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Dehydroepiandrosterone (DHEA)
Look Up > Drugs > Primidone
Primidone
Pronunciation
U.S. Brand Names
Generic Available
Canadian Brand Names
Synonyms
Pharmacological Index
Use
Pregnancy Risk Factor
Pregnancy/Breast-Feeding Implications
Contraindications
Warnings/Precautions
Adverse Reactions
Overdosage/Toxicology
Drug Interactions
Stability
Mechanism of Action
Pharmacodynamics/Kinetics
Usual Dosage
Dietary Considerations
Monitoring Parameters
Reference Range
Test Interactions
Dental Health: Local Anesthetic/Vasoconstrictor Precautions
Dental Health: Effects on Dental Treatment
Patient Information
Nursing Implications
Dosage Forms
References

Pronunciation
(PRI mi done)

U.S. Brand Names
Mysoline®

Generic Available

Yes: Tablet


Canadian Brand Names
Apo®-Primidone; Sertan®

Synonyms
Desoxyphenobarbital; Primaclone

Pharmacological Index

Anticonvulsant, Miscellaneous; Barbiturate


Use

Management of grand mal, psychomotor, and focal seizures


Pregnancy Risk Factor

D


Pregnancy/Breast-Feeding Implications

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.


Contraindications

Hypersensitivity to primidone, phenobarbital, or any component; porphyria


Warnings/Precautions

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.


Adverse Reactions

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


Overdosage/Toxicology

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.


Drug Interactions

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


Stability

Protect from light


Mechanism of Action

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


Pharmacodynamics/Kinetics

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%)


Usual Dosage

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


Dietary Considerations

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.


Monitoring Parameters

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.


Reference Range

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)


Test Interactions

alkaline phosphatase (S); calcium (S)


Dental Health: Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions


Dental Health: Effects on Dental Treatment

No effects or complications reported


Patient Information

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.


Nursing Implications

Observe patient for excessive sedation; institute safety measures


Dosage Forms

Suspension, oral: 250 mg/5 mL (240 mL)

Tablet: 50 mg, 250 mg


References

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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