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Iowa Neonatology Handbook: Pharmacology
Dosage Recommendations for Anticonvulsants Employed in Neonatal Seizures
Jeffrey L. Segar, MD
Peer Review Status: Internally Peer Reviewed
|
Drug |
Recommended Dosage |
Therapeutic Serum Level |
Toxicity / Remarks |
| Phenobarbital |
1Loading 15-20 mg/kg IV over 15 - 20 min.
2Maintenance: 3-5 mg/kg IV, IM , POq 12 - 24 hr. (first dose
given 12 to 24 hours after loading) |
15 - 40 mg/L |
Sedation, respiratory arrest, hypotension, T1/2 96 h /
increase 1st two wk of life; induces drug metabolism(interactions), sensitivity
reactions
IV push < 1 mg/kg/min. |
| 3Phenytoin |
Loading: 15 - 20 mg/kg IV *Maintenance: 5
- 8 mg/kg/d
q 8 - 12 hr IV |
10 - 20 mg/L4 |
*If >1 wk old, may need to increase dosage to ³ 8 mg/kg
IV q12 h or q 8h to maintain therapeutic effect / levels
*Give first maint. dose 24 hr after loading
IV push<0.5 mg/kg/min. Ø IM |
| Lorazepam |
0.05 - 0.1 mg/kg/dose slow IV push over 2 - 3 min. |
|
Onset within 5 min. Duration of action 3 - 24 hr. May
increase Phenobarbital level. May cause respiratory depression |
| Diazepam |
50.2 to 0.75 mg/kg slow IV push.
Give in maximum increments of 0.2 mg/kg q 2 min.
If seizures stop before completion of dosing, discontinue infusion.
Rectal dose: 0.5-1.0 mg/kg. |
0.15 - 0.3mcg/ml |
CNS depression, respiratory depression including apnea,
phlebitis.
Doses may be repeated q 15 - 30 min. x 2 to 3 doses total |
Footnotes:
- If seizures are noted to continue after the initial phenobarbital loading
dose, an additional 5 mg/kg bolus dose can be given every 15 - 30 minutes
(total load dose should not exceed 35 mg/kg). Sedation occurs at serum concentrations
above 40 mg/L. Respiratory depression may develop with larger loading doses
(serum concentrations above 60 mg/L) or if given in conjunction with diazepam.
- Maintenance phenobarbital doses of 5 mg/kg/day may occasionally result in
accumulation of serum levels to >30 mg/L in the neonate less than 1 week
of age. Unless undue sedation occurs (monitoring of serum phenobarbital levels
will be of assistance in identifying and managing such patients) little adverse
consequences should be anticipated from the higher serum levels. Therapeutic
levels may be > 45 mg/L and require very careful respiratory monitoring.
- Phenytoin is contraindicated in patients with heart block or sinus bradycardia.
- Maintenance doses of phenytoin are impossible to accurately establish because
of marked individual variation. Frequent plasma phenytoin concentration measurements
are essential, particularly in the rapidly changing period of the first 3
weeks of age. Drug is highly protein bound; free fraction of drug may be increased
in patients with hypoalbuminemia. If the therapeutic range is based on the
premise that in the neonate there is a greater concentration of unbound phenytoin
in plasma at any given total plasma concentration, then a total plasma phenytoin
concentration of 6-14 mcg/ml will provide the same concentration of unbound
phenytoin as a 10-20 mcg/ml total concentration in an adult (Loughnan et al,
1977). However, the actual relationship between serum levels and anticonvulsant
activity of phenytoin (alone) has not been demonstrated in the neonate. The
plasma level 8 hr. after dosing should be the most representative of the average
phenytoin concentration.
- The total acute IV dose of diazepam necessary to control neonatal seizures
has ranged from less than 0.1 mg/kg to 2.7 mg/kg. Based on the proposed therapeutic
serum level of diazepam, a dose of 0.5 mg/kg should produce levels in excess
of that ordinarily necessary. Only in very unusual circumstances should alternate
routes of administration be considered. Evidence does exist to support the
efficacy of rectal administration. The parenteral injection form is used in
conjunction with a syringe and catheter inserted 5 cm into the rectum. It
is important to note that there is no evident advantage in using diazepam
instead of phenobarbital, but to maintain anticonvulsant effect, a longer
acting anticonvulsant such as phenobarbital is generally used following diazepam
or lorazepam (as this combination often produces respiratory depression, close
monitoring of the patient is essential).
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