VALTOCO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VALTOCO (VALTOCO).
GABA-A receptor positive allosteric modulator; increases chloride ion conductance, hyperpolarizes neurons, and suppresses seizure activity.
| Metabolism | Hepatic via CYP3A4 and CYP2C9; active metabolite desmethyldiazepam (nordazepam) |
| Excretion | Renal (70% as unchanged drug and metabolites, primarily glucuronide conjugate, with <2% as unchanged drug); biliary/fecal (30%) |
| Half-life | Terminal elimination half-life: 15-17 hours (range 11-20 h) in adults; no dose adjustment for age or renal impairment is recommended, but clinical monitoring is prudent in hepatic impairment. |
| Protein binding | 96% bound, primarily to albumin |
| Volume of Distribution | 0.5-0.8 L/kg; approximates total body water, indicating extensive tissue distribution. |
| Bioavailability | Intranasal: 75% (range 65-85%) relative to intravenous; rectal: 70-90% relative to intravenous. |
| Onset of Action | Intravenous: rapid (minutes) for seizure cessation; intranasal: 2-5 minutes for seizure termination in status epilepticus based on clinical trials. |
| Duration of Action | 4-6 hours for seizure control; may require repeated dosing or alternative therapy if seizure persists beyond 5 minutes. |
5 mg, 10 mg, 15 mg, or 20 mg intranasally as a single dose based on weight; for patients weighing <50 kg: 5 mg, 10 mg for 50-75 kg, 15 mg for 75-100 kg, 20 mg for >100 kg. In adults, maximum dose is 20 mg per seizure cluster.
| Dosage form | SPRAY |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment. Severe renal impairment (eGFR <15 mL/min): consider using lower doses due to increased exposure; use with caution. |
| Liver impairment | Child-Pugh A or B: no adjustment needed. Child-Pugh C: reduce dose by 50% due to increased diazepam exposure. |
| Pediatric use | Age 6-17 years: 0.2 mg/kg intranasally, maximum single dose 20 mg. Administer as single dose per seizure cluster. Not recommended for children <6 years. |
| Geriatric use | Elderly patients may have increased sensitivity; consider starting at lower end of dosing range (5-10 mg) and titrate based on response and tolerability. Use with caution due to risk of sedation and falls. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VALTOCO (VALTOCO).
| Breastfeeding | Diazepam is excreted into breast milk with an M/P ratio approximately 0.3. The relative infant dose is low (2-5% of weight-adjusted maternal dose). Caution is advised due to potential accumulation in neonates (long half-life) causing sedation, poor feeding, and respiratory depression. Use only if clearly needed with infant monitoring. |
| Teratogenic Risk | Diazepam (active moiety in VALTOCO) is Pregnancy Category D. First trimester: Associated with increased risk of congenital malformations, particularly cleft lip/palate, when used chronically. Second and third trimesters: May cause fetal benzodiazepine exposure leading to floppy infant syndrome, neonatal withdrawal, and central nervous system depression. Late third trimester or delivery: Risk of neonatal respiratory depression, hypotonia, and feeding difficulties. |
■ FDA Black Box Warning
WARNING: RISK OF RESPIRATORY DEPRESSION AND CARDIAC ARREST WITH CONCOMITANT USE OF ALCOHOL OR OTHER CNS DEPRESSANTS; RISK OF SUBSTANCE ABUSE, DEPENDENCE, AND WITHDRAWAL; WITHDRAWAL SEIZURES; AND RISK OF SERIOUS SKIN REACTIONS.
| Serious Effects |
["Hypersensitivity to diazepam or any component of the formulation","Acute narrow-angle glaucoma","Concomitant use with opioid analgesics for acute treatment of seizure clusters (unless alternative treatments are not available)"]
| Precautions | ["Risk of CNS depression and impaired motor function","Risk of abuse and dependence","Risk of withdrawal seizures upon abrupt discontinuation","Risk of serious skin reactions (e.g., Stevens-Johnson syndrome)","Concomitant use with opioids may cause profound sedation, respiratory depression, coma, and death","Use in patients with compromised respiratory function or hepatic impairment requires caution"] |
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| Fetal Monitoring | Monitor maternal: vital signs, respiratory rate, sedation level, and seizure activity. Fetal/neonatal: Fetal heart rate monitoring during seizure management; after delivery, observe neonate for respiratory depression, hypotonia, withdrawal symptoms (tremors, irritability), and sedation. Consider umbilical cord blood drug levels if exposure near delivery. |
| Fertility Effects | No direct fertility effects reported. Benzodiazepines may affect libido or menstrual cycles in women. No significant impact on male or female fertility in animal studies. Long-term use may be associated with hormonal disturbances. |