically. After a single IV dose of radiolabeled palonosetron, roughly 80% of the dose was recovered in the urine within 144 hours.
-Special Populations
Hepatic Impairment
Hepatic impairment does not significantly affect the clearance of palonosetron; dosage adjustments are not required for patients with hepatic impairment.
Renal Impairment
Total systemic exposure of palonosetron increased roughly 28% in patients with severe renal impairment vs. controls; dosage adjustments are not required for any degree of renal impairment.
Pediatrics
The mean total body clearance of palonosetron is faster in younger pediatric patients with cancer compared to older patients and approaches values similar to those seen in healthy adults at 12 to 17 years of age. The mean clearance after a single IV dose of 20 mcg/kg in patients less than 2 years, 2 to 5 years, 6 to 11 years, and 12 to 16 years was 0.31 L/hour/kg, 0.23 L/hour/kg, 0.19 L/hour/kg, and 0.16 L/hour/kg, respectively. Peak plasma concentrations of palonosetron were highly variable across pediatric age groups, with patients less than 6 years of age having lower concentrations compared to older patients. The half-life of palonosetron ranged from 20 to 30 hours. Dose proportional increases in the mean AUC were seen in pediatric patients when the dose was increased from 10 mcg/kg to 20 mcg/kg.
Geriatric
Differences in the pharmacokinetic parameters of palonosetron have not have been identified in the elderly (65 years and older) vs. younger adult cancer patients (18 to 64 years).
Ethnic Differences
Although clearance has been shown to be 25% higher in the Japanese vs. Whites, no dosage adjustment is required. The pharmacokinetics of palonosetron in Blacks has not been fully evaluated.