"The U.S. Food and Drug Administration today approved Tretten, Coagulation Factor XIII A-Subunit (Recombinant), the first recombinant product for use in the routine prevention of bleeding in adults and children who have a rare clotting disorder, k"...
Hypersensitivity reactions may occur in patients who have exhibited hypersensitivity to other 5-HT3 receptor antagonists. Hypersensitivity reactions have been very rarely reported postmarketing for intravenous palonosetron: dyspnea, bronchospasm, swelling/edema, erythema, pruritus, rash, urticaria. No hypersensitivity reactions have been reported for oral palonosetron.
Patient Counseling Information
See FDA-Approved Patient Labeling
Instructions for Patients
- Patients should be instructed to read the patient insert.
Carcinogenesis, Mutagenesis, Impairment of Fertility
In a 104-week carcinogenicity study in CD-1 mice, animals were treated with oral doses of palonosetron at 10, 30 and 60 mg/kg/day. Treatment with palonosetron was not tumorigenic. The highest tested dose produced a systemic exposure to palonosetron (Plasma AUC) of about 90 to 173 times the human exposure (AUC= 49.7 ng·h/mL) at the recommended oral dose of 0.5 mg. In a 104-week carcinogenicity study in Sprague-Dawley rats, male and female rats were treated with oral doses of 15, 30 and 60 mg/kg/day and 15, 45 and 90 mg/kg/day, respectively. The highest doses produced a systemic exposure to palonosetron (Plasma AUC) of 82 and 185 times the human exposure at the recommended dose. Treatment with palonosetron produced increased incidences of adrenal benign pheochromocytoma and combined benign and malignant pheochromocytoma, increased incidences of pancreatic Islet cell adenoma and combined adenoma and carcinoma and pituitary adenoma in male rats. In female rats, it produced hepatocellular adenoma and carcinoma and increased the incidences of thyroid C-cell adenoma and combined adenoma and carcinoma.
Palonosetron was not genotoxic in the Ames test, the Chinese hamster ovarian cell (CHO/HGPRT) forward mutation test, the ex vivo hepatocyte unscheduled DNA synthesis (UDS) test or the mouse micronucleus test. It was, however, positive for clastogenic effects in the Chinese hamster ovarian (CHO) cell chromosomal aberration test.
Palonosetron at oral doses up to 60 mg/kg/day (about 921 times the recommended human oral dose based on body surface area) was found to have no effect on fertility and reproductive performance of male and female rats.
Use In Specific Populations
Pregnancy Category B. Reproduction studies have been performed in rats at oral doses up to 60 mg/kg/day (921 times the recommended human oral dose based on body surface area) and rabbits at oral doses up to 60 mg/kg/day (1841 times the recommended human oral dose based on body surface area) and have revealed no evidence of impaired fertility or harm to the fetus due to palonosetron. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, palonosetron should be used during pregnancy only if clearly needed.
Labor and Delivery
Palonosetron has not been administered to patients undergoing labor and delivery, so its effects on the mother or child are unknown.
It is not known whether palonosetron is excreted 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, 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.
Safety and effectiveness in patients below the age of 18 years have not been established.
Of the total number of adult cancer patients in a pivotal study of oral palonosetron, 181 were 65 years of age and over. The number of geriatric patients receiving 0.5 mg palonosetron was insufficient to draw any efficacy or safety conclusions.
In a cross-study comparison, after a single oral dose (0.75 mg) the systemic exposure of palonosetron (AUC) was similar, but mean Cmax was 15% lower in healthy elderly subjects 65 years of age compared with the subjects < 65 years of age. No dose adjustment is required for geriatric patients.
Mild to moderate renal impairment does not significantly affect palonosetron pharmacokinetic parameters. Total systemic exposure to intravenous ALOXI (palonosetron hcl capsules) increased by approximately 28% in severe renal impairment relative to healthy subjects. Dosage adjustment is not necessary in patients with mild to severe renal impairment. The pharmacokinetics of palonosetron have not been studied in subjects with end-stage renal disease.
Hepatic impairment does not significantly affect total body clearance of intravenous palonosetron compared to the healthy subjects. Dosage adjustment is not necessary in patients with any degree of hepatic impairment.
Oral pharmacokinetics of palonosetron were characterized in thirty-two healthy Japanese male subjects using solution over the dose range of 3-90 µg/kg. The apparent total body clear ance was 26% higher in Japanese males than in white males based on a cross-study comparison; however, no dose adjustment is necessary. The pharmacokinetics of palonosetron in other races have not been adequately characterized.
Although a single dose of 0.5 mg ALOXI (palonosetron hcl capsules) Capsule was associated with a 2635% higher systemic exposure in female subjects than in male subjects, dosage adjustment is not necessary based on gender.
Last reviewed on RxList: 9/19/2008
This monograph has been modified to include the generic and brand name in many instances.
Additional Aloxi Capsules Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.