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Diazepam

Class: Benzodiazepines
VA Class: CN302
CAS Number: 439-14-5
Brands: Diastat, Valium

Medically reviewed by Drugs.com. Last updated on Oct 28, 2019.

Warning

    Concomitant Use with Opiates
  • Concomitant use of benzodiazepines and opiates may result in profound sedation, respiratory depression, coma, and death.434 538 700 701 703 705 706 707

  • Reserve concomitant use for patients in whom alternative treatment options are inadequate; use lowest effective dosages and shortest possible duration of concomitant therapy and monitor closely for respiratory depression and sedation.434 538 700 703 (See Specific Drugs and Laboratory Tests under Interactions.)

Introduction

Benzodiazepine; anticonvulsant, anxiolytic, sedative, and skeletal muscle relaxant.434 538 713 a

Uses for Diazepam

Anxiety Disorders

Management of anxiety disorders and short-term relief of symptoms of anxiety.434 603 713 a b

Preoperative or Preprocedural Sedation, Anxiolysis, and Amnesia

Used prior to surgery or other procedures (e.g., endoscopy, cardioversion) to produce sedation, anxiolysis, and anterograde amnesia.713 a

Seizure Disorders

Treatment of status epilepticus and severe recurrent convulsive seizures.713 a b

Benzodiazepines are considered initial drugs of choice for management of status epilepticus because of their rapid onset of action, demonstrated efficacy, safety, and tolerability.545 563 756 757 758 759 761 762 763 764 765 766 767 771 Evidence supports use of IV lorazepam, IV diazepam, or IM midazolam.545 763 764 765 766 767 768 769 Individualize choice of therapy based on local availability, route of administration, pharmacokinetics, cost, and other factors (e.g., treatment setting).545 756 757 758 759 760 761 762 763 764 765 766 767 769

Rectal administration of diazepam may be useful for out-of-hospital management (e.g., at home or school, during transport to an emergency room) of status attacks and acute repetitive seizures (i.e., serial, cyclic, cluster, breakthrough, or crescendo seizures).543 545 546 547 548 549

Oral diazepam has been used for adjunctive therapy of seizure disorders;434 b however, loss of response to anticonvulsant effects may develop with prolonged use. (See Seizure Disorders under Cautions.)

Alcohol Withdrawal

Relief of agitation, tremor, impending or acute delirium tremens, and hallucinations associated with acute alcohol withdrawal.434 603 a b

Skeletal Muscle Spasticity

Adjunct to rest, physical activity, analgesics, and other measures for relief of discomfort associated with acute, painful musculoskeletal conditions.a b

Short- and long-term management of skeletal muscle spasticity such as reflex spasm secondary to local pathology (e.g., trauma, inflammation), spasticity caused by upper motor neuron disorders (e.g., cerebral palsy, paraplegia), athetosis, stiff-man syndrome, strychnine poisoning, and tetanus.434 603 a b

Sedation in Critical Care Settings

Has been used for sedation of intubated and mechanically ventilated patients in critical care settings (e.g., ICU).564 801

Nonbenzodiazepine sedatives (dexmedetomidine and propofol) are generally preferred to benzodiazepines in mechanically ventilated, critically ill adults because of some modest clinical benefits that have been demonstrated (e.g., reduced duration of mechanical ventilation, shorter time to extubation, reduced risk of delirium).800 801 If a benzodiazepine is required, midazolam or lorazepam is preferred; diazepam is rarely used for this indication.801

Night Terrors

Has been used effectively to prevent night terrors.a b

Drug-induced Cardiovascular Emergencies

Adjunct in the management of certain drug-induced cardiovascular emergencies.696 May be beneficial adjunctively in patients with cocaine-induced acute coronary syndrome.696

Neonatal Opiate Withdrawal

Relief of agitation in the management of neonatal opiate withdrawal.a b

Diazepam Dosage and Administration

General

  • Use smallest effective dosage to avoid oversedation.a b

  • Consider long half-life of diazepam and its metabolites when making dosage adjustments (see Half-life under Pharmacokinetics).a b

  • In patients who have received prolonged (e.g., for several months) therapy, avoid abrupt discontinuance, since manifestations of withdrawal can be precipitated; gradually taper dosage.a Do not discontinue abruptly in patients with a history of seizure disorder since seizures may be precipitated.a b

  • Periodically reassess usefulness for treatment of anxiety.a Administer for shortest possible duration.a

Administration

Administer orally,434 603 a by IM or IV injection,713 a or rectally.538

Oral Administration

Administer orally as tablets or oral solution.434 603

Dilute oral concentrate solution (e.g., with water, juice, carbonated or soda-like beverages) or mix with semi-solid foods (e.g., applesauce, pudding) using the calibrated dropper provided by manufacturer.603 Stir the liquid or food mixture gently for a few seconds and then consume immediately; do not store mixture for future use.603

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by slow IV injection.713 Although the injection has been diluted prior to IV administration, this is not recommended since precipitation may occur.713 b (See Compatibility under Stability.)

Equipment for resuscitation should be readily available whenever diazepam is administered IV.713 b (See Respiratory and Cardiovascular Effects under Cautions.)

For IV injection, administer directly into a large vein; if this is not possible, inject the drug into the tubing of a flowing IV solution as close as possible to the vein insertion site.713 b

Take care to avoid intra-arterial administration or extravasation.713 b

Switch patient to oral therapy as soon as possible.b

Do not mix or dilute with other solutions or drugs.713 Administer premedications (e.g., atropine, scopolamine) in a separate syringe.713

Rate of Administration

Adults: Administer IV injection slowly at rate not exceeding 5 mg/minute.713 b

Children and infants ≥30 days of age: Administer IV injection slowly over 3 minutes.713 b

IM Administration

May be administered as deep IM injection;713 a b however, absorption may be slow and erratic.a b IM route is rarely justified.b

Rectal Administration

Administer rectally as the commercially available gel via delivery device (plastic applicator with a flexible molded tip) provided by manufacturer.538 Consult manufacturer’s labeling for specific instructions for administration of the rectal gel.538

Also has been administered rectally as the parenteral solution via a syringe and rectally inserted tubing or via lubricated tuberculin syringe (without a needle) inserted 4–5 cm into the rectum.544 549

Commercially available gel is provided in prefilled syringe applicators containing 2.5, 10, or 20 mg of diazepam.538

Table 1. Commercial Availability of Rectal Diazepam Gel

Applicator

Dose Delivered

Plastic Applicator Tip

Diastat 2.5 mg

2.5 mg

4.4 cm in length

Diastat AcuDial 10 mg

5, 7.5, or 10 mg

4.4 cm in length

Diastat AcuDial 20 mg

12.5, 15, 17.5, or 20 mg

6 cm in length

Dose to be delivered by the AcuDial applicator is locked into the device prior to dispensing.538 602 If necessary, use 2 applicators to administer the prescribed dose.538

The 2.5-mg unit-dose applicator also may be used as a partial replacement dose (supplemental dose) for patients who partially expel the recommended dose538 540 within 5 minutes after administration.540

Dispensing

Pharmacist must dial in and lock the correct dose to be administered prior to dispensing Diastat AcuDial.538 602

While holding the barrel of the applicator in one hand, turn the cap of the applicator to select the dose.538 602 After confirming that the dose visible in the display window is correct, lock the dose by grasping the locking ring and pushing upward to lock both sides of the ring.538 602 A green “ready” band becomes visible at the base of the applicator once the dose-locking ring is engaged.602

Repeat the process for each applicator to be dispensed.538 602

Administration

Prior to administering the dose, check the diazepam gel expiration date, verify that the green “ready” band on the Diastat AcuDial applicator is visible, and verify the dose displayed in the AcuDial display window.538 602

Remove the protective cap from the syringe and ensure that the seal pin is removed with the cap.538

Lubricate the rectal applicator tip with the water-soluble lubricant (jelly) provided by the manufacturer.538 544

Turn the patient so that they are resting on their side facing the caregiver; the patient’s upper leg should be bent forward and the buttocks separated to expose the rectum.538 Insert the lubricated applicator tip into the rectum until the rim of the syringe is snug against the rectal opening; slowly push the plunger (counting aloud slowly to 3) until it stops (i.e., until the entire dose of the applicator has been expelled into the rectum).538 Count slowly to 3 before removing the syringe from the rectum; to prevent leakage of the administered dose, hold the buttocks together while again counting slowly to 3.538

Leave the patient on their side facing the caregiver, note the time the dose was given, and observe the patient.538

Disposal

Discard Diastat and Diastat AcuDial rectal delivery systems and all unused materials in the garbage in a safe place away from children; do not reuse.538

Prior to discarding AcuDial applicator in the garbage, dispose of any gel remaining in the applicator.538 With the applicator tip pointed over the sink or toilet, pull back and remove the plunger from the barrel; then, replace the plunger in the barrel and gently depress the plunger until it stops, forcing gel from the applicator.538 Flush toilet or rinse sink with water until gel is no longer visible.538

Dosage

Pediatric Patients

Anxiety Disorders
Oral

Children ≥6 months of age: Manufacturer recommends initial dosage of 1–2.5 mg 3 or 4 times daily.434 603 Increase dosage gradually as needed and tolerated.434 603

IV

Some clinicians recommend 0.04–0.2 mg/kg; may repeat in 3–4 hours.b Total dose should not exceed 0.6 mg/kg in an 8-hour period.b

Preoperative Sedation, Anxiolysis, and Amnesia
IM

Children >2 years of age: 0.4 mg/kg has been administered 1–2 hours before surgery.b

Seizure Disorders
Oral

6–15 mg daily (occasionally up to 30 mg daily) in divided doses has been used for adjunctive management of epilepsy.b

IV or IM

IV administration is preferred; may use IM route if IV administration not possible.713

Children 30 days to <5 years of age: Usual initial dose for status epilepticus or severe recurrent convulsant seizures is 0.2–0.5 mg; may repeat every 2–5 minutes up to a maximum total dose of 5 mg.563 713 771 May repeat therapy with diazepam in 2–4 hours if necessary.b

Children ≥5 years of age: Usual initial dose for status epilepticus or severe recurrent convulsant seizures is 1 mg; may repeat every 2–5 minutes up to a maximum total dose of 10 mg.713 b May repeat therapy with diazepam in 2–4 hours if necessary.713

Rectal

Children 2–5 years of age: Initially, 0.5 mg/kg as rectal gel, rounded up to the next available dose (i.e., the next multiple of 2.5 mg).538 540 544 If necessary, repeat initial dose in 4–12 hours.538 540 Administration of a third dose is not recommended by the manufacturer.538

Table 2. Recommended Doses of Diazepam Rectal Gel for Children 2–5 Years of Age

Weight (kg)

Rounded Dose (mg)

6–10

5

11–15

7.5

16–20

10

21–25

12.5

26–30

15

31–35

17.5

36–44

20

Children 6–11 years of age: Initially, 0.3 mg/kg as rectal gel, rounded up to the next available dose (i.e., the next multiple of 2.5 mg).538 540 544 If necessary, repeat initial dose in 4–12 hours.538 540 Administration of a third dose is not recommended by the manufacturer.538

Table 3. Recommended Doses of Diazepam Rectal Gel for Children 6–11 Years of Age

Weight (kg)

Rounded Dose (mg)

10–16

5

17–25

7.5

26–33

10

34–41

12.5

42–50

15

51–58

17.5

59–74

20

Children ≥12 years of age: Initially, 0.2 mg/kg as rectal gel, rounded up to the next available dose (i.e., the next multiple of 2.5 mg).538 540 544 If necessary, repeat initial dose in 4–12 hours. 538 540 Administration of a third dose is not recommended by the manufacturer.538

Table 4. Recommended Doses of Diazepam Rectal Gel for Children ≥12 Years of Age

Weight (kg)

Rounded Dose (mg)

14–25

5

26–37

7.5

38–50

10

51–62

12.5

63–75

15

76–87

17.5

88–111

20

For rectal administration of parenteral solutions, 0.5 mg/kg (up to 20 mg) has been used.545 546 547 549 601 Some clinicians state a second dose of 0.25 mg/kg may be administered in 10 minutes if needed.601

Skeletal Muscle Spasticity
Oral

When used as a sedative or muscle relaxant in children, some clinicians recommend 0.12–0.8 mg/kg daily in 3 or 4 divided doses.601

IV

Some clinicians recommend 0.04–0.3 mg/kg every 2–4 hours, not to exceed 0.6 mg/kg in an 8-hour period.601 b

Tetanus
IM or IV

Children >30 days to 5 years of age: 1–2 mg.713 b May repeat dose every 3–4 hours as needed.713 b

Children >5 years of age: 5–10 mg.713 b May repeat dose every 3–4 hours as needed.713 b

Neonatal Opiate Withdrawal
IM

0.5–2 mg has been administered every 8 hours, followed by gradual dosage reduction.b

Adults

Anxiety Disorders
Oral

2–10 mg 2–4 times daily, depending on severity of symptoms.434 603

IV or IM

Initially, 2–5 mg for moderate anxiety or 5–10 mg for severe anxiety; may repeat in 3–4 hours if necessary.b

Preoperative or Preprocedural Sedation, Anxiolysis, and Amnesia
Preoperative Sedation
IM or IV

10 mg 1–2 hours before surgery (IM administration preferred);713 b some clinicians recommend doses up to 20 mg.b

Cardioversion
IV

5–15 mg 5–10 minutes before the procedure.713 b

Endoscopy
IV

Titrate dosage to obtain desired sedative response (e.g., slurring of speech).713 b Generally 10 mg or less is adequate, but up to 20 mg may be required, especially if opiates are not given concomitantly.713 b

IM

If IV administration not possible, may give IM dose of 5–10 mg approximately 30 minutes prior to endoscopy.713 b

Alcohol Withdrawal
Oral

10 mg 3 or 4 times during the first 24 hours, followed by 5 mg 3 or 4 times daily as needed.434 603

IM or IV

Initially, 10 mg, then 5–10 mg in 3–4 hours if necessary.713

Alternatively, some clinicians recommend 10 mg initially, followed by 10 mg at 20- to 30-minute intervals until patient is calm.b

Seizure Disorders
Oral

2–10 mg 2–4 times daily for adjunctive management of seizure disorders.434 603

IV or IM

IV administration is preferred; may use IM route if IV administration not possible.713

Initially, 5–10 mg.713 May repeat at 10- to 15-minute intervals, if necessary, up to a maximum total dose of 30 mg.713 May repeat therapy with diazepam in 2–4 hours, if necessary.713

Rectal

Initially, 0.2 mg/kg as rectal gel, rounded up to next available dose (i.e., the next multiple of 2.5 mg).538 540 544 If necessary, repeat initial dose in 4–12 hours.538 540 Administration of a third dose is not recommended by the manufacturer.538

For rectal administration of parenteral solutions, 0.5 mg/kg (up to 20 mg) has been used.545 546 547 548 549 601 Some clinicians state a second dose of 0.25 mg/kg may be administered after 10 minutes if needed.601

Skeletal Muscle Spasticity
Oral

2–10 mg 2–4 times daily.434 b

IM or IV

Initially, 5–10 mg; may repeat in 3–4 hours if necessary.713 b

Higher doses (e.g., up to 20 mg) have been given every 2–8 hours for tetanus.713 b

Sedation in Critical Care Settings
IV

Loading dose of 5–10 mg, followed by intermittent injections of 0.03–0.1 mg/kg every 0.5–6 hours as needed.801 Titrate dosage to desired level of sedation.800 801

Night Terrors
Oral

Doses of 5–20 mg at bedtime have been used.b

Labor and Delivery
IV

10–20 mg.b

Prescribing Limits

Pediatric Patients

IV

Maximum initial dose of 0.25 mg/kg.b

Seizure Disorders
Rectal

Maximum recommended frequency for administration by caregivers outside hospital is 1 treatment course every 5 days and 5 treatment courses per month.538

Adults

Anxiety Disorders
IV

Some clinicians recommend maximum dosage of 30 mg in an 8-hour period.b

Seizure Disorders
Rectal

Maximum recommended frequency for administration by caregivers outside hospital is 1 treatment course every 5 days and 5 treatment courses per month.538

Special Populations

Hepatic Impairment

Reduce dosage;a use smallest effective dose to avoid oversedation.a

Renal Impairment

Use smallest effective dose to avoid oversedation.a

Geriatric or Debilitated Patients

Oral:

Initially, 2–2.5 mg once or twice daily.434 b Increase dosage gradually as needed and tolerated.434 b

IV or IM:

Lower doses (e.g., 2–5 mg) usually recommended.713 Increase dosage gradually.713

Rectal:

Dosage to be administered should be adjusted downward for the commercially available rectal gel.538 540 544

Other Populations

Use smallest effective dosage in debilitated patients and patients with low serum albumin concentrations.b In debilitated patients, observe maximum geriatric dosages. (See Geriatric Patients under Dosage and Administration.)434 b

Cautions for Diazepam

Contraindications

  • Known hypersensitivity to diazepam or any ingredient in the formulation.b 434 538

  • Manufacturers state that diazepam is contraindicated in patients with acute angle-closure glaucoma, but may be administered to patients with open-angle glaucoma who are receiving appropriate therapy;434 538 713 b however, clinical rationale for this contraindication has been questioned.a b

Warnings/Precautions

Warnings

Concomitant Use with Opiates

Concomitant use of benzodiazepines, including diazepam, and opiates may result in profound sedation, respiratory depression, coma, and death.538 700 701 703 705 706 707 Substantial proportion of fatal opiate overdoses involve concurrent benzodiazepine use.538 700 701 705 706 707 711 (See Boxed Warning.)

Reserve concomitant use of diazepam and opiates for patients in whom alternative treatment options are inadequate.538 700 703 (See Specific Drugs and Laboratory Tests under Interactions.)

CNS Effects

Performance of activities requiring mental alertness and physical coordination may be impaired.434 a

Concurrent use of other CNS depressants may cause additive or potentiated CNS depression.434 a b (See Concomitant Use with Opiates under Cautions and also see Specific Drugs and Laboratory Tests under Interactions.)

Psychiatric Indications

Do not use in patients with depressive neuroses or psychotic reactions in which anxiety is not prominent.434 a

Respiratory and Cardiovascular Effects

Possibility of apnea and/or cardiac arrest.713 Use parenterally (particularly by IV route) with caution in elderly and debilitated patients and in patients with compromised respiratory function.713 a b 538 Do not administer diazepam injection to patients in shock or coma or to those with acute alcohol intoxication with depression of vital signs.713

Consider possibility of respiratory depression with rectal administration.538 540 544 546 547 550 551 Out-of-hospital caregivers should avoid repeated administration at relatively short intervals (see Prescribing Limits under Dosage and Administration).538 547

Equipment for resuscitation should be readily available whenever diazepam injection is administered.713 b

Concomitant use of other CNS depressants may increase the risk of apnea.713 a

Abuse Potential

Psychologic and physical dependence may occur following prolonged use.a

Patients with a history of drug or alcohol dependence or abuse are at risk of habituation or dependence; use only with careful surveillance in such patients.434 538 a

Withdrawal Syndrome

Abrupt discontinuance following chronic use may result in symptoms of withdrawal (similar to those observed with barbiturates and alcohol).434 713 a More severe symptoms generally observed in patients receiving excessive doses over an extended period of time.713

After prolonged therapy, avoid abrupt discontinuance and follow a gradual dosage tapering schedule.434 713

Seizure Disorders

Abrupt withdrawal may be associated with a temporary increase in seizure frequency or severity.434 b

Effect on seizure activity after IV administration is short-lived; repeated administration may be necessary.713 Consider need for a longer-acting agent for continued seizure control.713

Chronic daily use as an anticonvulsant may increase the frequency and/or severity of tonic-clonic seizures; may necessitate increase in dosage of other anticonvulsants.434 538 a (See Prescribing Limits under Dosage and Administration.)

Tonic status epilepticus has been precipitated following IV administration to control absence status or Lennox-Gastaut syndrome status epilepticus.713 a

Local Reactions Following Parenteral Administration

Potential for local reactions (e.g., pain, thrombophlebitis) following parenteral administration;713 a possible tissue necrosis following intra-arterial administration.a (See IV Administration under Dosage and Administration.)

Precautions Associated with Use of Rectal Gel

Only caregivers who are deemed competent to recognize seizure episodes suitable for treatment, make the decision to initiate treatment, administer the drug, monitor the patient, and assess adequacy of response should administer diazepam rectal gel.538

General Precautions

Suicide

Use with caution in depressed patients; potential for suicidal tendencies.a Prescribe and dispense drug in the smallest feasible quantity.a

Laboratory Testing

Perform blood counts and liver function tests periodically during long-term therapy.434

Specific Populations

Pregnancy

Category D.538

Lactation

Diazepam and its metabolites are distributed into milk;538 discontinue nursing or the drug.a

Pediatric Use

Safety and efficacy of oral formulations not established in infants <6 months of age.434 b

Safety and efficacy of parenteral formulations not established in infants ≤30 days of age.713

Safety and efficacy of rectal diazepam not established via clinical studies in children <2 years of age; manufacturer states that gel is not recommended in infants <6 months of age.538

CNS depression in neonates may be prolonged because of apparent inability to convert drug to inactive metabolites.713

Geriatric Use

Increased risk of adverse CNS effects.a Clearance may be decreased.538 Use with caution.538 (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Clearance may be decreased.538 Use with caution.b 538 (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Clearance of metabolites may be decreased.538 Use with caution.b 538

Common Adverse Effects

Drowsiness,434 b 538 713 ataxia,434 713 b muscle weakness,713 fatigue.434 713 b

With parenteral therapy, local reactions (venous thrombosis, phlebitis) at injection site.713

Interactions for Diazepam

Metabolized by CYP2C19 and CYP3A4.538

Drugs Affecting Hepatic Microsomal Enzymes

CYP2C19 and CYP3A4 inducers or inhibitors: Potential pharmacokinetic interaction (altered diazepam elimination).434 538 a

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Amitriptyline

Possible increased plasma amitriptyline concentrationsa

Clinical importance not determineda

Antacids (e.g., aluminum- and magnesium-containing)

Possible decreased rate of diazepam absorptiona

Carbamazepine

Possible decreased plasma diazepam concentrations538

Cigarette smoking

Possible decreased sedative effecta

Cimetidine

Increased plasma diazepam concentrations200 202 204 205 206 434 538

Use with caution; consider reduction of diazepam dosage200

Clotrimazole

Possible increased plasma diazepam concentrations538

CNS depressants (e.g., barbiturates, sedatives, anticonvulsants, alcohol)

Possible additive CNS effect434 a

Use caution to avoid overdosagea

Avoid alcohol use700

Dexamethasone

Possible decreased plasma diazepam concentrations538

Digoxin

Possible decreased renal excretion and increased plasma concentrations of digoxin200 208 209

Monitor serum digoxin concentrations; reduction of digoxin dosage may be necessary200 208 209

Disulfiram

Potential for increased plasma diazepam concentrations200 201

Reduce diazepam dosage as necessarya

Fluvoxamine

Decreased clearance of diazepam613

Generally avoid concomitant use613

HIV protease inhibitors (e.g., fosamprenavir, ritonavir, saquinavir)

Possible increased plasma diazepam concentrations614 620 622

Clinical importance not determined; consider possible need for diazepam dosage reduction614 620 622

Ketoconazole

Possible increased plasma diazepam concentrations538

Levodopa

Potential for decreased control of parkinsonian symptomsa

Use with cautiona

Lithium

One case of hypothermia reporteda

Opiate agonists and partial agonists

Risk of profound sedation, respiratory depression, coma, or death700 701 703 705 706 707

Whenever possible, avoid concomitant use708 709 710 711

Opiate analgesics: Use concomitantly only if alternative treatment options are inadequate; use lowest effective dosages and shortest possible duration of concomitant therapy; monitor closely for respiratory depression and sedation700 703

In patients receiving diazepam, initiate opiate analgesic, if required, at reduced dosage and titrate based on clinical response700

Reduce opiate dosage by at least one-third and administer in small increments when diazepam is administered IV concurrently with an opiate analgesic713 b

In patients receiving an opiate analgesic, initiate diazepam, if required for any indication other than epilepsy, at lower dosage than indicated in the absence of opiate therapy and titrate based on clinical response700

Opiate antitussives: Avoid concomitant use700 704

Consider offering naloxone to patients receiving benzodiazepines and opiates concomitantly709 712

Mineral oil

Possible decreased GI absorption of diazepama

Phenobarbital

Possible decreased plasma diazepam concentrations538

Phenytoin

Possible decreased plasma diazepam concentrations538

Quinidine

Possible increased plasma diazepam concentrations538

Rifampin

Possible decreased plasma diazepam concentrations538

Tests for urinary glucose

Possible false positive reactions for glucose with Clinistix and Diastixa

Reaction does not occur with Tes-Tapea

Tranylcypromine

Possible increased plasma diazepam concentrations538

Diazepam Pharmacokinetics

Absorption

Bioavailability

Apparently well absorbed following oral administration.a

Absorption is slow and erratic following IM administration.a

Rapidly and well absorbed following rectal administration as gel or solution; bioavailability averages 80–102%.538 539 540 543 Peak plasma concentrations attained within 1.5 hours following rectal administration of the gel in adults; absorption from gel may be more rapid in children.539

Onset

Onset of anticonvulsant, anxiolytic, or sedative action occurs in 1–5 minutes following IV administration.a

Duration

Duration of anticonvulsant, anxiolytic, or sedative action is 15–60 minutes following IV administration.a

Distribution

Extent

Apparently widely distributed into body tissues; crosses the blood-brain barrier.a

Diazepam and its metabolites cross the placenta and are distributed into milk.713 a

Plasma Protein Binding

Diazepam and desmethyldiazepam: 95–98%.a 538

Elimination

Metabolism

Metabolized in the liver by CYP2C19 and CYP3A4 to active metabolites.a 538

Elimination Route

Excreted principally in urine as inactive conjugates.a

Half-life

Diazepam: 20–50 hours.538 a

Metabolites: Desmethyldiazepam: 30–200 hours.538 a Temazepam: 5–20 hours.a Oxazepam: 3–21 hours.a

Special Populations

In neonates and infants, half-life may be prolonged; half-life may be shorter in children ≥2 years of age and adolescents.538

Geriatric patients and patients with hepatic impairment may have prolonged elimination half-lives of diazepam538 and its metabolites.a

Stability

Storage

Oral

Tablets

Tight, light-resistant containers at 15–30°C.434

Solution and Solution Concentrate

20–25°C.603 Protect from light.603

Parenteral

Injection

15–30°C.b Protect from light; avoid freezing.b

Rectal

Gel

25°C (may be exposed to 15–30°C).538

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Addition of diazepam injection to an IV infusion solution or plastic syringes may result in adsorption of diazepam to the plastic container and tubing.b

Solution CompatibilityHID

Variable

Dextrose 5% in water

Ringer’s injection

Ringer’s injection, lactated

Sodium chloride 0.9%

Drug Compatibility
Admixture CompatibilityHID

Compatible

Levetiracetam

Verapamil HCl

Incompatible

Bleomycin sulfate

Dobutamine HCl

Doxorubicin HCl

Fluorouracil

Furosemide

Y-Site CompatibilityHID

Compatible

Dobutamine HCl

Fentanyl citrate

Methadone HCl

Morphine sulfate

Nafcillin sodium

Quinidine gluconate

Incompatible

Acetaminophen

Atracurium besylate

Bivalirudin

Cangrelor tetrasodium

Ceftaroline fosamil

Dexmedetomidine HCl

Diltiazem HCl

Doripenem

Fenoldopam mesylate

Fluconazole

Foscarnet sodium

Heparin sodium with hydrocortisone sodium succinate

Hetastarch in lactated electrolyte injection (Hextend)

Linezolid

Meropenem

Oxaliplatin

Pancuronium bromide

Potassium chloride

Propofol

Tigecycline

Tirofiban HCl

Vecuronium bromide

Variable

Cisatracurium besylate

Hydromorphone HCl

Remifentanil HCl

Actions

  • Effects appear to be mediated through the inhibitory neurotransmitter GABA; the site and mechanism of action within the CNS appear to involve a macromolecular complex (GABAA-receptor-chloride ionophore complex) that includes GABAA receptors, high-affinity benzodiazepine receptors, and chloride channels.320 358 359 360 361 362 363 364 365 366 367 368 369 370

Advice to Patients

  • Provide manufacturer's patient information (e.g., medication guide) to the patient each time diazepam tablets are dispensed.434

  • Importance of taking only as prescribed; do not increase dosage or duration of therapy or abruptly discontinue drug unless otherwise instructed by a clinician.434

  • Risk of potentially fatal additive effects (e.g., profound sedation, respiratory depression, coma) if used concomitantly with opiates either therapeutically or illicitly.700 703 Avoid concomitant use of opiate antitussives;700 704 also avoid concomitant use of opiate analgesics unless use is supervised by clinician.700 703

  • Potential for drug to impair mental alertness or physical coordination; use caution when operating machinery or performing hazardous tasks until effects on individual are known.a

  • Importance of caregivers understanding their role and obligations for administration of diazepam gel to individuals in their care; prescribers should routinely discuss all steps detailed in the manufacturer’s patient/caregiver information.538

  • Upon receiving Diastat AcuDial from the pharmacy and again prior to administering a dose, importance of verifying accuracy of prescription (e.g., prescribed dose is visible in the applicator display window; green “ready” band is visible on each applicator).538 602

  • Importance of properly disposing of diazepam gel applicators.538

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and alcohol consumption.434 a Importance of avoiding alcohol-containing beverages or products.434 a

  • Importance of informing clinicians about any concomitant illnesses, particularly depression.434 a

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.434 538

  • Importance of informing patients of other important precautionary information.434 538 713 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Subject to control under the Federal Controlled Substances Act of 1970 as a schedule IV (C-IV) drug.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

diazePAM

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Solution

5 mg/5 mL*

diazePAM Solution (C-IV)

Solution, concentrate

5 mg/mL*

diazePAM Intensol (C-IV)

West-ward

diazePAM Solution Concentrate (C-IV)

Tablets

2 mg*

diazePAM Tablets (C-IV)

Valium (C-IV; scored)

Genentech

5 mg*

diazePAM Tablets (C-IV)

Valium (C-IV; scored)

Genentech

10 mg*

diazePAM Tablets (C-IV)

Valium (C-IV; scored)

Genentech

Parenteral

Injection

5 mg/mL*

diazePAM Injection (C-IV)

Rectal

Gel

5 mg/mL (2.5, 10, and 20 mg)*

Diastat Rectal Delivery System (C-IV; in prefilled applicators with pediatric universal or adult applicator tips)

Valeant

diazePAM Gel Rectal Delivery System (C-IV; in prefilled applicators with pediatric universal or adult applicator tips)

AHFS DI Essentials™. © Copyright 2020, Selected Revisions October 28, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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