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Medication Safety Issues
Sound-alike/look-alike issues:
Diazepam may be confused with diazoxide, diltiazem, 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: Labeled Indications
Management of anxiety disorders, ethanol withdrawal symptoms; skeletal muscle relaxant; treatment of convulsive disorders; preoperative or preprocedural sedation and amnesia
Rectal gel: Management of selected, refractory epilepsy patients on stable regimens of antiepileptic drugs 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
Restrictions
C-IV
Pregnancy Risk Factor
D
Pregnancy Considerations
Teratogenic effects have been reported in animal studies. In humans, diazepam crosses the placenta. An increased risk of congenital malformations and other developmental abnormalities have been associated with diazepam; epilepsy itself may also increase the risk. Hypotonia, hypothermia, withdrawal symptoms, respiratory and feeding difficulties have been reported in the infant following 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); myasthenia gravis; severe respiratory insufficiency; severe hepatic insufficiency; sleep apnea syndrome; acute narrow-angle glaucoma; not for use in children <6 months of age (oral)
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).
• Psychiatric and paradoxical reactions: Reactions, including hyperactive or aggressive behavior, hallucinations, and psychoses, have been reported with benzodiazepines, particularly in adolescent/pediatric or elderly patients. Diazepam should be discontinued if reactions occur.
Disease-related concerns:
• Convulsive disorders: When used as an adjunct in treating convulsive disorders, an increase in frequency/severity of grand mal seizures may occur and require dose adjustment of anticonvulsant. Abrupt withdrawal may result in a temporary increase of seizures.
• Depression: Use caution in patients with depression or anxiety associated 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; a lower dose is recommended for chronic respiratory insufficiency.
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 one-third when diazepam is added.
Special populations:
• Debilitated/elderly patients: Use with caution; active metabolites with extended half-lives may lead to delayed accumulation and adverse effects; limit dose to smallest effective amount (2-2.5 mg once or twice daily initially, to be increased gradually and as tolerated) to avoid adverse reactions.
• 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.
• Psychotic patients: Use of diazepam is not recommended in place of appropriate therapy.
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.
• Propylene glycol: Parenteral formulation contains propylene glycol. May be associated with toxicity in high-dose and/or longer-term therapy.
• 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: Amnesia, ataxia, confusion, depression, drowsiness, fatigue, headache, slurred speech, paradoxical reactions (eg, aggressiveness, agitation, anxiety, delusions, hallucinations, inappropriate behavior, increased muscle spasms, insomnia, irritability, psychoses, rage, restlessness, sleep disturbances, stimulation), vertigo
Dermatologic: Rash
Endocrine & metabolic: Libido changes
Gastrointestinal: Constipation, diarrhea, nausea, salivation changes (dry mouth or hypersalivation)
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
Metabolism/Transport Effects
Substrate of CYP1A2 (minor), 2B6 (minor), 2C9 (minor), 2C19 (major), 3A4 (major); Inhibits CYP2C19 (weak), 3A4 (weak)
Drug Interactions
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
Aprepitant: May increase the serum concentration of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Calcium Channel Blockers (Nondihydropyridine): May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
CarBAMazepine: May increase the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Cimetidine: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Clozapine: Benzodiazepines may enhance the adverse/toxic effect of Clozapine. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
CYP2C19 Inducers (Strong): May increase the metabolism of CYP2C19 Substrates. Risk C: Monitor therapy
CYP2C19 Inhibitors (Moderate): May decrease the metabolism of CYP2C19 Substrates. Risk C: Monitor therapy
CYP2C19 Inhibitors (Strong): May decrease the metabolism of CYP2C19 Substrates. Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Disulfiram: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Fluconazole: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
Fosaprepitant: May increase the serum concentration of Benzodiazepines (metabolized by oxidation). Specifically, the active metabolite aprepitant is likely responsible for this effect. Risk C: Monitor therapy
Grapefruit Juice: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
Isoniazid: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Macrolide Antibiotics: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Exceptions: Azithromycin; Dirithromycin [Off Market]; Spiramycin. Risk D: Consider therapy modification
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce dosage of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification
Nefazodone: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
Oral Contraceptive (Estrogens): May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Oral Contraceptive (Progestins): May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Phenytoin: Benzodiazepines may increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy. Risk C: Monitor therapy
Protease Inhibitors: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Management: Amprenavir, atazanavir, darunavir, indinavir, nelfinavir, ritonavir, and tipranavir are contraindicated with midazolam and triazolam according to each protease inhibitor's prescribing information. Risk D: Consider therapy modification
Proton Pump Inhibitors: May increase the serum concentration of Benzodiazepines (metabolized by oxidation). Exceptions: Lansoprazole; Pantoprazole; Rabeprazole. Risk C: Monitor therapy
Rifamycin Derivatives: May increase the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: May decrease the metabolism of Benzodiazepines (metabolized by oxidation). Exceptions: Citalopram; Escitalopram; PARoxetine; Sertraline. Risk C: Monitor therapy
St Johns Wort: May increase the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Theophylline Derivatives: May diminish the therapeutic effect of Benzodiazepines. Risk D: Consider therapy modification
Yohimbine: May diminish the therapeutic effect of Antianxiety Agents. Risk C: Monitor therapy
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
Injection: Store at 20° to 25°C (68° to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect 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).
Tablet: Store at 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, fentanyl, morphine sulfate, nafcillin, quinidine gluconate, sufentanil. Incompatible: Amphotericin B cholesteryl sulfate complex, atracurium, cefepime, dexmedetomidine, diltiazem, fluconazole, foscarnet, gatifloxacin, heparin, heparin with hydrocortisone sodium succinate, hetastarch, 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
Muscle spasm associated with tetanus: I.V., I.M.:
Infants >30 days: 1-2 mg/dose every 3-4 hours as needed
Children ?5 years: 5-10 mg/dose every 3-4 hours as needed
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:
I.V.: Infants >30 days and Children: 0.1-0.3 mg/kg given over ?5 mg/minute; may repeat dose after 5-10 minutes; maximum: 10 mg/dose (Hegenbarth, 2008)
Rectal gel: 0.5 mg/kg, then 0.25 mg/kg in 10 minutes if needed
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:
Acute ethanol withdrawal: Oral: 10 mg 3-4 times during first 24 hours, then decrease to 5 mg 3-4 times/day as needed
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 (symptoms/disorders):
Oral: 2-10 mg 2-4 times/day
I.M., I.V.: 2-10 mg, may repeat in 3-4 hours if needed
Muscle spasm: I.V., I.M.: Initial: 5-10 mg; then 5-10 mg in 3-4 hours, if necessary. Larger doses may be required if associated with tetanus.
Sedation in the ICU patient: I.V.: 0.03-0.1 mg/kg every 30 minutes to 6 hours
Skeletal muscle relaxant (adjunct therapy): Oral: 2-10 mg 3-4 times/day
Status epilepticus:
I.V.: 5-10 mg every 5-10 minutes given over ?5 mg/minute; maximum dose: 30 mg
Rectal gel: Premonitory/out-of-hospital treatment: 10 mg once; may repeat once 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/debilitated patients:
Oral: 2-2.5 mg 1-2 times/day initially; increase gradually as needed and tolerated
Rectal gel: Due to the increased half-life in elderly and debilitated patients, consider reducing dose.
Dosing adjustment in renal impairment: No dose adjustment recommended; decrease dose if administered for prolonged periods.
I.V.: Risk of propylene glycol toxicity; monitor closely if using for prolonged periods or at high doses
Hemodialysis: Not dialyzable (0% to 5%); supplemental dose is not necessary
Dosing adjustment in hepatic impairment: Use with caution
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 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
Clinical Pearls/Comments: Oral absorption is more reliable than intramuscular, which is unpredictable. Intravenous administration is associated with thrombophlebitis. Diazepam does not have any analgesic effects and, in some patients, may cause paradoxical excitation. 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.
Evidence-Based Information: 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.
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
In 2007, the FDA requested that all manufacturers of sedative-hypnotic drug products revise labeling to include a greater emphasis on the risks of adverse effects. These risks include severe allergic reactions (anaphylaxis, angioedema) and complex sleep-related behaviors, which may include sleep-driving (driving while not fully awake and with no memory of the event), making phone calls, and preparing and eating food while asleep.
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 personal or family history of substance abuse and personality disorder.
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 [adult rectal tip (6 cm)]:
Diastat® AcuDial™: 20 mg (4 mL) [contains benzoic acid, benzyl alcohol, ethanol 10%, propylene glycol, and sodium benzoate; delivers set doses of 12.5 mg, 15 mg, 17.5 mg, and 20 mg]
Gel, rectal [pediatric rectal tip (4.4 cm)]:
Diastat®: 5 mg/mL (0.5 mL) [contains benzoic acid, benzyl alcohol, ethanol 10%, propylene glycol, and sodium benzoate]
Gel, rectal [pediatric/adult rectal tip (4.4 cm)]:
Diastat® AcuDial™: 10 mg (2 mL) [contains benzoic acid, benzyl alcohol, ethanol 10%, propylene glycol, sodium benzoate; delivers set doses of 5 mg, 7.5 mg, and 10 mg]
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) [contains ethanol 19%, propylene glycol]
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): $385.40
20 mg (1): $359.98
Gel (Diastat Universal)
10 mg (1): $211.99
Solution (Diazepam)
1 mg/mL (60): $16.47
Tablets (Diazepam)
2 mg (30): $11.99
5 mg (30): $11.99
10 mg (30): $12.99
Tablets (Valium)
2 mg (30): $60.43
5 mg (30): $89.72
10 mg (30): $133.96
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.
Hegenbarth MA and the American Academy of Pediatrics Committee on Drugs, “Preparing for Pediatric Emergencies: Drugs to Consider,” Pediatrics, 2008, 121(2):433-43.
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.
Kälviäinen R, “Status Epilepticus Treatment Guidelines,” Epilepsia, 2007, 48(Suppl 8):99-102.
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.
Wilson KC, Reardon C, Theodore AC, et al, “Propylene Glycol Toxicity: A Severe Iatrogenic Illness in ICU Patients Receiving IV Benzodiazepines: A Case Series and Prospective, Observational Pilot Study,” Chest, 2005, 128(3):1674-81.
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 September 2009
Content last modified September 2009
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