Palonosetron Hydrochloride .25 mg/5mL Injection, Solution
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Serotonin-3 Receptor Antagonist class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
- 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...
- What is palonosetron injection (Posfrea) actually used for?
- You'll always receive this in a clinical setting — a hospital, infusion center, or surgical suite. A nurse or other healthcare professional gives it as an IV infusion or injection....
- Will I receive this at home, or does it have to be given by a healthcare provider?
Patient education
Supplement & herbal interactions
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
Where does this data come from?
IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $55.43 | $277.16 / 5 ml |
| 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 | — |
Where does this data come from?
🧾 Billing & reimbursement
Where does this data come from?
🔁 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/5mLthis 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/5mL 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 | — |
Where does this data come from?
⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
🗺️ Medicaid utilization & spend
💊 Medicaid utilization by pack size
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
Where does this data come from?
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00781-3415-75 You're viewing this | 1 VIAL, SINGLE-DOSE in 1 CARTON (0781-3415-75) / 5 mL in 1 VIAL, SINGLE-DOSE | 2018-11-26 | Discontinued by firm |
| 00781-3415-95 | 10 VIAL, SINGLE-DOSE in 1 CARTON (0781-3415-95) / 5 mL in 1 VIAL, SINGLE-DOSE | 2024-10-01 | Discontinued by firm |
In Medicaid, this is the most-dispensed pack of this product — about 100% of fills over the last four reported quarters. See all packs ↓
Pack size FAQ
What quantity is in NDC 00781-3415-75?
What NDC number is used to bill for this package of Palonosetron Hydrochloride .25 mg/5mL Injection, Solution?
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| 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) | — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is 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 | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | ✓ Available |
Questions about this listing
Why is there no price listed?
What does the discontinued status mean for this NDC?
Is the NDC printed on the package the same as the 11-digit billing NDC?
What do the three segments of this NDC mean?
Does this product come in other package sizes?
Who lists this product with the FDA?
Do I need a prescription for this product?
Does this product have a billing J-code?
Where does this data come from?
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Palonosetron injection is indicated in adults for prevention of: • acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC). • acute nausea and vomiting associated with initial and repeat courses highly emetogenic cancer chemotherapy (HEC). • 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 is recommended even where the incidence of postoperative nausea and/or vomiting is low. Palonosetron HCl injection is indicated in pediatric patients 1 month to less than 17 years of age for prevention of: • acute nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including highly emetogenic cancer chemotherapy. Palonosetron is a serotonin-3 (5-HT 3 ) receptor antagonist indicated in: Adults for prevention of: • acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC).
( 1 ) • acute nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC). ( 1 ) • postoperative nausea and vomiting (PONV) for up to 24 hours following surgery. Efficacy beyond 24 hours has not been demonstrated.
( 1 ) 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 (HEC). ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Chemotherapy - Induced Nausea and Vomiting ( 2.1 ) Age Dose* Infusion Time Adults 0.25 mg as a single-dose Infuse over 30 seconds beginning approximately 30 minutes before the start of chemotherapy Pediatrics (1 month to less than 17 years) 20 micrograms per kilogram (maximum 1.5 mg) as a single-dose Infuse over 15 minutes beginning approximately 30 minutes before the start of chemotherapy *Note different dosing units in pediatrics Postoperative Nausea and Vomiting ( 2.1 ) • The recommended adult dosage is 0.075 mg as a single intravenous dose administered over 10 seconds immediately before the induction of anesthesia.
2.1Recommended Dosage Prevention of Chemotherapy-Induced Nausea and Vomiting The recommended dosage of palonosetron HCl injection for prevention of nausea and vomiting associated with HEC and MEC in adults and associated with emetogenic chemotherapy, including HEC in pediatric patients 1 month to less than 17 years of age is shown in Table 1 . Table 1: Recommended Dosage of Palonosetron HCl Injection for the Prevention of Nausea and Vomiting Associated with Chemotherapy in Adults and Pediatric Patients 1 Month to Less than 17 Years Age Dose Note different dosing units in pediatrics Infusion Time Adults 0.25 mg as a single-dose Infuse over 30 seconds beginning approximately 30 minutes before the start of chemotherapy Pediatrics (1 month to less than 17 years) 20 micrograms per kilogram (max 1.5 mg) as a single-dose Infuse over 15 minutes beginning approximately 30 minutes before the start of chemotherapy Postoperative Nausea and Vomiting The recommended dosage of palonosetron HCl injection in adults for PONV is 0.075 mg administered as a single intravenous dose over 10 seconds immediately before the induction of anesthesia.
2.2Instructions for Intravenous Administration • Palonosetron HCl injection is supplied ready for intravenous administration at a concentration of 0.05 mg/mL (50 mcg/mL). • Do not mix palonosetron HCl injection with other drugs. • Flush the infusion line with normal saline before and after administration of palonosetron HCl injection. • Inspect palonosetron HCl injection visually for particulate matter and discoloration before administration. • Discard unused portion.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORM AND STRENGTHS Palonosetron HCl injection is sterile, clear, colorless solution in glass vials that provide: • 0.25 mg palonosetron in 5 mL (0.05 mg/mL) in a single-dose vial Injection: 0.25 mg palonosetron in 5 mL (0.05 mg/mL) in a single-dose vial. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Palonosetron HCl injection is contraindicated in patients known to have hypersensitivity to palonosetron [see Warnings and Precautions ( 5.1 )]. Hypersensitivity to palonosetron or any of its components. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Hypersensitivity reactions, including anaphylaxis and anaphylactic shock: reported in patients with or without known hypersensitivity to other selective 5-HT 3 receptor antagonists. If symptoms occur, discontinue palonosetron and initiate appropriate medical treatment. ( 5.1 ) • Serotonin syndrome : reported with 5-HT 3 receptor antagonists alone, but particularly with concomitant use of serotonergic drugs. ( 5.2 , 7.1 )
5.1Hypersensitivity Reactions Hypersensitivity reactions, including anaphylaxis and anaphylactic shock, have been reported with administration of palonosetron HCl injection [see Adverse Reactions ( 6.2 )] . These reactions occurred in patients with or without known hypersensitivity to other 5-HT 3 receptor antagonists. If hypersensitivity reactions occur, discontinue palonosetron HCl injection and initiate appropriate medical treatment.
Do not reinitiate palonosetron HCl injection in patients who have previously experienced symptoms of hypersensitivity [see Contraindications ( 4 )].
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 HCl injection and other serotonergic drugs. If symptoms of serotonin syndrome occur, discontinue palonosetron HCl injection and initiate supportive treatment. Patients should be informed of the increased risk of serotonin syndrome, especially if palonosetron HCl injection is used concomitantly with other serotonergic drugs [see Drug Interactions ( 7.1 )].
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS Serious or otherwise clinically significant adverse reactions reported in other sections of labeling: • Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )] • Serotonin Syndrome [see Warnings and Precautions ( 5.2 )] Most common adverse reactions in • chemotherapy-induced nausea and vomiting in adults (≥5%) are: headache and constipation. ( 6.1 ) • postoperative nausea and vomiting (≥2%) are: QT prolongation, bradycardia, headache, and constipation. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience 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. Chemotherapy-Induced Nausea and Vomiting Adults In double-blind randomized clinical trials for the prevention of nausea and vomiting induced by MEC or HEC, 1374 adult patients received a single dose of palonosetron HCl injection, ondansetron (Studies 1 and 3) or dolasetron (Study 2) administered 30 minutes prior to chemotherapy [see Clinical Studies ( 14.1 )].
Adverse reactions were similar in frequency and severity in all 3 treatment groups. Common adverse reactions reported in at least 2% of patients in these trials are shown in Table 2. Table 2: Common Adverse Reactions Reported in at least 2% of patients in any treatment group in Adults with Receiving MEC (Studies 1 and 2) or HEC (Study 3) Adverse Reaction Palonosetron HCl injection 0.25 mg intravenously (N=633) Ondansetron 32 mg intravenously (N=410) Dolasetron 100 mg intravenously (N=194) Headache 9% 8% 16% Constipation 5% 2% 6% Diarrhea 1% 2% 2% Dizziness 1% 2% 2% Fatigue <1% 1% 2% Abdominal Pain <1% <1% 2% Insomnia <1% 1% 2% Less common adverse reactions, reported in 1% or less of patients, in Studies 1, 2 and 3 were: • Cardiovascular: non-sustained tachycardia, bradycardia, hypotension, hypertension, myocardial ischemia, extrasystoles, sinus tachycardia, sinus arrhythmia, supraventricular extrasystoles and QT prolongation. • Dermatological: allergic dermatitis, rash • Hearing and Vision: motion sickness, tinnitus, eye irritation and amblyopia • Gastrointestinal System: diarrhea, dyspepsia, abdominal pain, dry mouth, hiccups and flatulence • General: weakness, fatigue, fever, hot flash, flu-like syndrome • Liver: transient, asymptomatic increases in AST and/or ALT and bilirubin.
These changes occurred predominantly in patients receiving highly emetogenic chemotherapy • Metabolic: hyperkalemia, electrolyte fluctuations, hyperglycemia, metabolic acidosis, glycosuria, appetite decrease, anorexia • Musculoskeletal: arthralgia • Nervous System: dizziness, somnolence, insomnia, hypersomnia, paresthesia • Psychiatric: anxiety, euphoric mood • Urinary System: urinary retention • Vascular: vein discoloration, vein distention In other studies, 2 subjects experienced severe constipation following a single palonosetron HCl injection dose of approximately 0.75 mg (three times the recommended dose).
Pediatrics Aged 2 Months to 17 Years In a pediatric clinical trial, 163 pediatric cancer patients with a mean age of 8 years received a single 20 mcg/kg (maximum 1.5 mg) intravenous infusion of palonosetron HCl injection 30 minutes before beginning the first cycle of emetogenic chemotherapy [see Clinical Studies ( 14.2 )] . Adverse reactions were evaluated in pediatric patients receiving palonosetron HCl injection for up to 4 chemotherapy cycles. The following adverse reactions were reported in less than 1% of patients: • Nervous System: headache, dizziness, dyskinesia. • General: infusion site pain. • Dermatological: allergic dermatitis, skin disorder.
Postoperative Nausea and Vomiting The most common adverse reactions reported in at least 2% of adults receiving palonosetron HCl injecti…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Serotonergic Drugs : Monitor for serotonin syndrome; if symptoms occur, discontinue palonosetron and initiate supportive treatment. ( 7.1 )
7.1Serotonergic Drugs 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). Monitor for the emergence of serotonin syndrome. If symptoms occur, discontinue palonosetron and initiate supportive treatment [see Warnings and Precautions ( 5.2 )].
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary There are no available data on palonosetron HCl use in pregnant women to inform a drug-associated risk. In animal reproduction studies, no effects on embryo-fetal development were observed with the administration of oral palonosetron HCl during the period of organogenesis at doses up to 1,894 and 3,789 times the recommended human intravenous dose in rats and rabbits, respectively (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data In animal reproduction studies, no effects on embryo-fetal development were observed in pregnant rats given oral palonosetron HCl at doses up to 60 mg/kg/day (1,894 times the recommended human intravenous dose based on body surface area) or pregnant rabbits given oral doses up to 60 mg/kg/day (3,789 times the recommended human intravenous dose based on body surface area) during the period of organogenesis.
8.2Lactation Risk Summary 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. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for palonosetron and any potential adverse effect on the breastfed infant from palonosetron or from the underlying maternal condition.
8.4Pediatric Use Chemotherapy-Induced Nausea and Vomiting Safety and effectiveness of palonosetron HCl 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 HEC. Use is supported by a clinical trial where 165 pediatric patients aged 2 months to less than 17 years were randomized to receive a single dose of palonosetron HCl injection 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 HCl injection in neonates (less than 1 month of age) have not been established. Postoperative Nausea and Vomiting Studies Safety and effectiveness 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 (maximum 0.075 mg) versus 3 mcg/kg (maximum 0.25 mg). A total of 150 pediatric surgical patients participated, age range 1 month to less than 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 intravenous palonosetron HCl (1 mcg/kg, maximum 0.075 mg) versus intravenous ondansetron. A total of 670 pediatric surgical patients participated, age 30 days to less than 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 en…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary There are no available data on palonosetron HCl use in pregnant women to inform a drug-associated risk. In animal reproduction studies, no effects on embryo-fetal development were observed with the administration of oral palonosetron HCl during the period of organogenesis at doses up to 1,894 and 3,789 times the recommended human intravenous dose in rats and rabbits, respectively (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data In animal reproduction studies, no effects on embryo-fetal development were observed in pregnant rats given oral palonosetron HCl at doses up to 60 mg/kg/day (1,894 times the recommended human intravenous dose based on body surface area) or pregnant rabbits given oral doses up to 60 mg/kg/day (3,789 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 HCl 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 HEC. Use is supported by a clinical trial where 165 pediatric patients aged 2 months to less than 17 years were randomized to receive a single dose of palonosetron HCl injection 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 HCl injection in neonates (less than 1 month of age) have not been established. Postoperative Nausea and Vomiting Studies Safety and effectiveness 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 (maximum 0.075 mg) versus 3 mcg/kg (maximum 0.25 mg). A total of 150 pediatric surgical patients participated, age range 1 month to less than 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 intravenous palonosetron HCl (1 mcg/kg, maximum 0.075 mg) versus intravenous ondansetron. A total of 670 pediatric surgical patients participated, age 30 days to less than 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.
🧓 Geriatric Use ▾
8.5Geriatric Use Of the 1374 adult cancer patients in clinical studies of intravenously administered palonosetron HCl, 316 (23%) were 65 years and over, while 71 (5%) were at least 75 years and over. Of the 1520 adult patients in clinical studies of intravenously administered palonosetron HCl, 73 (5%) were at least 65 years old [see Clinical Studies ( 14.1 , 14.3 )] . No overall differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity in some older individuals cannot be ruled out.
Population pharmacokinetics analysis did not reveal any differences in palonosetron pharmacokinetics between cancer patients 65 years of age and older compared to younger patients [see Clinical Pharmacology ( 12.3 )] . No dose adjustment is required for geriatric patients.
🆘 Overdosage ▾
10 OVERDOSAGE There is no known antidote to palonosetron. Overdose should be managed with supportive care. 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 HCl 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 Cardiac Electrophysiology The effect of intravenous palonosetron on blood pressure, heart rate, and ECG parameters including QTc were comparable to intravenous 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.
At a dose of 9 times the maximum recommended adult dose, palonosetron HCl injection does not prolong the QT interval to any clinically relevant extent.
12.3Pharmacokinetics After intravenous dosing of palonosetron HCl in healthy subjects and cancer patients, an initial decline in palonosetron 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 to 90 mcg/kg in healthy subjects and in cancer patients. Following a single intravenous dose of palonosetron HCl 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 intravenous administration of palonosetron HCl injection 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 intravenous administration of palonosetron HCl injection 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 HCl injection 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. Elimination After a single intravenous dose of 10 mcg/kg [ 14 C]-palonosetron, approximately 80% of the dose was recovered within 144 hours in the urine with palonosetron representing approximately 40% of the administered dose.
In healthy subjects, the total body clearance of palonosetron was 0.160 ± 0.035 L/h/kg and renal clearance was 0.067 ± 0.018 L/h/kg. Mean terminal elimination half-life is approximately 40 hours. 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…
🧬 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 Palonosetron HCl injection is supplied as a sterile, clear and colorless solution. 0.25 mg palonosetron in 5 mL (0.05 mg/mL) single-dose vial NDC 0781-3415-75: Carton of 1 Vial NDC 0781-3415-95: Carton of 10 Vials Storage • Store at controlled room temperature of 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature]. • Protect from freezing. • Protect from light.
📋 Description ▾
11 DESCRIPTION Palonosetron hydrochloride 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 molecular 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: 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 HCl injection is a sterile, clear, colorless, non-pyrogenic, isotonic, buffered solution for intravenous administration. Palonosetron HCl injection is available as a 5 mL single-dose vial. Each 5 mL vial contains: 0.25 mg palonosetron equivalent to 0.28 mg palonosetron hydrochloride, 207.5 mg mannitol, disodium edetate and citrate buffer in water for intravenous administration.
Hydrochloric acid or sodium hydroxide may have been added to adjust pH. The pH of the solution in the 5 mL vial is 4.5 to 5.5. chemical-structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient or caregiver to read the FDA-approved patient labeling (Patient Information). Hypersensitivity Reactions Advise patients that hypersensitivity reactions, including anaphylaxis and anaphylactic shock, have been reported in patients with or without known hypersensitivity to other 5-HT 3 receptor antagonists. Advise patients to seek immediate medical attention if any signs or symptoms of a hypersensitivity reaction occur with administration of palonosetron HCl injection [see Warnings and Precautions ( 5.1 )].
Serotonin Syndrome Advise patients of the possibility of serotonin syndrome, especially with concomitant use of palonosetron HCl 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 )]. 5001442 Novaplus is a registered trademark of Vizient, Inc.
Distributed by Sandoz Inc., Princeton, NJ 08540