Lusedra (Fospropofol Disodium Injection) Drug Information: Side Effects and Drug Interactions

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May 27, 2012

Lusedra

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SIDE EFFECTS

The following serious adverse reactions are discussed elsewhere in the labeling:

Respiratory depression [see WARNINGS AND PRECAUTIONS]
Hypoxemia [see WARNINGS AND PRECAUTIONS]
Loss of purposeful responsiveness [see WARNINGS AND PRECAUTIONS]
Hypotension [see WARNINGS AND PRECAUTIONS]

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.

Clinical Trials Experience

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 open-label study in patients undergoing minor procedures. Patients enrolled in the studies who received the standard or modified dosing regimen included males and females, ≥ 18 years of age and ranging 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 who received the standard or the modified dosing regimen [see DOSAGE AND ADMINISTRATION]. 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 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 cannot be directly compared to rates in the clinical trials of another drug and may not accurately reflect the rates observed in practice.

Table 3. Common Adverse Reactions for Patients Receiving the Standard or Modified Dosing Regimen (Reactions Occurring at a Rate ≥ 2%)

Reaction Term	Colonoscopy (N=183) n(%)	Minor Procedures (N=123) n (%)	Bronchoscopy (N=149) n(%)
Gastrointestinal disorders
Nausea	0	5(4)	2(1)
Vomiting	0	4(3)	0
Injury, poisoning, and procedural complications
Procedural Pain	0	0	3(2)
Nervous system disorders
Paresthesia^a	135(74)	77 (63)	78 (52)
Headache	1 (1)	3(2)	1(1)
Respiratory, thoracic, and mediastinal disorders
Hypoxemia	3(2)	1 (1)	16(11)
Skin and subcutaneous tissue disorders
Pruritus^b	30(16)	34 (28)	24(16)
Vascular disorders
Hypotension	4(2)	4(3)	10(7)
^a 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 non-specific sensation in pubic area). ^b 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 of LUSEDRA (fospropofol disodium injection) 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.

Sedation-related adverse reactions were experienced at the following rates for subjects receiving the standard or modified LUSEDRA (fospropofol disodium injection) dosing regimen: 20/455 (4%) hypoxemia, 18/455 (4%) hypotension, 1/455 ( < 1%) apnea. A greater rate of sedation-related adverse reactions necessitating intervention was observed in patients undergoing bronchoscopy compared with colonoscopy and minor surgical procedures. In the colonoscopy studies, 5/183 (3%) patients were ASA P3. In the minor surgical procedures study, 23/123 (19%) 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 sedation-related adverse reactions are presented in Table 4.

Table 4. Patient Incidence of Airway Management Events

	Healthy Subjects^a 6 mg/kg N=69 n (%)	Colonoscopy^b 6.5 mg/kg (or modified dosing regimen) N=183 n (%)	Minor Procedures^b 6.5 mg/kg (or modified dosing regimen) N=123 n (%)	Flexible Bronchoscopy^b 6.5 mg/kg (or modified dosing regimen) N=149 n (%)
Increased O₂	0	0	0	21 (14)
Patient Repositioning	0	0	0	2(1)
Verbal Stimulation	0	2(1)	1 (1)	5(3)
Tactile Stimulation	0	0	0	3(2)
Face Mask (100% O₂)	0	0	0	1 (1)
Jaw Thrust	0	0	0	2(1)
Chin Lift	0	0	1 (1)	3(2)
Nasal Trumpet	0	0	0	0
Oral Airway	0	0	0	0
Suction	0	0	0	2(1)
Manual Ventilation (bag valve mask)	0	0	0	1 (1)
Mechanical Ventilation	0	0	0	0
^aNo concomitant medications administered. All subjects were healthy volunteers. ^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).

Adverse Reactions in Prolonged Exposure in Adults

The safety of LUSEDRA (fospropofol disodium injection) for continuous sedation has not been established and therefore its use is not recommended. LUSEDRA (fospropofol disodium injection) was administered to 38 intubated and mechanically ventilated patients in postoperative and intensive care settings. An occurrence of nonsustained ventricular tachycardia was observed as a serious adverse reaction in one patient in the study. Another patient with acute myeloid leukemia with renal and hepatic insufficiency experienced a further increase in plasma formate concentration from a baseline of 66 mcg/mL to a post-dose level of 212 mcg/mL after a 12-hour infusion. The clinical significance of these findings is unknown.

DRUG INTERACTIONS

LUSEDRA (fospropofol disodium injection) may produce additive cardiorespiratory effects when administered with other cardiorespiratory depressants such as sedative-hypnotics and narcotic analgesics.

Drug Abuse And Dependence

Controlled Substance

LUSEDRA (fospropofol disodium injection) is a Schedule IV controlled substance.

Abuse

No formal studies of the abuse potential of LUSEDRA (fospropofol disodium injection) have been conducted. Administration of LUSEDRA (fospropofol disodium injection) resulted in euphoria in a small number of subjects who received intravenous or oral dosing.