palonosetron hydrochloride .25 mg/5mL Injection
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Serotonin-3 Receptor Antagonist class.
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- It's an anti-nausea medicine given through an IV by your healthcare team. It's used to prevent nausea and vomiting that chemotherapy can cause — both the kind that hits within the...
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UNII 2968PHW8QP
A weak organic acid derived from citrus fruits or made through fermentation. It works as a buffer to control pH, a preservative to extend shelf life, and a flavoring agent in medications.
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Edetate disodium is a chemical compound that binds and removes certain metal ions. In medicines, it acts as a preservative and stabilizer by preventing metals like calcium from interfering with the product's shelf life and consistency.
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A natural sugar alcohol derived from seaweed or synthesized in the lab. It's used as a filler to add bulk, a sweetener in sugar-free formulas, and a disintegrant to help tablets break apart in the stomach.
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Sodium citrate is a salt derived from citric acid. It works as a buffer to maintain the medicine's pH level and may also help improve taste or act as a preservative in the formulation.
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Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
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| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J2469 | $0.574 / J2469 unit | — |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Palonosetron Hydrochloride .25 mg/5mL 00703-4094-01 | Teva | 1 vial | — | — | FDA listed | — |
| Palonosetron Hydrochloride .25 mg/5mL 00781-3312-75 | Sandoz | 1 vial | — | AP | FDA listed | — |
| Palonosetron Hydrochloride .25 mg/5mL 00781-3415-75 | Sandoz | 1 vial | — | AP | Discontinued | — |
| Palonosetron .05 mg/mL 16714-0834-01 | NorthStar | 1 vial | — | AP | FDA listed | — |
| palonosetron hydrochloride .05 mg/mL 25021-0783-05 | Sagent | 1 vial | — | AP | FDA listed | — |
| Palonosetron Hydrochloride .25 mg/5mL 36000-0326-02 | Baxter | 1 vial | — | — | FDA listed | — |
| Palonosetron .05 mg/mL 55111-0694-07 | Dr.Reddy's | 1 vial | — | AP | FDA listed | — |
| Palonosetron Hydrochloride .25 mg/5mL 55150-0186-05 | Eugia | 1 vial | — | AP | FDA listed | — |
| Palonosetron .25 mg/5mL 60505-6193-01 | Apotex | 1 vial | — | — | FDA listed | — |
| Palonosetron .25 mg/5mL 60505-6439-01 | Apotex | 1 vial | — | — | FDA listed | — |
| Palonosetron .25 mg/5mL 63323-0673-05 | Fresenius | 1 vial | — | AP | FDA listed | — |
| Palonosetron .25 mg/5mL 67184-0514-01 | Qilu | 1 vial | — | — | FDA listed | — |
| Palonosetron Hydrochloride .25 mg/5mL 67457-0317-25 | Mylan | 1 vial | — | AP | FDA listed | — |
| Palonosetron .05 mg/mL 68001-0355-25 | BluePoint | 1 vial | — | AP | FDA listed | — |
| palonosetron hydrochloride .25 mg/5mLthis 69097-0927-35 | Cipla | 1 vial | — | — | FDA listed | — |
| Palonosetron Hydrochloride .25 mg/5mL 71288-0409-05 | Meitheal | 1 vial | — | AP | FDA listed | — |
| Palonosetron Hydrochloride .05 mg/mL 83634-0777-05 | Avenacy, | 1 vial | — | — | Discontinued | — |
| posfrea .25 mg/5mL 83831-0105-01 | Avyxa | 1 vial | — | — | FDA listed | — |
| Palonosetron .25 mg/5mL 68001-0708-25 | BLuePoint | 1 vial | — | — | FDA listed | — |
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⏳ Availability & generic status
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 69097-0927-35 You're viewing this | 1 VIAL in 1 CARTON (69097-927-35) / 5 mL in 1 VIAL | 2018-03-23 | Active |
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | — Not published for this NDC No photo available yet for this listing. |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope. |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Palonosetron Hydrochloride Injection is a serotonin-3 (5-HT 3 ) receptor antagonist indicated in adults for: Moderately emetogenic cancer chemotherapy - prevention of acute and delayed nausea and vomiting associated with initial and repeat courses ( 1 .1) Highly emetogenic cancer chemotherapy - prevention of acute nausea and vomiting associated with initial and repeat courses ( 1.1 ) Prevention of postoperative nausea and vomiting (PONV) for up to 24 hours following surgery. Efficacy beyond 24 hours has not been demonstrated ( 1.3 ) Palonosetron Hydrochloride Injection is indicated in pediatric patients aged 1 month to less than 17 years for: Prevention of acute nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including highly emetogenic cancer chemotherapy ( 1.2 )
1.1Chemotherapy-Induced Nausea and Vomiting in Adults Palonosetron Hydrochloride Injection is indicated for: Moderately emetogenic cancer chemotherapy -- prevention of acute and delayed nausea and vomiting associated with initial and repeat courses Highly emetogenic cancer chemotherapy -- prevention of acute nausea and vomiting associated with initial and repeat courses
1.2Chemotherapy-Induced Nausea and Vomiting in Pediatric Patients Aged 1 Month to Less than 17 Years Palonosetron Hydrochloride Injection is indicated for prevention of acute nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including highly emetogenic cancer chemotherapy.
1.3Postoperative Nausea and Vomiting in Adults Palonosetron Hydrochloride Injection is indicated for prevention of postoperative nausea and vomiting (PONV) for up to 24 hours following surgery. Efficacy beyond 24 hours has not been demonstrated. As with other antiemetics, routine prophylaxis is not recommended in patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively.
In patients where nausea and vomiting must be avoided during the postoperative period, Palonosetron Hydrochloride Injection is recommended even where the incidence of postoperative nausea and/or vomiting is low.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Chemotherapy-Induced Nausea and Vomiting (2.1 ) *Note different dosing units in pediatrics Age Dose* Infusion Time Adults 0 . 2 5 mg x 1 Infuse over 30 seconds beginning approx. 30 min before the start of chemo Pediatrics (1 month to less than 17 years) 2 0 micrograms per k ilogram (max 1.5 mg) x 1 Infuse over 15 minutes beginning approx.
30 min before the start of chemo Postoperative Nausea and Vomiting ( 2.1 ) Adult Dosage: a single 0.075 mg intravenous dose administered over 10 seconds immediately before the induction of anesthesia.
2.1Recommended Dosing Chemotherapy-Induced Nausea and Vomiting *Note different dosing units in pediatrics Age Dose* Infusion Time Adults 0 . 2 5 mg x 1 Infuse over 30 seconds beginning approx. 30 min before the start of chemo Pediatrics (1 month to less than 17 years) 2 0 micrograms per kilogram (max 1.5 mg) x 1 Infuse over 15 minutes beginning approx.
30 min before the start of chemo Postoperative Nausea and Vomiting Dosage for Adults - a single 0.075 mg intravenous dose administered over 10 seconds immediately before the induction of anesthesia.
2.2Instructions for Intravenous Administration Palonosetron Hydrochloride Injection is supplied ready for intravenous administration at a concentration of 0.05 mg/mL (50 mcg/ mL). Palonosetron Hydrochloride Injection should not be mixed with other drugs. The infusion line should be flushed with normal saline before and after administration of Palonosetron Hydrochloride Injection.
Parenteral drug products should be inspected visually for particulate matter and discoloration before administration, whenever solution and container permit.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORM AND STRENGTHS Palonosetron Hydrochloride Injection is supplied as a single-use sterile, clear, colorless solution in glass vials that provide: 0.25 mg (free base) per 5 mL (concentration: 0.05 mg/mL, 50 mcg/mL) 0.25 mg/5mL (free base) single-use vial ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Palonosetron Hydrochloride Injection is contraindicated in patients known to have hypersensitivity to the drug or any of its components. [ see Adverse Reactions ( 6.2 ) ]. Palonosetron Hydrochloride Injection is contraindicated in patients known to have hypersensitivity to the drug or any of its components ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Hypersensitivity reactions, including anaphylaxis, have been reported with or without known hypersensitivity to other selective 5-HT 3 receptor antagonists ( 5.1 ) Serotonin syndrome has been reported with 5-HT 3 receptor antagonists alone but particularly with concomitant use of serotonergic drugs ( 5.2 )
5.1Hypersensitivity Hypersensitivity reactions, including anaphylaxis, have been reported with or without known hypersensitivity to other 5-HT 3 receptor antagonists.
5.2Serotonin Syndrome The development of serotonin syndrome has been reported with 5-HT 3 receptor antagonists. Most reports have been associated with concomitant use of serotonergic drugs (e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors, mirtazapine, fentanyl, lithium, tramadol, and intravenous methylene blue). Some of the reported cases were fatal.
Serotonin syndrome occurring with overdose of another 5-HT 3 receptor antagonist alone has also been reported. The majority of reports of serotonin syndrome related to 5-HT 3 receptor antagonist use occurred in a post-anesthesia care unit or an infusion center. Symptoms associated with serotonin syndrome may include the following combination of signs and symptoms: mental status changes (e.g. agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, with or without gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).
Patients should be monitored for the emergence of serotonin syndrome, especially with concomitant use of Palonosetron Hydrochloride Injection and other serotonergic drugs. If symptoms of serotonin syndrome occur, discontinue Palonosetron Hydrochloride Injection and initiate supportive treatment. Patients should be informed of the increased risk of serotonin syndrome, especially if Palonosetron Hydrochloride Injection is used concomitantly with other serotonergic drugs [ see Drug Interactions ( 7 ), Patient Counseling Information ( 17 ) ].
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The most common adverse reactions in chemotherapy-induced nausea and vomiting in adults (incidence ≥5%) are headache and constipation ( 6.1 ). The most common adverse reactions in postoperative nausea and vomiting (incidence ≥ 2%) are QT prolongation, bradycardia, headache, and constipation ( 6.2 ).
To report SUSPECTED ADVERSE REACTIONS, contact Cipla USA, Inc., at 1-866-604-3268 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Chemotherapy-Induced Nausea and Vomiting Adults In clinical trials for the prevention of nausea and vomiting induced by moderately or highly emetogenic chemotherapy, 1374 adult patients received palonosetron. Adverse reactions were similar in frequency and severity with Palonosetron Hydrochloride Injection and ondansetron or dolasetron. Following is a listing of all adverse reactions reported by 2% of patients in these trials (Table 1).
Table 1: Adverse Reactions from Chemotherapy-Induced Nausea and Vomiting Studies ≥ 2% in any Treatment Group Event Palonosetron Hydrochloride Injection 0.25 mg (N=633) Ondansetron 32 mg I.V. (N=410) Dolasetron 100 mg I.V. (N=194) Headache 60 (9%) 34 (8%) 32 (16%) Constipation 29 (5%) 8 (2%) 12 (6%) Diarrhea 8 (1%) 7 (2%) 4 (2%) Dizziness 8 (1%) 9 (2%) 4 (2%) Fatigue 3 (< 1%) 4 (1%) 4 (2%) Abdominal Pain 1 (< 1%) 2 (< 1%) 3 (2%) Insomnia 1 (< 1%) 3 (1%) 3 (2%) In other studies, 2 subjects experienced severe constipation following a single palonosetron dose of approximately 0.75 mg, three times the recommended dose.
One patient received a 10 mcg/kg oral dose in a post-operative nausea and vomiting study and one healthy subject received a 0.75 mg I.V. dose in a pharmacokinetic study. In clinical trials, the following infrequently reported adverse reactions, assessed by investigators as treatment-related or causality unknown, occurred following administration of Palonosetron Hydrochloride Injection to adult patients receiving concomitant cancer chemotherapy: Cardiovascular : 1%: non-sustained tachycardia, bradycardia, hypotension, < 1%: hypertension, myocardial ischemia, extrasystoles, sinus tachycardia, sinus arrhythmia, supraventricular extrasystoles and QT prolongation.
In many cases, the relationship to Palonosetron Hydrochloride Injection was unclear. Dermatological: < 1%: allergic dermatitis, rash. Hearing and Vision: < 1%: motion sickness, tinnitus, eye irritation and amblyopia.
Gastrointestinal System: 1%: diarrhea, < 1%: dyspepsia, abdominal pain, dry mouth, hiccups and flatulence. General: 1%: weakness, < 1%: fatigue, fever, hot flash, flu-like syndrome. Liver: < 1%: transient, asymptomatic increases in AST and/or ALT and bilirubin.
These changes occurred predominantly in patients receiving highly emetogenic chemotherapy. Metabolic: 1%: hyperkalemia, < 1%: electrolyte fluctuations, hyperglycemia, metabolic acidosis, glycosuria, appetite decrease, anorexia. Musculoskeletal: < 1%: arthralgia.
Nervous System: 1%: dizziness, < 1%: somnolence, insomnia, hypersomnia, paresthesia. Psychiatric: 1%: anxiety, < 1%: euphoric mood. Urinary System: < 1%: urinary retention.
Vascular: < 1%: vein discoloration, vein distention. Pediatrics In a pediatric clinical trial for the prevention of chemotherapy-induced nausea and vomiting 163 cancer patients received a single 20 mcg/kg (maximum 1.5 mg) intravenous infusion of palonosetron 30 minutes before beginning the first cycle of emetogenic chemotherapy. Patients had a mean age of 8.4 years (range 2 months to 16.9 years) and were 46% male; and 93% white.
The following adverse reactions were reported for palonosetron: Nervous System: <1%: headache, dizziness, dyskinesia. General: <1%: infusion site pain. Dermatological: <1%: allergic dermatitis, skin d…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Palonosetron is eliminated from the body through both renal excretion and metabolic pathways with the latter mediated via multiple CYP enzymes. Further in vitro studies indicated that palonosetron is not an inhibitor of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1 and CYP3A4/5 (CYP2C19 was not investigated) nor does it induce the activity of CYP1A2, CYP2D6, or CYP3A4/5. Therefore, the potential for clinically significant drug interactions with palonosetron appears to be low.
Serotonin syndrome (including altered mental status, autonomic instability, and neuromuscular symptoms) has been described following the concomitant use of 5-HT 3 receptor antagonists and other serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) [ see Warnings and Precautions ( 5.2 ) ]. Coadministration of 0.25 mg I.V. palonosetron and 20 mg I.V. dexamethasone in healthy subjects revealed no pharmacokinetic drug-interactions between palonosetron and dexamethasone.
In an interaction study in healthy subjects where palonosetron 0.25 mg (I.V. bolus) was administered on day 1 and oral aprepitant for 3 days (125 mg/80 mg/80 mg), the pharmacokinetics of palonosetron were not significantly altered (AUC: no change, C max : 15% increase). A study in healthy volunteers involving single-dose I.V. palonosetron (0.75 mg) and steady state oral metoclopramide (10 mg four times daily) demonstrated no significant pharmacokinetic interaction. In controlled clinical trials, Palonosetron Hydrochloride Injection has been safely administered with corticosteroids, analgesics, antiemetics /antinauseants, antispasmodics and anticholinergic agents.
Palonosetron did not inhibit the antitumor activity of the five chemotherapeutic agents tested (cisplatin, cyclophosphamide, cytarabine, doxorubicin and mitomycin C) in murine tumor models. The potential for clinically significant drug interactions with palonosetron appears to be low ( 7 )
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Chemotherapy-Induced Nausea and Vomiting Pediatric use: Safety and effectiveness in neonates (less than 1 month of age) have not been established ( 8.4) Postoperative Nausea and Vomiting Safety and Effectiveness in patients below the age of 18 years have not been established ( 8.4 )
8.1Pregnancy Pregnancy Category B Risk Summary Adequate and well controlled studies with Palonosetron Hydrochloride Injection have not been conducted in pregnant women. In animal reproduction studies, no effects on embryo-fetal development were observed with the administration of oral palonosetron during the period of organogenesis at doses up to 1894 and 3789 times the recommended human intravenous dose in rats and rabbits, respectively. Because animal reproduction studies are not always predictive of human response, Palonosetron Hydrochloride Injection should be used during pregnancy only if clearly needed.
Animal Data In animal studies, no effects on embryo-fetal development were observed in pregnant rats given oral palonosetron at doses up to 60 mg/kg/day (1894 times the recommended human intravenous dose based on body surface area) or pregnant rabbits given oral doses up to 60 mg/kg/day (3789 times the recommended human intravenous dose based on body surface area) during the period of organogenesis.
8.3Nursing Mothers It is not known whether Palonosetron Hydrochloride Injection is present in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants and the potential for tumorigenicity shown for palonosetron in the rat carcinogenicity study [ see Nonclinical Toxicology ( 13.1 )] , a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
8.4Pediatric Use Chemotherapy-Induced Nausea and Vomiting Safety and effectiveness of Palonosetron Hydrochloride Injection have been established in pediatric patients aged 1 month to less than 17 years for the prevention of acute nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including highly emetogenic cancer chemotherapy. Use is supported by a clinical trial where 165 pediatric patients aged 2 months to <17 years were randomized to receive a single dose of palonosetron 20 mcg/kg (maximum 1.5 mg) administered as an intravenous infusion 30 minutes prior to the start of emetogenic chemotherapy [ see Clinical Studies ( 14.2 )] .
While this study demonstrated that pediatric patients require a higher palonosetron dose than adults to prevent chemotherapy-induced nausea and vomiting, the safety profile is consistent with the established profile in adults [ see Adverse Reactions ( 6.1 )] . Safety and effectiveness of Palonosetron Hydrochloride Injection in neonates (less than 1 month of age) have not been established. Postoperative Nausea and Vomiting Studies Safety and efficacy have not been established in pediatric patients for prevention of postoperative nausea and vomiting.
Two pediatric trials were performed. Pediatric Study 1, a dose finding study was conducted to compare two doses of palonosetron, 1 mcg/kg (max 0.075 mg) versus 3 mcg/kg (max 0.25 mg). A total of 150 pediatric surgical patients participated, age range 1 month to <17 years.
No dose response was observed. Pediatric Study 2, a multicenter, double-blind, double-dummy, randomized, parallel group, active control, single-dose non-inferiority study, compared I.V. palonosetron (1 mcg/kg, max 0.075 mg) versus I.V. ondansetron. A total of 670 pediatric surgical patients participated, age 30 days to <17 years.
The primary efficacy endpoint, Complete Response (CR: no vomiting, no retching, and no antiemetic rescue medication) during the first 24 hours postoperatively was achieved in 78.2% of patients in the palonosetron group and 82.7% in the ondansetron group. Given the pre-specified non-inferiority margin of -…
🤰 Pregnancy ▾
8.1Pregnancy Pregnancy Category B Risk Summary Adequate and well controlled studies with Palonosetron Hydrochloride Injection have not been conducted in pregnant women. In animal reproduction studies, no effects on embryo-fetal development were observed with the administration of oral palonosetron during the period of organogenesis at doses up to 1894 and 3789 times the recommended human intravenous dose in rats and rabbits, respectively. Because animal reproduction studies are not always predictive of human response, Palonosetron Hydrochloride Injection should be used during pregnancy only if clearly needed.
Animal Data In animal studies, no effects on embryo-fetal development were observed in pregnant rats given oral palonosetron at doses up to 60 mg/kg/day (1894 times the recommended human intravenous dose based on body surface area) or pregnant rabbits given oral doses up to 60 mg/kg/day (3789 times the recommended human intravenous dose based on body surface area) during the period of organogenesis.
🧒 Pediatric Use ▾
8.4Pediatric Use Chemotherapy-Induced Nausea and Vomiting Safety and effectiveness of Palonosetron Hydrochloride Injection have been established in pediatric patients aged 1 month to less than 17 years for the prevention of acute nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including highly emetogenic cancer chemotherapy. Use is supported by a clinical trial where 165 pediatric patients aged 2 months to <17 years were randomized to receive a single dose of palonosetron 20 mcg/kg (maximum 1.5 mg) administered as an intravenous infusion 30 minutes prior to the start of emetogenic chemotherapy [ see Clinical Studies ( 14.2 )] .
While this study demonstrated that pediatric patients require a higher palonosetron dose than adults to prevent chemotherapy-induced nausea and vomiting, the safety profile is consistent with the established profile in adults [ see Adverse Reactions ( 6.1 )] . Safety and effectiveness of Palonosetron Hydrochloride Injection in neonates (less than 1 month of age) have not been established. Postoperative Nausea and Vomiting Studies Safety and efficacy have not been established in pediatric patients for prevention of postoperative nausea and vomiting.
Two pediatric trials were performed. Pediatric Study 1, a dose finding study was conducted to compare two doses of palonosetron, 1 mcg/kg (max 0.075 mg) versus 3 mcg/kg (max 0.25 mg). A total of 150 pediatric surgical patients participated, age range 1 month to <17 years.
No dose response was observed. Pediatric Study 2, a multicenter, double-blind, double-dummy, randomized, parallel group, active control, single-dose non-inferiority study, compared I.V. palonosetron (1 mcg/kg, max 0.075 mg) versus I.V. ondansetron. A total of 670 pediatric surgical patients participated, age 30 days to <17 years.
The primary efficacy endpoint, Complete Response (CR: no vomiting, no retching, and no antiemetic rescue medication) during the first 24 hours postoperatively was achieved in 78.2% of patients in the palonosetron group and 82.7% in the ondansetron group. Given the pre-specified non-inferiority margin of -10%, the stratum adjusted Mantel-Haenszel statistical non-inferiority confidence interval for the difference in the primary endpoint, complete response (CR), was [-10.5, 1.7%], therefore non-inferiority was not demonstrated.
Adverse reactions to palonosetron were similar to those reported in adults (Table 2).
🧓 Geriatric Use ▾
8.5Geriatric Use Population pharmacokinetics analysis did not reveal any differences in palonosetron pharmacokinetics between cancer patients ≥ 65 years of age and younger patients (18 to 64 years). Of the 1374 adult cancer patients in clinical studies of palonosetron, 316 (23%) were ≥ 65 years old, while 71 (5%) were ≥ 75 years old. No overall differences in safety or effectiveness were observed between these subjects and the younger subjects, but greater sensitivity in some older individuals cannot be ruled out.
No dose adjustment or special monitoring are required for geriatric patients. Of the 1520 adult patients in Palonosetron Hydrochloride Injection PONV clinical studies, 73 (5%) were ≥ 65 years old. No overall differences in safety were observed between older and younger subjects in these studies, though the possibility of heightened sensitivity in some older individuals cannot be excluded.
No differences in efficacy were observed in geriatric patients for the CINV indication and none are expected for geriatric PONV patients. However, Palonosetron Hydrochloride Injection efficacy in geriatric patients has not been adequately evaluated.
🆘 Overdosage ▾
10 OVERDOSAGE There is no known antidote to Palonosetron Hydrochloride Injection. Overdose should be managed with supportive care. Fifty adult cancer patients were administered palonosetron at a dose of 90 mcg/kg (equivalent to 6 mg fixed dose) as part of a dose ranging study.
This is approximately 25 times the recommended dose of 0.25 mg. This dose group had a similar incidence of adverse events compared to the other dose groups and no dose response effects were observed. Dialysis studies have not been performed, however, due to the large volume of distribution, dialysis is unlikely to be an effective treatment for palonosetron overdose.
A single intravenous dose of palonosetron at 30 mg/kg (947 and 474 times the human dose for rats and mice, respectively, based on body surface area) was lethal to rats and mice. The major signs of toxicity were convulsions, gasping, pallor, cyanosis and collapse.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Palonosetron is a 5-HT 3 receptor antagonist with a strong binding affinity for this receptor and little or no affinity for other receptors. Cancer chemotherapy may be associated with a high incidence of nausea and vomiting, particularly when certain agents, such as cisplatin, are used. 5-HT 3 receptors are located on the nerve terminals of the vagus in the periphery and centrally in the chemoreceptor trigger zone of the area postrema.
It is thought that chemotherapeutic agents produce nausea and vomiting by releasing serotonin from the enterochromaffin cells of the small intestine and that the released serotonin then activates 5-HT 3 receptors located on vagal afferents to initiate the vomiting reflex. Postoperative nausea and vomiting is influenced by multiple patient, surgical and anesthesia related factors and is triggered by release of 5-HT in a cascade of neuronal events involving both the central nervous system and the gastrointestinal tract.
The 5-HT 3 receptor has been demonstrated to selectively participate in the emetic response.
12.2Pharmacodynamics The effect of palonosetron on blood pressure, heart rate, and ECG parameters including QTc were comparable to ondansetron and dolasetron in CINV clinical trials. In PONV clinical trials the effect of palonosetron on the QTc interval was no different from placebo. In non-clinical studies palonosetron possesses the ability to block ion channels involved in ventricular de- and re‑polarization and to prolong action potential duration.
The effect of palonosetron on QTc interval was evaluated in a double blind, randomized, parallel, placebo and positive (moxifloxacin) controlled trial in adult men and women. The objective was to evaluate the ECG effects of I.V. administered palonosetron at single doses of 0.25, 0.75 or 2.25 mg in 221 healthy subjects. The study demonstrated no significant effect on any ECG interval including QTc duration (cardiac repolarization) at doses up to 2.25 mg.
12.3Pharmacokinetics After intravenous dosing of palonosetron in healthy subjects and cancer patients, an initial decline in plasma concentrations is followed by a slow elimination from the body. Mean maximum plasma concentration (C max ) and area under the concentration-time curve (AUC 0-∞ ) are generally dose-proportional over the dose range of 0.3–90 mcg/kg in healthy subjects and in cancer patients. Following single I.V. dose of palonosetron at 3 mcg/kg (or 0.21 mg/70 kg) to six cancer patients, mean ( ± SD) maximum plasma concentration was estimated to be 5630 ± 5480 ng/L and mean AUC was 35.8 ± 20.9 h mcg/L.
Following I.V. administration of palonosetron 0.25 mg once every other day for 3 doses in 11 cancer patients, the mean increase in plasma palonosetron concentration from Day 1 to Day 5 was 42±34%. Following I.V. administration of palonosetron 0.25 mg once daily for 3 days in 12 healthy subjects, the mean (±SD) increase in plasma palonosetron concentration from Day 1 to Day 3 was 110±45%. After intravenous dosing of palonosetron in patients undergoing surgery (abdominal surgery or vaginal hysterectomy), the pharmacokinetic characteristics of palonosetron were similar to those observed in cancer patients.
Distribution Palonosetron has a volume of distribution of approximately 8.3 ±
2.5L/kg. Approximately 62% of palonosetron is bound to plasma proteins. Metabolism Palonosetron is eliminated by multiple routes with approximately 50% metabolized to form two primary metabolites: N-oxide-palonosetron and 6-S-hydroxy-palonosetron.
These metabolites each have less than 1% of the 5-HT 3 receptor antagonist activity of palonosetron. In vitro metabolism studies have suggested that CYP2D6 and to a lesser extent, CYP3A4 and CYP1A2 are involved in the metabolism of palonosetron. However, clinical pharmacokinetic parameters are not significantly different between poor and extensive metabolizers of CYP2D6 substrates.
Elimination After a single intra…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Palonosetron is a 5-HT 3 receptor antagonist with a strong binding affinity for this receptor and little or no affinity for other receptors. Cancer chemotherapy may be associated with a high incidence of nausea and vomiting, particularly when certain agents, such as cisplatin, are used. 5-HT 3 receptors are located on the nerve terminals of the vagus in the periphery and centrally in the chemoreceptor trigger zone of the area postrema.
It is thought that chemotherapeutic agents produce nausea and vomiting by releasing serotonin from the enterochromaffin cells of the small intestine and that the released serotonin then activates 5-HT 3 receptors located on vagal afferents to initiate the vomiting reflex. Postoperative nausea and vomiting is influenced by multiple patient, surgical and anesthesia related factors and is triggered by release of 5-HT in a cascade of neuronal events involving both the central nervous system and the gastrointestinal tract.
The 5-HT 3 receptor has been demonstrated to selectively participate in the emetic response.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING NDC 69097-927-35, Palonosetron Hydrochloride Injection 0.25 mg/5 mL (free base) single-use vial individually packaged in a carton. Storage Store at controlled temperature of 20–25°C (68°F–77°F). Excursions permitted to 15–30°C (59-86°F). Protect from freezing. Protect from light.
📋 Description ▾
11 DESCRIPTION Palonosetron Hydrochloride Injection is an antiemetic and antinauseant agent. It is a serotonin-3 (5-HT 3 ) receptor antagonist with a strong binding affinity for this receptor. Chemically, palonosetron hydrochloride is: (3a S) -2-[( S )-1-Azabicyclo [2.2.2]oct-3-yl]-2,3,3a,4,5,6-hexahydro-1-oxo-1 H benz[ de ]isoquinoline hydrochloride.
The empirical formula is C 19 H 24 N 2 O.HCl, with a molecular weight of 332.87. Palonosetron hydrochloride exists as a single isomer and has the following structural formula: image Palonosetron hydrochloride is a white to off-white crystalline powder. It is freely soluble in water, soluble in propylene glycol, and slightly soluble in ethanol and 2-propanol.
Palonosetron Hydrochloride Injection is a sterile, clear, colorless, non pyrogenic, isotonic, buffered solution for intravenous administration. Palonosetron Hydrochloride Injection is available as 5 mL single use vial. Each 5 mL vial contains 0.25 mg palonosetron base as 0.28 mg palonosetron hydrochloride, 207.5 mg mannitol, disodium edetate and citrate buffer in water for intravenous administration.
The pH of the solution in the 5 mL vials is 4.5 to 5.5. description
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION See FDA-approved patient labelling (Patient Information). Instructions for Patients Patients should be advised to report to their physician all of their medical conditions, including any pain, redness, or swelling in and around the infusion site [see Adverse Reactions ( 6.3 )]. Advise patients of the possibility of serotonin syndrome, especially with concomitant use of Palonosetron Hydrochloride Injection and another serotonergic agent such as medications to treat depression and migraines.
Advise patients to seek immediate medical attention if the following symptoms occur: changes in mental status, autonomic instability, neuromuscular symptoms with or without gastrointestinal symptoms [ see Warnings and Precautions ( 5.2 ) ]. Patients should be instructed to read the Patient Information.