Posfrea

Drug overview for POSFREA (palonosetron hcl):

Generic name: PALONOSETRON HCL (PAL-oh-NOE-se-tron)
Drug class: Antiemetic
Therapeutic class: Gastrointestinal Therapy Agents

Palonosetron hydrochloride, a selective, second-generation inhibitor of type 3 serotonergic (5-HT3) receptors, is an antiemetic.

No enhanced Uses information available for this drug.

DRUG IMAGES

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The following indications for POSFREA (palonosetron hcl) have been approved by the FDA:

Indications:
Prevention of cancer chemotherapy-induced nausea and vomiting
Prevention of post-operative nausea and vomiting

Professional Synonyms:
Cancer chemotherapy-induced n & v prophylaxis
Postop nausea and vomiting prophylaxis
Postoperative nausea and vomiting prophylaxis

Dosing information for POSFREA
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
POSFREA 0.25 MG/5 ML VIAL	Maintenance	Adults inject 5 milliliters (0.25 mg) over 30 second(s) by intravenous route once 30 minutes before chemotherapy

Generic dosing information for PALONOSETRON HCL
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
PALONOSETRON 0.25 MG/5 ML VIAL	Maintenance	Adults inject 5 milliliters (0.25 mg) over 30 second(s) by intravenous routeonce 30 minutes before chemotherapy

The following drug interaction information is available for POSFREA (palonosetron hcl):

Contraindicated
Severe
Moderate

There are 0 contraindications.

There are 0 severe interactions.

There are 1 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
Tramadol/5-HT3 Antagonists SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The interaction may involve a reduction in the binding involving 5-HT3 receptors.(1) CLINICAL EFFECTS: Concurrent use of 5-HT3 antagonists may decrease the effectiveness of tramadol, resulting in increased use of tramadol.(1-3) 5-HT3 antagonists may not be effective in reducing tramadol-induced nausea.(4) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Consider the use of alternative anti-emetics in patients receiving tramadol, or the use of other opioids in patients receiving 5-HT3 antagonists. DISCUSSION: In a randomized study in 59 post-surgical patients in recovery, compared to tramadol alone, patients receiving concurrent ondansetron required significantly larger doses of tramadol at four hours (223 mg versus 71 mg), at 8 hours (285 mg versus 128 mg), and at 12 hours (406 mg versus 190 mg). Vomiting rates at 4 hours and 8 hours were significantly higher with tramadol and concurrent ondansetron compared to tramadol alone.(1) In a randomized, double-blind study in 40 surgical patients undergoing lumbar laminectomy, compared to tramadol alone, cumulative tramadol consumption with concurrent ondansetron during the first 24 hours was significantly increased (between 26% and 35%) as well as thereafter (22% to 25%).(2) In another randomized study in 120 post-surgical patients, it was discovered that tramadol consumption was increased in those patients receiving concurrent ondansetron compared to tramadol alone.(3) In a prospective, randomized, double-blinded study in dental patients, patients received one of four treatments: fentanyl and metoclopramide, tramadol and metoclopramide, fentanyl and ondansetron, or tramadol and ondansetron. The patients who received tramadol and ondansetron had the highest nausea scores among the treatment groups. There were no significant differences in the incidences of pain or nausea in the 24 hours following the procedure.(4) In a randomized, controlled trial in 40 surgical patients undergoing hernioplasty or thyroidectomy, compared to tramadol alone, cumulative tramadol consumption was higher at the 2-hour time point with concurrent ondansetron (0.24 +/- 0.1 vs. 0.17 +/- 0.16; p = 0.01).(5) A systematic review and meta-analysis of randomized controlled trials in the postoperative setting comparing tramadol alone and in combination with ondansetron were included. At 4-hours, 8-hours, 12-hours, and 24-hours post-procedure, patients had increased tramadol requirements when administered with concurrent ondansetron compared to tramadol alone.(6) 5-HT3 antagonists linked to this monograph include: alosetron, azasetron, dolasetron, granisetron, ondansetron, palonosetron, ramosetron, and tropisetron.	CONZIP, QDOLO, TRAMADOL HCL, TRAMADOL HCL ER, TRAMADOL HCL-ACETAMINOPHEN

Drug Interaction

Drug Names

Tramadol/5-HT3 Antagonists

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The interaction may involve a reduction in the binding involving 5-HT3 receptors.(1)

CLINICAL EFFECTS: Concurrent use of 5-HT3 antagonists may decrease the effectiveness of tramadol, resulting in increased use of tramadol.(1-3) 5-HT3 antagonists may not be effective in reducing tramadol-induced nausea.(4)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Consider the use of alternative anti-emetics in patients receiving tramadol, or the use of other opioids in patients receiving 5-HT3 antagonists.

DISCUSSION: In a randomized study in 59 post-surgical patients in recovery, compared to tramadol alone, patients receiving concurrent ondansetron required significantly larger doses of tramadol at four hours (223 mg versus 71 mg), at 8 hours (285 mg versus 128 mg), and at 12 hours (406 mg versus 190 mg). Vomiting rates at 4 hours and 8 hours were significantly higher with tramadol and concurrent ondansetron compared to tramadol alone.(1) In a randomized, double-blind study in 40 surgical patients undergoing lumbar laminectomy, compared to tramadol alone, cumulative tramadol consumption with concurrent ondansetron during the first 24 hours was significantly increased (between 26% and 35%) as well as thereafter (22% to 25%).(2)

In another randomized study in 120 post-surgical patients, it was discovered that tramadol consumption was increased in those patients receiving concurrent ondansetron compared to tramadol alone.(3) In a prospective, randomized, double-blinded study in dental patients, patients received one of four treatments: fentanyl and metoclopramide, tramadol and metoclopramide, fentanyl and ondansetron, or tramadol and ondansetron. The patients who received tramadol and ondansetron had the highest nausea scores among the treatment groups.

There were no significant differences in the incidences of pain or nausea in the 24 hours following the procedure.(4) In a randomized, controlled trial in 40 surgical patients undergoing hernioplasty or thyroidectomy, compared to tramadol alone, cumulative tramadol consumption was higher at the 2-hour time point with concurrent ondansetron (0.24 +/- 0.1 vs. 0.17 +/- 0.16; p = 0.01).(5) A systematic review and meta-analysis of randomized controlled trials in the postoperative setting comparing tramadol alone and in combination with ondansetron were included.

At 4-hours, 8-hours, 12-hours, and 24-hours post-procedure, patients had increased tramadol requirements when administered with concurrent ondansetron compared to tramadol alone.(6) 5-HT3 antagonists linked to this monograph include: alosetron, azasetron, dolasetron, granisetron, ondansetron, palonosetron, ramosetron, and tropisetron.

CONZIP, QDOLO, TRAMADOL HCL, TRAMADOL HCL ER, TRAMADOL HCL-ACETAMINOPHEN

Severe List
Neuroleptic malignant syndrome
Serotonin syndrome

The following adverse reaction information is available for POSFREA (palonosetron hcl):

Overview
Severe
Less Severe

Adverse reaction overview.

Adverse effects reported in >=5% of adults receiving palonosetron for prevention of chemotherapy-induced nausea and vomiting include headache and constipation. Adverse effects reported in >=2% of adults receiving palonosetron for PONV include QT prolongation, bradycardia, headache, and constipation.

There are 23 severe adverse reactions.

More Frequent	Less Frequent
None.	Bradycardia Hypoventilation

Rare/Very Rare
Anaphylaxis Dyskinesia Dyspnea Extrasystoles Gastrointestinal hypomotility Hyperglycemia Hyperkalemia Hypersensitivity drug reaction Hypertension Hypokalemia Hypotension Increased alanine transaminase Increased aspartate transaminase Laryngismus Metabolic acidosis Myocardial ischemia Serotonin syndrome Sinus node dysfunction Sinus tachycardia Supraventricular premature beats Tachycardia

There are 35 less severe adverse reactions.

More Frequent	Less Frequent
Constipation Headache disorder	Chills Diarrhea Dizziness General weakness Pruritus of skin Symptoms of anxiety

Rare/Very Rare
Abnormal hepatic function tests Acute abdominal pain Allergic dermatitis Anorexia Arthralgia Drowsy Dyspepsia Euphoria Fatigue Fever Flatulence Flu-like symptoms Flushing Glycosuria Hiccups Hypersomnia Injection site sequelae Insomnia Motion sickness Ocular irritation Paresthesia Skin rash Tinnitus Toxic amblyopia Urinary retention Urticaria Xerostomia

The following precautions are available for POSFREA (palonosetron hcl):

Pediatric
Pregnant
Lactation
Geriatric

The safety and effectiveness of palonosetron hydrochloride injection for the prevention of acute nausea and vomiting associated with initial and repeat courses of emetogenic chemotherapy have been established in pediatric patients 1 month to <17 years of age. This indication is supported by evidence from a randomized clinical trial in 165 pediatric patients 2 months to <17 years of age who received a single dose of palonosetron hydrochloride injection 20 mcg/kg (maximum 1.5 mg) 30 minutes before chemotherapy. The study demonstrated that pediatric patients require a higher dose than adults to achieve efficacy.

Adverse reactions in pediatric patients were generally consistent with those observed in adults. Safety and efficacy of palonosetron hydrochloride injection have not been established in neonates <1 month of age for the prevention of chemotherapy-induced nausea and vomiting. The safety and efficacy of palonosetron hydrochloride injection have not been established for the prevention of postoperative nausea and vomiting (PONV) in pediatric patients.

In a dose-finding trial with 150 pediatric surgical patients, no dose-response relationship was observed between palonosetron 1 mcg/kg and 3 mcg/kg. In a randomized, double-blind, active-controlled, noninferiority study of 670 pediatric patients, palonosetron (1 mcg/kg; maximum, 0.075 mg) was compared to ondansetron for the prevention of PONV; the primary endpoint, complete response within 24 hours postoperatively, was achieved by 78.2% of palonosetron-treated patients versus 82.7%

of ondansetron-treated patients. The prespecified margin for noninferiority was not met. Adverse reactions in pediatric patients were similar to those observed in adults.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

There are no available clinical data regarding the use of palonosetron in pregnant women to assess potential drug-related risks. In animal studies, no harmful effects on embryo-fetal development were observed when pregnant rats were administered oral doses of palonosetron hydrochloride up to 60 mg/kg/day (equivalent to 1894 times the recommended human IV dose, adjusted for body surface area), or when pregnant rabbits were given oral doses up to 60 mg/kg/day (3789 times the human IV dose), during the organogenesis phase.

It is not known whether palonosetron is distributed into human milk or whether the drug has any effects on milk production or on the breastfed infant. Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for palonosetron and any potential adverse effects on the nursing infant from the drug or underlying maternal condition.

Among 1374 adult cancer patients in clinical studies of palonosetron for chemotherapy-induced nausea and vomiting, 23% were 65 years of age or older and 5% were 75 years of age or older. No overall differences in safety and effectiveness were observed between geriatric patients and younger adults in these studies, but increased sensitivity in older patients cannot be ruled out. Among 1520 adult cancer patients in clinical studies of palonosetron for PONV, 5% were 65 years of age or older.

No overall differences in safety were observed between these older individuals and younger individuals in these studies; however, the possibility that some older patients may exhibit increased sensitivity to the drug cannot be ruled out. A population pharmacokinetic analysis did not reveal any differences in palonosetron pharmacokinetics between cancer patients 65 years of age or older and younger cancer patients. The manufacturer states that no dosage adjustment is required for geriatric patients receiving palonosetron.