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Diazepam

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

Warning

    Concomitant Use with Opiates
  • Concomitant use of benzodiazepines and opiates may result in profound sedation, respiratory depression, coma, and death.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.700 703 (See Specific Drugs and Laboratory Tests under Interactions.)

Introduction

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

Uses for Diazepam

Anxiety Disorders

Management of anxiety disorders and short-term relief of anxiety or anxiety associated with depressive symptoms.434 a b

Surgery

Relief of anxiety and provision of sedation, light anesthesia, and anterograde amnesia prior to endoscopy, cardioversion, and minor surgical procedures.a c

Seizure Disorders

A drug of choice for termination of status epilepticus or acute seizure episodes resulting from drug overdosage and poisons.a b c

Rectal administration 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

Has been used as adjunct to other anticonvulsants for prophylaxis of epileptic seizures;434 b however, tolerance to anticonvulsant effects often develops after short time.a (See Seizure Disorders under Cautions.)

Alcohol Withdrawal

Relief of agitation and tremor and prevention or symptomatic relief of delirium tremens and hallucinations associated with acute alcohol withdrawal.434 a b c

Skeletal Muscle Spasticity

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

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.a b c

Sedation in Critical-Care Settings

Sedation of intubated and mechanically ventilated patients during treatment in a critical-care setting.564 One of several benzodiazepines recommended for sedation of acutely agitated patients because of its rapid onset and short duration of action when given in single doses.564

Night Terrors

Has been used effectively to prevent night terrors.a b

Labor and Delivery

Is used as an adjunct to local anesthetics and systemic analgesics during labor and delivery to reduce requirements for opiate analgesics and to produce anterograde amnesia, although nor recommended by manufacturer.a b

Myocardial Infarction

Has been used to relieve anxiety associated with acute MI;531 532 however, AHA and ACC state that routine anxiolytic use is neither necessary nor recommended.531

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 the 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

Anxiety

  • Periodically reassess usefulness for treatment of anxiety.a Administer for the shortest period of time; frequent dosage adjustments may be required.a

Seizure Disorders

  • Do not discontinue diazepam abruptly in patients with a history of a seizure disorder, since seizures may be precipitated.a b

Administration

Administer orally,434 a by IM or IV injection,a c or rectally.c

Oral Administration

Initially, administer orally in 3 or 4 doses daily for the treatment of anxiety disorders or skeletal muscle spasticity.a b When dosage is stabilized, may administer orally in 1 or 2 doses daily, with all or most of the dosage given at bedtime to minimize daytime sedation.b

Dilute oral concentrate solution (e.g., with water, juice, carbonated beverages) or mix with semisolid foods (e.g., applesauce, pudding) just prior to administration.b

IV Administration

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

For IV injection, administer dose 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.b c

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

Switch patient to oral therapy as soon as possible.b

Dilution

Some clinicians recommend IV administration of a dilute solution to avoid extravasation; however, manufacturers do not recommend this method of administration, since precipitation may occur.b c

Rate of Administration

Adults: Inject dose slowly at rate of ≤5 mg per minute.b c

Children and infants ≥30 days of age: Administer dose slowly over 3 minutes.b c

IM Administration

May be administered as deep IM injection;a b c 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 the delivery device (a plastic applicator with a flexible molded tip) provided by the manufacturer.538 Consult the manufacturer’s labeling for specific instructions for administration of the rectal gel.538

Alternatively, administer 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

Pediatric (4.4 cm in length)

Diastat AcuDial 10 mg

5, 7.5, or 10 mg

Pediatric (4.4 cm in length)

Diastat AcuDial 20 mg

10, 12.5, 15, 17.5, or 20 mg

Adult (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

Prescribing

Prescription should indicate the appropriate dose to be locked into the applicator, the appropriate rectal tip size, and the number of packages (2 applicators per package) to be dispensed.603

Dispensing

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

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

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 aloud slowly to 3 before removing the syringe from the rectum; to prevent leakage of the administered dose from the rectum, hold the buttocks together while again counting aloud 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

If bowel leakage occurs, a supplemental dose may be required.538 (See Rectal Administration under Dosage and Administration.)

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: Initially, 1–2.5 mg 3 or 4 times daily.434 b Alternatively, 0.12–0.8 mg/kg or 3.5–24 mg/m2 in 3 or 4 divided doses daily.434 b Increase dosage gradually as needed and tolerated.434 b

IV

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

Surgery
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.b

IV or IM

Children 30 days to 5 years of age: Initially, 0.1–0.5 mg; may repeat every 2–5 minutes to a maximum total dose of 5–10 mg.b c May repeat dose in 2–4 hours.b

Children ≥5 years of age: Initially, 1 mg; may repeat every 2–5 minutes to a maximum total dose of 10 mg.b c May repeat dose in 2–4 hours.b

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

Usual dosage of parenteral solutions administered rectally in children: 0.5 mg/kg (not to exceed 20 mg).545 546 547 549

Skeletal Muscle Spasticity
Oral

0.12–0.8 mg/kg in 3 or 4 divided doses daily.e

IV

0.04–0.3 mg/kg has been administered every 2–4 hours, not to exceed 0.6 mg/kg in an 8-hour period.b

Tetanus
IV or IM

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

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

Sedation in Critical-Care Settings
IV

Children >12 years of age: 0.03–0.1 mg/kg as an intermittent injection every 0.5–6 hours; more frequent administration may be required for the management of acutely agitated patients.564

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 the severity of the symptoms.434 b

IV

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

Surgery
Preoperative Sedation
IV or IM

10 mg 1–2 hours before surgery;b c some clinicians recommend doses up to 20 mg.b

Cardioversion
IV

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

Endoscopy
IV

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

IM

5–10 mg approximately 30 minutes prior to endoscopy.b c

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 b

IV

Initially, 10 mg (some clinicians recommend up to 20 mg), then 5–10 mg every hour if necessary, although an interval of 3–4 hours may be satisfactory.b c

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

Seizure Disorders
Oral

2–10 mg 2–4 times daily.434 b

IV or IM

Initially, 5–10 mg.b c May repeat at 10- to 15-minute intervals, to a maximum total dose of 30 mg.b c May repeat dose in 2–4 hours.b c

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 (not to exceed 20 mg).545 546 547 548 549

Skeletal Muscle Spasticity
Oral

2–10 mg 2–4 times daily.434 b

IV

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

Tetanus
IV

Doses up to 20 mg have been given every 2–8 hours.b

Sedation in Critical-Care Settings
IV

0.03–0.1 mg/kg as an intermittent injection every 0.5–6 hours; more frequent administration may be required for the management of acutely agitated patients.564

Night Terrors
Oral

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

Labor and Delivery
IV

10–20 mg.b

Prescribing Limits

Pediatric Patients

IV

Maximum 0.25 mg/kg as a single initial dose,b c repeated at 15- to 30-minute intervals to a maximum total dose of 0.75 mg/kg.b c

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 the smallest effective dose to avoid oversedation.a

Renal Impairment

Use the smallest effective dose to avoid oversedation.a

Geriatric Patients

Oral

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

IV

Initially, 2–5 mg as a single dose.b c Increase dosage gradually as needed and tolerated.b c

Rectal

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

Other Populations

Use the smallest effective dosage in debilitated patient 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 c 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 b c 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.700 701 703 705 706 707 Substantial proportion of fatal opiate overdoses involve concurrent benzodiazepine use.700 701 705 706 707 711

Reserve concomitant use of diazepam and opiates for patients in whom alternative treatment options are inadequate.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.c Use parenterally with caution in debilitated patients and in those with compromised respiratory function.a b c 538 Do not administer IV to patients in shock or coma or to those with acute alcohol intoxication with depression of vital signs.c

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 is administered IV.b c

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

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 may result in symptoms of withdrawal (similar to barbiturates).434 a c Symptoms may be relieved by tapering the dosage.434 a c

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.c Consider need for a longer-acting agent for continued seizure control.c

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 occurred following IV administration to control absence status or Lennox-Gastaut syndrome status epilepticus.a c

Local Reactions Following Parenteral Administration

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

Out-of-Hospital 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 injection not established in infants ≤30 days of age.b c

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.c

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 c b 538 ataxia,434 c b fatigue.434 b With parenteral therapy, local reactions (venous thrombosis, phlebitis) at injection site.c

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 c

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 c

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 c f

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 concentrations=200 201

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 analgesicb c

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

Troleandomycin

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.a c

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

15–30°C.f Protect from moisture.f

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 Compatibilityd

Variable

Dextrose 5% in water

Ringer’s injection

Ringer’s injection, lactated

Sodium chloride 0.9%

Drug Compatibility
Admixture Compatibilityd

Compatible

Verapamil HCl

Incompatible

Bleomycin sulfate

Dobutamine HCl

Doxorubicin HCl

Fluorouracil

Furosemide

Y-Site Compatibilityd

Compatible

Dobutamine HCl

Fentanyl citrate

Methadone HCl

Morphine sulfate

Nafcillin sodium

Quinidine gluconate

Incompatible

Amphotericin B cholesteryl sulfate complex

Atracurium besylate

Bivalirudin

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

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

  • 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 f

  • 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; if the drug is intended for use in a child, each applicator has a 4.4-cm tip).538 603

  • 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 c

  • Importance of informing patients of other important precautionary information.434 538 c (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)

Westward

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 2017, Selected Revisions November 20, 2017. 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.

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