PALONOSETRON HYDROCHLORIDE
Clinical safety rating: safe
Animal studies have demonstrated safety
Palonosetron is a selective serotonin 5-HT3 receptor antagonist with high binding affinity, inhibiting serotonin binding and preventing chemotherapy-induced nausea and vomiting. It also exhibits allosteric interactions and prolonged dissociation from the receptor, leading to a longer duration of action compared to other 5-HT3 antagonists.
| Metabolism | Metabolized primarily by CYP2D6, with minor contributions from CYP3A4 and CYP1A2. About 50% of the dose is metabolized, with the remainder excreted unchanged in urine. |
| Excretion | Approximately 80% of the dose is excreted in urine (about 50% as unchanged drug) and 20% in feces. |
| Half-life | Terminal elimination half-life is approximately 40 hours (range 30–60 hours), which supports once-daily dosing for chemotherapy-induced nausea and vomiting. |
| Protein binding | Approximately 62% bound to plasma proteins, primarily to albumin. |
| Volume of Distribution | Volume of distribution is about 8.3 L/kg (8.3 L/kg), indicating extensive tissue distribution beyond plasma volume. |
| Bioavailability | Oral bioavailability is approximately 97% due to high absorption and minimal first-pass metabolism. |
| Onset of Action | Intravenous: onset within 1–3 minutes; oral: onset within 30–60 minutes. |
| Duration of Action | Duration of action persists for up to 24 hours, covering the acute and delayed phases of chemotherapy-induced nausea and vomiting. |
0.25 mg intravenously over 30 seconds, administered approximately 30 minutes before the start of chemotherapy; not to be repeated within 7 days.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment; insufficient data for severe renal impairment (CrCl <30 mL/min) but use with caution. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B); not recommended for severe hepatic impairment (Child-Pugh C) due to lack of data. |
| Pediatric use | 1 month to <17 years: 20 mcg/kg (maximum 1.5 mg) IV as a single dose over 15 minutes, beginning approximately 30 minutes before chemotherapy. |
| Geriatric use | No specific dose adjustment; clinical studies included elderly patients with no overall differences in safety or efficacy; consider renal function in very elderly. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
No significant drug interactions Generally well-tolerated with constipation being the most common side effect.
| Breastfeeding | Unknown if excreted in human milk. M/P ratio not determined. Caution advised; consider benefit vs risk. |
| Teratogenic Risk | Pregnancy Category B. No evidence of teratogenicity in animal studies. Human data limited; risk cannot be excluded. Use during first trimester only if clearly needed. |
| Fetal Monitoring | No specific monitoring required. Standard prenatal care adequate. |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | Headache |
| Serious Effects |
["Hypersensitivity to palonosetron or any component of the formulation"]
| Precautions | ["Serotonin syndrome: Risk with concomitant use of serotonergic drugs","QT prolongation: Use caution in patients with pre-existing arrhythmias or electrolyte disturbances","Hypersensitivity reactions including anaphylaxis","Serotonin syndrome risk with concomitant serotonergic drugs","Use in patients with hepatic impairment (dose adjustment not required but caution)","Use in patients with renal impairment (dose adjustment not required for mild to moderate; no data for severe)"] |
Loading safety data…
| Fertility Effects | No known adverse effects on fertility in animal studies. Human data lacking. |