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Pronunciation |
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(PRI
mi
done) |
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U.S. Brand
Names |
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Mysoline® |
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Generic
Available |
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Yes: Tablet |
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Canadian Brand
Names |
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Apo®-Primidone;
Sertan® |
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Synonyms |
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Desoxyphenobarbital; Primaclone |
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Pharmacological Index |
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Anticonvulsant, Miscellaneous; Barbiturate |
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Use |
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Management of grand mal, psychomotor, and focal seizures
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Pregnancy Risk
Factor |
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D |
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Pregnancy/Breast-Feeding
Implications |
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Clinical effects on the fetus: Crosses the placenta. Dysmorphic facial
features; hemorrhagic disease of newborn due to fetal vitamin K depletion,
maternal folic acid deficiency may occur. Epilepsy itself, number of
medications, genetic factors, or a combination of these probably influence the
teratogenicity of anticonvulsant therapy. Benefit:risk ratio usually favors
continued use during pregnancy and breast-feeding.
Breast-feeding/lactation: Crosses into breast milk
Clinical effects on the infant: Sedation; feeding problems reported. American
Academy of Pediatrics recommends USE WITH CAUTION. |
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Contraindications |
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Hypersensitivity to primidone, phenobarbital, or any component;
porphyria |
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Warnings/Precautions |
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Use with caution in patients with renal or hepatic impairment, pulmonary
insufficiency; abrupt withdrawal may precipitate status epilepticus. Potential
for drug dependency exists. Do not administer to patients in acute pain. Use
caution in elderly, debilitated, or pediatric patients - may cause paradoxical
responses. May cause CNS depression, which may impair physical or mental
abilities. Patients must be cautioned about performing tasks which require
mental alertness (ie, operating machinery or driving). Effects with other
sedative drugs or ethanol may be potentiated. Use with caution in patients with
depression or suicidal tendencies, or in patients with a history of drug abuse.
Tolerance or psychological and physical dependence may occur with prolonged use.
Primidone's metabolite, phenobarbital, has been associated with cognitive
deficits in children. Use with caution in patients with
hypoadrenalism. |
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Adverse
Reactions |
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Central nervous system: Drowsiness, vertigo, ataxia, lethargy, behavior
change, fatigue, hyperirritability
Dermatologic: Rash
Gastrointestinal: Nausea, vomiting, anorexia
Genitourinary: Impotence
Hematologic: Agranulocytopenia, agranulocytosis, anemia
Ocular: Diplopia, nystagmus |
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Overdosage/Toxicology |
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Symptoms of overdose include unsteady gait, slurred speech, confusion,
jaundice, hypothermia, fever, hypotension, coma, respiratory arrest
Assure adequate hydration and renal function. Urinary alkalinization with
I.V. sodium bicarbonate also helps to enhance elimination. Repeated oral doses
of activated charcoal significantly reduces the half-life of primidone resulting
from an enhancement of nonrenal elimination. The usual dose is 0.1-1 g/kg every
4-6 hours for 3-4 days unless the patient has no bowel movement causing the
charcoal to remain in the GI tract. Hemodialysis or hemoperfusion is of
uncertain value. Patients in stage IV coma due to high serum drug levels may
require charcoal hemoperfusion. |
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Drug
Interactions |
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CYP1A2, 2B6, 2C, 2C8, 3A3/4, and 3A5-7 enzyme inducer
Primidone may reduce the efficacy of beta-blockers, chloramphenicol,
cimetidine, clozapine, corticosteroids, cyclosporine, disopyramide, doxycycline,
ethosuximide, furosemide, griseofulvin, haloperidol, lamotrigine, methadone,
nifedipine, oral contraceptives, phenothiazine, phenytoin, propafenone,
quinidine, tacrolimus, TCAs, theophylline, warfarin, and verapamil
Increased toxicity when combined with other CNS depressants, benzodiazepine,
valproic acid, chloramphenicol, or antidepressants; respiratory and CNS
depression may be additive
MAOIs may prolong the effect of primidone
Barbiturates inhibit the hypoprothombinemic response to warfarin
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Stability |
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Protect from light |
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Mechanism of
Action |
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Decreases neuron excitability, raises seizure threshold similar to
phenobarbital; primidone has two active metabolites, phenobarbital and
phenylethylmalonamide (PEMA); PEMA may enhance the activity of
phenobarbital |
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Pharmacodynamics/Kinetics |
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Distribution: Vd: 2-3 L/kg in adults
Protein binding: 99%
Metabolism: In the liver to phenobarbital (active) and phenylethylmalonamide
(PEMA)
Bioavailability: 60% to 80%
Half-life (age dependent): Primidone: 10-12 hours; PEMA: 16 hours;
Phenobarbital: 52-118 hours
Time to peak serum concentration: Oral: Within 4 hours
Elimination: Urinary excretion of both active metabolites and unchanged
primidone (15% to 25%) |
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Usual Dosage |
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Oral:
Children >8 years and Adults: Initial: 125-250 mg/day at bedtime; increase
by 125-250 mg/day every 3-7 days; usual dose: 750-1500 mg/day in divided doses
3-4 times/day with maximum dosage of 2 g/day
Dosing interval in renal impairment:
Clcr 50-80 mL/minute: Administer every 8 hours
Clcr 10-50 mL/minute: Administer every 8-12 hours
Clcr <10 mL/minute: Administer every 12-24 hours
Hemodialysis: Moderately dialyzable (20% to 50%); administer dose
postdialysis or administer supplemental 30% dose |
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Dietary
Considerations |
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Food:
Folic acid: Low erythrocyte and CSF folate concentrations. Megaloblastic
anemia has been reported. To avoid folic acid deficiency and megaloblastic
anemia, some clinicians recommend giving patients on anticonvulsants
prophylactic doses of folic acid and cyanocobalamin.
Protein-deficient diets: Increases duration of action of primidone. Should
not restrict or delete protein from diet unless discussed with physician. Be
consistent with protein intake during primidone therapy.
Fresh fruits containing vitamin C: Displaces drug from binding sites,
resulting in increased urinary excretion of primidone. Educate patients
regarding the potential for decreased primidone effect with consumption of foods
high in vitamin C. |
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Monitoring
Parameters |
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Serum primidone and phenobarbital concentration, CBC, neurological status.
Due to CNS effects, monitor closely when initiating drug in elderly. Monitor CBC
at 6-month intervals to compare with baseline obtained at start of therapy.
Since elderly metabolize phenobarbital at a slower rate than younger adults, it
is suggested to measure both primidone and phenobarbital levels
together. |
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Reference Range |
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Therapeutic: Children <5 years: 7-10 mg/mL (SI:
32-46 mmol/L); Adults: 5-12
mg/mL
(SI: 23-55 mmol/L); toxic effects rarely present with
levels <10 mg/mL (SI: 46
mmol/L)
if phenobarbital concentrations are low. Dosage of primidone is adjusted with
reference mostly to the phenobarbital level; Toxic: >15
mg/mL (SI: >69
mmol/L) |
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Test
Interactions |
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alkaline phosphatase
(S);
calcium (S) |
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Dental Health: Local
Anesthetic/Vasoconstrictor
Precautions |
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No information available to require special precautions |
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Dental Health:
Effects on Dental Treatment |
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No effects or complications reported |
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Patient
Information |
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Take exactly as directed (do not increase dose or frequency or discontinue
without consulting prescriber); may cause physical and/or psychological
dependence. While using this medication, do not use alcohol and other
prescription or OTC medications (especially pain medications, sedatives,
antihistamines, or hypnotics) without consulting prescriber. Maintain adequate
hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You
may experience drowsiness, dizziness, or blurred vision (use caution when
driving or engaging in tasks requiring alertness until response to drug is
known); nausea, vomiting, or loss of appetite (small frequent meals, frequent
mouth care, chewing gum, or sucking lozenges may help); impotence (reversible).
Wear identification of epileptic status and medications. Report behavioral or
CNS changes (confusion, depression, increased sedation, excitation, headache,
insomnia, or lethargy); muscle weakness, or tremors; unusual bruising or
bleeding (mouth, urine, stool); worsening of seizure activity, or loss of
seizure control. Pregnancy/breast-feeding precautions: Do not get
pregnant while taking this drug; use appropriate barrier contraceptive measures.
Breast-feeding is not recommended. |
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Nursing
Implications |
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Observe patient for excessive sedation; institute safety
measures |
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Dosage Forms |
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Suspension, oral: 250 mg/5 mL (240 mL)
Tablet: 50 mg, 250 mg |
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References |
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Lane GP, Lewis CG, and Zail SC,
"Macroscopic Crystalluria After Primidone Overdosage," Med J Aust, 1987,
147(11-12):624-5.
Schwankhaus JD, Kattah JC, Lux WE, et al,
"Primidone/Phenobarbital-Induced Periodic Alternating Nystagmus," Ann
Ophthalmol, 1989, 21(6):230-2. |
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