Lusedra

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

• Burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings

• Bluish lips or skin
• blurred vision
• confusion
• dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly
• sweating
• unusual tiredness or weakness

• Difficult or troubled breathing
• irregular, fast or slow, or shallow breathing
• pale or blue lips, fingernails, or skin
• shortness of breath

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Itching skin

• Headache
• nausea
• vomiting

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

None.

Lusedra may produce additive cardiorespiratory effects when administered with other cardiorespiratory depressants such as sedative-hypnotics and narcotic analgesics.

Lusedra is an injection solution intended for intravenous administration as a sedative-hypnotic agent. Lusedra is an aqueous, sterile, nonpyrogenic, clear, colorless, iso-osmotic solution containing 35 mg/mL of fospropofol disodium. Fospropofol disodium is a water-soluble prodrug of propofol, chemically described as 2,6-diisopropylphenoxymethyl phosphate, disodium salt. The structural and molecular formulas are shown in Figure 1.

Molecular Formula: C13H19O5PNa2
Molecular Weight: 332.24
Figure 1. Structural and Molecular Formulas of Fospropofol Disodium

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 single-use administration.

  Use in Sedation for Diagnostic or Therapeutic Procedures

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 intravenously before study sedative medication. The primary endpoint was the rate of "sedation success," defined as the proportion of 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 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 were administered intravenously to sedate patients so that they did not respond readily to their name spoken in a normal tone and 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 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, dose-controlled 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.

The standard and modified Lusedra dosing regimens were also evaluated in a randomized, blinded, dose-controlled 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 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.

1. Kost, M. Moderate Sedation/Analgesia: Core Competencies for Practice. Elsevier Health Sciences, 2004; 62-63.
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):244-251.

Lusedra (fospropofol disodium) Injection is a proprietary water-soluble prodrug of propofol that, after intravenous injection, is converted by alkaline phosphatase enzymes in the body into propofol. Lusedra is an intravenous sedative-hypnotic agent indicated for monitored anesthesia care (MAC) sedation in adult patients undergoing diagnostic or therapeutic procedures.

Lusedra 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. Patients should be continuously monitored during sedation and through the recovery process for early signs of hypotension, apnea, airway obstruction, and/or oxygen desaturation. Facilities for providing cardiopulmonary resuscitation must be immediately available.

The following serious adverse reactions have been reported with the use of Lusedra.

• Hypotension
  • Hypotension was reported in 18/455 (4%) patients treated with Lusedra using the standard or modified dosing regimen.
  • Patients with compromised myocardial function, reduced vascular tone, or who have reduced intravascular volume may be at an increased risk for hypotension.
• Hypoxemia
  • Hypoxemia was reported in 20/455 (4%) patients treated with Lusedra using the standard or modified dosing regimen. Retention of purposeful responsiveness did not prevent patients from becoming hypoxemic following administration of Lusedra.
• Respiratory depression
  • Apnea was reported in 1/455 (< 1%) patients treated with Lusedra using the standard or modified dosing regimen.
• Loss of purposeful responsiveness
  • Lusedra has not been studied for use in general anesthesia. However, administration of Lusedra may inadvertently cause patients to become unresponsive or minimally responsive to vigorous tactile or painful stimulation. The incidence of patients who became minimally responsive or unresponsive to vigorous tactile or painful stimulation was 7/183 (4%) for colonoscopy and 24/149 (16%) for bronchoscopy. The duration of minimal or complete unresponsiveness ranged from 2 to 16 minutes in colonoscopy patients and from 2 to 20 minutes in bronchoscopy patients.

The use of supplemental oxygen is recommended in all patients receiving Lusedra. Airway assistance maneuvers may be required. As with other sedative-hypnotic agents, Lusedra may produce additive cardio-respiratory effects when administered with other cardio-respiratory depressants such as benzodiazepines and narcotic analgesics. When Lusedra is used at greater than the recommended doses, the incidence of serious adverse reactions is increased.

The most common adverse reactions (reported in greater than 20%) are paresthesia and pruritis.

Applies to fospropofol: intravenous solution

Respiratory

Very common (10% or more): Hypoxemia (up to 11%)
Common (1% to 10%): Procedural pain (bronchoscopy)
Uncommon (0.1% to 1%): Apnea[Ref]

Nervous system

-Paresthesia includes the following terms: paresthesia genital male; burning sensation; genital burning sensation; vaginal burning sensation; skin burning sensation; genital pain (reported as burning); perineal pain (reported as 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 stinging); pain (reported as stinging); sensory disturbance (reported as nonspecific sensation in pubic area).
-Pruritus includes the following terms: genital pruritus female; genital pruritus male; pruritus genital; pruritus ani; pruritus generalized.
-Paresthesias (including burning, tingling, stinging) and/or pruritus, usually manifested in the perineal region, were the most frequently recorded adverse reactions in clinical trials. Paresthesias and pruritus generally occurred within 5 minutes after administration of the initial dose and were generally transient and mild to moderate in intensity. The pharmacologic basis of these sensory phenomena is unknown. No pretreatments, including the use of nonsteroidal anti-inflammatory drugs, opioids, or lidocaine, are known to have an effect on or to reduce the incidence of these sensations.[Ref]

Very common (10% or more): Paresthesia (up to 74%)
Common (1% to 10%): Headache[Ref]

Cardiovascular

Common (1% to 10%): Hypotension[Ref]

Gastrointestinal

Common (1% to 10%): Nausea, vomiting[Ref]

Other

Common (1% to 10%): Procedural pain[Ref]

Dermatologic

Very common (10% or more): Pruritus (up to 28%)[Ref]

Some side effects of Lusedra may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.