A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Cerebyx Overdose, Contraindications and Information - Fosphenytoin
Cerebyx Overdose, Contraindications and Information - Fosphenytoin
OVERDOSE
Nausea, vomiting, lethargy, tachycardia, bradycardia, asystole, cardiac arrest, hypotension,
syncope, hypocalcemia, metabolic acidosis, and death have been reported in cases of
overdosage with fosphenytoin.
The median lethal dose of fosphenytoin given intravenously in mice and rats was 156 mg PE/kg
and approximately 250 mg PE/kg, or about 0.6 and 2 times, respectively, the maximum human
loading dose on a mg/m2 basis. Signs of acute toxicity in animals included ataxia, labored
breathing, ptosis, and hypoactivity.
Because Cerebyx is a prodrug
of phenytoin, the following information may be helpful. Initial
symptoms of acute phenytoin
toxicity are nystagmus,
ataxia, and dysarthria. Other signs include tremor,
hyperreflexia,
lethargy, slurred speech, nausea,
vomiting, coma,
and hypotension.
Depression of respiratory
and circulatory
systems leads to death. There are marked variations among individuals
with respect to plasma
phenytoin concentrations where toxicity
occurs. Lateral gaze nystagmus
usually appears at 20 µg/mL,ataxia at 30 µg/mL, and
dysarthria and lethargy
appear when the plasma
concentration
is over 40 µg/mL.However, phenytoin concentrations as high
as 50 µg/mL have been reported without evidence of toxicity.
As much as 25 times the therapeutic
phenytoin dose
has been taken, resulting in plasma
phenytoin concentrations
over 100 µg/mL, with complete recovery.
Treatment is nonspecific
since there is no known antidote
to Cerebyx or phenytoin
overdosage. The adequacy of the respiratory
and circulatory systems should be carefully observed, and appropriate
supportive measures employed. Hemodialysis can be considered since
phenytoin is not completely
bound to plasma proteins.
Total exchange transfusion
has been used in the treatment of severe intoxication
in children. In acute
overdosage the possibility of other CNS
depressants, including alcohol,
should be borne in mind.
Formate and phosphate
are metabolites of fosphenytoin and therefore may contribute to
signs of toxicity following
overdosage. Signs of formate toxicity are similar to those of methanol
toxicity and are associated
with severe anion-gap metabolic acidosis. Large amounts of phosphate,
delivered rapidly, could potentially cause
hypocalcemia with
paresthesia, muscle
spasms, and seizures. Ionized free calcium
levels can be measured and, if low, used to guide
treatment.
CONTRAINDICATIONS
Cerebyx is contraindicated in patients who have demonstrated hypersensitivity
to Cerebyx or its ingredients, or to phenytoin
or other hydantoins.
Because of the effect
of parenteral phenytoin
on ventricular automaticity,
Cerebyx is contraindicated in patients with sinus
bradycardia, sino-atrial
block, second and third degree
A-V block, and Adams-Stokes
syndrome.
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