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Lusedra

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Lusedra

Warnings
Precautions

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Monitoring

LUSEDRA (fospropofol disodium injection) should be administered only by persons trained in the administration of general anesthesia and not involved in the conduct of the diagnostic or therapeutic procedure. Sedated patients should be continuously monitored, and facilities for maintenance of a patent airway, providing artificial ventilation, administering supplemental oxygen, and instituting cardiovascular resuscitation must be immediately available. Patients should be continuously monitored during sedation and through the recovery process for early signs of hypotension, apnea, airway obstruction, and/or oxygen desaturation.

Respiratory Depression

LUSEDRA (fospropofol disodium injection) may cause loss of spontaneous respiration. Apnea was reported in 1/455 ( < 1%) patients treated with LUSEDRA (fospropofol disodium injection) using the standard or modified dosing regimen [see DOSAGE AND ADMINISTRATION]. In patients treated with greater than the recommended LUSEDRA (fospropofol disodium injection) dose, apnea was reported in 14/556 (3%).

Supplemental oxygen is recommended for all patients receiving LUSEDRA (fospropofol disodium injection) . Dosages of LUSEDRA (fospropofol disodium injection) must be individualized for each patient and titrated to effect [see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY]. Use lower doses of LUSEDRA (fospropofol disodium injection) in patients who are ≥ 65 years of age or who have severe systemic disease [see DOSAGE AND ADMINISTRATION]. The additive cardiorespiratory effects of narcotic analgesics and sedative-hypnotic agents should be considered when administered concomitantly with LUSEDRA (fospropofol disodium injection) .

Patients should be assessed for their ability to demonstrate purposeful response while sedated with LUSEDRA (fospropofol disodium injection) as patients who are unable to do so may lose protective reflexes. Airway assistance maneuvers may be required in the management of respiratory depression (see Table 4).

Hypoxemia

LUSEDRA (fospropofol disodium injection) may cause hypoxemia detectable by pulse oximetry. Hypoxemia was reported in 20/455 (4%) patients treated with LUSEDRA (fospropofol disodium injection) using the standard or modified dosing regimen [see DOSAGE AND ADMINISTRATION]. Hypoxemia was reported among patients who retained the ability to respond purposefully to their heath care provider following administration of LUSEDRA (fospropofol disodium injection) . Therefore, retention of purposeful responsiveness did not prevent patients from becoming hypoxemic following administration of LUSEDRA (fospropofol disodium injection) . In patients treated with greater than the recommended LUSEDRA (fospropofol disodium injection) dose, hypoxemia was reported in 151/556 (27%).

The risk of hypoxemia is reduced by appropriate positioning of the patient and the use of supplemental oxygen in all patients receiving LUSEDRA (fospropofol disodium injection) . Airway assistance maneuvers may be required in the management of hypoxemia (see Table 4). The additive cardiorespiratory effects of narcotic analgesics and other sedative-hypnotic agents should be considered when administered concomitantly with LUSEDRA (fospropofol disodium injection) .

Patient Unresponsiveness to Vigorous Tactile or Painful Stimulation

LUSEDRA (fospropofol disodium injection) has not been studied for use in general anesthesia. However, administration of LUSEDRA (fospropofol disodium injection) may inadvertently cause patients to become unresponsive or minimally responsive to vigorous tactile or painful stimulation. The incidence of patients sedated for colonoscopy who became minimally responsive or unresponsive to vigorous tactile or painful stimulation was 7/183 (4%). The duration of minimal or complete unresponsiveness in colonoscopy patients ranged from 2 to 16 minutes. Among patients sedated for bronchoscopy, the incidence of patients who became minimally or completely unresponsive to vigorous tactile or painful stimulation was 24/149 (16%). The duration of minimal to complete unresponsiveness in bronchoscopy patients ranged from 2 to 20 minutes.

Hypotension

Hypotension following the use of LUSEDRA (fospropofol disodium injection) may occur. Hypotension was reported in 18/455 (4%) patients treated with LUSEDRA (fospropofol disodium injection) using the standard or modified dosing regimen [see DOSAGE AND ADMINISTRATION]. In patients treated with greater than the recommended LUSEDRA (fospropofol disodium injection) dose, hypotension was reported in 31/556 (6%).

Patients with compromised myocardial function, reduced vascular tone, or who have reduced intravascular volume may be at an increased riskfor hypotension. A secure intravenous access catheter and supplemental volume replacement fluids should be readily available during the procedure. Additional pharmacological management may be necessary.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Long-term studies in animals have not been performed to evaluate the carcinogenic potential of fospropofol disodium.

Mutagenesis

Fospropofol was not genotoxic in the Ames bacterial reverse mutation assay, with or without metabolic activation, and in the in vivo mouse micronucleus assay. Fospropofol was positive in the L5178Y TK+/- mouse lymphoma forward mutation assay in the presence of metabolic activation. In contrast, fospropofol was negative in this assay in the presence of formaldehyde-metabolizing enzymes, suggesting that the positive finding is likely due to an artifact of the culture conditions.

Impairment of Fertility

Male rats were treated with 5, 10, or 20 mg/kg fospropofol for 4 weeks prior to mating. Male fertility was not altered in animals treated with 20 mg/kg (0.3-fold the total human dose for a procedure of 16 minutes based on a mg/m2 basis).

Female rats were treated with 5,10, or 20 mg/kg fospropofol for two weeks prior to mating. There were no clear treatment-related effects on female fertility at a dose of 20 mg/kg (0.3-fold the total human dose for a procedure of 16 minutes based on a mg/m2 basis).

Use In Specific Populations

Pregnancy

Teratogenic Effects: Pregnancy Category B.

There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Reproduction studies have been performed in rats and rabbits at doses up to 0.6 and 1.7 times the anticipated human dose for a procedure of 16 minutes based on a comparison of doses expressed as mg/m2 and have revealed no evidence of impaired fertility or harm to the fetus due to LUSEDRA.

Pregnant rats were treated with fospropofol disodium (5, 20, or 45 mg/kg/day, IV) from gestation day 7 through 17 (the highest dose is 0.6 times the anticipated human dose for a procedure of 16 minutes based on a comparison of doses expressed as mg/m2). Doses of 20 and 45 mg/kg/day produced significant maternal toxicity. No drug-related adverse effects on embryo-fetal development were noted.

Pregnant rabbits were treated with fospropofol disodium (14, 28, 56 or 70 mg/kg/day, IV) from gestation day 6 through 18 (the highest dose is 1.7 times the anticipated human dose for a procedure of 16 minutes based on a comparison of doses expressed as mg/m2). Significant maternal toxicity was noted at all doses. No drug-related adverse effects on embryo-fetal development were noted.

Nonteratogenic Effects:

Pregnant rats were administered 0, 5, 10, or 20 mg/kg/day fospropofol disodium from gestation day 7 through lactation day 20 to evaluate perinatal and postnatal development (the highest dose is 0.2 times the anticipated human dose for a procedure of 16 minutes based on a comparison of doses expressed as mg/m2). There were no clear treatment-related effects on growth, development, behavior (passive avoidance and water maze) or fertility and mating capacity of the offspring.

Labor and Delivery

LUSEDRA (fospropofol disodium injection) is not recommended for use in labor and delivery, including Cesarean section deliveries. It is not known if fospropofol crosses the placenta; however, propofol is known to cross the placenta, and as with other sedative-hypnotic agents, the administration of LUSEDRA (fospropofol disodium injection) may be associated with neonatal respiratory and cardiovascular depression.

Nursing Mothers

It is not known whether fospropofol is excreted in human milk; however, propofol has been reported to be excreted in human milk, and the effects of oral absorption of fospropofol or propofol are not known. LUSEDRA (fospropofol disodium injection) is not recommended for use in nursing mothers.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established because LUSEDRA (fospropofol disodium injection) has not been studied in persons < 18 years of age. LUSEDRA (fospropofol disodium injection) is not recommended for use in this population.

Geriatric Use

In studies of LUSEDRA (fospropofol disodium injection) for sedation in brief diagnostic and therapeutic procedures, 17% of patients were ≥ 65 years of age and 5% of patients were ≥ 75 years of age. Patients ≥ 65 years of age should receive the modified dosing regimen [see DOSAGE AND ADMINISTRATION]. Hypoxemia was reported more frequently among patients aged ≥ 75 years than among patients aged 65 to < 75 years and less frequently among younger patients, aged 18 to < 65 years.

Patients with Renal Impairment

In studies of LUSEDRA (fospropofol disodium injection) for sedation in brief diagnostic and therapeutic procedures, 21 % of patients had a creatinine clearance < 80 mL/min, and 4% had a creatinine clearance < 50 mL/min. Pharmacokinetics of fospropofol or propofol were not altered in patients with mild to moderate renal insufficiency. No dosing adjustments are required for patients with creatinine clearance ≥ 30 mL/min. Limited safety and efficacy data are available for LUSEDRA (fospropofol disodium injection) in patients with creatinine clearance < 30 mL/min.

Patients with Hepatic Impairment

LUSEDRA (fospropofol disodium injection) has not been adequately studied in patients with hepatic impairment. Caution should be exercised when using fospropofol disodium in patients with hepatic impairment.

Last reviewed on RxList: 2/10/2010
This monograph has been modified to include the generic and brand name in many instances.

Warnings
Precautions
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