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Medication Safety Issues
Sound-alike/look-alike issues:
Diazepam may be confused with diazoxide, Ditropan®, lorazepam
Valium® may be confused with Valcyte™
Pronunciation
(dye AZ e pam)
U.S. Brand Names
Generic Available
Yes: Injection, tablet, solution only
Canadian Brand Names
Pharmacologic Category
Use
Management of anxiety disorders, ethanol withdrawal symptoms; skeletal muscle relaxant; treatment of convulsive disorders
Rectal gel: Management of selected, refractory epilepsy patients on stable regimens of antiepileptic drugs (AEDs) requiring intermittent use of diazepam to control episodes of increased seizure activity
Use: Dental
Oral medication for preoperative dental anxiety; sedative component in I.V. conscious sedation in oral surgery patients; skeletal muscle relaxant
Use: Unlabeled/Investigational
Panic disorders; preoperative sedation, light anesthesia, amnesia
Restrictions
C-IV
Pregnancy Risk Factor
D
Pregnancy Implications
Teratogenic effects have been reported in animal studies. In humans, diazepam crosses the placenta. An increased risk of fetal malformations has been associated with diazepam and other minor tranquilizers; epilepsy itself may also increase the risk. Hypotonia, hypothermia, withdrawal symptoms, respiratory and feeding difficulties have reported in the infant following use maternal use of benzodiazepines near time of delivery.
Lactation
Enters breast milk/contraindicated (AAP rates “of concern”)
Breast-Feeding Considerations
Clinical effects on the infant include sedation; AAP reports that USE MAY BE OF CONCERN.
Contraindications
Hypersensitivity to diazepam or any component of the formulation (cross-sensitivity with other benzodiazepines may exist); narrow-angle glaucoma; not for use in children <6 months of age (oral); pregnancy
Warnings/Precautions
Concerns related to adverse effects:
• Anterograde amnesia: Benzodiazepines have been associated with anterograde amnesia.
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Paradoxical reactions: Paradoxical reactions, including hyperactive or aggressive behavior, have been reported with benzodiazepines, particularly in adolescent/pediatric or psychiatric patients.
Disease-related concerns:
• Depression: Use caution in patients with depression, particularly if suicidal risk may be present.
• Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use (generally >10 days).
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Impaired gag reflux: Use with caution in patients with an impaired gag reflux.
• Renal impairment: Use with caution in patients with renal impairment.
• Respiratory disease: Use with caution in patients with respiratory disease.
Concurrent drug therapy issues:
• CNS depressants/psychoactive medications: Use with caution in patients receiving other CNS depressants or psychoactive medication; effects with other sedative drugs or ethanol may be potentiated.
• High potential for interactions: Use with caution in patients taking strong CYP3A4 inhibitors, moderate or strong CYP3A4 and CYP2C19 inducers and major CYP3A4 substrates (see Drug Interactions); consider alternative agents that avoid or lessen the potential for CYP-mediated interactions.
• Narcotics: The dosage of narcotics should be reduced by approximately 1/3 when diazepam is added.
Special populations:
• Debilitated patients: Use with caution in debilitated patients; active metabolites with extended half-lives may lead to delayed accumulation and adverse effects.
• Elderly: Use with caution in the elderly; benzodiazepines have been associated with falls and traumatic injury. Active metabolites with extended half-lives may lead to delayed accumulation and adverse effects.
• Fall risk: Use with extreme caution in patients who are at risk of falls; benzodiazepines have been associated with falls and traumatic injury.
• Neonates: Safety and efficacy of the injection have not been established in children <1 month of age. Solution for injection may contain sodium benzoate, benzyl alcohol, or benzoic acid. Large amounts have been associated with “gasping syndrome” in neonates.
• Obese patients: Use with caution in obese patients; may have prolonged action when discontinued.
• Pediatrics: Safety and efficacy of oral use have not been established in children <6 months of age. Safety and efficacy in rectal gel have not been established in children <2 years of age.
Dosage form specific issues:
• Parenteral: Acute hypotension, muscle weakness, apnea, and cardiac arrest have occurred with parenteral administration. Acute effects may be more prevalent in patients receiving concurrent barbiturates, narcotics, or ethanol. Appropriate resuscitative equipment and qualified personnel should be available during administration and monitoring. Avoid use of the injection in patients with shock, coma, or acute ethanol intoxication. Intra-arterial injection or extravasation of the parenteral formulation should be avoided. Parenteral formulation contains propylene glycol, which has been associated with toxicity when administered in high dosages.
• Rectal gel: Administration of rectal gel should only be performed by individuals trained to recognize characteristic seizure activity for which the product is indicated, and capable of monitoring response to determine need for additional medical intervention.
Other warnings/precautions:
• Appropriate use: Does not have analgesic, antidepressant, or antipsychotic properties.
• Withdrawal: Rebound or withdrawal symptoms may occur following abrupt discontinuation or large decreases in dose. Use caution when reducing dose or withdrawing therapy; decrease slowly and monitor for withdrawal symptoms. Flumazenil may cause withdrawal in patients receiving long-term benzodiazepine therapy.
Adverse Reactions
Frequency not defined. Adverse reactions may vary by route of administration.
Cardiovascular: Hypotension, vasodilatation
Central nervous system: Agitation, amnesia, anxiety, ataxia, confusion, depression, dizziness, drowsiness, emotional lability, euphoria, fatigue, headache, incoordination, insomnia, memory impairment, paradoxical excitement or rage, seizure, slurred speech, somnolence, vertigo
Dermatologic: Rash
Endocrine & metabolic: Libido changes
Gastrointestinal: Constipation, diarrhea, nausea, salivation changes
Genitourinary: Incontinence, urinary retention
Hepatic: Jaundice
Local: Phlebitis, pain with injection
Neuromuscular & skeletal: Dysarthria, tremor, weakness
Ocular: Blurred vision, diplopia
Respiratory: Apnea, asthma, respiratory rate decreased
Drug Interactions
Substrate of CYP1A2 (minor), 2B6 (minor), 2C9 (minor), 2C19 (major), 3A4 (major); Inhibits CYP2C19 (weak), 3A4 (weak)
Calcium channel blockers, nondihydropyridine (diltiazem, verapamil): May decrease the metabolism, via CYP isoenzymes, of diazepam.
Clozapine: Benzodiazepines may enhance the adverse/toxic effect of clozapine.
CNS depressants: Sedative effects and/or respiratory depression may be additive with CNS depressants; includes ethanol, barbiturates, opioid analgesics, and other sedative agents; monitor for increased effect.
CYP2C19 inducers: May decrease the levels/effects of diazepam. Example inducers include aminoglutethimide, carbamazepine, phenytoin, and rifampin.
CYP2C19 inhibitors: May increase the levels/effects of diazepam. Example inhibitors include delavirdine, fluconazole, fluvoxamine, gemfibrozil, isoniazid, omeprazole, and ticlopidine.
CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of diazepam. Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins.
CYP3A4 inhibitors: May increase the levels/effects of diazepam. Example inhibitors include azole antifungals, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, telithromycin, and verapamil.
Levodopa: Therapeutic effects may be diminished in some patients following the addition of a benzodiazepine; limited/inconsistent data.
Oral contraceptives: May decrease the clearance of some benzodiazepines (those which undergo oxidative metabolism); monitor for increased benzodiazepine effect.
Theophylline: May partially antagonize some of the effects of benzodiazepines; monitor for decreased response; may require higher doses for sedation.
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may increase CNS depression).
Food: Diazepam serum levels may be increased if taken with food. Diazepam effect/toxicity may be increased by grapefruit juice; avoid concurrent use.
Herb/Nutraceutical: St John's wort may decrease diazepam levels. Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).
Storage
Protect parenteral dosage form from light. Potency is retained for up to 3 months when kept at room temperature. Most stable at pH 4-8; hydrolysis occurs at pH <3.
Rectal gel: Store at 25°C (77°F); excursion permitted to 15°C to 30°C (59°F to 86°F).
Reconstitution
Per manufacturer, do not mix I.V. product with other medications.
Compatibility
Per manufacturer, do not mix I.V. product with other medications. Variable stability (consult detailed reference) in D5W, LR, NS.
Y-site administration: Compatible: Dobutamine, nafcillin, quinidine gluconate, sufentanil. Incompatible: Amphotericin B cholesteryl sulfate complex, atracurium, cefepime, diltiazem, fluconazole, foscarnet, gatifloxacin, heparin, heparin with hydrocortisone sodium succinate, hydromorphone, linezolid, meropenem, pancuronium, potassium chloride, propofol, vecuronium, vitamin B complex with C. Variable (consult detailed reference): Cisatracurium, remifentanil.
Compatibility in syringe: Compatible: Cimetidine. Incompatible: Doxapram, glycopyrrolate, heparin, hydromorphone, nalbuphine, sufentanil. Variable (consult detailed reference): Ketorolac, ranitidine.
Compatibility when admixed: Compatible: Verapamil. Incompatible: Bleomycin, buprenorphine, dobutamine, doxorubicin, floxacillin, fluorouracil, furosemide.
Mechanism of Action
Binds to stereospecific benzodiazepine receptors on the postsynaptic GABA neuron at several sites within the central nervous system, including the limbic system, reticular formation. Enhancement of the inhibitory effect of GABA on neuronal excitability results by increased neuronal membrane permeability to chloride ions. This shift in chloride ions results in hyperpolarization (a less excitable state) and stabilization.
Pharmacodynamics/Kinetics
I.V.: Status epilepticus:
Onset of action: Almost immediate
Duration: 20-30 minutes
Absorption: Oral: 85% to 100%, more reliable than I.M.
Protein binding: 98%
Metabolism: Hepatic
Half-life elimination: Parent drug: Adults: 20-50 hours; increased half-life in neonates, elderly, and those with severe hepatic disorders; Active major metabolite (desmethyldiazepam): 50-100 hours; may be prolonged in neonates
Dosage
Oral absorption is more reliable than I.M.
Children:
Conscious sedation for procedures: Oral: 0.2-0.3 mg/kg (maximum: 10 mg) 45-60 minutes prior to procedure
Sedation/muscle relaxant/anxiety:
Oral: 0.12-0.8 mg/kg/day in divided doses every 6-8 hours
I.M., I.V.: 0.04-0.3 mg/kg/dose every 2-4 hours to a maximum of 0.6 mg/kg within an 8-hour period if needed
Status epilepticus:
Infants 30 days to 5 years: I.V.: 0.05-0.3 mg/kg/dose given over 2-3 minutes, every 15-30 minutes to a maximum total dose of 5 mg; repeat in 2-4 hours as needed or 0.2-0.5 mg/dose every 2-5 minutes to a maximum total dose of 5 mg
>5 years: I.V.: 0.05-0.3 mg/kg/dose given over 2-3 minutes every 15-30 minutes to a maximum total dose of 10 mg; repeat in 2-4 hours as needed or 1 mg/dose given over 2-3 minutes, every 2-5 minutes to a maximum total dose of 10 mg
Rectal: 0.5 mg/kg, then 0.25 mg/kg in 10 minutes if needed (prepare dose using parenteral formulation)
Anticonvulsant (acute treatment): Rectal gel:
Children <2 years: Safety and efficacy have not been studied
Children 2-5 years: 0.5 mg/kg
Children 6-11 years: 0.3 mg/kg
Children ?12 years: 0.2 mg/kg
Note: Dosage should be rounded upward to the next available dose, 2.5, 5, 7.5, 10, 12.5, 15, 17.5, and 20 mg/dose; dose may be repeated in 4-12 hours if needed; do not use for more than 5 episodes per month or more than one episode every 5 days
Adolescents: Conscious sedation for procedures:
Oral: 10 mg
I.V.: 5 mg, may repeat with 1/2 dose if needed
Adults:
Anticonvulsant (acute treatment): Rectal gel: 0.2 mg/kg
Note: Dosage should be rounded upward to the next available dose, 2.5, 5, 7.5, 10, 12.5, 15, 17.5, and 20 mg/dose; dose may be repeated in 4-12 hours if needed; do not use for more than 5 episodes per month or more than one episode every 5 days.
Anxiety/sedation/skeletal muscle relaxant:
Oral: 2-10 mg 2-4 times/day
I.M., I.V.: 2-10 mg, may repeat in 3-4 hours if needed
Sedation in the ICU patient: I.V.: 0.03-0.1 mg/kg every 30 minutes to 6 hours
Status epilepticus: I.V.: 5-10 mg every 10-20 minutes, up to 30 mg in an 8-hour period; may repeat in 2-4 hours if necessary
Rapid tranquilization of agitated patient (administer every 30-60 minutes): Oral: 5-10 mg; average total dose for tranquilization: 20-60 mg
Elderly:
Anticonvulsant: Rectal gel: Due to the increased half-life in elderly and debilitated patients, consider reducing dose.
Anxiety: Oral: Initial: 1-2 mg 1-2 times/day; increase gradually as needed, rarely need to use >10 mg/day (watch for hypotension and excessive sedation)
Skeletal muscle relaxant: Oral: Initial: 2-5 mg 2-4 times/day
Hemodialysis: Not dialyzable (0% to 5%); supplemental dose is not necessary
Dosing adjustment in hepatic impairment: Reduce dose by 50% in cirrhosis and avoid in severe/acute liver disease
Dental Usual Dosing
Anxiety/sedation/skeletal muscle relaxant: Adults:
Oral: 2-10 mg 2-4 times/day
I.M., I.V.: 2-10 mg, may repeat in 3-4 hours if needed
Anxiety: Elderly: Oral: Initial: 1-2 mg 1-2 times/day; increase gradually as needed, rarely need to use >10 mg/day (watch for hypotension and excessive sedation)
Skeletal muscle relaxant: Elderly: Oral: Initial: 2-5 mg 2-4 times/day
Administration: Oral
Intensol® should be diluted before use.
Administration: I.V.
Continuous infusion is not recommended because of precipitation in I.V. fluids and absorption of drug into infusion bags and tubing. In children, do not exceed 1-2 mg/minute IVP; in adults 5 mg/minute.
Administration: Other
Rectal gel: Prior to administration, confirm that prescribed dose is visible and correct, and that the green “ready” band is visible. Patient should be positioned on side (facing person responsible for monitoring), with top leg bent forward. Insert rectal tip (lubricated) into rectum and push in plunger gently over 3 seconds. Remove tip of rectal syringe after 3 additional seconds. Buttocks should be held together for 3 seconds after removal. Dispose of syringe appropriately.
Administration: I.V. Detail
pH: 6.2-6.9
Monitoring Parameters
Respiratory, cardiovascular, and mental status; check for orthostasis
Reference Range
Therapeutic: Diazepam: 0.2-1.5 mcg/mL (SI: 0.7-5.3 ?mol/L); N-desmethyldiazepam (nordiazepam): 0.1-0.5 mcg/mL (SI: 0.35-1.8 ?mol/L)
Test Interactions
False-negative urinary glucose determinations when using Clinistix® or Diastix®
Patient Education
Take exactly as directed; do not increase dose or frequency. Drug 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, loss of appetite, or dry mouth (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); constipation (increased exercise, fluids, fruit, or fiber may help). If medication is used to control seizures, wear identification that you are taking an antiepileptic medication. Report CNS changes (confusion, depression, increased sedation, excitation, headache, agitation, insomnia or nightmares, dizziness, fatigue, or impaired coordination) or changes in cognition; respiratory difficulty or shortness of breath; changes in urinary pattern; changes in sexual activity; muscle cramping, weakness, tremors, or rigidity; ringing in ears or visual disturbances; excessive perspiration; excessive GI symptoms (cramping, constipation, vomiting, anorexia); or worsening of seizure activity or loss of seizure control. Pregnancy/breast-feeding precautions: Do not get pregnant while taking this medication; use appropriate contraceptive measures. Do not breast-feed.
Geriatric Considerations
Due to its long-acting metabolite, diazepam is not considered a drug of choice in the elderly. Long-acting benzodiazepines have been associated with falls in the elderly. Interpretive guidelines from the Centers for Medicare and Medicaid Services (CMS) strongly discourage the use of this agent in residents of long-term care facilities.
Additional Information
Diazepam does not have any analgesic effects.
Diastat® AcuDial™: When dispensing, consult package information for directions on setting patient's dose; confirm green "ready" band is visible prior to dispensing product.
Anesthesia and Critical Care Concerns/Other Considerations
Oral absorption more reliable than intramuscular. Intensol® should be diluted before use. Diazepam does not have any analgesic effects. Chronic use of this agent may increase the perioperative benzodiazepine dose needed to achieve desired effect. Abrupt discontinuation after sustained use (generally >10 days) may cause withdrawal symptoms. Hypotension may result in orthostatic lightheadedness or syncope. Benzodiazepines, as a class, may depress respiration. The 2002 ACCM/SCCM guidelines for the sustained use of sedatives and analgesics in critically-ill adults recommend diazepam or midazolam for rapid sedation of acutely-agitated patients.
Status Epilepticus: A randomized, double-blind trial (Treiman, 1998) evaluated the efficacy of four treatments in overt status epilepticus. Treatment arms were designed based upon accepted practices of North American neurologists. The treatments were: 1) lorazepam 0.1 mg/kg, 2) diazepam 0.15 mg/kg followed by phenytoin 18 mg/kg, 3) phenytoin 18 mg/kg alone, and 4) phenobarbital 15 mg/kg. Treatment was considered successful if the seizures were terminated (clinically and by EEG) within 20 minutes of start of therapy without seizure recurrence within 60 minutes from the start of therapy. Patients who failed the first treatment received a second and a third, if necessary. Patients did not receive randomized treatments after the first one but the treating physician remained blinded. Treatment success: Lorazepam 64.9%, phenobarbital 58.2%, diazepam/phenytoin 55.8%, and phenytoin alone 43.6%. Using an “intention-to-treat” analysis, there was no statistical difference between the groups. Results of subsequent treatments in patients who failed the first therapy indicated that response rate significantly dropped regardless of treatment. Aggregate response rate to the second treatment was 7.0% and third treatment 2.3%.
Cardiovascular Considerations
Hypotension may result in orthostatic lightheadedness or syncope. Benzodiazepines, as a class, may depress respiration. These medications may often be prescribed for difficulty in sleeping but may exacerbate sleep-disordered breathing.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia and changes in salivation (normal salivary flow resumes upon discontinuation).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Comment
There are two subtypes of GABA receptors (GABA-A and GABA-B) and three different benzodiazepine receptors (Bz1, Bz2, and Bz3). Benzodiazepine receptors and effects appear to be linked to the GABA-A receptors. Benzodiazepines do not bind to GABA-B receptors. The role of GABA-B receptors is unclear. Benzodiazepines have no specificity for benzodiazepine receptor subtypes.
Diazepam is a long half-life benzodiazepine. Duration of action after a single dose is determined by redistribution rather than metabolism. Tolerance develops to the sedative, hypnotic, and anticonvulsant effects. It does not develop to the anxiolytic or skeletal muscle relaxing effects. Psychological and physical dependence may occur with prolonged use of benzodiazepines. The onset of withdrawal symptoms is usually seen on the first day without drug and lasts 5-7 days in patients receiving short half-life benzodiazepines, whereas, the onset occurs after 5 days with a duration of 10-14 days after abrupt discontinuance of long half-life benzodiazepines. Risk factors for abuse include alcohol abuse, personality disorders in the patient or the patient's parent(s).
Diazepam is the most rapidly absorbed benzodiazepine; poorly and erratically absorbed after I.M. administration; undergoes phase I metabolism; injection contains propylene glycol which may cause hypotension and bradycardia when injected rapidly. Therefore, maximum rate of infusion is 5 mg/minute.
Nursing: Physical Assessment/Monitoring
Assess effectiveness and interactions of other medications patient may be taking. Assess for history of addiction; long-term use can result in dependence, abuse, or tolerance; periodically evaluate need for continued use. Monitor blood pressure, CNS status. For inpatient use, institute safety measures and monitor effectiveness and adverse reactions. For outpatients, monitor therapeutic effectiveness and adverse reactions at beginning of therapy and periodically with long-term use. Taper dosage slowly when discontinuing. Assess knowledge/teach patient seizure precautions (if administered for seizures), appropriate use, interventions to reduce side effects, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gel, rectal:
Diastat®: Pediatric rectal tip [4.4 cm]: 5 mg/mL (2.5 mg, 5 mg) [contains ethyl alcohol 10%, sodium benzoate, benzyl alcohol 1.5%; twin pack]
Diastat® AcuDial™ delivery system:
10 mg: Pediatric/adult rectal tip [4.4 cm]: 5 mg/mL (delivers set doses of 5 mg, 7.5 mg, and 10 mg) [contains ethyl alcohol 10%, sodium benzoate, benzyl alcohol 1.5%; twin pack]
20 mg: Adult rectal tip [6 cm]: 5 mg/mL (delivers set doses of 10 mg, 12.5 mg, 15 mg, 17.5 mg, and 20 mg) [contains ethyl alcohol 10%, sodium benzoate, benzyl alcohol 1.5%; twin pack]
Injection, solution: 5 mg/mL (2 mL, 10 mL)
Solution, oral: 5 mg/5 mL (5 mL, 500 mL)
Solution, oral concentrate:
Diazepam Intensol®: 5 mg/mL (30 mL)
Tablet: 2 mg, 5 mg, 10 mg
Valium®: 2 mg, 5 mg, 10 mg
Pricing: U.S. (www.drugstore.com)
Gel (Diastat AcuDial)
10 mg (1): $330.45
Gel (Diastat Universal)
10 mg (1): $211.99
Solution (Diazepam)
1 mg/mL (60): $15.99
Tablets (Diazepam)
2 mg (30): $10.99
5 mg (30): $7.99
10 mg (30): $7.99
Tablets (Valium)
2 mg (30): $46.99
5 mg (30): $70.99
10 mg (30): $105.99
References
Abernathy DR and Greenblatt DJ, “Drug Disposition in Obese Humans. An Update,” Clin Pharmacokinet, 1986, 11(3):199-213.
Allikmets E, et al, “Long-Term Use of Benzodiazepines: Abrupt Withdrawal Versus Withdrawal Under Nifedipine Cover,” Pharmacol Toxicol, 1995, 76(Suppl 3):Abstr 8.
“American Academy of Pediatrics Committee on Drugs. The Transfer of Drugs and Other Chemicals Into Human Milk,” Pediatrics, 2001, 108(3):776-89.
Bleck TB, Seizures, Stroke, and Other Neurologic Emergencies. In: Zimmerman JL, Roberts PR, eds. Multidisciplinary Critical Care Review, Des Plains, IL: Society of Critical Care Medicine; 2003, 325-34.
Jacobi J, Fraser GL, Coursin DB, et al, “Clinical Practice Guidelines for the Sustained Use of Sedatives and Analgesics in the Critically Ill Adult,” Crit Care Med, 2002, 30(1):119-41. Available at: http://www.sccm.org/pdf/sedatives.pdf. Accessed August 2, 2003.
Marshall JD, Farrar HC, and Kearns GL, “Diarrhea Associated With Enteral Benzodiazepine Solutions,” J Pediatr, 1995, 126(4):657-9.
Mokhlesi B, Leikin JB, Murray P, et al, “Adult Toxicology in Critical Care: Part II: Specific Poisonings,” Chest, 2003, 123(3):897-922.
Rosman NP, Colton T, Labazzo J, et al, “A Controlled Trial of Diazepam Administered During Febrile Illnesses to Prevent Recurrence of Febrile Seizures,” N Engl J Med, 1993, 329(2):79-84.
Traeger SM and Haug MT 3d, “Reduction of Diazepam Serum Half-Life and Reversal of Coma by Activated Charcoal in a Patient With Severe Liver Disease,” J Toxicol Clin Toxicol, 1986, 24(4):329-37.
“Treatment of Convulsive Status Epilepticus. Recommendations of the Epilepsy Foundation of America's Working Group on Status Epilepticus,” JAMA, 1993, 270(7):854-9.
Treiman DM, Meyers PD, Walton NY, et al, “A Comparison of Four Treatments for Generalized Convulsive Status Epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group,” N Engl J Med, 1998, 339(12):792-8.
Votey SR, Bosse GM, Bayer MJ, et al, “Flumazenil: A New Benzodiazepine Antagonist,” Ann Emerg Med, 1991, 20(2):181-8.
Zeltzer LK, Altman A, Cohen D, et al, “Report of the Subcommittee on the Management of Pain Associated With Procedures in Children With Cancer,” Pediatrics, 1990, 86(5 Pt 2):826-31.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2008
Content last modified March 2008
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