Serotonin (5HT3) antagonists

Palonosetron Hydrochloride

Approved 19 Sept 2018IntravenousInjectable

The FDA lists this product in 26 strengths and forms.

Indications

Palonosetron hydrochloride 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 of 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 hydrochloride is recommended even where the incidence of postoperative nausea and/or vomiting is low. Palonosetron hydrochloride 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 hydrochloride 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 )

Contraindications

Palonosetron hydrochloride 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 )

Indications

Palonosetron hydrochloride 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 of 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 hydrochloride is recommended even where the incidence of postoperative nausea and/or vomiting is low. Palonosetron hydrochloride 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 hydrochloride 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 )

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 Mylan at 1-877-446-3679 (1-877-4-INFO-RX) 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 hydrochloride 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 Hydrochloride 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 hydrochloride 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 hydrochloride 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 hydrochloride 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 hydrochloride injection 0.075 mg intravenously immediately before induction of anesthesia in 3 randomized placebo-controlled trials [see Clinical Studies (14.3) ] are shown in Table 3. Rates of adverse reactions between palonosetron hydrochloride injection and placebo groups were similar. Some events are known to be associated with, or may be exacerbated by, concomitant perioperative and intraoperative medications administered in this surgical population. A thorough QT/QTc study demonstrated palonosetron hydrochloride injection does not prolong the QT interval to any clinically relevant extent [see Clinical Pharmacology (12.2) ] . Table 3: Common Adverse Reactions Reported in at least 2% of patients in any treatment group in Trials of Adults with Postoperative Nausea and Vomiting Adverse Reaction Palonosetron Hydrochloride Injection 0.075 mg intravenously (N = 336) Placebo (N = 369) Electrocardiogram QT prolongation 5% 3% Bradycardia 4% 4% Headache 3% 4% Constipation 2% 3% Less common adverse reactions, reported in 1% of less of patients, in these PONV clinical trials were:
Cardiovascular: QTc prolongation, sinus bradycardia, tachycardia, blood pressure decreased, hypotension, hypertension, arrhythmia, ventricular extrasystoles, generalized edema, ECG T wave amplitude decreased, platelet count decreased. The frequency of these adverse effects did not appear to be different from placebo.
Dermatological: pruritus
Gastrointestinal System: flatulence, dry mouth, upper abdominal pain, salivary hypersecretion, dyspepsia, diarrhea, intestinal hypomotility, anorexia
General: chills
Liver: increases in AST and/or ALT, hepatic enzyme increased
Metabolic: hypokalemia, anorexia
Nervous System: dizziness
Respiratory: hypoventilation, laryngospasm
Urinary System: urinary retention

6.2Postmarketing Experience

The following adverse reactions have been identified during postapproval use of palonosetron hydrochloride. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Hypersensitivity reactions: including dyspnea, bronchospasm, swelling/edema, erythema, pruritus, rash, urticaria, anaphylaxis and anaphylactic shock [see Warnings and Precautions (5.1) ]
Injection site reactions: including burning, induration, discomfort and pain

Palonosetron Hydrochloride

Indications

Contraindications

Two medicines in one question?

Palonosetron Hydrochloride

Indications

Contraindications

Two medicines in one question?

Warnings and precautions

5.1Hypersensitivity Reactions

5.2Serotonin Syndrome

Interactions

7.1Serotonergic Drugs

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Strengths and forms

Official product information

At a glance