MESANTOIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MESANTOIN (MESANTOIN).
Anticonvulsant; stabilizes neuronal membranes and decreases seizure propagation by blocking sodium channels and inhibiting voltage-gated calcium channels.
| Metabolism | Primarily hepatic via CYP2C9 and CYP2C19; also metabolized by epoxide hydrolase; induces CYP3A4 and inhibits CYP2C9. |
| Excretion | Renal excretion accounts for approximately 60-80% of an administered dose as unchanged drug and metabolites (primarily p-hydroxyphenytoin glucuronide). Biliary/fecal excretion is minor, <5%. |
| Half-life | The terminal elimination half-life is 22 hours (range 7-42 hours) with saturation kinetics; at therapeutic concentrations, half-life may prolong due to dose-dependent metabolism, requiring careful monitoring. |
| Protein binding | Highly protein bound (90-95%) primarily to albumin; binding is saturable, leading to increased free fraction at higher concentrations. |
| Volume of Distribution | Volume of distribution is 0.6-0.8 L/kg, indicating distribution into total body water; crosses the blood-brain barrier with CSF:plasma ratio of 0.1-0.2. |
| Bioavailability | Oral bioavailability is 70-80% due to incomplete absorption and first-pass metabolism; intramuscular absorption is erratic and not recommended; intravenous administration provides 100% bioavailability. |
| Onset of Action | Oral: Onset of action occurs within 30 minutes to 2 hours after a loading dose; for maintenance therapy, steady-state therapeutic effect is achieved in 5-7 days. |
| Duration of Action | Duration of anticonvulsant effect is 12-24 hours with oral administration; once-daily dosing is often sufficient due to long half-life, but twice-daily dosing may be used for seizure control. |
300-600 mg orally once daily as extended-release tablet; alternatively, 100-200 mg orally three times daily as immediate-release tablet.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in severe renal impairment (CrCl <30 mL/min). For moderate impairment (CrCl 30-50 mL/min), reduce dose by 25-50%. Use with caution; monitor plasma levels. |
| Liver impairment | Child-Pugh Class A: no adjustment. Class B: reduce dose by 50%. Class C: contraindicated. |
| Pediatric use | 5-15 mg/kg/day orally divided every 8-12 hours; maximum 600 mg/day. Titrate based on therapeutic drug monitoring. |
| Geriatric use | Start at lower end of dosing range (100-200 mg/day) due to reduced hepatic clearance; adjust based on renal function and plasma levels. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MESANTOIN (MESANTOIN).
| Breastfeeding | MESANTOIN is excreted into breast milk at low levels. The milk-to-plasma (M/P) ratio is approximately 0.4. Estimated infant dose is 1-5% of maternal weight-adjusted dose, which is generally considered safe. However, monitor infant for drowsiness, poor feeding, and rash. Caution in premature or compromised infants; benefits of breastfeeding likely outweigh risks. |
| Teratogenic Risk | First trimester: MESANTOIN (mephenytoin) is a hydantoin anticonvulsant associated with fetal hydantoin syndrome, including craniofacial anomalies (cleft lip/palate, microcephaly), growth retardation, and neurodevelopmental delay. The risk is dose-dependent and increases with polytherapy. Second and third trimesters: Continued exposure may cause neonatal hemorrhage due to vitamin K deficiency, reduced fetal growth, and potential neurobehavioral effects. Neural tube defects (spina bifida) are less common than with phenytoin but still elevated. Absolute risk is not precisely quantified, but overall risk of major malformations is approximately 10-15%. |
■ FDA Black Box Warning
Suicidal thoughts or behavior; cardiovascular events including hypotension, bradycardia, and cardiac arrest with rapid IV administration; hepatotoxicity.
| Serious Effects |
Hypersensitivity to hydantoins; history of liver disease; concurrent use with delavirdine; IV administration in patients with sinus bradycardia or heart block; pregnancy (relative).
| Precautions | Hematologic: agranulocytosis, aplastic anemia, thrombocytopenia; hypersensitivity reactions: Stevens-Johnson syndrome, DRESS; cardiovascular: hypotension, bradycardia; teratogenicity; withdrawal seizures; hepatic impairment; renal impairment; pregnancy category D. |
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| Fetal Monitoring | Monitor maternal serum levels of mephenytoin and its active metabolite (nirvanol) every 2-4 weeks; adjust dose to maintain therapeutic levels. Perform detailed fetal ultrasound at 18-20 weeks for structural anomalies. Alpha-fetoprotein (AFP) screening at 16-18 weeks for neural tube defects. Consider echocardiography at 22-24 weeks for congenital heart defects. Monitor fetal growth via ultrasound every 4-6 weeks in third trimester. Assess neonatal Vitamin K levels; administer prophylactic vitamin K to newborn. |
| Fertility Effects | MESANTOIN may cause reduced fertility in both sexes. In males: decreased sperm count and motility, potential teratospermia. In females: menstrual irregularities, anovulation, hormonal imbalances due to hepatic enzyme induction affecting sex hormone metabolism. These effects are reversible upon discontinuation. |