(fos PROE po fole)
Monitored anesthesia care (MAC) sedation in patients undergoing diagnostic or therapeutic procedures
There are no contraindications in the manufacturer 's FDA approved labeling.
Note: Applicable contraindications to propofol include: Hypersensitivity to propofol; when general anesthesia or sedation is contraindicated
Note: Onset of effect is delayed as compared to propofol-emulsion due to need for conversion to active component. If <60 kg, base dosing on 60 kg; however, lower doses may be used to achieve lower levels of sedation. If >90 kg, base dosing on 90 kg.
Monitored anesthesia care sedation: IV:
Healthy adults <65 years or with mild systemic disease (ASA-PS1 or -PS2): Standard dosing regimen: Initial: 6.5 mg/kg (maximum initial dose: 577.5 mg or 16.5 mL), followed by supplemental doses of 1.6 mg/kg (maximum supplemental dose: 140 mg or 4 mL) no more frequently than every 4 minutes as needed to achieve desired level of sedation.
Patients with severe systemic disease (ASA-PS3 or -PS4): Modified dosing regimen: Initial: 4.9 mg/kg (maximum initial dose: 437.5 mg or 12.5 mL), followed by supplemental doses of 1.2 mg/kg (maximum supplemental dose: 105 mg or 3 mL) no more frequently than every 4 minutes as needed to achieve desired level of sedation.
Note: Onset of effect is delayed as compared to propofol-emulsion due to need for conversion to active component. If <60 kg, base dosing on 60 kg; however, lower doses may be used to achieve lower levels of sedation. If >90 kg, base dosing on 90 kg.
Monitored anesthesia care sedation: IV: Patients ≥65 years:Modified dosing regimen: Initial: 4.9 mg/kg (maximum initial dose: 437.5 mg or 12.5 mL), followed by supplemental doses of 1.2 mg/kg (maximum supplemental dose: 105 mg or 3 mL) no more frequently than every 4 minutes as needed to achieve desired level of sedation.
No dosage adjustment recommended. Use with caution in patients with severe renal impairment (CrCl <30 mL/minute); limited safety and efficacy data available in these patients.
No dosage adjustment recommended. Use with caution in patients with hepatic impairment; has not been adequately studied in this population.
Single-use vials do not need to be diluted prior to administration. Draw into sterile syringes immediately after opening vials. Discard any unused portion at the end of procedure.
Administer as an IV bolus (no recommendations on rate of administration provided by manufacturer) via via a secure, freely flowing, peripheral IV line. Flush IV line with NS or other compatible fluid before and after administration. Strict aseptic technique must be maintained in handling. Discard any unused portion at the end of the procedure. Do not filter.
Store at controlled room temperature of 25 ‚ °C (77 ‚ °F); excursions permitted between 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F).
Stable in D51/4NS, D51/2NS, D51/2NS with 20 mEq KCl, D5W, D5LR, LR, 1/2NS, NS. Per manufacturer, do not mix with other therapeutic agents prior to administration.
Alfentanil: May enhance the adverse/toxic effect of Fospropofol. Specifically, the development of opisthotonus (severe hyperextension and spasticity resulting in arching or bridging position) and/or grand mal seizures. Monitor therapy
ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy
CYP2B6 Inhibitors (Moderate): May decrease the metabolism of CYP2B6 Substrates. Monitor therapy
CYP2B6 Inhibitors (Strong): May decrease the metabolism of CYP2B6 Substrates. Consider therapy modification
Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Limit the maximum adult dose of lomitapide to 30 mg daily when used in combination with any weak CYP3A4 inhibitor. Consider therapy modification
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination
Quazepam: May increase the serum concentration of CYP2B6 Substrates. Monitor therapy
Ropivacaine: Fospropofol may increase the serum concentration of Ropivacaine. Specifically, propofol (the active metabolite of fospropofol) is the entity with the potential to interact with ropivacaine. Monitor therapy
ECG, blood pressure, respiration, oxygen saturation; patient responsiveness
>10%:
Dermatologic: Pruritus (see Note" below; 8% to 28%)
Neuromuscular & skeletal: Paresthesia (see Note" below; 52% to 74%)
Respiratory: Hypoxemia (1% to 11%)
1% to 10%:
Cardiovascular: Hypotension (2% to 7%)
Central nervous system: Headache (1% to 2%)
Gastrointestinal: Nausea ( ≤4%), vomiting ( ≤3%)
Miscellaneous: Procedural pain ( ≤2%)
<1% (Limited to important or life-threatening): Apnea, myoclonus, systolic blood pressure increased, heart rate increased
Note: Paresthesias (including perineal discomfort or burning sensation) and pruritus (including genital, perineal, and generalized pruritus) are mostly limited to the first 5 minutes of administration and usually described as mild-moderate in intensity. No pretreatments are helpful in reducing the incidence of these adverse effects.
Does not affect the pharmacokinetics.
Pharmacokinetics have not been adequately studied.
Concerns related to adverse effects:
- Hypotension: The major cardiovascular effect is hypotension. Use with caution in patients who are hemodynamically unstable, hypovolemic, or have abnormally low vascular tone (eg, sepsis), or compromised myocardial function (eg, heart failure).
- Respiratory depression: May cause loss of spontaneous respiration and/or hypoxemia; supplemental oxygen is recommended for all patients receiving fospropofol; monitor patient closely. The risk of these effects may be increased with the concomitant use of opioids and/or other sedatives.
- Unresponsiveness: May cause patients to become unresponsive or minimally responsive to vigorous tactile or painful stimuli.
Disease-related concerns:
- Hepatic impairment: Use with caution in patients with hepatic impairment; has not been adequately studied in this population.
- Renal impairment: Use with caution in patients with severe renal impairment (CrCl <30 mL/minute); limited safety and efficacy data available in these patients.
- Respiratory disease: Use with caution in patients with respiratory disease; risk of cardiorespiratory depression may be increased.
- Seizure disorder: Use with caution in patients with a history of epilepsy or seizures; seizure may occur during recovery phase.
Concurrent drug therapy issues:
- Opioids/sedative-hypnotics: Concomitant use may lead to increased sedative or respiratory depressant effects of fospropofol, more pronounced decreases in systolic, diastolic, and mean arterial pressures, heart rate, and cardiac output.
Special populations:
- ASA-PS (American Society of Anesthesiologists - Physical Status) 3/4 patients: Use lower doses in ASA-PS 3/4 patients to reduce the incidence of unwanted cardiorespiratory and neurologic depressive events.
- Elderly: Use lower doses in patients ≥65 years to reduce the incidence of unwanted cardiorespiratory and neurologic depressive events.
- Pediatrics: Safety and efficacy have not been established in patients <18 years of age.
- Pregnancy: Fospropofol should only be used in pregnancy if clearly needed. Not recommended for use in obstetrics, including cesarean section deliveries.
Other warnings/precautions:
- Analgesic supplementation: Fospropofol lacks analgesic properties; pain management requires specific use of analgesic agents.
- Appropriate use: Use only for sedation during procedures as an IV bolus with supplemental doses as needed; not recommended for use as a continuous infusion (safety has not been established).
- Experienced personnel: Use requires careful patient monitoring; should only be administered 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. Use to induce moderate (conscious) sedation in patients warrants monitoring equivalent to that seen with general anesthesia.
- Onset of action: The onset of action will be delayed due to need for conversion to the active metabolite, propofol. If supplemental doses are administered before full effect occurs, the risk of dose-stacking may be elevated resulting in deeper sedation than intended.
B
Adverse events were not observed in animal reproduction studies; however, fospropofol should only be used in pregnancy if clearly needed. Fospropofol is not recommended for obstetrics, including cesarean section deliveries. It is not known if fospropofol crosses the placenta. However, propofol crosses the placenta, and therefore, may be associated with neonatal CNS and respiratory depression.
Fospropofol disodium is a prodrug of propofol. Propofol interacts with the GABAA receptor, which is the presumed mechanism of action whereby it produces a sedative/hypnotic effect. Propofol is an alkyl-phenolic compound with intravenous general anesthetic properties.
Fospropofol: Vd: 0.26-0.4 L/kg
Propofol: Vd: ~6 L/kg; decreased in the elderly
Fospropofol is completely metabolized by plasma alkaline phosphatases to propofol, formaldehyde (rapidly converted to formate), and phosphate. Propofol is further metabolized hepatically to water-soluble sulfate and glucuronide conjugates (~50%).
Fospropofol: Urine (<0.02% unchanged)
Propofol: Urine (~88% as metabolites, 40% as glucuronide metabolite); feces (<2%)
Bolus (dose dependent): Attainment of adequate sedation was achieved between 2-28 minutes (median: 8 minutes)
Propofol (from fospropofol): Median: 12 minutes
Duration of sedation: Time to fully alert: ≤1 hour (median: 5 minutes)
Fospropofol: 0.8-0.96 hours
Propofol: 0.85-1.41 hours
Fospropofol: ~98% to albumin; does not affect protein binding of propofol (also ~98% bound to albumin)
Discuss specific use of drug and side effects with patient as it relates to treatment. Patient may experience presyncope, fatigue, blurred vision, illogical thinking, dizziness, injection site irritation, or paresthesia. Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.