HIGHLIGHTS OF PRESCRIBING INFORMATION

(fospropofol disodium) Injection

LUSEDRATM

(fospropofol disodium) Injection

These highlights do not include all the information needed to use ­­­­­­­­­­­­­­­­­­­­­­­­­­­CONTRAINDICATIONS­­­­­­­­­­­­­­­­­­­­­­­­­­­
LUSEDRA safely and effectively. See full prescribing information for
LUSEDRA. None

LUSEDRA (fospropofol disodium) Injection, for intravenous use, CIV ­­­­­­­­­­­­­­­­­­­­­­WARNINGS AND PRECAUTIONS­­­­­­­­­­­­­­­­­­­­­

LUSEDRATM
Initial U.S. Approval: 2008
• A person trained in the administration of general anesthesia
­­­­­­­­­­­­­­­­­­­­­­­­­INDICATIONS AND USAGE­­­­­­­­­­­­­­­­­­­­­­­­­­ and not involved in the conduct of the diagnostic/therapeutic
procedure should manage treatment of patients with
LUSEDRA is a sedative­hypnotic agent indicated for monitored anesthesia LUSEDRA. (5.1)
care (MAC) sedation in adult patients undergoing diagnostic or therapeutic • Respiratory depression (5.2)
procedures. (1) • Hypoxemia (5.3)
• Hypotension (5.5)
­­­­­­­­­­­­­­­­­­­­­DOSAGE AND ADMINISTRATION­­­­­­­­­­­­­­­­­­­­­­­
­­­­­­­­­­­­­­­­­­­­­­­­­­­ADVERSE REACTIONS­­­­­­­­­­­­­­­­­­­­­­­­­­
• Use supplemental oxygen in all patients undergoing sedation with
LUSEDRA. (2.1) Continuously monitor with pulse oximetry, electrocardiogram, Most common adverse reactions (>20%) are paresthesia and

007101
007101
and frequent blood pressure measurements. (5.1) pruritus. (6)
• Standard dosing regimen: initial intravenous bolus dose of 6.5 mg/kg
followed by supplemental doses of 1.6 mg/kg as needed. No initial To report SUSPECTED ADVERSE REACTIONS, contact Eisai Inc. at
dose should exceed 16.5 mL; no supplemental dose should exceed 1-888-422-4743 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
4 mL. (2.2)
• Modified dosing regimen [for patients who are ≥65 years of age or who ­­­­­­­­­­­­­­­­­­­­­­­­­­­DRUG INTERACTIONS­­­­­­­­­­­­­­­­­­­­­­­­­­­
have severe systemic disease (ASA P3 or P4)]: 75% of the standard
dosing regimen. (2.3) As with other sedative­hypnotic agents, LUSEDRA may produce additive
• Administer supplemental doses only when patients can demonstrate cardiorespiratory effects when administered with other cardiorespiratory
purposeful movement in response to verbal or light tactile stimulation depressants such as benzodiazepines and narcotic analgesics. (7)
and no more frequently than every 4 minutes. (2.1)
• Adults who weigh >90 kg should be dosed as if they are 90 kg; adults ­­­­­­­­­­­­­­­­­­­­­USE IN SPECIFIC POPULATIONS­­­­­­­­­­­­­­­­­­­­­­
who weigh <60 kg should be dosed as if they are 60 kg. (2.2)
• Intended for single­use administration only. • Patients ≥65 years of age should receive the modified dosing
regimen. (2.3, 8.5)
­­­­­­­­­­­­­­­­­­­­DOSAGE FORMS AND STRENGTHS­­­­­­­­­­­­­­­­­­­­­­ • Patients with severe systemic disease (ASA P3 or P4) should
receive the modified dosing regimen. (2.3)
Injection, solution containing 1,050 mg fospropofol disodium per 30 mL. (3)
See 17 for PATIENT COUNSELING INFORMATION.

Revised 10/2009

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE 9 DRUG ABUSE AND DEPENDENCE

2 DOSAGE AND ADMINISTRATION 9.1 Controlled Substance
2.1 Dosing Guidelines 9.2 Abuse
2.2 Standard Dosing Regimen for Sedation 9.3 Dependence
2.3 Modified Dosing Regimen for Sedation in Patients ≥65 10 OVERDOSE
years or Those with Severe Systemic Disease (ASA P3 or P4) 11 DESCRIPTION
2.4 Preparation 12 CLINICAL PHARMACOLOGY
3 DOSAGE FORM AND STRENGTH 12.1 Mechanism of Action
4 CONTRAINDICATIONS 12.2 Pharmacodynamics
5 WARNINGS AND PRECAUTIONS 12.3 Pharmacokinetics
5.1 Monitoring 13 NONCLINICAL TOXICOLOGY
5.2 Respiratory Depression 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
5.3 Hypoxemia 14 CLINICAL STUDIES
5.4 Patient Unresponsiveness to Vigorous Tactile or Painful 14.1 Use in Sedation for Diagnostic or Therapeutic Procedures
Stimulation 15 REFERENCES
5.5 Hypotension 16 HOW SUPPLIED/STORAGE AND HANDLING
6 ADVERSE REACTIONS 17 PATIENT COUNSELING INFORMATION
6.1 Clinical Trials Experience
6.2 Adverse Reactions in Prolonged Exposure in Adults
7 DRUG INTERACTIONS
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Labor and Delivery
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Patients with Renal Impairment *Sections or subsections omitted from full prescribing
8.7 Patients with Hepatic Impairment information are not listed.

FULL PRESCRIBING INFORMATION Patients should be assessed for their ability to demonstrate purposeful response while sedated with LUSEDRA as patients
who are unable to do so may lose protective reflexes. Airway assistance maneuvers may be required in the management of
1 INDICATIONS AND USAGE respiratory depression (see Table 4).
LUSEDRATM (fospropofol disodium) injection is an intravenous sedative­hypnotic agent indicated for monitored anesthesia
care (MAC) sedation in adult patients undergoing diagnostic or therapeutic procedures. 5.3 Hypoxemia
LUSEDRA may cause hypoxemia detectable by pulse oximetry. Hypoxemia was reported in 20/455 (4%) patients treated with
2 DOSAGE AND ADMINISTRATION LUSEDRA using the standard or modified dosing regimen [see Dosage and Administration (2.2, 2.3)]. Hypoxemia was reported among
patients who retained the ability to respond purposefully to their heath care provider following administration of LUSEDRA. Therefore,
2.1 Dosing Guidelines retention of purposeful responsiveness did not prevent patients from becoming hypoxemic following administration of LUSEDRA.
• Administer LUSEDRA intravenously as a bolus injection. In patients treated with greater than the recommended LUSEDRA dose, hypoxemia was reported in 151/556 (27%).
• Use supplemental oxygen for all patients undergoing sedation with LUSEDRA. The risk of hypoxemia is reduced by appropriate positioning of the patient and the use of supplemental oxygen in all patients
• Individualize the dosage of LUSEDRA and titrate to the level of sedation required for the procedure. receiving LUSEDRA. Airway assistance maneuvers may be required in the management of hypoxemia (see Table 4). The additive
• In adults aged 18 to <65 years who are healthy or have mild systemic disease as categorized by the American Society cardiorespiratory effects of narcotic analgesics and other sedative­hypnotic agents should be considered when administered
of Anesthesiologists (ASA P1 or P2), the standard dosing regimen of LUSEDRA should be followed [see Standard Dosing concomitantly with LUSEDRA.
Regimen for Sedation (2.2)].
• In adults who are ≥65 years of age or who have severe systemic disease (ASA P3 or P4), the modified dosing regimen 5.4 Patient Unresponsiveness to Vigorous Tactile or Painful Stimulation
should be followed [see Modified Dosing Regimen for Sedation in Patients ≥65 years or Those with Severe Systemic LUSEDRA has not been studied for use in general anesthesia. However, administration of LUSEDRA may inadvertently cause
Disease (2.3)]. patients to become unresponsive or minimally responsive to vigorous tactile or painful stimulation. The incidence of patients sedated
• Administer supplemental doses of LUSEDRA based on the patient’s level of sedation and the level of sedation required for colonoscopy who became minimally responsive or unresponsive to vigorous tactile or painful stimulation was 7/183 (4%). The
for the procedure. Give supplemental doses only when patients can demonstrate purposeful movement in response to duration of minimal or complete unresponsiveness in colonoscopy patients ranged from 2 to 16 minutes. Among patients sedated for
verbal or light tactile stimulation and no more frequently than every 4 minutes. Use only the minimum dosage required bronchoscopy, the incidence of patients who became minimally or completely unresponsive to vigorous tactile or painful stimulation
to facilitate the procedure. was 24/149 (16%). The duration of minimal to complete unresponsiveness in bronchoscopy patients ranged from 2 to 20 minutes.
• Consider the potential for worsened cardiorespiratory depression prior to using LUSEDRA concomitantly with other drugs
that have the same potential (e.g., sedative­hypnotics or narcotic analgesics) [see Warnings and Precautions (5.2, 5.3)]. 5.5 Hypotension
• In clinical studies, an opioid premedication (fentanyl citrate 50 mcg intravenously) was administered five minutes prior to Hypotension following the use of LUSEDRA may occur. Hypotension was reported in 18/455 (4%) patients treated with LUSEDRA
the initial dose of LUSEDRA. using the standard or modified dosing regimen [see Dosage and Administration (2.2, 2.3)]. In patients treated with greater than the
recommended LUSEDRA dose, hypotension was reported in 31/556 (6%).
2.2 Standard Dosing Regimen for Sedation Patients with compromised myocardial function, reduced vascular tone, or who have reduced intravascular volume may be at an
In adults aged 18 to <65 years who are healthy or have mild systemic disease (ASA P1 or P2)1, the standard dosing regimen increased risk for hypotension. A secure intravenous access catheter and supplemental volume replacement fluids should be readily
of LUSEDRA is an initial intravenous bolus of 6.5 mg/kg followed by supplemental doses of 1.6 mg/kg intravenously (25% available during the procedure. Additional pharmacological management may be necessary.
of initial dosage) as needed to achieve the desired level of sedation as shown in Table 1.
The dosage of LUSEDRA is limited by lower and upper weight bounds of 60 kg and 90 kg. Adults who weigh >90 kg 6 ADVERSE REACTIONS
should be dosed as if they weigh 90 kg. No initial dose should exceed 16.5 mL; no supplemental dose should exceed 4 mL. The following serious adverse reactions are discussed elsewhere in the labeling:
Adults who weigh <60 kg should be dosed as if they weigh 60 kg. Dosages lower than those specified for the lower weight
limit may be used to achieve lesser levels of sedation. In clinical studies, an opioid premedication (fentanyl citrate 50 mcg IV) • Respiratory depression [see Warnings and Precautions (5.2)]
was administered five minutes prior to the initial dose of LUSEDRA. • Hypoxemia [see Warnings and Precautions (5.3)]
• Loss of purposeful responsiveness [see Warnings and Precautions (5.4)]
• Hypotension [see Warnings and Precautions (5.5)]
Table 1. Standard Dosing Regimen, Adults 18 to <65 Years of Age Who are Healthy or Have Mild
Systemic Disease (ASA P1 or P2) The most common adverse reactions (reported in greater than 20%) are paresthesia and pruritus.
The most commonly reported reasons for discontinuation are paresthesia and cough.
Supplemental Dose
No more frequently 6.1 Clinical Trials Experience
Initial Dose than every 4 min. Adverse reactions presented in this section are derived from 332 patients in 3 controlled clinical trials in patients undergoing
colonoscopy or flexible bronchoscopy and 123 patients in one open­label study in patients undergoing minor procedures. Patients enrolled
Weight (kg) mg mL mg mL in the studies who received the standard or modified dosing regimen included males and females, ≥18 years of age and ranging
≤60 from healthy (359/455 [79%] ASA P1 or P2) to those with severe systemic disease (96/455 [21%] ASA P3 or P4). Of the 455 patients
enrolled, 345 (76%) were ≥18 to <65 years of age and 110 (24%) were ≥65 years of age. Adverse reactions are reported for patients
385 11 105 3
61 to 63 402.5 11.5 105 3 who received the standard or the modified dosing regimen [see Dosage and Administration (2)]. The majority of procedures were less
than thirty minutes in duration. All patients in these studies received 50 mcg fentanyl citrate intravenously as premedication, and some
of the patients received additional 25 mcg fentanyl citrate supplemental doses. Adverse reactions occurring in ≥2% of patients in
64 to 65 420 12 105 3
66 to 68 437.5 12.5 105 3 these studies are presented in Table 3.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug
69 to 71 455 13 105 3 cannot be directly compared to rates in the clinical trials of another drug and may not accurately reflect the rates observed in practice.
72 to 74 472.5 13.5 122.5 3.5
75 to 76 490 14 122.5 3.5
Table 3. Common Adverse Reactions for Patients Receiving the Standard or Modified Dosing Regimen
77 to 79 507.5 14.5 122.5 3.5 (Reactions Occurring at a Rate ≥2%)
80 to 82 525 15 140 4
Colonoscopy Minor Procedures Bronchoscopy
83 to 84 542.5 15.5 140 4 (N=183) (N=123) (N=149)
85 to 87 560 16 140 4 Reaction Term n (%) n (%) n (%)
88 to 89 577.5 16.5 140 4 Gastrointestinal disorders
≥90
Nausea 0 5 (4) 2 (1)
577.5 16.5 140 4
Vomiting 0 4 (3) 0
Note: Doses in this table are rounded to the nearest half­milliliter volume to facilitate practical measurement;
hence, they may differ slightly from the dose recommended on the basis of mg/kg. Injury, poisoning, and
procedural complications
Procedural Pain 0 0 3 (2)
2.3 Modified Dosing Regimen for Sedation in Patients ≥65 years or Those with Severe Systemic Disease (ASA P3 or P4)
Adults ≥65 years of age or those with severe systemic disease (ASA P3 or P4)1 should receive initial and supplemental
Nervous system disorders
intravenous dosages of 75% of the standard dosing regimen, as presented in Table 2. LUSEDRA is administered intravenously Paresthesiaa 135 (74) 77 (63) 78 (52)
as a bolus injection. In clinical studies, an opioid premedication (fentanyl citrate 50 mcg IV) was administered five minutes Headache 1 (1) 3 (2) 1 (1)
prior to the initial dose of LUSEDRA.
Respiratory, thoracic, and
mediastinal disorders
Table 2. Modified Dosing Regimen, Ages ≥65 Years Or Those with Severe Systemic Disease Hypoxemia 3 (2) 1 (1) 16 (11)
(ASA P3 or P4)
Skin and subcutaneous tissue disorders
Supplemental Dose Pruritusb 30 (16) 34 (28) 24 (16)
No more frequently
Initial Dose than every 4 min. Vascular disorders
Weight (kg) mg mL mg mL Hypotension 4 (2) 4 (3) 10 (7)

≤60 297.5 8.5 70 2 a

Paresthesia includes the following terms: Paresthesia genital male; Burning sensation; Genital burning sensation;
61 to 62 297.5 8.5 70 2 Vaginal burning sensation; Skin burning sensation; Genital pain (reported as burning); Perineal pain (reported as
63 to 64 315 9 87.5 2.5 burning); Anal discomfort (reported as burning); Chest pain (reported as burning); Ear discomfort (reported as
burning); Nasal discomfort (reported as burning); Buttock pain (reported as stinging); Groin pain (reported as
65 to 66 315 9 87.5 2.5 stinging); Pain (reported as stinging); Sensory disturbance (reported as non­specific sensation in pubic area).
b
67 to 69 332.5 9.5 87.5 2.5 Pruritus includes the following terms: Genital pruritus female; Genital pruritus male; Pruritus genital; Pruritus ani;
Pruritus generalized.
70 to 73 350 10 87.5 2.5
74 to 77 367.5 10.5 87.5 2.5
78 to 80 385 11 105 3 Paresthesias (including burning, tingling, stinging) and/or pruritus, usually manifested in the perineal region, were the most frequently
81 to 84 402.5 11.5 105 3 recorded adverse reactions in clinical trials. Paresthesias and pruritus generally occurred within 5 minutes after administration of the
initial dose of LUSEDRA and were generally transient and mild to moderate in intensity. The pharmacologic basis of these sensory
85 to 87 420 12 105 3 phenomena is unknown. No pretreatments, including the use of nonsteroidal anti­inflammatory drugs, opioids, or lidocaine, are known
88 to 89 437.5 12.5 105 3 to have an effect on or to reduce the incidence of these sensations.

≥90
Sedation­related adverse reactions were experienced at the following rates for subjects receiving the standard or modified LUSEDRA
437.5 12.5 105 3 dosing regimen: 20/455 (4%) hypoxemia, 18/455 (4%) hypotension, 1/455 (<1%) apnea. A greater rate of sedation­related adverse
reactions necessitating intervention was observed in patients undergoing bronchoscopy compared with colonoscopy and minor surgical
Note: Doses in this table are rounded to the nearest half­milliliter volume to facilitate practical measurement; procedures. In the colonoscopy studies, 5/183 (3%) patients were ASA P3. In the minor surgical procedures study, 23/123 (19%)
hence, they may differ slightly from the dose recommended on the basis of mg/kg.
patients were ASA P3 or P4. In the flexible bronchoscopy study, 68/150 (46%) patients were ASA P3 or P4. The type and incidence of
airway assistance interventions required for patients who experienced sedation­related adverse reactions are presented in Table 4.
2.4 Preparation
LUSEDRA is provided as a ready to use formulation intended for single­patient use only. Prepare LUSEDRA following strict
aseptic techniques. Draw LUSEDRA into sterile syringes immediately after vials are opened. Discard any unused portion at
the end of the procedure. Table 4. Patient Incidence of Airway Management Events
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.
Do not use if there is evidence of particulate matter or discoloration. Minor Flexible
Healthy Subjectsa Colonoscopyb Proceduresb Bronchoscopyb
LUSEDRA has been shown to be compatible with the following fluids:
6 mg/kg 6.5 mg/kg 6.5 mg/kg 6.5 mg/kg
• 5% Dextrose Injection, USP (or modified (or modified (or modified
• 5% Dextrose and 0.2% Sodium Chloride, USP dosing regimen) dosing regimen) dosing regimen)
• 5% Dextrose and 0.45% Sodium Chloride Injection, USP
• 0.9% Sodium Chloride Injection, USP N=69 N=183 N=123 N=149
• Lactated Ringer’s Injection, USP n (%) n (%) n (%) n (%)
• Lactated Ringer’s and 5% Dextrose Injection, USP
• 0.45% Sodium Chloride Injection, USP
• 5% Dextrose, 0.45% NaCl and 20 mEq KCl, USP Increased O2 0 0 0 21 (14)
Do not mix LUSEDRA with other drugs or fluids prior to administration. LUSEDRA is not physically compatible with Patient Repositioning 0 0 0 2 (1)
midazolam HCl or meperidine HCl, and compatibility with other agents has not been adequately evaluated.
Administer LUSEDRA through a secure, freely flowing, peripheral intravenous line using commonly available intravenous Verbal Stimulation 0 2 (1) 1 (1) 5 (3)
administration sets. Flush the infusion line with normal saline before and after administration of LUSEDRA. Tactile Stimulation 0 0 0 3 (2)
LUSEDRA is not light sensitive. LUSEDRA does not need to be filtered before use.
Face Mask (100% O2) 0 0 0 1 (1)
3 DOSAGE FORMS AND STRENGTHS
Single­use vial contents: Solution for intravenous administration containing 35 mg of fospropofol disodium per mL (1,050 mg Jaw Thrust 0 0 0 2 (1)
of fospropofol disodium in 30 mL). Chin Lift 0 0 1 (1) 3 (2)
4 CONTRAINDICATIONS Nasal Trumpet 0 0 0 0
None.
Oral Airway 0 0 0 0
5 WARNINGS AND PRECAUTIONS Suction 0 0 0 2 (1)
5.1 Monitoring Manual Ventilation
LUSEDRA should be administered only by persons trained in the administration of general anesthesia and not involved (bag valve mask) 0 0 0 1 (1)
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 Mechanical Ventilation 0 0 0 0
instituting cardiovascular resuscitation must be immediately available. Patients should be continuously monitored a
during sedation and through the recovery process for early signs of hypotension, apnea, airway obstruction, and/or No concomitant medications administered. All subjects were healthy volunteers.
oxygen desaturation. b
All patients premedicated with 50 mcg fentanyl citrate. Subjects ranged from healthy to those with severe systemic
disease that is a constant threat to life (ASA P1 to P4).
5.2 Respiratory Depression
LUSEDRA may cause loss of spontaneous respiration. Apnea was reported in 1/455 (<1%) patients treated with LUSEDRA
using the standard or modified dosing regimen [see Dosage and Administration (2.2, 2.3)]. In patients treated with greater
than the recommended LUSEDRA dose, apnea was reported in 14/556 (3%). 6.2 Adverse Reactions in Prolonged Exposure in Adults
Supplemental oxygen is recommended for all patients receiving LUSEDRA. Dosages of LUSEDRA must be individualized The safety of LUSEDRA for continuous sedation has not been established and therefore its use is not recommended. LUSEDRA
for each patient and titrated to effect [see Dosage and Administration (2.1) and Clinical Pharmacology (12.2)]. Use lower was administered to 38 intubated and mechanically ventilated patients in postoperative and intensive care settings. An occurrence of
doses of LUSEDRA in patients who are ≥65 years of age or who have severe systemic disease [see Dosage and Adminis­ nonsustained ventricular tachycardia was observed as a serious adverse reaction in one patient in the study. Another patient with
tration (2.3)]. The additive cardiorespiratory effects of narcotic analgesics and sedative­hypnotic agents should be considered acute myeloid leukemia with renal and hepatic insufficiency experienced a further increase in plasma formate concentration from a
when administered concomitantly with LUSEDRA. baseline of 66 mcg/mL to a post­dose level of 212 mcg/mL after a 12­hour infusion. The clinical significance of these findings is unknown.
 LUSEDRA was evaluated in randomized, blinded, dose­controlled studies for sedation in patients undergoing colonoscopy and
flexible bronchoscopy [see Clinical Studies (14.1)]. Figure 3 shows MOAA/S scores over time in each of the studies for those
patients who received the standard and modified dosing regimens. In the study of patients undergoing colonoscopy, patients who
received the standard and modified dosing regimens had a median [range] time to sedation (time from first dose of sedative to the
first of 2 consecutive MOAA/S scores of ≤4) of 8.0 [2, 28] minutes and a median time to Fully Alert (3 consecutive responses to
their name spoken in a normal tone, measured every 2 minutes beginning at or after the end of the procedure) of 5.0 [0, 47] minutes.
In the study of patients undergoing flexible bronchoscopy, patients who received the standard and modified LUSEDRA dosing regimens
had a median time to sedation of 4 [2, 22] minutes and a median time to Fully Alert of 5.5 [0, 61] minutes.

Patients Undergoing Colonoscopy

MOAA/S

Patients (%)
Time (min)

Patients Undergoing Flexible Bronchoscopy

MOAA/S

Patients (%)
7 DRUG INTERACTIONS
LUSEDRA may produce additive cardiorespiratory effects when administered with other cardiorespiratory depressants
such as sedative­hypnotics and narcotic analgesics.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy
Teratogenic Effects:
Pregnancy Category B.
There are no adequate and well­controlled 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 Time (min)
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 Figure 3. Percentage of Patients at Each MOAA/S Score Over Time
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 drug­related adverse effects on
embryo­fetal development were noted. Within the recommended dose range, there were no differences in matched QTc interval changes between LUSEDRA and placebo.
Pregnant rabbits were treated with fospropofol disodium (14, 28, 56 or 70 mg/kg/day, IV) from gestation day 6 through 18 The effect of LUSEDRA on the QTcF interval was measured in a crossover study in which healthy subjects (n=68) received the following
(the highest dose is 1.7 times the anticipated human dose for a procedure of 16 minutes based on a comparison of doses treatments: 6 mg/kg intravenous LUSEDRA; 18 mg/kg intravenous LUSEDRA; moxifloxacin 400 mg orally (positive control); and normal
expressed as mg/m2). Significant maternal toxicity was noted at all doses. No drug­related adverse effects on embryo­fetal saline IV. After baseline and placebo adjustment, the maximum mean QTcF change was 2 ms (1­sided 95% Upper CI: 6 ms) for the
development were noted. 6­mg/kg dose and 8 ms (1­sided 95% Upper CI: 12 ms) for the 18­mg/kg dose. Used as a positive control, moxifloxacin had a
maximum mean change in QTcF of 12 ms (1­sided 95% Lower CI: 6 ms).
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 12.3 Pharmacokinetics
procedure of 16 minutes based on a comparison of doses expressed as mg/m2). There were no clear treatment­related PK parameters were evaluated in a crossover study of 68 healthy subjects, 18 to 45 years of age, who received 6­ and 18­mg/kg
effects on growth, development, behavior (passive avoidance and water maze) or fertility and mating capacity of the offspring. intravenous bolus doses of LUSEDRA. PK parameters are shown in Table 6. The Cmax and AUC0­∞ values of fospropofol were dose
proportional. The intersubject variability in Cmax and AUC0­∞ was low. Propofol was rapidly liberated reaching plasma Cmax at a
8.2 Labor and Delivery median Tmax of 12 minutes for LUSEDRA 6 mg/kg and 8 minutes for LUSEDRA 18 mg/kg. Concentration­time profiles showed a
LUSEDRA is not recommended for use in labor and delivery, including Cesarean section deliveries. It is not known if biexponential decline. The increase in Cmax and AUC0­∞ of propofol was dose proportional.
fospropofol crosses the placenta; however, propofol is known to cross the placenta, and as with other sedative­hypnotic
agents, the administration of LUSEDRA may be associated with neonatal respiratory and cardiovascular depression.
Table 6. Pharmacokinetic Parameters (mean±SD) for Fospropofol and Propofol from LUSEDRA Administration
8.3 Nursing Mothers
It is not known whether fospropofol is excreted in human milk; however, propofol has been reported to be excreted in Fospropofol
human milk, and the effects of oral absorption of fospropofol or propofol are not known. LUSEDRA is not recommended for Parameter Healthy Healthy Patient
use in nursing mothers.
(6 mg/kg) (18 mg/kg) (6.5 mg/kg)
8.4 Pediatric Use N=68 N=68 N=667
Safety and effectiveness in pediatric patients have not been established because LUSEDRA has not been studied in
persons <18 years of age. LUSEDRA is not recommended for use in this population. Cmax (mcg/mL) 78.7±15.4 211±48.6 ­­
8.5 Geriatric Use Tmax (min) 4 2 ­­
In studies of LUSEDRA 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 AUC0­∞ (mcg•h/mL) 19.2±3.59 50.3±8.4 19.0±7.2
[see Dosage and Administration (2.3)]. Hypoxemia was reported more frequently among patients aged ≥75 years than CLp (L/h/kg) 0.28±0.053 0.32±0.058 0.36±0.16
among patients aged 65 to <75 years and less frequently among younger patients, aged 18 to <65 years.
t1/2 (h) 0.81±0.08 0.81±0.09 0.88±0.08
8.6 Patients with Renal Impairment
In studies of LUSEDRA for sedation in brief diagnostic and therapeutic procedures, 21% of patients had a creatinine Propofol from LUSEDRA
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 Parameter Healthy Healthy Patient
clearance ≥30 mL/min. Limited safety and efficacy data are available for LUSEDRA in patients with creatinine clearance (6 mg/kg) (18 mg/kg) (6.5 mg/kg)
<30 mL/min. N=68 N=68 N=400

8.7 Patients with Hepatic Impairment

LUSEDRA has not been adequately studied in patients with hepatic impairment. Caution should be exercised when Cmax (mcg/mL) 1.08±0.33 3.90±0.822 ­­
using fospropofol disodium in patients with hepatic impairment.
Tmax (min) 12 8 ­­
9 DRUG ABUSE AND DEPENDENCE AUC0­∞ (mcg•h/mL) 1.70±0.29 5.67±1.28 1.2±0.39
9.1 Controlled Substance CLp (L/h/kg) 1.95±0.34 1.79±0.39 3.2±0.92
LUSEDRA is a Schedule IV controlled substance.
t1/2 (h) 2.06±0.77 1.76±0.54 1.13±0.28
9.2 Abuse
No formal studies of the abuse potential of LUSEDRA have been conducted. Administration of LUSEDRA resulted in
euphoria in a small number of subjects who received intravenous or oral dosing. Distribution
Fospropofol has a low volume of distribution of 0.33±0.069 L/kg, and the liberated propofol has a large volume of distribution
9.3 Dependence (5.8 L/kg).
No formal studies of dependence have been conducted. Both fospropofol and its active metabolite propofol are highly protein bound (approximately 98%), primarily to albumin.
Fospropofol does not affect the binding of propofol to albumin.
10 OVERDOSE
Overdosage with LUSEDRA can cause cardiorespiratory depression. If overdosage occurs, LUSEDRA administration Metabolism
should be discontinued immediately. Respiratory depression may require manual or mechanical ventilation. Cardiovascular Fospropofol is completely metabolized by alkaline phosphatases to propofol, formaldehyde, and phosphate. Formaldehyde and
depression may require elevation of lower extremities, intravascular volume replacement, and/or pharmacological management. phosphate plasma concentrations are comparable to endogenous levels when fospropofol disodium is administered as recommended.
Formate and phosphate are metabolites of LUSEDRA and may contribute to signs of toxicity following overdosage. Signs Formaldehyde is further metabolized to formate by several enzyme systems, including formaldehyde dehydrogenase, present in
of formate toxicity are similar to those of methanol toxicity and are associated with anion­gap metabolic acidosis. Intravenous various tissues. Propofol liberated from fospropofol is further metabolized to major metabolites propofol glucuronide (34.8%),
exposure to a large amount of phosphate could potentially cause hypocalcemia with paresthesia, muscle spasms, and seizures. quinol­4­sulfate (4.6%), quinol­1­glucuronide (11.1%), and quinol­4­glucuronide (5.1%). Oxidation to CO2 is the primary means
of eliminating excess formate.
11 DESCRIPTION Fospropofol is not a substrate of CYP450 enzymes.
LUSEDRA is an injection solution intended for intravenous administration as a sedative­hypnotic agent. LUSEDRA is
an aqueous, sterile, nonpyrogenic, clear, colorless, iso­osmotic solution containing 35 mg/mL of fospropofol disodium. Elimination
Fospropofol disodium is a water­soluble prodrug of propofol, chemically described as 2,6­diisopropylphenoxymethyl After a single 400­mg intravenous dose of [14C]­fospropofol disodium in humans, approximately 71% of radioactivity was recovered
phosphate, disodium salt. The structural and molecular formulas are shown in Figure 1. in the urine within 192 hours. Total body clearance (CLp) of fospropofol was 0.280±0.053 L/h/kg, and renal elimination of fospropofol
was insignificant (<0.02% of dose). The terminal phase elimination half­life (t1/2) of fospropofol was 0.81±0.08 and 0.88±0.08 hours
in healthy subjects and patients, respectively. In healthy subjects, the apparent total body clearance of liberated propofol (CLp/F) was
1.95±0.345 L/h/kg and t1/2 was 2.06±0.77 hours. In patients, the CLp of fospropofol was 0.31±0.14 L/h/kg, and CLp/F for propofol
was 2.74±0.80 L/h/kg and is similar to that observed in healthy subjects.

Special Populations
Population pharmacokinetic analysis indicated no influence of race, gender, age, renal impairment or alkaline phosphatase
concentrations on the pharmacokinetics of fospropofol. Pharmacokinetics of propofol derived from fospropofol was not influenced
by race, gender, or renal impairment.
LUSEDRA has not been adequately studied in patients with hepatic impairment. Caution should be exercised when using
fospropofol disodium in patients with hepatic impairment.

Drug Interactions
Molecular Formula: C13H19O5PNa2 There was no effect of analgesic premedication [fentanyl (1 mcg/kg); meperidine (0.75 mg/kg); midazolam (0.01 mg/kg);
Molecular Weight: 332.24 morphine (0.1 mg/kg)] on plasma pharmacokinetics of fospropofol.
Figure 1. Structural and Molecular Formulas of Fospropofol Disodium In an in vitro protein­binding study, there was no significant interaction between fospropofol and propofol at concentrations up to
200 mcg/mL and 5 mcg/mL, respectively. The interaction of fospropofol with other highly protein­bound drugs given concomitantly
has not been studied.
Potential of fospropofol or its major metabolite, propofol, to inhibit or induce major cytochrome P450 enzymes is not known.
The inactive components include monothioglycerol (0.25 wt%) and tromethamine (0.12 wt%). LUSEDRA has a pH
of 8.2 to 9.0. LUSEDRA does not contain any antimicrobial preservatives and is intended for single­use administration. 13 NONCLINICAL TOXICOLOGY
12 CLINICAL PHARMACOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
12.1 Mechanism of Action Long­term studies in animals have not been performed to evaluate the carcinogenic potential of fospropofol disodium.
Fospropofol disodium is a prodrug of propofol. Following intravenous injection, fospropofol is metabolized by alkaline
phosphatases. For every millimole of fospropofol disodium administered, one millimole of propofol is produced (1.86 mg Mutagenesis
of fospropofol disodium is the molar equivalent of 1 mg propofol). 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
12.2 Pharmacodynamics presence of metabolic activation. In contrast, fospropofol was negative in this assay in the presence of formaldehyde­metabolizing
The pharmacology of fospropofol, once metabolized to propofol, is comparable to that of propofol lipid emulsion; however, enzymes, suggesting that the positive finding is likely due to an artifact of the culture conditions.
the liberation of propofol from fospropofol results in differences in the timing of the pharmacodynamic effects. To characterize
the pharmacokinetic/pharmacodynamic (PK/PD) profile of propofol derived from LUSEDRA, 12 healthy subjects were admin­ Impairment of Fertility
istered a 10­mg/kg intravenous bolus dose of LUSEDRA, and the sedative effect was measured as a decrease in Modified 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
Observer’s Assessment of Alertness/Sedation (MOAA/S) score (Table 5).2 The PK and PD results are shown in Figure 2. Peak with 20 mg/kg (0.3­fold the total human dose for a procedure of 16 minutes based on a mg/m2 basis).
plasma levels of propofol (2.2±0.4 µg/mL) released from fospropofol were noted by 8 minutes (range 4­13 minutes) and Female rats were treated with 5, 10, or 20 mg/kg fospropofol for two weeks prior to mating. There were no clear treatment­related
minimum mean MOAA/S score of 1.2 (range 0­3) was noted in 7 minutes (range 1­15 minutes). Subjects completely recovered effects on female fertility at a dose of 20 mg/kg (0.3­fold the total human dose for a procedure of 16 minutes based on a mg/m2 basis).
from sedative effects between 21 to 45 minutes after LUSEDRA administration.
14 CLINICAL STUDIES
Table 5. Modified Observer’s Assessment of Alertness/Sedation Scale2
14.1 Use in Sedation for Diagnostic or Therapeutic Procedures
Responsiveness Score The standard and modified LUSEDRA dosing regimens were evaluated in two controlled studies in patients dosed with LUSEDRA
who were over 18 years of age and undergoing diagnostic or therapeutic procedures. All patients received 50 mcg of fentanyl citrate
Responds readily to name spoken in normal tone 5
intravenously before study sedative medication. The primary endpoint was the rate of “sedation success,” defined as the proportion of
Lethargic response to name spoken in normal tone 4 patients who did not respond readily to their name spoken in a normal tone of voice (Modified Observer’s Assessment of Alertness/Sedation
Scale score of 4 or less) on 3 consecutive measurements taken every 2 minutes and who completed the procedure without the use of
Responds only after name is called loudly and/or repeatedly 3 alternative sedative medication and without the use of manual or mechanical ventilation.2
In both studies, an initial bolus dose and up to 3 supplemental doses at 25% of the initial bolus of study sedative medication
Responds only after mild prodding or shaking 2 were administered intravenously to sedate patients so that they did not respond readily to their name spoken in a normal tone and
Responds only after painful trapezius squeeze 1 to allow the investigator to start the procedure. During the procedure, supplemental doses at 25% of the initial bolus were allowed to
maintain sedation. Patients who were not adequately sedated with study drug received alternative sedative medication per the site’s
Does not respond to painful trapezius squeeze 0 standard of care; however, sites were instructed not to use propofol as it would interfere with PK measurements.
The standard and modified LUSEDRA dosing regimens were evaluated in a randomized, blinded, dose­controlled study for sedation
in patients undergoing colonoscopy. All of the patients who received alternative sedative medication (n=19) received midazolam.
Patients randomized to receive the LUSEDRA standard or modified dosing regimen had a sedation success rate of 87% and required a
mean number of supplemental doses of 2.3 (±1.4 SD). Patients randomized to receive LUSEDRA had a median procedure duration
of 11 minutes.
Mean (SD) Propofol The standard and modified LUSEDRA dosing regimens were also evaluated in a randomized, blinded, dose­controlled study for
sedation in patients undergoing flexible bronchoscopy. All of the patients who received alternative sedative medication (n=12) received
midazolam. Patients randomized to receive the LUSEDRA standard or modified dosing regimen had a sedation success rate of 89% and
Plasma Propofol Concentration (ng/mL)

required a mean number of supplemental doses of 1.7 (±1.6 SD). Patients randomized to LUSEDRA had a median procedure duration
of 10 minutes.

15 REFERENCES
1. Kost, M. Moderate Sedation/Analgesia: Core Competencies for Practice. Elsevier Health Sciences, 2004: 62­63.
2. Chernik DA, Gillings D, Laine H, Hendler J, Silver JM, Davidson AB, et al. Validity and reliability of the Observer’s Assessment
of Alertness/Sedation Scale: study with intravenous midazolam. J Clin Psychopharmacol. 1990;10(4):244­251.

16 HOW SUPPLIED/STORAGE AND HANDLING

LUSEDRA, 35 mg/mL (total of 1,050 mg/30 mL) fospropofol disodium, is supplied as a single­use, aqueous, sterile, nonpyrogenic,
clear, colorless solution in glass vials ready for intravenous injection. Each vial is filled with 32.1 mL intended to deliver a minimum
of 30 mL of fospropofol disodium solution. Store at controlled room temperature 25°C (77°F). Excursions permitted between 15° and
30°C (59° and 86°F).

NDC 62856­350­08

17 PATIENT COUNSELING INFORMATION

Paresthesias (including burning, tingling, stinging) and/or pruritus, usually manifested in the perineal region are frequently
experienced upon injection of the initial dose of LUSEDRA. Inform the patient that these sensations are typically mild to moderate
in intensity, last a short time, and require no treatment.
Requirement for a patient escort should be considered. The decision as to when patients who have received LUSEDRA,
particularly on an outpatient basis, may again engage in activities requiring complete mental alertness, coordination and/or
physical dexterity (e.g., operate hazardous machinery, sign legal documents, or drive a motor vehicle) must be individualized.
Time post dose (min)

Eisai Inc.
100 Tice Boulevard
Mean (SE) MOAA/S Woodcliff Lake, NJ 07677
USA

LUSEDRA is a trademark used by Eisai Inc. under license from Eisai R&D Management Co., Ltd.

©2009 Eisai Inc.

All rights reserved. 10/09
MOAA/S Score

Time (min)

Figure 2. Pharmacokinetic and Pharmacodynamic Profiles after a 10-mg/kg Bolus Dose of LUSEDRA 201219 007101 Revised October 2009
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