Pill Identifier App

Primidone (Systemic)


VA CLASSIFICATION
Primary: CN400

Commonly used brand name(s): Apo-Primidone; Myidone; Mysoline; PMS Primidone; Sertan.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Anticonvulsant—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Epilepsy (treatment)—Primidone, either alone or used concomitantly with other anticonvulsants {05} {07}, is indicated in the control of generalized tonic-clonic (grand mal) {05} {06} {07} {08}, nocturnal myoclonic {15}, complex partial (psychomotor) {05} {06} {07} {08}, and simple partial (cortical focal) {05} {07} {08} epileptic seizures.

[Essential tremor (treatment)]1—Primidone is used in the treatment of essential (familial) tremor. {29} {30} {31} {32} {33} {34} {35} {36} {37} Although propranolol is considered to be the treatment of choice for essential tremor {30}, primidone provides effective treatment for some patients {32}.

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    218.25

Mechanism of action/Effect:

Unknown, but anticonvulsant effects are thought to be due to the parent compound, primidone, as well as its two active metabolites, phenobarbital and phenylethylmalonamide (PEMA) {05} {07}, whose actions may be synergistic.

Absorption:

Rapid, usually complete with wide individual variation. Bioavailability—90 to 100% (indirect estimates) {04}.

Distribution:

Primidone has a volume of distribution (V D) of 0.64 to 0.86 liters per kg. {16}

Primidone and its metabolites pass into breast milk, reaching a mean concentration of 75% of maternal steady-state serum levels. {16}

Half-life:

Primidone—3 to 23 hours. {16}

Phenobarbital metabolite—75 to 126 hours. {16}

PEMA metabolite—10 to 25 hours. {16}

Time to peak concentration:

Average 3 to 4 hours {16}.

Therapeutic serum concentration

5 to 12 mcg of primidone per mL {05} {07} (mcg/mL) (23 to 55 mmol/L), which produces phenobarbital serum concentrations of 20 to 40 mcg/mL (86 to 172 mmol/L) {18}. Some clinicians have suggested that the optimal mean plasma primidone concentration is 12 mcg/mL with an associated mean derived phenobarbital concentration of 15 mcg/mL resulting in a primidone-to-phenobarbital ratio of 0.8; however, much variation occurs among patients. {16}


  Protein
Binding
(%)
Biotransformation
Elimination
(% unchanged)
Primidone
0–20 {16} {22}
Hepatic; 2 active metabolites: phenobarbital (15–25%) and PEMA. PEMA is the major metabolite and less active than phenobarbital
Renal {16}(64) {16}
PEMA
(metabolite)
Negligible
No further
metabolism
Renal {16} (6.6) {16}
Phenobarbital
(metabolite)
50 {22}
Hepatic (therapeutic doses of primidone produce therapeutic blood concentrations of phenobarbital)
Renal {16} (5.1) {16}


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to barbiturates may be sensitive to this medication also.

Pregnancy/Reproduction

Pregnancy—
Adequate and well-controlled studies in humans have not been done. However, reports have suggested an association between the use of other anticonvulsant drugs and an increased incidence of birth defects (fetal hydantoin syndrome) in newborns. {05} {06} {07} Symptoms similar to fetal hydantoin syndrome, i.e., growth retardation, craniofacial and heart abnormalities, and hypoplasia of the fingernails and distal phalanges, have been shown to occur with primidone also. {09}

Neonatal hemorrhage, with a coagulation defect resembling vitamin K deficiency, has been described in newborns whose mothers were taking primidone and other anticonvulsants. {05} {06} {07} {08} Risk may be reduced by administering water-soluble vitamin K prophylactically {05} {06} {07} {08} {16} to the mother 1 month prior to and during delivery {05} {06} {07} {08} and also to the neonate, intramuscularly or subcutaneously, immediately after birth {38}.

Breast-feeding

Primidone is distributed into breast milk in substantial amounts, {05} {06} {07} {08} and the use of primidone by nursing mothers may cause unusual drowsiness in the neonate. {05} {06} {07} {08}

Pediatrics

Some children may react to primidone with paradoxical excitement and restlessness.


Geriatrics


Unusual restlessness and excitement may sometimes occur as a paradoxical reaction in the elderly.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.
Although not all of the following interactions have been documented to pertain specifically to primidone, a potential exists for their occurrence because of the barbiturate metabolite of primidone.

Acetaminophen{16}    (when acetaminophen in therapeutic doses is used concurrently in patients receiving chronic primidone therapy, its effects may be decreased because of increased metabolism resulting from induction of hepatic microsomal enzymes by the phenobarbital metabolite; also, risk of hepatotoxicity with single toxic doses or prolonged use of acetaminophen may be increased in chronic alcoholics or in patients regularly using hepatic-enzyme inducing agents)


» Adrenocorticoids,{13}{16}{20}{21} glucocorticoid and mineralocorticoid or
» Anticoagulants,{16}{20}{21} coumarin- or indandione-derivative or
Antidepressants, tricyclic{12}{16}{19} or
Chloramphenicol{16}{23}{24} or
» Contraceptives, oral, estrogen-containing{12}{14}{16}{20}{21} or
» Corticotropin (ACTH) or
Cyclosporine{11}{16}{20} or
Dacarbazine or
Digitalis glycosides{16} , with possible exception of digoxin or
Disopyramide or
Doxycycline{16}{20} or
Levothyroxine or
Metronidazole{16}{20}{25}{26}{27} or
Mexiletine{20} or
Quinidine{13}{16}{20}{21}    (concurrent use with primidone may decrease the effects of these medications because of increased metabolism resulting from induction of hepatic microsomal enzymes by the barbiturate metabolite; dosage increases may be necessary during and after primidone therapy)

    (use of a nonhormonal method of birth control or a progestin-only oral contraceptive may be necessary during primidone therapy)

    (also, concurrent use of tricyclic antidepressants with primidone may enhance central nervous system [CNS] depression, lower convulsive threshold, and decrease the effects of primidone; dosage adjustments may be necessary to control seizures)


» Alcohol{16}{21} or
» CNS depression–producing medications, other{16} (See Appendix II )    (concurrent use may potentiate the CNS and respiratory depressant effects of either these medications or primidone; dosage adjustment of primidone may be necessary)


Amphetamines    (concurrent use may cause a delay in the intestinal absorption of the phenobarbital metabolite {01})


» Anticonvulsants, other{12}{13}{16}{20}    (concurrent use may cause a change in the pattern of epileptiform seizures because of altered medication metabolism; monitoring of plasma concentrations of both medications is recommended; dosage adjustments may be necessary)

    (carbamazepine induces metabolism and decreases effects of primidone; monitoring of plasma concentrations is recommended as a guide to dosage if either medication is added or withdrawn from an existing regimen)

    (concurrent use of valproic acid with primidone may cause higher serum concentrations of primidone {20} leading to increased CNS depression and neurological toxicity because of protein binding displacement and reduced metabolism; half-life of valproic acid may be decreased; in addition, primidone may enhance valproic acid hepatotoxicity, presumably through the formation of hepatotoxic valproate metabolites {02}; dosage adjustment of primidone may be necessary)


Carbonic anhydrase inhibitors{16}{20}    (osteopenia induced by primidone may be enhanced; it is recommended that patients receiving concurrent therapy be monitored for early signs of osteopenia and that the carbonic acid anhydrase inhibitor be discontinued and appropriate treatment initiated if necessary)


Cyclophosphamide    (concurrent use with primidone may induce microsomal metabolism to increase the formation of alkylating metabolites of cyclophosphamide, thereby reducing the half-life and increasing the leukopenic activity of cyclophosphamide)


Enflurane or
Halothane or
Methoxyflurane    (chronic use of primidone prior to anesthesia may increase anesthetic metabolism, leading to increased risk of hepatotoxicity)

    (also, chronic use of primidone prior to anesthesia with methoxyflurane may increase formation of nephrotoxic metabolites, leading to increased risk of nephrotoxicity)


Fenoprofen{16}    (concurrent use with primidone may decrease the elimination half-life of fenoprofen, possibly because of increased metabolism resulting from induction of hepatic microsomal enzyme activity; fenoprofen dosage adjustment may be required)


Folic acid{13}    (requirements for folic acid may be increased in patients receiving anticonvulsant therapy)


Griseofulvin{16}{20}{21}    (antifungal effects may be decreased when griseofulvin is used concurrently with primidone because of impaired absorption resulting in decreased serum concentrations; although the effect of decreased serum concentrations on therapeutic response has not been established, concurrent use preferably should be avoided)


Guanadrel or
Guanethidine    (concurrent use with primidone may aggravate orthostatic hypotension)


Haloperidol{16}{20}{39} or
Loxapine{39} or
Maprotiline{19}{39} or
Molindone{39} or
Phenothiazines{16}{20}{39} or
Thioxanthenes{39}    (concurrent use may lower the seizure threshold because of altered metabolism; CNS depression may be increased; decreases in primidone dosage may be necessary)

    (serum concentrations of neuroleptics may be significantly reduced when these medications are used concurrently with primidone because of increased metabolism {02})


Leucovorin    (large doses may counteract the anticonvulsant effects of primidone)


Methylphenidate{13}{16}    (concurrent use may increase serum concentrations of primidone because of metabolism inhibition, possibly resulting in toxicity; dosage adjustments may be necessary)


» Monoamine oxidase (MAO) inhibitors{19} , including furazolidone, procarbazine, or selegiline    (concurrent use may prolong the effects of primidone because metabolism of the barbiturate metabolite may be inhibited; changes in the pattern of epileptiform seizures may occur; dosage adjustments of primidone may be necessary)


Phenobarbital    (although concurrent use with primidone is rarely indicated, since primidone is metabolized to phenobarbital, it may cause a change in the pattern of epileptiform seizures because of altered medication metabolism and also increase the sedative effect of either primidone or the barbiturate anticonvulsant {02}; decreases in primidone dosage may be necessary)


Phenylbutazone    (concurrent use may decrease the efficacy of the phenobarbital metabolite of primidone by inducing hepatic microsomal enzymes and increasing its metabolism; also, hepatic enzyme inducers such as barbiturates may increase phenylbutazone metabolism and decrease its half-life {03})


Posterior pituitary    (concurrent use with primidone may increase the risk of cardiac arrhythmias and coronary insufficiency)


Rifampin{28}    (concurrent use of rifampin with barbiturates may enhance the metabolism of hexobarbital by induction of hepatic microsomal enzymes, resulting in lower serum concentrations; there is conflicting data on rifampin's effect on phenobarbital blood levels; dosage adjustment may be required)


Vitamin D{16}    (effects may be reduced by primidone, because of accelerated metabolism by hepatic microsomal enzyme induction; vitamin D supplementation may be required in patients on long-term primidone therapy to prevent osteomalacia, although rickets is rare)


Xanthines, such as:
Aminophylline
Caffeine
Oxtriphylline
Theophylline{16}{20}    (concurrent use with primidone, because of the barbiturate metabolite, may increase metabolism of the xanthines [except dyphylline] by induction of hepatic microsomal enzymes, resulting in increased theophylline clearance)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test results
Cyanocobalamin Co 57    (absorption of radioactive cyanocobalamin may be impaired by concurrent use of primidone)


Metyrapone test{20}    (increased metabolism of metyrapone by an hepatic enzyme inducer such as primidone may decrease the response to metyrapone)


Phentolamine test    (primidone may cause a false-positive phentolamine test; it is recommended that all medications be withdrawn at least 24 hours, preferably 48 to 72 hours, prior to a phentolamine test)

With physiology/laboratory test values
Bilirubin concentrations, serum    (may be decreased in patients with congenital nonhemolytic unconjugated hyperbilirubinemia and in epileptics; this effect is presumably due to induction of glucuronyl transferase, the enzyme responsible for the conjugation of bilirubin)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


This medication should not be used when the following medical problem exists:
» Porphyria,{05}{06}{07} acute intermittent or variegate, or history of    (barbiturate metabolite of primidone may aggravate symptoms of porphyria by inducing enzymes responsible for porphyrin synthesis)


Risk-benefit should be considered when the following medical problems exist
Hepatic function impairment{16}    (possible systemic accumulation of barbiturate metabolite)


Hyperkinesia    (may be precipitated or aggravated by primidone)


Renal function impairment{16}    (possible systemic accumulation of barbiturate metabolite)


» Respiratory diseases such as asthma, emphysema, or those involving dyspnea or obstruction    (serious ventilatory depression may occur)


Sensitivity to primidone or barbiturates{05}{06}{07}

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Blood cell counts, complete and
Blood chemistry profiles    (manufacturer recommends that these tests be completed every 6 months {05} {06} {07} {08})


Folate concentrations, serum    (determinations recommended periodically because of increased folate requirements of patients on long-term anticonvulsant therapy {02} {10})


Phenobarbital concentrations, serum, and
Primidone concentrations, serum{05}{07}    (since phenobarbital is a major metabolite of primidone, serum concentrations of both may be required in some patients at periodic intervals to maintain maximum therapeutic efficacy)




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent
    
Paradoxical reaction (unusual excitement or restlessness)—especially in children and the elderly{05}{06}{07}{08}

Incidence rare
    
Anemia, megaloblastic{05}{06}{07}{08} (unusual tiredness or weakness)
    
skin rash{05}{06}{07}{08}
Note: Megaloblastic anemia may respond to folic acid without discontinuation of anticonvulsant therapy. {05} {06} {07} {08}



Signs of intolerance or overdose
    
Confusion{05}
    
diplopia{05}{06}{07}{08} (double vision)
    
nystagmus{05}{06}{07}{08} (continuous, uncontrolled back-and-forth and/or rolling eye movements)
    
shortness of breath or troubled breathing



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Ataxia{05}{06}{07} (clumsiness or unsteadiness)
    
dizziness{05}{06}{07}

Incidence less frequent
    
Anorexia{05}{07}{08} (loss of appetite)
    
drowsiness{05}{06}{07}
    
impotence{05} (decreased sexual ability)
    
mood or mental changes{05}{06}{07}{08}
    
nausea or vomiting{05}{06}{07}{08} —usually decreases or disappears with continued use of medication





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Primidone (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to primidone or barbiturates

Pregnancy—Abnormalities similar to fetal hydantoin syndrome may occur; neonatal hemorrhaging may occur at delivery





Breast-feeding—Distributed into breast milk, causing drowsiness in the baby





Use in children—Paradoxical excitement and restlessness may occur






Use in the elderly—Paradoxical excitement and restlessness may occur
Other medications, especially adrenocorticoids, anticoagulants, estrogens, estrogen-containing contraceptives, CNS depression–producing medications, other anticonvulsants, or monoamine oxidase inhibitors
Other medical problems, especially acute intermittent porphyria, or respiratory diseases

Proper use of this medication
» Compliance with therapy; taking every day in doses spaced as directed

» Proper dosing
Missed dose: Taking as soon as possible, unless within an hour of next scheduled dose; not doubling doses

» Proper storage

Precautions while using this medication
Regular visits to physician to check progress of therapy

Checking with physician before discontinuing medication; gradual dosage reduction may be needed

Caution if any kind of surgery, dental treatment, or emergency treatment is required

» Avoiding use of alcoholic beverages; not taking other CNS depressants unless prescribed by physician

» Possible drowsiness; caution when driving or doing other things requiring alertness

» Possible dizziness or lightheadedness; caution when getting up suddenly from a lying or sitting position

Caution if any laboratory tests required; possible interference with results of cyanocobalamin Co 57, metyrapone, or phentolamine tests.


Side/adverse effects
Signs of potential side effects, especially excitement or restlessness, allergic reaction, or megaloblastic anemia


General Dosing Information
Because primidone serum concentrations vary greatly among patients after oral administration, it is very important that the dosage be individualized. One of primidone's metabolites, phenobarbital, greatly influences its serum concentration, side effects, and interactions, as well as its therapeutic effect.

When primidone is to be discontinued, dosage should be reduced gradually. Abrupt withdrawal may precipitate status epilepticus. {05} {06} {07} {08}

When used with or to replace other anticonvulsant therapy, the dosage of primidone should be increased gradually while that of the other medication is maintained or decreased gradually in order to maintain seizure control. When therapy with primidone alone is the objective, the transition should not be completed in less than 2 weeks. {05} {06} {07}

Many of the common side effects such as nausea, dizziness, and drowsiness diminish in frequency and intensity with continued use of the medication or reduction of dosage. {05} {06} {07} {08}

Diet/Nutrition
Patients on long-term anticonvulsant therapy have increased folate requirements. {02} {10} In addition, patients on long-term therapy may require vitamin D supplementation to prevent osteomalacia. {16}


Oral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

PRIMIDONE ORAL SUSPENSION USP

Usual adult and adolescent dose
Anticonvulsant


Initial:
Oral, 100 or 125 mg once a day at bedtime for the first three days, the daily dose being increased to 100 or 125 mg two times a day for the fourth, fifth, and sixth days, and then increased to 100 or 125 mg three times a day for the seventh, eighth, and ninth days. On the tenth day a maintenance dosage of 250 mg three times a day may be established and then adjusted according to patient needs and tolerance but not to exceed 2 grams a day. {05}

Note: Initial doses as low as 25 mg twice a day have been used in patients experiencing troublesome nausea and vomiting. {17}




Maintenance:
Oral, 250 mg three or four times a day. {05}


[Tremorlytic]1
Oral, initially 50 to 62.5 mg a day {37}, the dosage being increased as needed and tolerated up to a maximum of 750 mg a day. {36} {37}


Usual pediatric dose
Anticonvulsant


Children up to 8 years of age:
Initial—Oral, 50 mg at bedtime for the first three days, the daily dose being increased to 50 mg two times a day for the fourth, fifth, and sixth days and then increased to 100 mg two times a day for the seventh, eighth, and ninth days. {05}

Maintenance—Oral, on the tenth day, 125 to 250 mg three times a day (or 10 to 25 mg per kg of body weight a day given in divided doses), the dosage being adjusted according to patient needs and tolerance. {05}



Children 8 years of age and over:
See Usual adult and adolescent dose.



Strength(s) usually available
U.S.—


250 mg per 5 mL (Rx) [Mysoline (ammonia solution [diluted]) (citric acid) (D&C Yellow No. 10) (FD&C Yellow No. 6) (magnesium aluminum silicate) ( methylparaben) (propylparaben) (saccharin sodium) (sodium alginate) (sodium citrate) (sodium hypochlorite solution) (sorbic acid) (sorbitan monolaurate) (purified water) (flavors)]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container. Protect from freezing.

Auxiliary labeling:
   • Shake well.
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Do not freeze.


PRIMIDONE TABLETS USP

Usual adult and adolescent dose
See Primidone Oral Suspension USP .

Usual pediatric dose
See Primidone Oral Suspension USP .

Strength(s) usually available
U.S.—


50 mg (Rx) [Mysoline (lactose)]


250 mg (Rx) [Myidone] [Mysoline][Generic]

Canada—


125 mg (Rx) [Apo-Primidone] [PMS Primidone] [Sertan]


250 mg (Rx) [Apo-Primidone] [Mysoline (lactose)] [PMS Primidone] [Sertan][Generic]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. {07} {08} Store in a well-closed container. {08}

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


PRIMIDONE CHEWABLE TABLETS

Usual adult and adolescent dose
See Primidone Oral Suspension USP .

Usual pediatric dose
See Primidone Oral Suspension USP .

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


125 mg (Rx) [Mysoline (lactose)]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a well-closed container unless otherwise specified by manufacturer.

Auxiliary labeling:
   • Chew tablets before swallowing
   • May cause drowsiness.
   • Avoid alcoholic beverages.



Revised: 08/16/1994



References

Note: All references used in the development and earlier revisions of this monograph have not yet been incorporated into the computer database and, therefore, are not listed below. Citations for information not yet referenced in the monograph will be provided upon request.

  1. USP DI 1988.
  1. Panelist comment in Barbiturates (Systemic) monograph, USP DI 1989.
  1. Barbiturates (Systemic) monograph, USP DI.
  1. Panelist comment—9/88.
  1. MYSOLINE Monograph (Wyeth-Ayerst), PDR 1989: 2325–6; Package insert: rev. 11/1/90, rec. 6/5/91.
  1. MYSOLINE Monograph (Ayerst), CPS 1989: 645.
  1. Primidone package insert (Bolar), rev. 10/87, rec. 11/88.
  1. Primidone package insert (Danbury), rev. 11/85, rec. 1/89.
  1. Krauss C M, et al. J Pediatrics 1984 Nov; 105: 750.
  1. Inoue F. Clinical implications of anticonvulsant-induced folate deficiency. Clin Pharm 1982 Jul-Aug; 1: 372–3.
  1. Hachinski. Clin Pharmacokinet 1986; 11: 107–32.
  1. Hansten's, 5th ed., 1985: 115, 120, 134, 138–40.
  1. EDI, 3rd ed., l985: 124, 218, 227, 244, 259, 271–3.
  1. Mattson RH, et al. Use of oral contraceptives by women with epilepsy. JAMA 1986 Jul 11; 256(2): 238–40.
  1. Panelist comment, 2/90.
  1. Levy R, et al, eds. Antiepileptic Drugs. 3rd ed. New York: Raven Press Ltd, 1989: 379–445.
  1. Panel comment, 6/90.
  1. U.S. Pharmacist: The clinical lab. Blood levels: phenobarbital, primidone, ethosuximide, valproic acid, carbamazepine and clonazepam. May 1980: 33–9. which cited: Gibaldi M. Biopharmaceutics and clinical pharmacokinetics. 2nd ed. Philadelphia: Lea and Febiger, 1977: 161–2.
  1. Personal communication, 7/22/85.
  1. Pisani F, Perucca E, and DiPerri R. Clinically relevant antiepileptic drug interactions. J Int Med Res 1990; 18: 1–15.
  1. McInnes GT, Brodie MJ. Drug interactions that matter. A critical reappraisal. Drugs 1988; 36: 83–110.
  1. Clinical pharmacokinetics drug data handbook 1989. Auckland: Adis Press, 1989: 28.
  1. Facts and Comparisons' Drug Information Facts, 1983: 190.
  1. Shinn and Shrewsbury. Evaluation of Drug Interactions, 3rd ed.: 141, 358.
  1. Package insert, Flagyl IV and IV RTU (Searle), Rev 3/88, Rec 3/89.
  1. Mead PB, et al. Possible alteration of metronidazole metabolism by phenobarbital. N Eng J Med 1982 Jun 17; 306: 1490.
  1. Gupte S. Phenobarbital and metabolism of metronidazole. N Eng J Med 1983; 308(9): 529.
  1. Baciewicz AM, Self TH. Rifampin drug interactions. Arch Intern Med 1984 Aug; 144: 1667–71.
  1. Koller WC, Royse VL. Efficacy of primidone in essential tremor. Neurology 1986 Jan; 36(1): 121–4.
  1. Findley LJ, Koller WC. Essential tremor: A review. Neurology 1987 Jul; 37: 1194–7.
  1. Koller WC, Vetere-Overfield B. Acute and chronic effects of propranolol and primidone in essential tremor. Neurology 1989 Dec; 39(12): 1587–8.
  1. Koller WC, Huber SJ. Tremor disorders of aging: diagnosis and management. Geriatrics 1989 May; 44(5): 33–6, 41.
  1. Sasso E, Perucca E, Fava R, Calzetti S. Primidone in the long-term treatment of essential tremor: a prospective study with computerized quantitative analysis. Clin Neuropharmacol 1990 Feb; 13(1): 67–76.
  1. Lou JS, Jankovic J. Essential tremor: clinical correlates in 350 patients. Neurology 1991 Feb; 41(2) (Pt 1): 234–8.
  1. Sasso E, Perucca E, Fava R, Calzetti S. Quantitative comparison of barbiturates in essential hand and head tremor. Mov Disord 1991; 6(1): 65–8.
  1. Panel comment, 9/91.
  1. Findley LJ, Cleeves L, Calzetti S. Primidone in essential tremor of the hands and head: a double blind controlled clinical study. J Neurology, Neurosurgery, and Psychiatry 1985; 48:911–5.
  1. Cleland PG. Risk-benefit assessment of anticonvulsants in women of child-bearing potential. Drug Safety 1991 Jan-Feb; 6: 70–81.
  1. Reviewers' responses to Psychiatric Disease Advisory Panel Memo #6 of 9/16/91.
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