DiazePAM (Lexi-Drugs)

ALERT: US Boxed Warning
  Risks from concomitant use with opioids
Special Alerts
  FDA Extends Expiration Dates for Certain Meridian Autoinjectors: UpdatedJuly 2017
Drug Shortages

One or more forms of this drug may be in short supply or unavailable. Refer to the following for additional information:

ASHP: http://www.ashp.org/menu/DrugShortages

FDA: https://www.accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=Diazepam+Injection%2C+USP&st=c&tab=tabs-4&panels=0

Pronunciation

(dye AZ e pam)

Brand Names: US

Diastat AcuDial; Diastat Pediatric; diazePAM Intensol; Valium

Brand Names: Canada

BIO-Diazepam; Diastat; Diazemuls [DSC]; Diazepam 10 [DSC]; Diazepam 5 [DSC]; NOVO-Dipam [DSC]; PMS-Diazepam; Valium

Dosing: Adult

Note: Oral absorption is more reliable than IM

Acute ethanol withdrawal:

IV, IM: 10 mg initially; may administer 5 to 10 mg 3 to 4 hours later, if needed

Oral: 10 mg 3 to 4 times during first 24 hours, then decrease to 5 mg 3 to 4 times daily as needed

Anxiety (symptoms/disorders):

Oral: 2 to 10 mg 2 to 4 times daily if needed

IM, IV: 2 to 10 mg; may repeat in 3 to 4 hours, if needed

Muscle spasm:

Oral: 2 to 10 mg 3 or 4 times daily

IV, IM: Initial: 5 to 10 mg; then 5 to 10 mg in 3 to 4 hours, if necessary. Larger doses may be required if associated with tetanus.

Preoperative: Anxiety: IM: 10 mg prior to surgery

Sedation in the ICU patient: IV: Loading dose: 5 to 10 mg; Maintenance dose: 0.03 to 0.1 mg/kg every 30 minutes to 6 hours (Barr 2013)

Seizures:

Adjunctive maintenance therapy: Oral: 2 to 10 mg 2 to 4 times daily.

Intermittent management of seizures: Rectal gel (Diastat): 0.2 mg/kg; may be repeated in 4 to 12 hours if needed; do not use for more than 5 episodes per month or more than one episode every 5 days. Note: Round dose to the nearest 2.5 mg increment.

Status epilepticus:

IV:

American Epilepsy Society recommendations: 0.15 to 0.2 mg/kg (maximum dose: 10 mg); may repeat once (AES [Glauser 2016])

Neurocritical Care Society recommendations: 0.15 mg/kg (maximum dose: 10 mg) given at a rate of ≤5 mg/minute; may repeat in 5 minutes (NCS [Brophy 2012]).

Rectal (formulation not specified) (off-label use): Note: The parenteral formulation of diazepam may be given rectally if rectal gel (Diastat) is not available (Arif 2008).

American Epilepsy Society recommendations: 0.2 to 0.5 mg/kg (maximum dose: 20 mg) (AES [Glauser 2016])

Premonitory/Out-of-hospital treatment: 10 mg once; may repeat once if necessary (Kälviäinen 2007)

Skeletal muscle relaxant (adjunct therapy): Oral: 2 to 10 mg 3 to 4 times daily

Dosing: Geriatric

Oral absorption is more reliable than IM Elderly and/or debilitated patients:

Oral: 2 to 2.5 mg 1 to 2 times daily initially; increase gradually as needed and tolerated.

Rectal gel: Due to the increased half-life in elderly and debilitated patients, consider reducing dose.

Dosing: Renal Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.

Hemodialysis: Not dialyzable (0% to 5%); supplemental dose is not necessary.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution. The oral tablets are contraindicated in severe hepatic impairment.

Dosing: Pediatric

Seizures, acute:

Rectal gel formulation:

Infants and Children 6 months to 2 years: Rectal: Dose not established

Children 2 to 5 years: Rectal: 0.5 mg/kg

Children 6 to 11 years: Rectal: 0.3 mg/kg

Children ≥12 years and Adolescents: Rectal: 0.2 mg/kg

Note: Round dose to the nearest 2.5 mg increment, not exceeding a 20 mg/dose; dose may be repeated in 4 to 12 hours if needed; do not use more than 5 times per month or more than once every 5 days

Rectal: Undiluted 5 mg/mL parenteral formulation (filter if using ampul): Infants, Children, and Adolescents: 0.5 mg/kg/dose then 0.25 mg/kg/dose in 10 minutes if needed. Maximum dose: 20 mg/dose (Hegenbarth 2008; Kliegman 2007)

Status epilepticus:

Weight-directed: Infants >30 days, Children, and Adolescents: IV: 0.1 to 0.3 mg/kg/dose given over 3 to 5 minutes, every 5 to 10 minutes; maximum dose: 10 mg/dose (Brophy 2012; Hegenbarth 2008)

Fixed dosing: Manufacturer’s labeling:

Infants >30 days and Children <5 years: IV: 0.2 to 0.5 mg slow IV every 2 to 5 minutes up to a maximum total dose of 5 mg; repeat in 2 to 4 hours if needed

Children ≥5 years and Adolescents: IV: 1 mg slow IV every 2 to 5 minutes up to a maximum of 10 mg; repeat in 2 to 4 hours if needed

Febrile seizure, prophylaxis: Limited data available: Children: Oral: 1 mg/kg/day divided every 8 hours; initiate therapy at first sign of fever and continue for 24 hours after fever resolves (Rosman 1993; Steering Committee 2008)

Spasticity/muscle spasms:

General dosing: Note: Initiate therapy with lowest dose; dose should be individualized and titrated to effect and tolerability:

Manufacturer’s labeling: Infants ≥6 months, Children, and Adolescents: Oral: Initial: 1 to 2.5 mg 3 to 4 times daily; increase gradually as needed and tolerated

Alternate dosing (Kliegman 2016):

Oral:

Infants ≥6 months and Children <12 years: 0.12 to 0.8 mg/kg/day in divided doses every 6 to 8 hours; maximum dose: 10 mg/dose

Children ≥12 years and Adolescents: 2 to 10 mg 2 to 4 times daily

Cerebral palsy-associated spasticity: Limited data available. Note: Dose should be individualized and titrated to effect and tolerability:

Weight-based dosing: Children: Oral: 0.01 to 0.3 mg/kg/day divided 2 or 4 times daily (Kliegman 2016)

Low-dose fixed dosing (Mathew 2005): Children <12 years: Oral:

<8.5 kg: 0.5 to 1 mg at bedtime

8.5 to 15 kg: 1 to 2 mg at bedtime

Fixed dosing: Children ≥5 years and Adolescents: Oral: Initial: 1.25 mg 3 times daily; may titrate to 5 mg 4 times daily (Engle 1966)

Tetanus-associated spasm:

Manufacturer’s labeling:

Infants >30 days and children <5 years: IV, IM: 1 to 2 mg every 3 to 4 hours as needed

Children ≥5 years and Adolescents: IV, IM: 5 to 10 mg every 3 to 4 hours as needed

Alternate dosing (WHO 2010):

Infants and Children: IV: Initial: 0.1 to 0.2 mg/kg/dose every 2 to 6 hours; titrate as needed

Adolescents: IV: Initial: 5 mg every 2 to 6 hours, titrate as needed. Large doses may be required.

Muscle spasm/spasticity associated with chronic/terminal illness (eg, palliative care settings): Limited data available: Infants, Children, and Adolescents:

Oral: 0.12 to 0.8 mg/kg/day divided every 6 to 12 hours; maximum dose: 10 mg/dose (Wustoff 2007)

IM, IV: 0.05 to 0.2 mg/kg/dose every 6 to 12 hours; maximum total dose: 0.6 mg/kg cumulative in 8 hours (Wustoff 2007); Note: In palliative situations, the usual initial dose for children <5 years is 5 mg/dose and in children ≥5 years and adolescents is 10 mg/dose (Kliegman 2016).

Sedation, anxiolysis, and amnesia prior to procedure: Limited data available:

Oral:

Infants ≥6 months: 0.2 to 0.3 mg/kg 45 to 60 minutes prior to procedure. Maximum dose: 10 mg/dose (Zeltzer 1990)

Children: 0.2 to 0.5 mg/kg 45 to 60 minutes prior to procedure; maximum dose: 10 mg/dose (Everitt 2002; Fell 1985; Tyagi 2012; Zeltzer 1990)

Adolescents: 0.2 to 0.3 mg/kg 45 to 60 minutes prior to procedure. Maximum dose: 10 mg/dose (Zeltzer 1990)

IV:

Infants and Children: Initial: 0.05 to 0.1 mg/kg over 3 to 5 minutes, titrate slowly to effect (maximum total dose: 0.25 mg/kg) (Krauss 2006)

Adolescents: IV: 5 mg; may repeat with 2.5 mg if needed (Zeltzer 1990)

Dosing: Renal Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.

Hemodialysis: Not dialyzable (0% to 5%); supplemental dose is not necessary.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution. The oral tablets are contraindicated in severe hepatic impairment.

Use: Labeled Indications

Acute ethanol withdrawal (oral and injection): May be useful in symptomatic relief of acute agitation, tremor, impending or acute delirium, delirium tremens, and hallucinosis.

Anxiety (oral and injection): Management of anxiety disorders; short-term relief of the symptoms of anxiety.

Muscle spasm (oral and injection): As an adjunct for the relief of skeletal muscle spasm due to reflex spasm caused by local pathology (eg, inflammation of muscles or joints, secondary to trauma); spasticity caused by upper motor neuron disorders (eg, cerebral palsy, paraplegia); athetosis; stiff-man syndrome; tetanus.

Preoperative (injection): Relief of anxiety and tension in patients undergoing surgical procedures; prior to cardioversion for the relief of anxiety and tension and to diminish patient’s recall (IV only); as an adjunct prior to endoscopic procedures for apprehension, anxiety, or acute stress reactions and to diminish patient’s recall.

Note: Use of diazepam in patients undergoing cardioversion or endoscopic procedures has been superseded by agents with a more pharmacokinetically favorable profile (eg, midazolam) (Thomas 2014; Triantafillidis 2013)

Seizures: Adjunct in convulsive disorders (oral); management of select, refractory epilepsy patients on stable regimens of antiepileptic drugs requiring intermittent use of diazepam to control episodes of increased seizure activity (rectal); adjunct in severe recurrent convulsive seizures (injection).

Status epilepticus (injection): Adjunct in status epilepticus.

Use: Off-Label: Adult

  Sedation in the intensive care unitLevel of Evidence [G]

Based on the 2013 Society of Critical Care Medicine Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit diazepam is an effective treatment option in patients who require sedation while in the intensive care unit. However, nonbenzodiazepine sedation (propofol or dexmedetomidine) is preferred over benzodiazepine sedation with midazolam or lorazepam being more commonly employed.

  Status epilepticus (rectal)Level of Evidence [G]

Based on the American Epilepsy Society guidelines for the treatment of convulsive status epilepticus in children and adults and the Neurocritical Care Society guidelines for the evaluation and management of Status Epilepticus, diazepam (rectal) is an effective and recommended treatment option for initial therapy in outpatient/prehospital settings or when preferred initial therapy (eg, midazolam IM [no IV access], lorazepam IV, diazepam IV) is contraindicated or not available.

Level of Evidence Definitions
  Level of Evidence Scale
Clinical Practice Guidelines

Anxiety:

American Psychiatric Association (APA), “Practice Guideline for the Treatment of Patients with Panic Disorder,” January 2009

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders, First Revision,” 2008

Critical Care:

“Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit,” January 2013.

Status Epilepticus:

American Epilepsy Society, “Treatment of Convulsive Status Epilepticus in Children and Adults,” January 2016

Substance Abuse:

American Psychiatric Association, “Practice Guideline for the Treatment of Patients with Substance Use Disorders,” April 2007

World Federation of Societies of Biological Psychiatry, “WFSBP Guidelines for the Biological Treatment of Substance Use and Related Disorders, Part 1: Alcoholism,” 2008

Other:

“Pharmacologic Treatment of Spasticity in Children and Adolescents with Cerebral Palsy (An Evidence-Based Review),” Practice Parameters, 2010

Administration: IV

Administer undiluted by slow IV push; do not mix with other solutions or medications. Rapid injection may cause respiratory depression or hypotension. In adults, maximum infusion rate is 5 mg/minute. Do not administer through small veins (eg, dorsum of hand/wrist). Avoid intra-arterial administration. Continuous infusion is not recommended because of precipitation in IV fluids and absorption of drug into infusion bags and tubing.

Vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation.

Extravasation management: If extravasation occurs, stop IV administration immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOTflush the line); remove needle/cannula; elevate extremity. Apply dry cold compresses (Hurst 2004).

Administration: Injectable Detail

pH: 6.2 to 6.9 (5 mg/mL solution in vial)

Administration: Oral

Administer with food or water. Dilute or mix oral concentrate with water, juice, soda, applesauce, or pudding before use; measure dose only with calibrated dropper provided.

Administration: Rectal

Rectal gel: Prior to administration, confirm that prescribed dose is visible and correct, and that the green “ready” band is visible. Place patient on side (facing person responsible for monitoring), with top leg bent forward. Insert rectal tip (lubricated) gently into rectum until rim fits snug against rectal opening; push plunger gently over 3 seconds. After additional 3 seconds, remove syringe; hold buttocks together while slowly counting to 3 to prevent leakage; keep patient on side, facing towards you and continue to observe patient; discard any unused medication, syringe, and all used materials; do not reuse; see manufacturer’s Administration and Disposal Instructions.

Administration: Pediatric

Oral: Administer with food or water.

Oral concentrate solution (5 mg/mL): Dilute or mix product before use. Measure dose only with calibrated dropper provided.

Parenteral: IV: Administer undiluted (5 mg/mL) direct IV; do not mix with other solutions or medications. Rapid injection may cause respiratory depression or hypotension; infants and children: Do not exceed 1 to 2 mg/minute IV push; adults: 5 mg/minute. Continuous infusion is not recommended because of precipitation in IV fluids and absorption of drug into infusion bags and tubing.

Vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation. If extravasation occurs, stop IV administration immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity. Apply dry cold compresses (Hurst 2004).

Rectal: Diastat AcuDial: Prior to administration, confirm that the prescribed dose is visible and correct and that the green “ready” band is visible.

Diastat AcuDial and Diastat: Place patient on side (facing person responsible for monitoring), with top leg bent forward. Insert rectal tip (lubricated) gently into rectum until rim fits snug against rectal opening; push plunger gently over 3 seconds. After additional 3 seconds, remove syringe; hold buttocks together while slowly counting to 3 to prevent leakage; keep patient on side, facing towards you and continue to observe patient; discard any unused medication, syringe, and all used materials safely away from children; do not reuse; see Administration and Disposal Instructions that come with product.

Vesicant/Extravasation Risk

Vesicant

Storage/Stability

Injection: Store at 20°C to 25°C (68°F to 77°F). Protect from light. Do not refrigerate autoinjector.

Oral solution: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light. Discard opened bottle of concentrated oral solution after 90 days.

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).

Preparation for Administration: Pediatric

Oral: Oral concentrate solution (5 mg/mL): Dilute or mix with water, juice (except grapefruit juice), soda, applesauce, or pudding before use.

Rectal: Diastat AcuDial: Prescribed dose must be “dialed in” and locked before dispensing; consult package insert for directions on setting prescribed dose.

Compatibility

See Trissel’s IV Compatibility Database

Medication Patient Education with HCAHPS Considerations

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache, fatigue, or muscle weakness. Have patient report immediately to prescriber signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), shortness of breath, change in balance, confusion, hallucinations, memory impairment, severe dizziness, passing out, severe loss of strength and energy, seizures, muscle spasms, twitching, insomnia, vision changes, or severe injection site redness, burning, edema, pain or irritation (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Medication Safety Issues
  Sound-alike/look-alike issues:
  Geriatric Patients: High-Risk Medication:
Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Valium: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/013263s094lbl.pdf#page=14

Contraindications

Hypersensitivity to diazepam or any component of the formulation; acute narrow-angle glaucoma; untreated open-angle glaucoma; infants <6 months of age (oral); myasthenia gravis, severe respiratory impairment, severe hepatic impairment, sleep apnea syndrome (oral tablet).

Documentation of allergenic cross-reactivity for benzodiazepines is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Warnings/Precautions

Concerns related to adverse effects:

• Anterograde amnesia: Benzodiazepines have been associated with anterograde amnesia (Nelson 1999).

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).

• Paradoxical reactions: Paradoxical reactions, including hyperactive or aggressive behavior, have been reported with benzodiazepines; risk may be increased in adolescent/pediatric, geriatric patients, or patients with a history of alcohol use disorder or psychiatric/personality disorders (Mancuso 2004).

• Sleep-related activities: Hazardous sleep-related activities such as sleep-driving, cooking and eating food, and making phone calls while asleep have been noted with benzodiazepines (Dolder 2008).

Disease-related concerns:

• Convulsive disorders: When used as an adjunct in treating convulsive disorders, an increase in frequency/severity of tonic-clonic seizures may occur and require dose adjustment of anticonvulsant. Abrupt withdrawal may result in a temporary increase in the frequency and/or severity 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 extreme caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance and psychological and physical dependence may occur with prolonged use (generally >10 days).

• Glaucoma: May be used in patients with open-angle glaucoma who are receiving appropriate therapy; contraindicated in acute narrow-angle glaucoma and untreated open-angle glaucoma.

• Hepatic impairment: Use with caution in patients with hepatic impairment. Oral tablet is contraindicated in patients with severe hepatic impairment.

• 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. Oral tablet is contraindicated in patients with severe respiratory impairment or sleep apnea syndrome.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

• Concomitant use with opioids: [US Boxed Warning]: Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death; reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate, and limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.

Special populations:

• Debilitated patients: Use with caution; active metabolites with extended half-lives may lead to delayed accumulation and adverse effects; limit dose to smallest effective amount and increase gradually and as tolerated to avoid adverse reactions.

• 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 and increase gradually and as tolerated to avoid adverse reactions. Elderly patients may be at an increased risk of death with use; risk has been found highest within the first 4 months of use in elderly dementia patients (Jennum 2015; Saarelainen 2018).

• Fall risk: Use with extreme caution in patients who are at risk of falls; benzodiazepines have been associated with falls and traumatic injury (Nelson 1999).

• Obese patients: Use benzodiazepines with caution in obese patients; may have prolonged action when discontinued.

• Psychotic patients: Use of diazepam is not recommended in place of appropriate therapy.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol and/or sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP [“Inactive” 1997]; CDC 1982); some data suggest that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol and/or benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.

• Parenteral: Vesicant; ensure proper needle or catheter placement prior to and during administration; avoid extravasation. Acute hypotension, muscle weakness, apnea, and/or cardiac arrest have occurred with parenteral administration. Acute effects may be more prevalent in patients receiving concurrent barbiturates, opioids, or ethanol. Appropriate resuscitative equipment and qualified personnel should be available during administration and monitoring. Avoid use of the injection in patients in shock, coma, or in acute ethanol intoxication with depression of vital signs. Intra-arterial injection should be avoided. Tonic status epilepticus has been precipitated in patients treated with diazepam IV for absence status or absence variant status.

• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP [“Inactive” 1997]; Wilson 2000; Wilson 2005; Zar 2007).

• 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. Not recommended for chronic, daily use. Use with caution in patients with neurologic damage.

Other warnings/precautions:

• Appropriate use: Does not have analgesic, antidepressant, or antipsychotic properties.

• Tolerance: 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 (Vinkers 2012). Chronic use of this agent may increase the perioperative benzodiazepine dose needed to achieve desired effect.

• 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. The benzodiazepine receptor antagonist flumazenil may cause withdrawal in patients receiving long-term benzodiazepine therapy.

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. Guidelines from the Centers for Medicare and Medicaid Services (CMS) strongly discourage the use of this agent in residents of long-term care facilities.

Warnings: Additional Pediatric Considerations

Neonates and young infants have decreased metabolism of diazepam and desmethyldiazepam (active metabolite), both can accumulate with repeated use and cause increased toxicity.

Pregnancy Risk Factor

D

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. In humans, diazepam and its metabolites (N-desmethyldiazepam, temazepam, and oxazepam) cross the placenta. Teratogenic effects have been observed with diazepam; however, additional studies are needed. The incidence of premature birth and low birth weights may be increased following maternal use of benzodiazepines; hypoglycemia and respiratory problems in the neonate may occur following exposure late in pregnancy. Neonatal withdrawal symptoms may occur within days to weeks after birth and “floppy infant syndrome” (which also includes withdrawal symptoms) has been reported with some benzodiazepines (including diazepam) (Bergman 1992; Iqbal 2002; Wikner 2007). A combination of factors influences the potential teratogenicity of anticonvulsant therapy. When treating women with epilepsy, monotherapy with the lowest effective dose and avoidance of medications known to have a high incidence of teratogenic effects is recommended (Harden 2009; Wlodarczyk 2012).

Breast-Feeding Considerations

Diazepam and its metabolites are present in breast milk.

Using data from one study, the relative infant dose (RID) of diazepam is 8.9% when compared to a weight-adjusted maternal dose of 10 mg/day.

In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000). However some sources note breastfeeding should only be considered if the RID is <5% for psychotropic agents (Larsen 2015).

The RID of diazepam was calculated using a milk concentration of 85 ng/mL, providing an estimated daily infant dose via breast milk of 0.01275 mg/kg/day. This was the highest milk concentration obtained in one study following maternal administration of diazepam 10 mg once daily at bedtime to four postpartum women (this sample was obtained after five maternal doses) (Brandt 1976). Higher milk concentrations have been reported; however, milk concentration related to maternal dose was not stated (Dusci 1990; Wesson 1985). The active metabolites of diazepam (desmethyldiazepam, oxazepam, and temazepam) have also been detected in breast milk and the urine of exposed infants (Brandt 1976; Cole 1975; Dusci 1990; Erkkola 1972; Wesson 1985). Relative infant doses of up to 11% have been reported (McElhatton 1994).

Sedation and weight loss have been observed in some infants exposed to diazepam via breast milk (Patrick 1972; Wesson 1985)

Diazepam has a long half-life and may accumulate in the breastfed infant, especially preterm infants or those exposed to chronic maternal doses (Davanzo 2013). Significant accumulation may occur even if the maternal dose is low (Wesson 1985). A single maternal dose may be compatible with breastfeeding (WHO 2002). If chronic use of a benzodiazepine is needed in breastfeeding women, use of shorter acting agents is preferred (Davanzo 2013; WHO 2002). Infants should be monitored for drowsiness, decreased feeding, and poor weight gain (Veiby 2015).

Briggs’ Drugs in Pregnancy & Lactation
Adverse Reactions

Adverse reactions may vary by route of administration.

>10%: Central nervous system: Drowsiness (23%)

1% to 10%:

Cardiovascular: Hypotension (1% to 2%), vasodilation (1% to 2%)

Central nervous system: Headache (5%), ataxia (3%), dizziness (3%), euphoria (3%), abnormality in thinking (1% to 2%), agitation (≥1%), confusion (≥1%), emotional lability (≥1%), nervousness (≥1%), pain (≥1%), speech disturbance (≥1%)

Dermatologic: Skin rash (3%)

Gastrointestinal: Diarrhea (4%), abdominal pain (≥1%)

Neuromuscular & skeletal: Asthenia (1% to 2%)

Respiratory: Asthma (2%), rhinitis (≥1%)

Frequency not defined:

Cardiovascular: ECG changes, localized phlebitis, venous thrombosis

Central nervous system: Anterograde amnesia, central nervous system depression, depression, drug dependence, drug withdrawal, dysarthria, fatigue, hypoactivity, myasthenia, paradoxical central nervous system stimulation, psychiatric signs and symptoms, slurred speech, vertigo

Endocrine & metabolic: Change in libido

Gastrointestinal: Altered salivation, constipation, gastrointestinal distress, hiccups, nausea

Genitourinary: Urinary incontinence, urinary retention

Hematologic & oncologic: Neutropenia

Hepatic: Increased serum alkaline phosphatase, increased serum transaminases, jaundice

Neuromuscular & skeletal: Tremor

Ophthalmic: Blurred vision, diplopia

<1%, postmarketing, and/or case reports: Anemia, anorexia, bradycardia, circulatory shock, cough, diaphoresis, hyperkinesia, infection, lymphadenopathy, mydriasis, neutropenia, nystagmus, pruritus, syncope, tonic clonic type of status epilepticus, urinary tract infection, urticaria, vomiting

Allergy and Idiosyncratic Reactions
Toxicology
Metabolism/Transport Effects

Substrate of CYP1A2 (minor), CYP2B6 (minor), CYP2C19 (major), CYP2C9 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions 

Ajmaline: DiazePAM may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Risk C: Monitor therapy

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Alfentanil: DiazePAM may enhance the CNS depressant effect of Alfentanil. Hypotension may also occur. Risk C: Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Risk X: Avoid combination

Benznidazole: May enhance the adverse/toxic effect of Products Containing Propylene Glycol. Risk X: Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Risk D: Consider therapy modification

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants.Risk D: Consider therapy modification

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CloZAPine: Benzodiazepines may enhance the adverse/toxic effect of CloZAPine. Management: Consider decreasing the dose of (or possibly discontinuing) benzodiazepines prior to initiating clozapine. Risk D: Consider therapy modification

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Cosyntropin: May enhance the hepatotoxic effect of DiazePAM. Risk C: Monitor therapy

CYP2C19 Inducers (Moderate): May decrease the serum concentration of CYP2C19 Substrates (High risk with Inducers). Risk C: Monitor therapy

CYP2C19 Inducers (Strong): May increase the metabolism of CYP2C19 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D: Consider therapy modification

CYP2C19 Inhibitors (Moderate): May decrease the metabolism of CYP2C19 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP2C19 Inhibitors (Strong): May decrease the metabolism of CYP2C19 Substrates (High risk with Inhibitors). Risk D: Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Risk D: Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Risk D: Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP2C19 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP2C19 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Risk D: Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Disulfiram: May increase the serum concentration of DiazePAM. Risk C: Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk D: Consider therapy modification

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Risk D: Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP2C19 Substrates (High risk with Inducers). Conversely, concentrations of active metabolites may be increased for those drugs activated by CYP2C19. Management: Concurrent use of enzalutamide with CYP2C19 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP2C19 substrate should be performed with caution and close monitoring. Risk D: Consider therapy modification

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Etravirine: May decrease the serum concentration of DiazePAM. Etravirine may increase the serum concentration of DiazePAM. Risk C: Monitor therapy

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Risk D: Consider therapy modification

Fosamprenavir: May increase the serum concentration of DiazePAM. Risk C: Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.Risk D: Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk C: Monitor therapy

Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Risk D: Consider therapy modification

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Melatonin: May enhance the sedative effect of Benzodiazepines. Risk C: Monitor therapy

Methadone: Benzodiazepines may enhance the CNS depressant effect of Methadone. Management: Clinicians should generally avoid concurrent use of methadone and benzodiazepines when possible; any combined use should be undertaken with extra caution. 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 adult dose 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

MetroNIDAZOLE (Systemic): May enhance the adverse/toxic effect of Products Containing Propylene Glycol. A disulfiram-like reaction may occur. Risk X: Avoid combination

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Risk D: Consider therapy modification

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Risk C: Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Risk D: Consider therapy modification

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

OLANZapine: May enhance the adverse/toxic effect of Benzodiazepines. Management: Avoid concomitant use of parenteral benzodiazepines and IM olanzapine due to risks of additive adverse events (e.g., cardiorespiratory depression). Olanzapine prescribing information provides no specific recommendations regarding oral administration. Risk X: Avoid combination

Ombitasvir, Paritaprevir, and Ritonavir: May decrease the serum concentration of DiazePAM. Risk C: Monitor therapy

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir: May decrease the serum concentration of DiazePAM. Risk C: Monitor therapy

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.Risk D: Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Risk D: Consider therapy modification

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Pitolisant: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. Risk D: Consider therapy modification

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

Ritonavir: May increase the serum concentration of DiazePAM. Risk C: Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Saquinavir: May increase the serum concentration of DiazePAM. Risk C: Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Sodium Oxybate: Benzodiazepines may enhance the CNS depressant effect of Sodium Oxybate. Risk X: Avoid combination

St John’s Wort: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D: Consider therapy modification

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Risk D: Consider therapy modification

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Teduglutide: May increase the serum concentration of Benzodiazepines. Risk C: Monitor therapy

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Theophylline Derivatives: May diminish the therapeutic effect of Benzodiazepines. Risk D: Consider therapy modification

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Yohimbine: May diminish the therapeutic effect of Antianxiety Agents. Risk C: Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification

Test Interactions

False-negative urinary glucose determinations when using Clinistix® or Diastix®

Monitoring Parameters

Heart rate, respiratory rate, blood pressure, and mental status; liver enzymes and CBC with long-term therapy; clinical signs of propylene glycol toxicity (for continuous high-dose and/or long duration intravenous use) including serum creatinine, BUN, serum lactate, osmol gap. Note: An osmol gap of ≥10 was predictive of elevated propylene glycol concentrations; values of ≥12 suggest propylene glycol toxicity (Barnes 2006; Yahwak 2008)

Critically-ill mechanically-ventilated patients: Monitor depth of sedation with either the Richmond Agitation-Sedation Scale (RASS) or Sedation-Agitation Scale (SAS) (Barr 2013)

Advanced Practitioners Physical Assessment/Monitoring

Assess for history of addiction; long-term use can result in dependence, abuse, or tolerance; periodically evaluate need for continued use. Monitor blood pressure and CNS status. For inpatient use, institute safety measures to prevent falls. Taper dosage slowly when discontinuing. Teach patient seizure precautions (if administered for seizures).

Nursing Physical Assessment/Monitoring

Assess for history of addiction; long-term use can result in dependence, abuse, or tolerance; periodically evaluate need for continued use. Monitor blood pressure and CNS status. For inpatient use, institute safety measures to prevent falls. Taper dosage slowly when discontinuing. Teach patient seizure precautions (if administered for seizures).

Controlled Substance

C-IV

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Concentrate, Oral:

diazePAM Intensol: 5 mg/mL (30 mL) [contains alcohol, usp; unflavored flavor]

Generic: 5 mg/mL (30 mL)

Gel, Rectal:

Diastat AcuDial: 10 mg (1 ea); 20 mg (1 ea) [contains alcohol, usp, benzoic acid, sodium benzoate]

Diastat Pediatric: 2.5 mg (1 ea) [contains benzoic acid, benzyl alcohol, propylene glycol, sodium benzoate]

Generic: 2.5 mg (1 ea); 10 mg (1 ea); 20 mg (1 ea)

Solution, Injection:

Generic: 5 mg/mL (2 mL, 10 mL)

Solution, Oral:

Generic: 5 mg/5 mL (500 mL)

Solution Auto-injector, Intramuscular:

Generic: 10 mg/2 mL (2 mL)

Tablet, Oral:

Valium: 2 mg, 5 mg, 10 mg [scored]

Generic: 2 mg, 5 mg, 10 mg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Emulsion, Injection:

Diazemuls: 5 mg/mL (2ml[DSC]) [contains EGG PHOSPHOLIPIDS (EGG LECITHIN), SOYBEAN OIL]

Gel, Rectal:

Diastat: 5 mg/mL (0.5ml, 1ml, 2ml, 3ml, 4ml) [contains BENZOIC ACID, BENZYL ALCOHOL, SODIUM BENZOATE]

Solution, Injection:

Generic: 5 mg/mL (2ml)

Solution, Oral:

Generic: 1 mg/mL (500ml)

Solution Auto-injector, Intramuscular:

Generic: 10 mg/2 mL (2ml)

Tablet, Oral:

Valium: 5 mg

Generic: 2 mg, 5 mg, 10 mg

Anatomic Therapeutic Chemical (ATC) Classification
  • N05BA01
Generic Available (US)

Yes

Pricing: US

Concentrate (diazePAM Intensol Oral)

5 mg/mL (per mL): $1.43

Concentrate (diazePAM Oral)

5 mg/mL (per mL): $1.25

Gel (Diastat AcuDial Rectal)

10 mg (per each): $412.64

20 mg (per each): $412.64

Gel (Diastat Pediatric Rectal)

2.5 mg (per each): $347.86

Gel (diazePAM Rectal)

2.5 mg (per each): $306.90

10 mg (per each): $364.06

20 mg (per each): $364.06

Solution (diazePAM Injection)

5 mg/mL (per mL): $4.31 – $4.38

Solution Auto-injector (diazePAM Intramuscular)

10 mg/2 mL (per mL): $21.53

Tablets (diazePAM Oral)

2 mg (per each): $0.10 – $0.24

5 mg (per each): $0.16 – $0.32

10 mg (per each): $0.31 – $0.43

Tablets (Valium Oral)

2 mg (per each): $4.08

5 mg (per each): $6.31

10 mg (per each): $10.65

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer’s AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

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. Benzodiazepine receptors and effects appear to be linked to the GABA-A receptors. Benzodiazepines do not bind to GABA-B receptors.

Pharmacodynamics/Kinetics

Onset of action:

Sedation: Pediatric patients: IV: 4 to 5 minutes (Krauss 2006)

Status epilepticus: IV: 1 to 3 minutes; Rectal: 2 to 10 minutes

Duration of action:

Sedation: Pediatric patients: 60 to 120 minutes (Krauss 2006)

Status epilepticus: 15 to 30 minutes

Absorption:

Oral: Well absorbed (>90%); delayed and decreased when administered with a moderate fat meal

Rectal: Well absorbed

Distribution: Vd:

IV: 1.2 L/kg (range: 0.6 to 2 L/kg) (Greenblatt 1989a)

Oral: 1.1 L/kg (range: 0.6 to 1.8 L/kg (Greenblatt 1989b)

Rectal: 1 L/kg

Protein binding:

Oral: Neonates: 84% to 86% (Milsap 1994; Morselli 1980); Adults: 98%

Rectal: 95% to 98%

Metabolism: Hepatic; diazepam is N-demethylated by CYP3A4 and 2C19 to the active metabolite N-desmethyldiazepam, and is hydroxylated by CYP3A4 to the active metabolite temazepam. N-desmethyldiazepam and temazepam are both further metabolized to oxazepam. Temazepam and oxazepam are largely eliminated by glucuronidation.

Bioavailability:

IM: >90% (Lamson 2011)

Oral: >90%

Rectal: 90%

Half-life elimination: Note: Diazepam accumulates upon multiple dosing and the terminal elimination half-life is slightly prolonged.

IM:

Premature neonates (GA: 28 to 34 weeks): 54 hours

Infants: ~30 hours (Morselli 1973)

Children 3 to 8 years: 18 hours (Morselli 1973)

Adults: Parent: ~60 to 72 hours; Desmethyldiazepam: ~152 to 174 hours (Lamson 2011)

IV: Parent: 33 to 45 hours; Desmethyldiazepam: 87 hours (Cloyd 1998; Greenblatt 1989a)

Oral: Parent: 44 to 48 hours; Desmethyldiazepam: 100 hours (Greenblatt 1989b)

Rectal: Parent: 45 to 46 hours; Desmethyldiazepam: 71 to 99 hours (Cloyd 1998)

Time to peak:

IM: Median: 1 hour (range: 0.25 to 2 hours) (Lamson 2011)

IV: ~1 minute (Cloyd 1998)

Oral: 15 minutes to 2.5 hours (1.25 hours when fasting; 2.5 hours with food) (Greenblatt 1989b)

Rectal: 1.5 hours

Excretion: Urine (predominantly as glucuronide conjugates)

Pharmacodynamics/Kinetics: Additional Considerations

Hepatic function impairment: The half-life is prolonged and clearance is decreased.

Geriatric: The half-life is increased and clearance is decreased.

Dental Use

Oral medication for preoperative dental anxiety; sedative component in IV conscious sedation in oral surgery patients; skeletal muscle relaxant

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Dental Health Professional Considerations

An adult companion should accompany the patient to and from dental office.

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Xerostomia and changes in salivation (normal salivary flow resumes upon discontinuation) (see Dental Health Professional Considerations)

Effects on Bleeding

No information available to require special precautions

Dental Usual Dosing

Anxiety/sedation/skeletal muscle relaxant: Adults:

Oral: 2 to 10 mg 2 to 4 times daily

IM, IV: 2 to 10 mg, may repeat in 3 to 4 hours if needed

Anxiety: Elderly: Oral: Initial: 1 to 2 mg 1 to 2 times daily; increase gradually as needed, rarely need to use >10 mg daily (watch for hypotension and excessive sedation)

Skeletal muscle relaxant: Elderly: Oral: Initial: 2 to 5 mg 2 to 4 times daily

FDA Approval Date
November 15, 1963
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Diazepam carpuject [prescribing information]. Lake Forest, IL: Hospira; March 2014.

Diazepam injection [prescribing information]. Upper Saddle River, NJ: DASH Pharmaceuticals, LLC; December 2018.

Diazepam intramuscular autoinjector [prescribing information]. Columbia, MD: Meridian Medical Technologies; July 2005.

Diazepam oral solution and Diazepam Intensol oral solution concentrate [prescribing information]. Columbus, OH: Roxane Laboratories; July 2012.

Dieckmann RA. Rectal diazepam for prehospital pediatric status epilepticus. Ann Emerg Med. 1994;23(2):216-224.[PubMed 8304602]

Dolder CR, Nelson MH. Hypnosedative-induced complex behaviours: incidence, mechanisms and management. CNS Drugs. 2008;22(12):1021-1036. doi:10.2165/0023210-200822120-00005.[PubMed 18998740]

Dusci LJ, Good SM, Hall RW, Ilett KF. Excretion of diazepam and its metabolites in human milk during withdrawal from combination high dose diazepam and oxazepam. Br J Clin Pharmacol. 1990;29(1):123-126.[PubMed 2105100]

Engle HA, “The Effect of Diazepam (Valium) in Children With Cerebral Palsy: A Double-Blind Study,” Dev Med Child Neurol, 1966, 8(6):661-67.[PubMed 5339679]

Erkkola R, Kanto J. Diazepam and breast-feeding. Lancet. 1972;1(7762):1235-1236.[PubMed 4113217]

Glauser T, Shinnar S, Gloss D, et al. Evidence-based guideline: treatment of convulsive status epilepticus in children and adults: report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016;16(1):48-61. doi:10.5698/1535-7597-16.1.48.[PubMed 26900382]

Greenblatt DJ, Ehrenberg BL, Gunderman J, et al. Pharmacokinetic and electroencephalographic study of intravenous diazepam, midazolam, and placebo. Clin Pharmacol Ther. 1989a;45(4):356-365.[PubMed 2702793]

Greenblatt DJ, Harmatz JS, Friedman H, Locniskar A, Shader RI. A large-sample study of diazepam pharmacokinetics. Ther Drug Monit. 1989b;11(6):652-657.[PubMed 2512694]

Hadaway L, “Infiltration and Extravasation,” Am J Nurs, 2007, 107(8):64-72.[PubMed 17667395]

Harden CL, Meador KJ, Pennell PB, et al, “Practice Parameter Update: Management Issues for Women With Epilepsy-Focus on Pregnancy (an Evidence-Based Review): Teratogenesis and Perinatal Outcomes: Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society,” Neurology, 2009, 73(2):133-41.[PubMed 19398681]

Hegenbarth MA and the American Academy of Pediatrics Committee on Drugs, “Preparing for Pediatric Emergencies: Drugs to Consider,” Pediatrics, 2008, 121(2):433-43.[PubMed 18245435]

Hurst S and McMillan M, “Innovative Solutions in Critical Care Units: Extravasation Guidelines,” Dimens Crit Care Nurs, 2004, 23(3):125-8.[PubMed 15192356]

“Inactive” ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics Committee on Drugs. Pediatrics. 1997;99(2):268-278.[PubMed 9024461]

Iqbal MM, Sobhan T, Ryals T, et al, “Effects of Commonly Used Benzodiazepines on the Fetus, the Neonate, and the Nursing Infant,” Psychiatr Serv, 2002, 53(1):39-49.[PubMed 11773648]

Ito S. Drug therapy for breast-feeding women. N Engl J Med. 2000;343(2):118-126.[PubMed 10891521]

Jennum P, Baandrup L, Ibsen R, et al. Increased all-cause mortality with use of psychotropic medication in dementia patients and controls: A population-based register study. Eur Neuropsychopharmacol. 2015;25(11):1906-1913. doi: 10.1016/j.euroneuro.2015.08.014.[PubMed 26342397]

Kalviainen R. Status epilepticus treatment guidelines. Epilepsia. 2007;48(suppl 8):99-102.[PubMed 18330014]

Kliegman RM, Stanton BMD, St. Geme J, Schor NF, eds. Nelson’ s Textbook of Pediatrics. 20th ed. Philadelphia, PA: Saunders Elsevier; 2015.

Krauss B and Green SM, “Procedural Sedation and Analgesia in Children,” Lancet, 2006, 367(9512):766-80.[PubMed 16517277]

Lamson MJ, Sitki-Green D, Wannarka GL, Mesa M, Andrews P, Pellock J. Pharmacokinetics of diazepam administered intramuscularly by autoinjector versus rectal gel in healthy subjects: a phase I, randomized, open-label, single-dose, crossover, single-centre study. Clin Drug Investigl. 2011;31(8):585-597.[PubMed 21721594]

Larsen ER, Damkier P, Pedersen LH, et al. Use of psychotropic drugs during pregnancy and breast-feeding. Acta Psychiatr Scand Suppl. 2015;(445):1-28.[PubMed 26344706]

Mancuso CE, Tanzi MG, Gabay M. Paradoxical reactions to benzodiazepines: literature review and treatment options. Pharmacotherapy. 2004;24(9):1177-1185.[PubMed 15460178]

Marshall JD, Farrar HC, and Kearns GL, “Diarrhea Associated With Enteral Benzodiazepine Solutions,” J Pediatr, 1995, 126(4):657-9.[PubMed 7699551]

Mathew A, Mathew MC, Thomas M, et al, “The Efficacy of Diazepam in Enhancing Motor Function in Children With Spastic Cerebral Palsy,” J Trop Pediatr, 2005, 51(2):109-13.[PubMed 15840761]

McElhatton PR. The effects of benzodiazepine use during pregnancy and lactation. Reprod Toxicol. 1994;8(6):461-475.[PubMed 7881198]

Milsap RL, Jusko WJ. Pharmacokinetics in the infant. Environ Health Perspect. 1994;102 Suppl 11:107-110.[PubMed 7737034]

Morselli PL, Franco-Morselli R, Bossi L. Clinical pharmacokinetics in newborns and infants. Age-related differences and therapeutic implications. Clin Pharmacokinet. 1980;5(6):485-527.

Morselli PL, Principi N, Tognoni G, et al. Diazepam elimination in premature and full term infants, and children. J Perinat Med. 1973;1(2):133-141.

Nelson J, Chouinard G. Guidelines for the clinical use of benzodiazepines: pharmacokinetics, dependency, rebound and withdrawal. Canadian Society for Clinical Pharmacology. Can J Clin Pharmacol. 1999;6(2):69-83.[PubMed 10519733]

Patrick MJ, Tilstone WJ, Reavey P. Diazepam and breast-feeding. Lancet. 1972;1(7749):542-543.[PubMed 4110044]

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.[PubMed 8510706]

Saarelainen L, Tolppanen AM, Koponen M, et al. Risk of death associated with new benzodiazepine use among persons with Alzheimer disease: A matched cohort study. Int J Geriatr Psychiatry. 2018;33(4):583-590. doi: 10.1002/gps.4821.[PubMed 29143367]

Thomas SP, Thakkar J, Kovoor P, et al. Sedation for electrophysiological procedures. Pacing Clin Electrophysiol. 2014;37(6):781-790.[PubMed 24697803]

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.[PubMed 3746988]

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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.[PubMed 9738086]

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Valium (diazepam) [prescribing information]. Roche Laboratories Inc; Little Falls, NJ: June 2017.

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Brand Names: International

Aliseum (IT); Alsaval (SY); Anlin (TW); Ansiolin (IT); Antenex (AU); Anxicalm (IE); Apaurin (CZ, HR, RU, SI, SK); Apo-diazepam (CZ); Apozepam (DK); Assival (IL); Azepam (BD); Azepan (AE, CY, IQ, IR, JO, KW, LY, OM, SA, SY, YE); Baogin (TW); Benzopin (ZA); Calium (EG); Calmpose (BF, BJ, CI, ET, GH, GM, GN, IN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Calmvita (LK); Cercine (JP); Ceregulart (JP); Compaz (BR); Condition (JP); D-Pam (NZ); Dialag (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM, ZW); Diapam (FI, TR); Diapine (MY, SG, TH, TW); Diapo (MY); Diazem (TR); Diazemuls (GB, IE, IT); Diazepam (HK); Diazepam Desitin (HU); Diazepam-Eurogenerics (LU); Diazepam-ratiopharm (LU); Diazepan (AE, BF, BJ, CI, CY, ES, ET, GH, GM, GN, IQ, IR, JO, KE, KW, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZM, ZW); Diazepeks (LV); Diazetop (BE); Dipezona (AR); Dizam (ZW); Dizep (BD); Doval (ZA); Dupin (TW); DZP (MY); Elcion CR (IN); Epival (EG); Euphorin (JP); Evalin (BD); Gewacalm (AT); Horizon (JP); Ifa Fonal (MX); Kratium (BF, BJ, BM, BS, BZ, CI, ET, GH, GM, GN, GY, JM, KE, LB, LR, MA, ML, MR, MU, MW, NE, NG, NL, PR, SC, SD, SL, SN, SR, TN, TR, TT, TZ, UG, ZM, ZW); Lembrol (AR); Melode (KR); Nercon (CR, DO, GT, HN, MX, NI, PA, SV); Nivalen (AE, BF, BJ, CI, CY, ET, GH, GM, GN, IQ, IR, JO, KE, KW, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZM, ZW); Nixtensyn (PH); Noan (BR, IT); Normabel (HR); Orinil (BD); Ortopsique (CR, DO, GT, HN, MX, NI, PA, SV); Paceum (CH); Pacitran (PE); Pamizep (PH); Paranten (CR, DO, GT, HN, NI, PA, SV); Pax (ZA); Paxum (IN); Placidox 10 (IN); Placidox 2 (IN); Placidox 5 (IN); Plidan (AR); Propam (NZ); Prozepam (ID); Psychopax (AT, CH); Radizepam (AE, BF, BJ, CI, CY, ET, GH, GM, GN, IQ, IR, JO, KE, KW, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZM, ZW); Ranzepam (AU); Relanium (LT, PL, RU, UA); Remedium (MT, TR); Renborin (JP); Sedium (PY); Seduxen (BD, BM, BS, BZ, EE, GY, JM, NL, PR, SR, TT, VN); Serenzin (JP); Sibazon (UA); Sincronex (UY); Sipam (TH); Solina (LK); Stedon (MT); Stesolid (AE, CH, CY, DE, DK, ES, FI, ID, IE, IL, IQ, IR, IS, JO, LK, LY, NO, OM, SA, SE, SY, TW, YE); Stesolid Rectal Tube (DE, HK); Sunzepam (MX); Sunzepan (CR, DO, GT, HN, NI, PA, SV); Talema (VE); Tranquirit (IT); Valaxona (DK); Valdimex (ID); Valiquid (DE); Valisanbe (ID); Valium (AE, AR, AT, AU, BB, BE, BF, BG, BH, BJ, BR, CH, CI, CR, CU, CY, DE, DK, DO, EC, EE, ES, ET, FR, GH, GM, GN, GR, GT, HN, HR, IE, IN, IQ, IR, IT, JO, KE, KR, KW, LB, LR, LU, LY, MA, ML, MR, MT, MU, MW, MX, MY, NE, NG, NI, NO, OM, PA, PE, PH, PK, PL, PT, PY, QA, SA, SC, SD, SK, SL, SN, SV, SY, TN, TR, TZ, UG, UY, VN, YE, ZM, ZW); Valiuzam (AE, CY, IQ, IR, JO, KW, LY, OM, SA, SY, YE); Valpam (AE, AU, CY, EG, HK, IQ, IR, JO, KW, LY, OM, SA, SY, YE); Valzepam (PH); Vanconin (TW); Vatran (IT); Vescopam (TH); Vexepam (PH); Vodin (ID); Zopam (MY, TH)

Diazepam (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(dye AZ e pam)

Brand Names: US

Diastat AcuDial; Diastat Pediatric; diazePAM Intensol; Valium

Brand Names: Canada

Diastat; Diazemuls; Diazepam Auto Injector; Diazepam Injection SDZ; Diazepam Injection USP; Novo-Dipam; Valium

Warning
  • This drug is a benzodiazepine. The use of a benzodiazepine drug along with opioid drugs has led to very bad side effects. Side effects that have happened include slowed or trouble breathing and death. Opioid drugs include drugs like codeine, oxycodone, and morphine. Opioid drugs are used to treat pain and some are used to treat cough. Talk with the doctor.
  • If you are taking this drug with an opioid drug, get medical help right away if you feel very sleepy or dizzy; if you have slow, shallow, or trouble breathing; or if you pass out. Caregivers or others need to get medical help right away if the patient does not respond, does not answer or react like normal, or will not wake up.
What is this drug used for?
  • It is used to calm muscles.
  • It is used to treat alcohol withdrawal.
  • It is used to treat anxiety.
  • It is used to help control certain kinds of seizures.
  • It may be given to you for other reasons. Talk with the doctor.
What do I need to tell my doctor BEFORE I take this drug?
  • All products:
  • If you have an allergy to diazepam or any other part of this drug.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have any of these health problems: Breathing problems, glaucoma, liver disease, myasthenia gravis, or sleep apnea.
  • If you have psychosis.
  • If you have recently drunk a lot of alcohol or taken a big amount of drugs that may slow your actions like phenobarbital or some pain drugs like oxycodone.
  • If you are breast-feeding. Do not breast-feed while you take this drug. You may also need to avoid breast-feeding for some time after your last dose. Talk with your doctor to see if you need to avoid breast-feeding after your last dose.
  • Oral and rectal products:
  • If your child is younger than 6 months of age. Do not give this drug to an infant younger than 6 months of age.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • All products:
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert or have clear eyesight until you see how this drug affects you.
  • Avoid drinking alcohol while taking this drug.
  • Talk with your doctor before you use other drugs and natural products that slow your actions.
  • If you are 65 or older, use this drug with care. You could have more side effects.
  • Use with care in children. Talk with the doctor.
  • This drug may cause harm to the unborn baby if you take it while you are pregnant. If you are pregnant or you get pregnant while taking this drug, call your doctor right away.
  • Rectal:
  • This drug is not meant for regular, daily use. Talk with the doctor.
  • All other products:
  • This drug may be habit-forming with long-term use.
  • Do not change the dose or stop this drug. This could cause seizures. Talk with your doctor.
  • If you have been taking this drug on a regular basis and you stop it all of a sudden, you may have signs of withdrawal. Do not stop taking this drug all of a sudden without calling your doctor. Tell your doctor if you have any bad effects.
  • Have your blood work checked if you are on this drug for a long time. Talk with your doctor.
What are some side effects that I need to call my doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
  • All products:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of low mood (depression), thoughts of killing yourself, nervousness, emotional ups and downs, thinking that is not normal, anxiety, or lack of interest in life.
  • Shortness of breath.
  • Change in balance.
  • Feeling confused.
  • Hallucinations (seeing or hearing things that are not there).
  • Memory problems or loss.
  • Very bad dizziness or passing out.
  • Feeling very tired or weak.
  • If seizures are worse or not the same after starting this drug.
  • Muscle spasm.
  • Twitching.
  • Not able to sleep.
  • Change in eyesight.
  • Injection (I.M., I.V.):
  • Very bad irritation where the shot was given.
  • Injection (I.V.):
  • This drug may cause tissue damage if the drug leaks from the vein. Tell your nurse if you have any redness, burning, pain, swelling, blisters, skin sores, or leaking of fluid where the drug is going into your body.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
  • All products:
  • Feeling sleepy.
  • Feeling tired or weak.
  • Muscle weakness.
  • Rectal:
  • Headache.
  • Injection:
  • Irritation where the shot is given.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • All oral products:
  • Take with or without food. Take with food if it causes an upset stomach.
  • All liquid products:
  • Make sure you have the right liquid; there is more than one strength.
  • Liquid (solution):
  • Measure liquid doses carefully. Use the measuring device that comes with this drug. If there is none, ask the pharmacist for a device to measure this drug.
  • Liquid (concentrate):
  • Use the dropper that comes with this drug to measure the drug.
  • Mix the liquid with water, juice, soda, applesauce, or pudding before taking it.
  • Swallow the mixture right away. Do not store for use at a later time.
  • Rectal:
  • Follow how to use as you have been told by the doctor or read the package insert.
  • Do not use more than 5 times in a month or more than once every 5 days.
  • Check to make sure the right dose is locked in. You will see a green ready band.
  • Call the doctor right away if you keep having seizures for 15 minutes after you give this drug, unless your doctor has told you to do something else.
  • Injection:
  • It is given as a shot into a muscle or vein.
What do I do if I miss a dose?
  • All oral products:
  • If you take this drug on a regular basis, take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
  • Many times this drug is taken on an as needed basis. Do not take more often than told by the doctor.
  • Rectal:
  • Get medical help right away.
  • Injection:
  • Call your doctor to find out what to do.
How do I store and/or throw out this drug?
  • Injection:
  • If you need to store this drug at home, talk with your doctor, nurse, or pharmacist about how to store it.
  • All other products:
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • All oral products:
  • Protect from light.
  • Liquid (concentrate):
  • Throw away any part not used after 3 months.
  • Rectal:
  • Store in the case you were given.
  • All products:
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.
Diazepam (Patient Education – Pediatric Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(dye AZ e pam)

Brand Names: US

Diastat AcuDial; Diastat Pediatric; diazePAM Intensol; Valium

Brand Names: Canada

Diastat; Diazemuls; Diazepam Auto Injector; Diazepam Injection SDZ; Diazepam Injection USP; Novo-Dipam; Valium

Warning
  • This drug is a benzodiazepine. The use of a benzodiazepine drug along with opioid drugs has led to very bad side effects. Side effects that have happened include slowed or trouble breathing and death. Opioid drugs include drugs like codeine, oxycodone, and morphine. Opioid drugs are used to treat pain and some are used to treat cough. Talk with the doctor.
  • If your child is taking this drug with an opioid drug, get medical help right away if your child feels very sleepy or dizzy; if your child has slow, shallow, or trouble breathing; or if your child passes out. Get medical help right away if your child does not respond, does not answer or react like normal, or will not wake up.
What is this drug used for?
  • It is used to calm muscles.
  • It is used to treat alcohol withdrawal.
  • It is used to help control certain kinds of seizures.
  • It is used to treat anxiety.
  • It is used to calm a child before care.
  • It may be given to your child for other reasons. Talk with the doctor.
What do I need to tell the doctor BEFORE my child takes this drug?
  • All products:
  • If your child has an allergy to this drug or any part of this drug.
  • If your child is allergic to any drugs like this one or any other drugs, foods, or other substances. Tell the doctor about the allergy and what signs your child had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If your child has any of these health problems: Breathing problems, glaucoma, liver disease, myasthenia gravis, or sleep apnea.
  • If your child has psychosis.
  • If your child has recently drunk a lot of alcohol or taken a big amount of drugs that may slow your child’s actions like phenobarbital or some pain drugs like oxycodone.
  • If your child is breast-feeding a baby:
  • If your child is breast-feeding a baby. Be sure your child does not breast-feed while taking this drug. Your child may also need to avoid breast-feeding for some time after her last dose. Talk with your child’s doctor to see if your child needs to avoid breast-feeding after her last dose.
  • Oral and rectal products:
  • If your child is younger than 6 months of age. Do not give this drug to an infant younger than 6 months of age.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell the doctor and pharmacist about all of your child’s drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for your child to take this drug with all of his/her drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.
What are some things I need to know or do while my child takes this drug?
  • All products:
  • Tell all of your child’s health care providers that your child is taking this drug. This includes your child’s doctors, nurses, pharmacists, and dentists.
  • Have your child avoid tasks or actions that call for alertness or clear eyesight until you see how this drug affects your child. These are things like riding a bike, playing sports, or using items such as scissors, lawnmowers, electric scooters, toy cars, or motorized vehicles.
  • Alcohol may interact with this drug. Be sure your child does not drink alcohol.
  • Talk with the doctor before giving your child other drugs and natural products that may slow your child’s actions.
  • Use with care in children. Talk with the doctor.
  • If your child is pregnant:
  • This drug may cause harm to the unborn baby if your child takes it during pregnancy. If your child is pregnant or gets pregnant while taking this drug, call the doctor right away.
  • Rectal:
  • This drug is not meant for regular, daily use. Talk with the doctor.
  • All other products:
  • This drug may be habit-forming with long-term use.
  • Do not change the dose or stop your child’s drug. This could cause seizures. Talk with your child’s doctor.
  • If your child has been taking this drug on a regular basis and stops taking it all of a sudden, your child may have signs of withdrawal. Do not stop giving this drug all of a sudden without calling the doctor. Tell the doctor if your child has any bad effects.
  • Have your child’s blood work checked if he/she is on this drug for a long time. Talk with your child’s doctor.
What are some side effects that I need to call my child’s doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child’s doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:
  • All products:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • If your child shows signs of low mood (depression), thoughts of killing him/herself, nervousness, emotional ups and downs, thinking that is not normal, anxiety, or lack of interest in life.
  • Shortness of breath.
  • Change in balance.
  • Feeling confused.
  • Hallucinations (seeing or hearing things that are not there).
  • Memory problems or loss.
  • Very bad dizziness or passing out.
  • Muscle spasm.
  • Twitching.
  • Not able to sleep.
  • Change in eyesight.
  • If seizures are worse or not the same after starting this drug.
  • Feeling very tired or weak.
  • Injection (I.M., I.V.):
  • Very bad irritation where the shot was given.
  • Injection (I.V.):
  • This drug may cause tissue damage if the drug leaks from the vein. Tell your child’s nurse if your child has any redness, burning, pain, swelling, blisters, skin sores, or leaking of fluid where the drug is going into your child’s body.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child’s doctor or get medical help if any of these side effects or any other side effects bother your child or do not go away:
  • All products:
  • Feeling sleepy.
  • Feeling tired or weak.
  • Muscle weakness.
  • Rectal:
  • Headache.
  • Injection:
  • Irritation where the shot is given.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your child’s doctor. Call your child’s doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best given?
  • Give this drug as ordered by your child’s doctor. Read all information given to you. Follow all instructions closely.
  • All oral products:
  • Give this drug with or without food. Give with food if it causes an upset stomach.
  • All liquid products:
  • Make sure you have the right liquid; there is more than one strength.
  • Liquid (solution):
  • Measure liquid doses carefully. Use the measuring device that comes with this drug. If there is none, ask the pharmacist for a device to measure this drug.
  • Liquid (concentrate):
  • Use the dropper that comes with this drug to measure the drug.
  • Mix liquid with water, fruit juice, soda, applesauce, or pudding.
  • Give the mixture right away. Do not store for use at a later time.
  • Rectal:
  • Follow how to give this drug as you have been told by your child’s doctor or read the package insert.
  • Do not give more than 5 times in a month or more than once every 5 days.
  • Check to make sure the right dose is locked in. You will see a green ready band.
  • Call the doctor right away if your child keeps having seizures for 15 minutes after you give this drug, unless the doctor has told you to do something else.
  • Injection:
  • It is given as a shot into a muscle or vein.
What do I do if my child misses a dose?
  • All oral products:
  • If your child takes this drug on a regular basis, give a missed dose as soon as you think about it.
  • If it is close to the time for your child’s next dose, skip the missed dose and go back to your child’s normal time.
  • Do not use 2 doses at the same time or extra doses.
  • Many times this drug is given on an as needed basis. Do not give to your child more often than told by the doctor.
  • Rectal:
  • Get medical help right away.
  • Injection:
  • Call your child’s doctor to find out what to do.
How do I store and/or throw out this drug?
  • Injection:
  • If you need to store this drug at home, talk with your child’s doctor, nurse, or pharmacist about how to store it.
  • All other products:
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • All oral products:
  • Protect from light.
  • Liquid (concentrate):
  • Throw away any part not used after 3 months.
  • Rectal:
  • Store in the case you were given.
  • All products:
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your child’s symptoms or health problems do not get better or if they become worse, call your child’s doctor.
  • Do not share your child’s drug with others and do not give anyone else’s drug to your child.
  • Keep a list of all your child’s drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your child’s doctor.
  • Talk with your child’s doctor before giving your child any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your child’s doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.