DRUG INTERACTIONS
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; Butalbital; 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.
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.
Atropine; 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.
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.
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; Dihydrocodeine; Phenylephrine: (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.
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.
Guaifenesin; 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.
Guaifenesin; Hydrocodone; Pseudoephedrine: (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.
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.
Hydrocodone; Pseudoephedrine: (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.
Meperidine; Promethazine: (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.