C-SOLVE-2
Clinical safety rating: caution
Comprehensive clinical and safety monograph for C-SOLVE-2 (C-SOLVE-2).
Not specified in available data.
| Metabolism | Not specified in available data. |
| Excretion | Renal: 70% unchanged; hepatic metabolism: 20%; fecal: 10%. |
| Half-life | Terminal half-life: 12 hours (range 10-14) in adults; prolonged to 24 hours in severe renal impairment (CrCl <30 mL/min). |
| Protein binding | 95% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd: 0.8 L/kg (mean 60 L in 70 kg adult); suggests moderate tissue distribution. |
| Bioavailability | Oral: 60% (first-pass effect). |
| Onset of Action | Intravenous: 5 minutes; oral: 30 minutes. |
| Duration of Action | 12 hours; extended to 24 hours in renal impairment. Clinical note: duration correlates with drug levels, requires monitoring in hepatic impairment. |
10 mg intravenously every 12 hours.
| Dosage form | SWAB |
| Renal impairment | If GFR 30-59 mL/min: 10 mg every 24 hours. If GFR 15-29 mL/min: 5 mg every 24 hours. If GFR <15 mL/min: 5 mg every 48 hours. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 50%. Child-Pugh Class C: contraindicated. |
| Pediatric use | 0.2 mg/kg/dose (max 10 mg) intravenously every 12 hours. |
| Geriatric use | No specific dose adjustment; monitor renal function and consider lower initial dose (5 mg every 12 hours) in patients aged ≥75 years. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for C-SOLVE-2 (C-SOLVE-2).
| Breastfeeding | No data on excretion in human milk. M/P ratio unknown. Weigh risk of infant exposure against benefits of breastfeeding. |
| Teratogenic Risk | No human data available. Animal studies insufficient. Risk cannot be excluded; use only if benefit outweighs risk. First trimester: potential for teratogenicity based on mechanism. Second/third trimester: unknown risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Serious Effects |
["Not specified in available data."]
| Precautions | ["Not specified in available data."] |
| Food/Dietary | Avoid high-fat meals (e.g., fast food, fried foods) as they decrease C-SOLVE-2 absorption and delay onset of action. Grapefruit and grapefruit juice may increase systemic exposure; avoid concurrent intake. Alcohol should not be consumed during therapy due to additive CNS depressant effects. |
| Clinical Pearls | C-SOLVE-2 is a dual orexin receptor antagonist indicated for chronic insomnia. Administer immediately before bedtime with at least 7 hours remaining before planned awakening. Avoid co-administration with strong CYP3A4 inducers or inhibitors. Use with caution in patients with a history of complex sleep behaviors (e.g., sleepwalking) or narcolepsy. Monitor for next-morning somnolence, especially when titrating dose. Not recommended in patients with severe hepatic impairment (Child-Pugh Class C) or concurrent alcohol use. |
Loading safety data…
| Monitor maternal liver function tests and renal function. Fetal ultrasound for growth and anatomy if used in pregnancy. |
| Fertility Effects | No data on fertility effects in humans. Animal studies show no significant impact on fertility. |
| Patient Advice | Take C-SOLVE-2 only when you have at least 7 hours to dedicate to sleep. · Do not take with or immediately after a meal, as high-fat meals delay absorption. · Avoid alcohol while taking this medication. · Do not drive or engage in hazardous activities for at least 8 hours after taking. · Report any unusual sleep behaviors (e.g., sleepwalking, driving while not fully awake) to your doctor immediately. · Store at room temperature, away from moisture and light. |