A drug of choice for termination of status epilepticus or acute seizure episodes resulting from drug overdosage and poisons.
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).
Has been used as adjunct to other anticonvulsants for prophylaxis of epileptic seizures; however, tolerance to anticonvulsant effects often develops after short time. (See Seizure Disorders under Cautions.)
Adjunct to rest, physical activity, analgesics, and other measures for relief of discomfort associated with acute, painful musculoskeletal conditions.
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.
Sedation in Critical-Care Settings
Sedation of intubated and mechanically ventilated patients during treatment in a critical-care setting†. 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.
Night Terrors
Has been used effectively to prevent night terrors†.
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.
Myocardial Infarction
Has been used to relieve anxiety associated with AMI; however, AHA and ACC state that routine anxiolytic use is neither necessary not recommended.
Drug-Induced Cardiovascular Emergencies
Adjunct in the management of certain drug-induced cardiovascular emergencies† (e.g., drug-induced hemodynamically significant tachycardia†, hypertensive emergency†, acute coronary syndrome†, or acute anticholinergic syndrome†) when standard emergency cardiovascular care (ECC) guidelines may not be optimal or appropriate. Adjunct in the initial treatment of cocaine-induced acute coronary syndrome†.
Neonatal Opiate Withdrawal
Relief of agitation in the management of neonatal opiate withdrawal†.
Dosage and Administration
General
Use the smallest effective dosage to avoid oversedation.
Consider long half-life of diazepam and its metabolites when making dosage adjustments (see Half-life under Pharmacokinetics).
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.
Anxiety
Periodically reassess usefulness for treatment of anxiety. Administer for the shortest period of time; frequent dosage adjustments may be required.
Seizure Disorders
Do not discontinue diazepam abruptly in patients with a history of a seizure disorder, since seizures may be precipitated.
Administration
Administer orally, by IM or IV injection, or rectally.
Oral Administration
Initially, administer orally in 3 or 4 doses daily for the treatment of anxiety disorders or skeletal muscle spasticity. 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.
Dilute oral concentrate solution (e.g., with water, juice, carbonated beverages) or mix with semisolid foods (e.g., applesauce, pudding) just prior to administration.
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.
Take care to avoid intra-arterial administration or extravasation.
Switch patient to oral therapy as soon as possible.
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.
Rate of Administration
Adults: Inject dose slowly at rate of ≤5 mg per minute.
Children and infants ≥30 days of age: Administer dose slowly over 3 minutes.
IM Administration
May be administered as deep IM injection; however, absorption may be slow and erratic. IM route is rarely justified.
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. Consult the manufacturer’s labeling for specific instructions for administration of the rectal gel.
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.
Commercially available gel is provided in prefilled syringe applicators containing 2.5, 10, or 20 mg of diazepam.
Dose to be delivered by the AcuDial® applicator is locked into the device prior to dispensing. If necessary, use 2 applicators to administer the prescribed dose.
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 dose within 5 minutes after administration.
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.
Dispensing
Pharmacist must dial in and lock the correct dose to be administered prior to dispensing Diastat® AcuDial®.
While holding the barrel of the applicator in one hand, turn the cap of the applicator to select the dose. 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. A green “ready” band becomes visible at the base of the applicator once the dose-locking ring is engaged.
Repeat the process for each applicator to be dispensed.
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.
Remove the protective cap from the syringe and ensure that the seal pin is removed with the cap.
Lubricate the rectal applicator tip with the water-soluble lubricant (jelly) provided by the manufacturer.
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. 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). 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.
Leave the patient on their side facing the caregiver, note the time the dose was given, and observe the patient.
If bowel leakage occurs, a supplemental dose may be required. (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.
Prior to discarding AcuDial® applicator in the garbage, dispose of any gel remaining in the applicator. 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. Flush toilet or rinse sink with water until gel is no longer visible.
Inspection for Cracks in Applicator Tip
Formation of cracks at the base of the plastic tip of Diastat® AcuDial® applicators has been reported. (See Manufacturing Problem with Diazepam Rectal Gel [Diastat® AcuDial®] Applicators under Cautions.) Until the problem is resolved, Diastat® AcuDial® applicators should be inspected for cracks at the base of the applicator tip, without removal of the applicator cap, prior to dispensing and frequently (i.e., monthly) thereafter.
Obtain detailed instructions for inspecting syringe applicator from the manufacturer at 877-361-2719 or http://www.diastat.com.
Instruct patients and/or their caregivers to return any cracked applicators to the pharmacy for immediate replacement.
Pharmacists should contact RxHope at 800-511-2120 or http://www.rxhope.com to obtain replacements for damaged products.
Dosage
Pediatric Patients
Anxiety Disorders
Oral
Children ≥6 months of age: Initially, 1–2.5 mg 3 or 4 times daily. Alternatively, 0.12–0.8 mg/kg or 3.5–24 mg/m2 in 3 or 4 divided doses daily. Increase dosage gradually as needed and tolerated.
IV
0.04–0.2 mg/kg; may repeat in 3–4 hours. Total dose should not exceed 0.6 mg/kg in an 8-hour period.
Surgery
IM
Children >2 years of age: 0.4 mg/kg has been administered 1–2 hours before surgery.
Seizure Disorders
Oral
6–15 mg daily (occasionally up to 30 mg daily) in divided doses has been used.
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. May repeat dose in 2–4 hours.
Children ≥5 years of age: Initially, 1 mg; may repeat every 2–5 minutes to a maximum total dose of 10 mg. May repeat dose in 2–4 hours.
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). If necessary, repeat initial dose in 4–12 hours. Administration of a third dose is not recommended by the manufacturer.
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). If necessary, repeat initial dose in 4–12 hours. Administration of a third dose is not recommended by the manufacturer.
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). If necessary, repeat initial dose in 4–12 hours. Administration of a third dose is not recommended by the manufacturer.
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).
Skeletal Muscle Spasticity
Oral
0.12–0.8 mg/kg in 3 or 4 divided doses daily.
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.
Tetanus
IV or IM
Children >30 days to 5 years of age: 1–2 mg. May repeat dose every 3–4 hours as needed.
Children >5 years of age: 5–10 mg. May repeat dose every 3–4 hours as needed.
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.†
Neonatal Opiate Withdrawal
IM
0.5–2 mg has been administered every 8 hours, followed by gradual dosage reduction.†
Adults
Anxiety Disorders
Oral
2–10 mg 2–4 times daily, depending on the severity of the symptoms.
IV
Initially, 2–5 mg for moderate or 5–10 mg for severe acute anxiety; may repeat in 3–4 hours.
Surgery
Preoperative Sedation
IV or IM
10 mg 1–2 hours before surgery; some clinicians recommend doses up to 20 mg.
Cardioversion
IV
5–15 mg 5–10 minutes before the procedure.
Endoscopy
IV
Titrate dosage to obtain desired sedative response (e.g., slurring of speech). Initially, 10 mg, but up to 20 mg may be required, especially if opiates are not given concomitantly.
IM
5–10 mg approximately 30 minutes prior to endoscopy.
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.
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.
Alternatively, some clinicians recommend 10 mg initially, followed by 10 mg at 20–30 minutes intervals until patient is calm.
Seizure Disorders
Oral
2–10 mg 2–4 times daily.
IV or IM
Initially, 5–10 mg. May repeat at 10- to 15-minute intervals, to a maximum total dose of 30 mg. May repeat dose in 2–4 hours.
Rectal
Initially, 0.2 mg/kg as rectal gel, rounded up to next available dose (i.e., the next multiple of 2.5 mg). If necessary, repeat initial dose in 4–12 hours. Administration of a third dose is not recommended by the manufacturer.
For rectal administration of parenteral solutions†, 0.5 mg/kg (not to exceed 20 mg).
Skeletal Muscle Spasticity
Oral
2–10 mg 2–4 times daily.
IV
Initially, 5–10 mg; may repeat in 3–4 hours if necessary.
Tetanus
IV
Doses up to 20 mg have been given every 2–8 hours.
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.†
Night Terrors
Oral
Dosages of 5–20 mg at bedtime have been used.†
Labor and Delivery
IV
10–20 mg.†
Prescribing Limits
Pediatric Patients
IV
Maximum 0.25 mg/kg as a single initial dose, repeated at 15- to 30-minute intervals to a maximum total dose of 0.75 mg/kg.
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.
Adults
Anxiety Disorders
IV
Some clinicians recommend maximum dosage of 30 mg in an 8-hour period.
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.
Special Populations
Hepatic Impairment
Reduce dosage; use the smallest effective dose to avoid oversedation.
Renal Impairment
Use the smallest effective dose to avoid oversedation.
Geriatric Patients
Oral
Initially, 2–2.5 mg once or twice daily. Increase dosage gradually as needed and tolerated.
IV
Initially, 2–5 mg as a single dose. Increase dosage gradually as needed and tolerated.
Rectal
Dosage to be administered should be adjusted downward for the commercially available prefilled applicators of rectal gel.
Other Populations
Use the smallest effective dosage in debilitated patient and patients with low serum albumin concentrations. In debilitated patients, observe maximum geriatric dosages. (See Geriatric Patients under Dosage and Administration.)
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; however, clinical rationale for this contraindication has been questioned.
Warnings/Precautions
Warnings
CNS Effects
Performance of activities requiring mental alertness and physical coordination may be impaired.
Concurrent use of other CNS depressants may cause additive or potentiated CNS depression. (See Specific Drugs under Interactions.)
Psychiatric Indications
Do not use in patients with depressive neuroses or psychotic reactions in which anxiety is not prominent.
Respiratory and Cardiovascular Effects
Possibility of apnea and/or cardiac arrest. Use parenterally with caution in debilitated patients and in those with compromised respiratory function. Do not administer IV to patients in shock or coma or to those with acute alcohol intoxication with depression of vital signs.
Consider possibility of respiratory depression with rectal administration. Out-of-hospital caregivers should avoid repeated administration at relatively short intervals (see Prescribing Limits under Dosage and Administration).
Equipment for resuscitation should be readily available whenever diazepam is administered IV.
Concomitant use of other CNS depressants may increase the risk of apnea.
Abuse Potential
Psychologic and physical dependence may occur following prolonged use.
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.
Withdrawal Syndrome
Abrupt discontinuance may result in symptoms of withdrawal (similar to barbiturates). Symptoms may be relieved by tapering the dosage.
Seizure Disorders
Abrupt withdrawal may be associated with a temporary increase in seizure frequency or severity.
Effect on seizure activity after IV administration is short-lived; repeated administration may be necessary. Consider need for a longer-acting agent for continued seizure control.
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. (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.
Local Reactions Following Parenteral Administration
Potential for local reactions (e.g., pain, thrombophlebitis) following parenteral administration; possible tissue necrosis following intra-arterial administration. (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.
General Precautions
Suicide
Use with caution in depressed patients; potential for suicidal tendencies. Prescribe and dispense drug in the smallest feasible quantity.
Manufacturing Problem with Diazepam Rectal Gel (Diastat® AcuDial®) Applicators
Formation of cracks in the plastic tips of 10- and 20-mg diazepam rectal gel (Diastat® AcuDial®) applicators has been reported; problem is evident in up to 6% of applicators in some product lots; problem not reported with the 2.5-mg Diastat® applicators.
Can result in leakage of gel when the plunger is depressed during rectal administration and delivery of a potentially subtherapeutic dose of diazepam. There also is a risk that skin may be pinched by the cracked applicator tip during administration.
If delivery of the full dose of diazepam gel cannot be verified, caregiver should immediately contact emergency medical services.
Until the manufacturing problem is resolved, regularly inspect AcuDial® applicators for cracks at the base of the applicator tip. (See Rectal Administration under Dosage and Administration.)
Specific Populations
Pregnancy
Category D.
Lactation
Diazepam and its metabolites are distributed into milk; discontinue nursing or the drug.
Pediatric Use
Safety and efficacy of oral formulations not established in infants <6 months of age.
Safety and efficacy of injection not established in infants ≤30 days of age.
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.
CNS depression in neonates may be prolonged because of apparent inability to convert drug to inactive metabolites.
Geriatric Use
Increased risk of adverse CNS effects. Clearance may be decreased. Use with caution. (See Geriatric Patients under Dosage and Administration.)
Hepatic Impairment
Clearance may be decreased. Use with caution. (See Hepatic Impairment under Dosage and Administration.)
Renal Impairment
Clearance of metabolites may be decreased. Use with caution.
Common Adverse Effects
Drowsiness, ataxia, fatigue. With parenteral therapy, local reactions (venous thrombosis, phlebitis) at injection site.
Interactions
Metabolized by CYP2C19 and CYP3A4.
Drugs Affecting Hepatic Microsomal Enzymes
CYP2C19 and CYP3A4 inducers or inhibitors: Potential pharmacokinetic interaction (altered diazepam elimination).
Use caution to avoid overdosage; reduce opiate dosage by at least one-third and administer in small increments when diazepam is administered IV concurrently with an opiate analgesic
Apparently well absorbed following oral administration.
Absorption is slow and erratic following IM administration.
Rapidly and well absorbed following rectal administration as gel or solution; bioavailability averages 80–102%. 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.
Onset
Onset of anticonvulsant, anxiolytic, or sedative action occurs in 1–5 minutes following IV administration.
Duration
Duration of anticonvulsant, anxiolytic, or sedative action is 15–60 minutes following IV administration.
Distribution
Extent
Apparently widely distributed into body tissues; crosses the blood-brain barrier.
Diazepam and its metabolites cross the placenta and are distributed into milk.
Plasma Protein Binding
Diazepam and desmethyldiazepam: 95–98%.
Elimination
Metabolism
Metabolized in the liver by CYP2C19 and CYP3A4 to active metabolites.
Elimination Route
Excreted principally in urine as inactive conjugates.
In neonates and infants, half-life may be prolonged; half-life may be shorter in children ≥2 years of age and adolescents.
Geriatric patients and patients with hepatic impairment may have prolonged elimination half-lives of diazepam and its metabolites.
Stability
Storage
Oral
Tablets
Tight, light-resistant containers at 15–30°C.
Solution and Solution Concentrate
15–30°C. Protect from moisture.
Parenteral
Injection
15–30°C. Protect from light; avoid freezing.
Rectal
Gel
25°C (may be exposed to 15–30°C).
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.
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.
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.
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.
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.
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).
Importance of properly disposing of diazepam gel applicators.
Potential for cracks to form at the base of the applicator tip of Diastat® AcuDial®; importance of inspecting applicators frequently (i.e., monthly) and of immediately returning any cracked applicators to the pharmacy for replacement.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and alcohol consumption. Importance of avoiding alcohol-containing beverages or products.
Importance of informing clinicians about any concomitant illnesses, particularly depression.
Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.
Importance of informing patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Subject to control under the Federal Controlled Substances Act of 1970 as a schedule IV (C-IV) drug.
Diastat® Rectal Delivery System ( C-IV; in prefilled applicators with pediatric universal or adult applicator tips)
Valeant
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Comparative Pricing
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 10/2009. For the most current and up-to-date pricing information, please visit www.drugstore.com. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
Remember, keep this and all other medicines out of the reach of children,
never share your medicines with others, and use this medication only for the indication prescribed.
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