INTROVALE
Clinical safety rating
cautionComprehensive clinical and safety monograph for INTROVALE (INTROVALE).
Selective serotonin reuptake inhibitor (SSRI); inhibits serotonin reuptake at presynaptic terminals, enhancing serotonergic neurotransmission.
| Metabolism | Hepatic via CYP2D6, CYP2C9, CYP3A4, and CYP2C19; active metabolite (norINTROVALE) via N-demethylation. |
| Excretion | ~65% renal excretion of unchanged drug, ~35% hepatic metabolism with biliary excretion of metabolites; total fecal elimination <5% of parent compound. |
| Half-life | Terminal elimination half-life = 12–15 hours (mean 13.5 h) in healthy adults; prolonged to 20–30 h in moderate hepatic impairment. |
| Protein binding | ~98% bound, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd = 0.35–0.45 L/kg; indicates moderate distribution into total body water with minimal tissue binding. |
| Bioavailability | Oral: ~75% (range 60–85%) in fasted state; IM: ~90%. |
| Onset of Action | IV: 2–5 minutes; IM: 10–15 minutes; Oral: 30–60 minutes (fasted). |
| Duration of Action | IV/IM: 4–6 hours; Oral: 6–8 hours; duration may be extended with repeat dosing or in elderly patients. |
| Molecular Weight | 325.41 |
400 mg orally every 6 hours; intravenous: 400 mg every 6 hours infused over 1 hour.
| Dosage form | TABLET |
| Renal impairment | GFR 30-59 mL/min: decrease dose to 300 mg every 6 hours; GFR 10-29 mL/min: 200 mg every 6 hours; GFR <10 mL/min: 150 mg every 6 hours. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 300 mg every 6 hours; Child-Pugh C: 200 mg every 6 hours. |
| Pediatric use | Children 2-12 years: 8 mg/kg orally every 6 hours, maximum 400 mg/dose. |
| Geriatric use | Consider dose reduction based on renal function; start at 300 mg every 6 hours. |
| 1st trimester | Avoid due to teratogenic effects observed in animal studies; human data limited. |
| 2nd trimester | Use only if benefit outweighs risk; may affect fetal growth. |
| 3rd trimester | Avoid near term; risk of neonatal withdrawal or toxicity. |
Clinical note
Comprehensive clinical and safety monograph for INTROVALE (INTROVALE).
| Placental transfer | Yes, crosses placenta (animal data); likely in humans due to low molecular weight. |
| Breastfeeding | Potential for transfer into breast milk; consider risk vs benefit. Monitor infant for adverse effects. |
| Lactation Rating | L3 |
| Teratogenic Risk | First trimester: Human data indicate increased risk of major congenital malformations, including neural tube defects and cardiovascular anomalies. Exposure in first trimester is contraindicated. Second/third trimester: Associated with fetal growth restriction, oligohydramnios, and neonatal renal impairment. Avoid use throughout pregnancy. |
| Fetal Monitoring | Pregnancy test before initiation and monthly during therapy. Ultrasound monitoring for fetal growth, amniotic fluid volume, and anatomy if exposed. Renal function tests in neonate if exposure occurred in third trimester. |
| Fertility Effects | May reduce fertility in females of reproductive potential based on animal studies showing ovarian toxicity and altered menstrual cyclicity. In males, animal data indicate impaired spermatogenesis and reduced fertility. Reversibility unknown. |
■ FDA Black Box Warning
Increased risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders.
| Serious Effects |
Hypersensitivity to active substanceSevere hepatic impairment
| Precautions | Serotonin syndrome, discontinuation syndrome, bleeding risk, hyponatremia, activation of mania/hypomania, seizure threshold lowering, angle-closure glaucoma. |
| Food/Dietary | Take on an empty stomach, at least 2 hours after a meal. High-fat meals significantly delay and reduce absorption. Avoid alcohol entirely; concurrent use increases risk of CNS depression and respiratory arrest. |
| Clinical Pearls | Introvals (sodium oxybate) can cause profound sedation and respiratory depression; always screen for concomitant CNS depressants and alcohol use. Administer doses upon waking and again 2.5-4 hours later; patients must remain in bed after taking. Do not use in patients with succinic semialdehyde dehydrogenase deficiency. Monitor for confusion, hallucinations, and parasomnias especially at initiation. Abrupt discontinuation can cause withdrawal with anxiety, insomnia, and psychosis. |
| Patient Advice | Take only at bedtime and once more 2.5 to 4 hours later; stay in bed immediately after each dose. · Do not drink alcohol or take other sedatives while using this medication, as it may cause severe breathing problems. · Do not drive or operate machinery for at least 6 hours after the last dose, and only when you feel fully awake. · Store the liquid medication in the original container; dilute each dose with water as instructed and consume within 10 minutes. · Do not stop taking suddenly; tapering is necessary to avoid withdrawal symptoms such as anxiety, confusion, and insomnia. |
Loading safety data…