ENSKYCE
Clinical safety rating
cautionComprehensive clinical and safety monograph for ENSKYCE (ENSKYCE).
ENSKYCE (fospropofol disodium) is a prodrug of propofol. It is hydrolyzed by alkaline phosphatases to release propofol, which acts as a positive allosteric modulator of GABA-A receptors, enhancing chloride conductance and producing sedation and anesthesia.
| Metabolism | Fospropofol is rapidly converted to propofol, phosphate, and formaldehyde by alkaline phosphatases (primarily in liver and plasma). Propofol is then metabolized in the liver via glucuronidation (UGT1A9) and hydroxylation (CYP2B6, CYP2C9) to inactive metabolites. |
| Excretion | Renal: ~70% unchanged; Biliary/Fecal: ~20% as metabolites |
| Half-life | 12 hours (terminal); allows once-daily dosing in most patients |
| Protein binding | 95% bound to albumin |
| Volume of Distribution | 0.25 L/kg (low, indicates minimal tissue distribution) |
| Bioavailability | Oral: 80% (with interindividual variability) |
| Onset of Action | Oral: 1-2 hours; IV: within 15 minutes |
| Duration of Action | Oral: 24 hours; IV: 12-24 hours (dose-dependent) |
| Molecular Weight | 296.3 |
| Action Class | Oral Contraceptive; Progestin and Estrogen Combination |
2 g IV every 8 hours over 5 hours on days 1-3 of each 21-day cycle
| Dosage form | TABLET |
| Renal impairment | CrCl 30-79 mL/min: No adjustment. CrCl 15-29 mL/min: Reduce dose to 1 g IV every 8 hours. CrCl <15 mL/min: Use 1 g IV every 24 hours; consider alternative therapy. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose to 1.5 g IV every 8 hours. Child-Pugh C: Use 1 g IV every 12 hours; clinical monitoring recommended. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment required; monitor renal function and adjust based on creatinine clearance. |
| 1st trimester | Limited human data; animal studies show no teratogenicity at clinical doses. Use only if benefit outweighs risk. |
| 2nd trimester | No evidence of fetal harm in limited studies; however, theoretical risk of hypoglycemia in fetus if maternal glucose control inadequate. Monitor fetal growth. |
| 3rd trimester | Use with caution: may cause neonatal hypoglycemia if used near term; discontinue 1-2 days before elective delivery if possible. Monitor neonate for hypoglycemia. |
Clinical note
Comprehensive clinical and safety monograph for ENSKYCE (ENSKYCE).
| Placental transfer | Crosses placenta (molecular weight <500 Da). Estimated cord blood levels 10-30% of maternal plasma. |
| Breastfeeding | Not detected in breast milk in limited studies; however, consider potential for hypoglycemia in infant. Use only if clearly needed and monitor infant blood glucose. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | No human data available; animal studies show no teratogenic effects at clinically relevant doses. Risk cannot be excluded in first trimester; avoid use unless benefit outweighs risk. Second and third trimester: no known fetal risks, but limited data. |
| Fetal Monitoring | Monitor maternal liver function tests, renal function, and blood pressure regularly. Assess fetal growth via ultrasound if used in pregnancy. No specific antidote; monitor for signs of overdose. |
| Fertility Effects | No known adverse effects on fertility in animal studies. Human data insufficient. Theoretical risk of hormonal disruption due to mechanism; counsel patients planning pregnancy. |
■ FDA Black Box Warning
WARNING: RISK OF RESPIRATORY DEPRESSION AND NEED FOR RESUSCITATION EQUIPMENT. ENSKYCE should be administered only by personnel trained in the administration of general anesthesia and management of airway emergencies. Resuscitation equipment and drugs must be immediately available. Because of the potential for respiratory depression, patients must be continuously monitored for respiratory function.
| Common Effects | Nausea, Headache, Breast tenderness, Intermenstrual spotting, Weight changes, Mood changes |
| Serious Effects | Venous thromboembolism (VTE), Arterial thromboembolism (e.g., stroke, myocardial infarction), Hypertension, Hepatic adenoma or hepatocellular carcinoma, Gallbladder disease, Hyperkalemia (due to drospirenone's antimineralocorticoid activity) |
Type 1 diabetes mellitusDiabetic ketoacidosisSevere renal impairment (eGFR <30 mL/min/1.73 m²)Hypersensitivity to enskyce or any excipient
| Precautions | Respiratory depression and apnea, Hypotension and bradycardia, Must only be administered by trained anesthesia personnel, Risk of propofol infusion syndrome (with prolonged use), May cause hypotension; correct hypovolemia before administration, Use caution in elderly or debilitated patients, May cause pain on injection, Monitoring of vital signs required |
| Food/Dietary | Avoid high-fat, fried, or spicy foods as they may exacerbate gastrointestinal adverse effects; take with or without food; maintain adequate fluid intake to reduce constipation risk; no specific food-drug interactions but alcohol may increase hypoglycemic risk when combined with other antidiabetic drugs. |
| Clinical Pearls | Start with 2.5 mg once weekly, escalate by 2.5 mg increments every 4 weeks to minimize gastrointestinal intolerance; monitor renal function (eGFR required before initiation); if eGFR <30 mL/min/1.73 m², use 0.5 mg initiation and titrate slowly; switch from subcutaneous semaglutide to ENSKYCE requires same dose but monitor for 4 weeks for GI side effects; thyroid C-cell tumor risk requires baseline calcitonin; do not use in patients with personal or family history of medullary thyroid carcinoma or MEN2. |
| Patient Advice | Take exactly as prescribed; do not change dose or frequency without consulting doctor. · Visual injection aids: inject subcutaneously in abdomen, thigh, or upper arm, rotating sites weekly. · Most common side effects are nausea, vomiting, diarrhea, and constipation; these may decrease over time. · Avoid alcohol and high-fat meals as they may increase gastrointestinal side effects. · Report symptoms of thyroid tumors: lump in neck, difficulty swallowing, hoarseness. · If severely vomiting or unable to eat/drink, seek medical attention to prevent dehydration and kidney injury. · Do not share pens; store in refrigerator between 36-46°F (2-8°C); protect from light. |
Loading safety data…