PRECAUTIONS
|
|
 |
General
Proceed slowly when increasing or decreasing dosage, as well
as when adding or eliminating other medication. Abrupt withdrawal
of anticonvulsant medications may precipitate petit mal status.
Methsuximide, when used alone in mixed types of epilepsy, may increase
the frequency of grand mal seizures in some patients.
Hematopoietic Effect
Blood dyscrasias, including some with fatal outcome, have been reported
to be associated with the use of succinimides; therefore, periodic
blood counts should be performed. Patients should be instructed
to promptly contact their physician if they develop signs and/or
symptoms suggesting an infection (eg. Sore throat, fever); blood
counts should be considered at that point.
Hepatic/Renal Impairment
It has been reported that succinimides, including methsuximide,
have produced morphological and functional changes in animal liver.
For this reason, administer methsuximide with extreme caution to
patients with known liver or renal disease. Periodic urinalysis
and liver function studies are advised for all patients receiving
the drug.
Autoimmune Disorders
Cases of systemic lupus erythematosus have been reported with the
use of methsuximide. The physician should be alerted to this possibility.
Psychiatric
It is recommended that the physician withdraw the drug slowly on
the appearance of unusual depression, aggression, or other behavioral
alterations.
Information to be Provided to the Patient
Methsuximide may impair the mental and/or physical abilities required
for the performance of potentially hazardous tasks, such as driving
a motor vehicle or other such activity requiring alertness; therefore
the patient should be cautioned accordingly.
Patients taking methsuximide should be advised of the importance
of adhering strictly to the prescribed dosage regimen.
Patients should be instructed to promptly contact their physician
if they develop signs and/or symptoms (e.g., sore throat, fever)
suggesting an infection.
Drug Interactions: Since CELONTIN (methsuximide) may interact with
concurrently administered antiepileptic drugs, periodic serum level
determinations of these drugs may be necessary (eg, methsuximide
may increase the plasma concentrations of phenytoin and phenobarbital).
Lamotrigine: Methsuximide may lower the serum concentrations of
lamotrigine. When methsuximide is used in combination with lamotrigine,
adjustment of the lamotrigine dose may be necessary when methsuximide
is started or stopped.
Pregnancy: Recent reports indicate an association between the use
of anticonvulsant drugs and an elevated incidence of birth defects
in children born to epileptic women taking such medications during
pregnancy. The incidence of congenital malformations in the general
population is regarded to be approximately 2%; in children of treated
epileptic women this incidence may be increased 2- to 3-fold. The
increase is largely due to specific defects, e.g., congenital malformations
of the heart, and cleft lip and/or palate. Nevertheless, the great
majority of mothers receiving anticonvulsant medications deliver
normal infants.
Data are more extensive with respect to phenytoin and phenobarbital,
but these drugs are also the most commonly prescribed anticonvulsants.
Some reports indicate a possible similar association with the use
of other anticonvulsants, including trimethadione and paramethadione.
However, the possibility also exists that other factors, e.g., genetic
predisposition or the epileptic condition itself may contribute
to or may be mainly responsible for the higher incidence of birth
defects.
Anticonvulsant drugs should not be discontinued in patients in whom
the drug is administered to prevent major seizures, because of the
strong possibility of precipitating status epilepticus with attendant
hypoxia and risk to both the mother and the unborn child. With regard
to drugs given for minor seizures, the risk of discontinuing medications
prior to or during pregnancy should be weighed against the risk
of congenital defects in the particular case and with the particular
family history.
Epileptic women of childbearing age should be encouraged to seek
professional counsel and should report the onset of pregnancy promptly
to their physician. Where the necessity for continued use of the
antiepileptic medication is in doubt, appropriate consultation might
be indicated.
The preceding considerations should be borne in mind and methsuximide
should be used in women of childbearing potential only when the
expected benefits to the patients warrant the possible risk to a
fetus.
Lactation: Methsuximide is excreted in human breast milk. Because
the effects of methsuximide on the nursing infant are unknown, caution
should be exercised when methsuximide is administered to a nursing
mother. Methsuximide should be used in nursing mothers only if the
benefits clearly outweigh the risks.
Occupational Hazards: Methsuximide may impair the mental and/or
physical abilities required for the performance of potentially hazardous
tasks, such as driving a motor vehicle or other such activities
requiring alertness; therefore, caution the patient accordingly.
ADVICE TO THE PHARMACIST AND PATIENT: Since methsuximide has a relatively
low melting temperature (51.1 °C), storage conditions which
may promote high temperatures (closed cars, delivery vans, or storage
near steam pipes) should be avoided. Do not dispense or use capsules
that are not full or in which contents have melted. Effectiveness
may be reduced. Protect from excessive heat (40.0 °C).
ADVERSE
REACTIONS
|
|
|
Body as a Whole: Abdominal
pain, fever, headache and systemic lupus erythematosus (see PRECAUTIONS,
Autoimmune Disorders).
Digestive System: Anorexia,
constipation, diarrhea, epigastric pain, nausea, vomiting.
Hemic and Lymphatic System:
Eosinophilia, leukopenia, monocytosis, pancytopenia with or without
bone marrow suppression (see PRECAUTIONS, Hematopoietic Effect).
Metabolism and Nutrition:
Porphyria, weight loss.
Nervous System: Aggression,
ataxia, auditory hallucinations, depression, dizziness, drowsiness,
insomnia, irritability, nervousness, psychosis.
Drowsiness, ataxia, and dizziness have been the most frequent adverse
effects noted.
Psychological abnormalities have included confusion, instability,
mental slowness, depression, hypochondriacal behavior, and aggression.
There have been rare reports of psychosis, suicidal behavior and
auditory hallucinations (see PRECAUTIONS, Psychiatric).
Respiratory System: Hiccups
Skin/Appendages: Rash, Stevens-Johnson syndrome, urticaria.
,
Special Senses: Blurred vision, photophobia.
Urogenital: Microscopic hematuria, proteinuria.
Miscellaneous: Periorbital edema, hyperemia.
SYMPTOMS
AND TREATMENT OF OVERDOSAGE
|
|
|
Acute overdoses may produce nausea,
vomiting, and CNS depression including coma with respiratory depression.
Methsuximide poisoning may follow a biphasic course. Following an
initial comatose state, patients have awakened and then relapsed
into a coma within 24 hours. It is believed that an active metabolite
of methsuximide, N-desmethylmethsuximide, is responsible for this
biphasic profile. It is important to follow plasma levels of N-desmethylmethsuximide
in methsuximide poisonings. Levels greater than 40 mcg/mL have caused
toxicity, and coma has been seen at levels of 150 mcg/mL. (see
ACTION AND CLINICAL PHARMACOLOGY)
Treatment: Treatment should include emesis (unless the patient
is or could rapidly become obtunded, comatose, or convulsing) or
gastric lavage, activated charcoal, cathartics, and general
supportive measures. Charcoal hemoperfusion may be useful in removing
the N-desmethyl metabolite of methsuximide. Forced diuresis and
exchange transfusions are ineffective.
| DOSAGE
AND ADMINISTRATION |
|
|
Optimal dosage (that which is just
sufficient to control seizures without causing disturbing side effects)
must be determined by trial and should be individualized according
to the needs of each patient. A suggested schedule is 300 mg daily
for the first week. If required, the daily dosage may be increased
at weekly intervals by 300 mg/day for the 3 weeks following to a
daily dosage of 1200 mg.
Capsule Composition
Each yellow capsule with orange cap contains: methsuximide 300 mg.
Nonmedicinal ingredients: cornstarch; capsule shell: D&C Yellow
No. 10, FD&C Red No. 3, FD&C Yellow No. 6 and gelatin. Energy:
1.57 kJ (0.38 kcal). Gluten-, lactose-, paraben-, sodium-, sulfite-
and tartrazine-free.
Stability and Storage Recommendation
Store CELONTIN (methsuximide) between
15 and 30°C. Protect from light, moisture and excessive heat.
AVAILABILITY
OF DOSAGE FORMS
|
|
|
CELONTIN (methsuximide) capsules are
available in the dosage strength of 300 mg per capsule.
Each capsule with yellow body and orange cap, is imprinted with
"Parke-Davis".
Available in bottles of 100.
PHARMACOLOGY
|
|
|
Drug Substance
Proper Name: Methsuximide
Chemical Name: (±)-1,3-dimethyl-3-phenylpyrrolidine-2,5-dione
Empirical Formula: C12H13NO2
Molecular Weight: 203.24
Melting Range: 50o to 56oC
|
