Dosing & Uses
Dosage Forms & Strengths
tablet: Schedule IV
- 15mg
- 16.2mg
- 30mg
- 32.4mg
- 60mg
- 64.8mg
- 97.2
- 100mg
elixir: Schedule IV
- 20mg/5mL
injectable solution: Schedule IV
- 65mg/mL
- 130mg/mL
Status Epilepticus
Typically used after benzodiazepines and phenytoin fail to abort status epilepticus
15-20 mg/kg IV loading dose infused at 25-100 mg/min; may repeat once after 10 min with additional 5-10 mg/kg; respiratory support may be necessary when maximum dose administered
Seizures
All types of seizure disorders, including partial, tonic-clonic, and myoclonic seizures
1-3 mg/kg/day PO/IV in 1-2 divided doses initially; adjust accordingly to maintain at a therapeutic steady state level of 20 mg/L
Sedation
30-120 mg/day PO divided BID/TID; do not exceed 400 mg/day
Hypnotic
100-320 mg/day PO/IV/IM; do not administer for >2 weeks
Insomnia
100-200 mg PO qHS; do not exceed 400 mg/day
Dosing Considerations
Antiepileptic therapeutic concentration range: 10-40 mcg/L (43-172 micromoles/L)
Long half-life permits once-daily dosing, if tolerated, for seizures; single daily dosing at bedtime recommended because of sedation
Dosage Forms & Strengths
tablet: Schedule IV
- 15mg
- 16.2mg
- 30mg
- 32.4mg
- 60mg
- 64.8mg
- 97.2mg
- 100mg
elixir: Schedule IV
- 20mg/5mL
injectable solution: Schedule IV
- 65mg/mL
- 130mg/mL
Status Epilepticus
Infants and children: 15-20 mg/kg IV infused at a rate not to exceed 2 mg/kg/min; not to exceed 1000 mg/dose
<60 kg: IV rate at <30 mg/min
May repeat with 5-10 mg/kg bolus dose after 15-30 min PRN; not to exceed cumulative dose of 40 mg/kg
Seizures
Neonates (<28 days): 3-5 mg/kg/day IV/PO in 1-2 divided doses
Infants: 5-6 mg/kg/day IV/PO in 1-2 divided doses
1-5 years: 6-8 mg/kg/day IV/PO in 1-2 divided doses
6-12 years: 4-6 mg/kg/day IV/PO in 1-2 divided doses
>12 years: 1-3 mg/kg/day IV/PO in 1-2 divided doses, OR 50-100 mg BID/TID
Sedation
Hypnotic
Preoperative Sedation
1-3 mg/kg PO/IV/IM 1-1.5 hours before procedure
Dosing Considerations
<6 years: Potential toxic dose 8 mg/kg
Antiepileptic therapeutic concentration range: 15-30 mcg/L (43-129 micromoles/L)
Long half-life permits once-daily dosing, if tolerated, for seizures; single daily dosing at bedtime recommended because of sedation
Hyperbilirubinemia (Off-label)
Neonates: 5 mg/kg/day PO/IV qDay, OR divided q12hr for 3-6 days following birth
<12 years (chronic cholestasis): 1.5-4 mg/kg PO q12hr
Encephalopathy (Orphan)
Orphan designation for treatment of neonatal hypoxic ischemic encephalopathy to prevent seizures
Orphan sponsor
- Fera Pharmaceuticals, LLC; 134 Birch Hill Road; Locust Valley, NY 11560
Neonatal Seizures (Orphan)
Orphan designation for treatment of neonatal seizures
Sponsor
- Renaissance SSA, LLC; 411 South State Street, Suite E100; Newtown, Pennsylvania 18940
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
Frequency Not Defined
IV
- Respiratory depression
Common
- Ataxia
- Dizziness
- Drowsiness
- Dysarthria
- Fatigue
- Headache
- Irritability
- Nystagmus
- Paresthesia restlessness
- Vertigo
- Geriatric patients: Excitement, confusion, depression
- Pediatric patients: Paradoxical excitement/hyperactivity
Less Common
- Mental dullness
- Constipation
- Diarrhea
- Nausea
- Vomiting
- Megaloblastic (folate-deficiency) anemia
Uncommon
- Rash
- Hypocalcemia
- Hepatotoxicity
Rare
- Stevens-Johnson syndrome
- Rickets
- Osteomalacia
Warnings
Contraindications
Hypersensitivity
Porphyria
Intra-arterial or subcutaneous administration
Severe hepatic impairment
Dyspnea or airway obstruction
History of sedative hyponotic addiction
Nephritic patients (large doses)
Pregnancy/lactation
Cautions
Commercial injection is highly alkaline and may cause tissue necrosis if given SC or if it extravasates (if happens, treat with application of moist heat and injection of 0.5% procaine)
May render oral contraceptives ineffective
Paradoxical responses may occur, especially in pediatric patients and patients experiencing acute or chronic pain
May cause CNS depression, causing physical and mental impairment; caution patient about performing tasks that require mental alertness
May cause respiratory depression, especially with intravenous administration; use caution in patients with respiratory disease and status asthmaticus
Withdraw therapy gradually; abrupt discontinuation, may increase seizure frequency
Use caution in patients with severe anemia, patients experiencing depression, cardiac disease, hemodynamically unstable patients, hyperthyroidism, renal impairment, hypoadrenalism, and in patients with diabetes
May mask important symptoms when used in patients with acute or chronic pain; use caution
Pregnancy & Lactation
Pregnancy category: D
Lactation: Do not nurse
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Depresses sensory and motor cortex, cerebellum
Antiseizure activity occurs primarily where GABA mediates neurotransmission
Hypnotic effects of barbiturates result from activity at GABA receptor in the polysynaptic midbrain reticular formation (controls CNS arousal)
Off-label use for hyperbilirubinemia: Phenobarbital induces glucuronyl transferase and hepatic bilirubin-binding Y-protein to lower serum bilirubin concentrations
Absorption
Bioavailability: 70-90%
Onset: 5 min (IV)
Duration: 4-6 hr (IV/IM)
Peak plasma time: 8-12 hr
Therapeutic plasma concentration: 10-40 mcg/mL; may require 3-4 weeks of treatment to achieve therapeutic levels
Distribution
Protein bound: 20-45%
Metabolism
Metabolized by hepatic oxidative hydroxylation
Metabolites: Inactive
Enzymes induced: CYP1A2, CYP2B6, CYP2C19, CYP2C9/10, CYP3A4
Elimination
Half-life: 50-140 hr
Excretion: Urine (major)
Administration
IV Incompatibilities
Additive: Chlorpromazine, ephedrine, hydralazine, hydrocortisone Na-succinate, hydroxyzine, insulin, levorphanol, meperidine, morphine, norepinephrine, pentazocine, procaine, prochlorperazine, promazine, promethazine, streptomycin, vancomycin
Syringe: Hydromorphone, ranitidine, sufentanil
Y-site: Amphotericin B cholSO4
IV Compatibilities
Solution: Dextrose Ringer, dextrose LR, dextrose saline, Ringer, LR, NS, ½ NS, Na-lactate 1/6 M, D5W, D10W
Additive: Amikacin, aminophylline, CaCl2, Ca-gluconate, colistimethate, dimenhydrinate, meropenem, polymyxin B, thiopental, verapamil
Syringe: Caffeine, heparin
Y-site: Doxapram, enalaprilat, fentanyl, fosphenytoin gatifloxacin, hydromorphone (may be incompatible at high concentrations of both), levofloxacin, linezolid, meropenem, methadone, morphine SO4, propofol, sufentanil
IV Administration
Slow injection at <60 mg/min
May be given IM into large muscle but not SC
Commercial injection is highly alkaline and can cause local tissue necrosis
Stability
Store intact vials at room temperature, protected from light
Images
Patient Handout
Formulary
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