Introduction ⬇
VA Class:CN302
AHFS Class:
Generic Name(s):
Associated Monographs
Diazepam is a benzodiazepine. The drug has anticonvulsant, anxiolytic, sedative, and skeletal muscle relaxant properties.434,538,713
Uses ⬆ ⬇
Anxiety Disorders, Preoperative or Preprocedural Anxiolysis, Alcohol Withdrawal, and Musculoskeletal Conditions 
Diazepam is used for preoperative sedation, anxiolysis, and anterograde amnesia; for relief of anxiety and stress in patients undergoing procedures (e.g., endoscopic procedures,713 cardioversion713 ); for the management of agitation associated with acute alcohol withdrawal; as an adjunct for the relief of acute, painful musculoskeletal conditions; to manage 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, or tetanus; and for the management of anxiety disorders or for the short-term relief of symptoms of anxiety.
The efficacy of diazepam for long-term use (i.e., longer than 4 months) has not been evaluated.434
Seizures
Diazepam is used parenterally (IV administration preferred) for the treatment of status epilepticus and severe recurrent convulsive seizures.713 Oral diazepam may be used for adjunctive therapy of seizure disorders; however, loss of response to the anticonvulsant effects of the drug often develops with prolonged use.434
Diazepam also may be administered rectally either as a commercially available gel (e.g., Diastat®) or using parenteral† formulations for the management of seizure disorders and status epilepticus.538,544,549
Status Epilepticus
Benzodiazepines are considered the initial drugs of choice for the 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
Status epilepticus is a medical emergency that must be treated promptly to reduce substantial morbidity and mortality.545,763,764,766,767 Initial treatment should include standard critical care and supportive therapy (e.g., blood pressure and respiratory support, oxygen, IV access, identification and correction of underlying causes), followed by administration of a benzodiazepine.545,763,765,766 Although IV lorazepam is generally preferred because of its longer duration of action, studies generally have not identified any substantial differences between IV lorazepam, IV diazepam, and IM midazolam in terms of seizure cessation, and experts consider these therapies to be equivalent first-line options.545,763,764,765,766,767,768,769 Selection of an appropriate benzodiazepine should be individualized 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 To achieve a rapid therapeutic effect, IV administration of a benzodiazepine is preferred; however, administration via other routes (e.g., IM, rectal, intranasal, buccal) may be considered when IV administration is not possible (e.g., in the prehospital setting).543,545,546,547,763,764,765,766,768,769 If seizures continue after initial therapy with a benzodiazepine, a second-line anticonvulsant agent (e.g., IV fosphenytoin or phenytoin, IV valproate sodium, IV levetiracetam, IV phenobarbital) should be administered.757,759,760,762,763,765,766 If refractory status epilepticus occurs, continuous IV infusion of anticonvulsants, IV barbiturates, or general anesthetics may be necessary.757,758,759,760,761,765,766
To achieve a rapid therapeutic effect, IV administration of a benzodiazepine generally is preferred for the management of status epilepticus; however, administration via other routes (e.g., rectal) may be considered when IV administration is not possible (e.g., in a prehospital setting).543,545,547,763,764,765,766,768,769 Rectal administration of diazepam may be particularly useful for out-of-hospital management of status attacks (e.g., at home or school, during transport to an emergency room).543,545,546,547,548,549,763,764,765,766,768,769
Early treatment with benzodiazepines in the prehospital setting can improve outcomes in patients with status epilepticus.563,768 Results of a placebo-controlled study in adults with out-of-hospital status epilepticus indicated that IV administration of benzodiazepines by paramedics was safe and effective in the management of this condition.563 Findings from this study indicated that both IV lorazepam and IV diazepam were more effective than placebo in controlling status epilepticus by the time of patient arrival in the emergency department.563 Because the need to establish IV access may delay administration of an IV benzodiazepine in the prehospital environment, use of other less invasive routes of administration may decrease the time to active treatment.763,765,768
Acute Repetitive Seizures
Rectal diazepam also may be used for the management of acute repetitive seizures (also referred to as serial, cyclic, cluster, breakthrough, or crescendo seizures), especially for out-of-hospital management.538,540,544,547,550,551,775
Acute repetitive seizures are exacerbations of an underlying seizure disorder that exhibit a pattern distinct from the patient's usual seizure pattern; the repetitive, periodic episodes often are predictable by the patient and caregivers according to a prodrome/aura, time of day when they originate, particular seizure type, and/or accompanying patient behavioral changes.538,540,544 Patients typically experience recovery between the repetitions; however, if untreated, acute repetitive seizures can evolve into more serious problems, including status epilepticus.540 The distinguishing features of these seizures are their predictability and pattern that differs from the underlying disorder rather than the actual seizure type; thus, while the pattern of presentation and patient and caregiver recognition are common features of the diagnosis, the actual seizure type can be different albeit definable for each individual patient.538,540,544
In the 2 clinical studies establishing efficacy of rectal diazepam for the management of acute repetitive seizures in adults and children 2 years of age and older, the drug was more effective than placebo in reducing seizure frequency and improving global assessment of treatment outcome as judged by caregivers (e.g., frequency and severity of seizures and patient tolerance of therapy).538,540,544,775 In these studies, the time to next seizure was prolonged in diazepam-treated patients relative to placebo, and about 55-62% of patients were seizure-free during the 12-hour observation period versus 20-34% for placebo recipients.538,540,544 In these studies, patients with a history of acute repetitive seizures that typically progressed to status epilepticus were excluded from study entry.540,544 Similar efficacy has been reported in other placebo-controlled and open-label studies.550,551 Although formal economic analyses have not been performed to date, patients treated with rectal diazepam out of the hospital required emergency medical treatment less commonly than did placebo recipients.540,544
Sedation in Critical Care Settings
Diazepam has been used for the sedation of intubated and mechanically ventilated patients in critical care settings† (e.g., intensive care unit [ICU]).564,801 Because of some modest clinical benefits (e.g., reduced duration of mechanical ventilation, shorter time to extubation, reduced risk of delirium) and an overall favorable benefit-to-risk profile, nonbenzodiazepine sedatives (dexmedetomidine or propofol) are generally preferred to benzodiazepines (midazolam or lorazepam) in mechanically ventilated, critically ill adults.800,801 If a benzodiazepine is required, midazolam or lorazepam generally is used; diazepam is rarely used for this indication.801
Drug-induced Cardiovascular Emergencies
Diazepam has been used adjunctively in the management of certain drug-induced cardiovascular emergencies† and cocaine-induced acute coronary syndrome†.696
Other Uses
Diazepam has been used orally to prevent night terrors†. Although not recommended by the manufacturer, parenteral diazepam is used to reduce the requirements for opiate analgesics and produce anterograde amnesia during labor and delivery†. The drug has been used parenterally to manage neonatal opiate withdrawal†.
Dosage and Administration ⬆ ⬇
Diazepam is administered orally, by IV or IM injection, or rectally.
Administration
Oral Administration
Diazepam is administered orally as tablets or oral solution.434,603
When diazepam oral concentrate solution is used, the dose should be diluted (e.g., with water, juice, carbonated or soda-like beverages) or mixed with semi-solid foods (e.g., applesauce, pudding) using only the calibrated dropper provided by the manufacturer.603 The liquid or food mixture should be stirred gently for a few seconds and then consumed immediately; the mixture should not be stored for future use.603
Parenteral Administration
When oral therapy is not feasible or when a rapid therapeutic effect is necessary, diazepam may be administered by slow IV injection at a rate not exceeding 5 mg/minute in adults and over a 3-minute period in children. When given IV, diazepam should be administered directly into a large vein to avoid thrombosis; if this is not feasible, the drug should be given into the tubing of a flowing IV solution as close as possible to the vein insertion. Small veins such as those of the wrist or the dorsum of the hand should not be used. Care should be taken to avoid intra-arterial administration or extravasation. Some clinicians have suggested IV administration of dilute solutions of the drug to avoid extravasation; however, the drug may precipitate when diluted and the manufacturers do not recommend this method of administration. (See Chemistry and Stability: Stability.)
Although diazepam may also be given by deep IM injection, this route of administration of the drug is rarely justified because absorption is slow and erratic.
Therapy with oral diazepam should replace parenteral administration as soon as possible.
Rectal Administration
When diazepam is administered rectally, the drug may be given as a commercially available rectal gel via the delivery device (a plastic applicator with a flexible molded tip) provided by the manufacturer.538 Diazepam also has been administered rectally as the parenteral solution† via a syringe and rectally inserted tubing or via a lubricated tuberculin syringe ( without a needle) inserted 4-5 cm into the rectum.544,549
Diazepam rectal gel is commercially available in prefilled syringe applicators containing 2.5, 10, or 20 mg of diazepam.538 The 2.5-mg Diastat® applicator delivers a dose of 2.5 mg of diazepam; the 10-mg Diastat® AcuDial® applicator can be set to deliver a dose of 5, 7.5, or 10 mg of the drug; and the 20-mg Diastat® AcuDial® applicator can be set to deliver a dose of 12.5, 15, 17.5, or 20 mg of the drug.538 Both the 2.5- and 10-mg applicators are fitted with a plastic applicator tip that is 4.4 cm in length; the 20-mg applicator is fitted with an applicator tip that is 6 cm in length.538 The 4.4-cm rectal tip applicator generally is used for pediatric patients.601 Although dosage of diazepam rectal gel is calculated on a mg/kg basis by age, the actual dose administered is approximate and determined by rounding upward to the next available dose (i.e., the next multiple of 2.5 mg).538
Prior to dispensing the Diastat® AcuDial® preparation, the pharmacist must dial in and lock the correct dose to be administered.602 While holding the barrel of the applicator in one hand, the pharmacist turns the cap of the applicator to select the dose.538,602 After confirming that the dose visible in the display window is correct, the pharmacist locks the dose by grasping the locking ring and pushing upward to lock both sides of the ring.538,602 Once the dose-locking ring on the device is engaged, a green “ready” band becomes visible at the base of the applicator.602 The process should be repeated for each applicator to be dispensed.538,602 Upon receiving the drug from the pharmacy, the patient or caregiver should verify that the prescribed dose is visible in the display window and that the green “ready” band is visible.538
Caregivers should be instructed carefully in the use of diazepam rectal gel and should be given a copy of the administration instructions provided by the manufacturer.538 As soon as an episode of acute repetitive seizures is recognized, the caregiver should place the patient on their side so they won't fall and administer the prescribed dose of rectal diazepam.544 Before the prescribed dose is administered, the expiration date of the appropriate applicator(s) should be checked to ensure that it is in date; with the AcuDial® applicators, the visibility of the green “ready” band and the dose displayed in the display window also should be checked.538 The applicator is prepared for use by removing the protective cap from the syringe and ensuring that the seal pin is removed with the cap.538 The rectal applicator tip should be lubricated with the water-soluble lubricant (jelly) provided by the manufacturer538,544 and the patient should be turned 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 The lubricated applicator tip should then be inserted rectally until the rim of the syringe is snug against the rectal opening; once inserted, the plunger should be pushed slowly (counting aloud slowly to 3) until it stops (i.e., until the entire dose of the applicator has been expelled into the rectum).538 The caregiver should again count aloud slowly to 3 before removing the syringe from the rectum; to prevent leakage of the administered dose from the rectum, the buttocks should then be held together while again counting aloud slowly to 3.538 The patient should be left on their side facing the caregiver, the time the dose was given noted, and the patient observed.538 If bowel leakage occurs during rectal administration, it may be necessary to administer a supplemental dose.538 (See Dosage: Rectal Dosage, in Dosage and Administration.)
The rectal delivery system and all unused materials should be discarded in the garbage and not reused.538 Such disposal should be in a safe place away from children.538 Any diazepam rectal gel remaining in the AcuDial® applicator after use should be disposed of before the applicator is discarded.538 With the applicator tip pointed over the sink or toilet, the plunger should be pulled back and removed from the barrel of the syringe applicator and then replaced in the barrel and gently depressed until it stops, thereby forcing gel from the applicator tip into the sink or toilet.538 The toilet then should be flushed or the sink rinsed with water until gel is no longer visible.538 The applicator may then be discarded.538
Dosage
Dosage of diazepam must be individualized, and the smallest effective dosage should be used (especially in geriatric or debilitated patients or in those with liver disease or low serum albumin) to avoid oversedation. The doses recommended by the manufacturers for IM and IV administration are identical. When parenteral diazepam is used with an opiate analgesic, the dosage of the opiate should be reduced by at least one-third and administered in small increments. Because of the unpredictable response of children to CNS drugs, diazepam therapy should be initiated with the lowest dosage and increased as required. Since diazepam and its metabolites have long elimination half-lives, time to reach steady-state plasma concentrations should be considered when dosage adjustments are made.
In patients who have received prolonged (e.g., for several months) diazepam therapy, abrupt discontinuance of the drug should be avoided since manifestations of withdrawal can be precipitated; if the drug is to be discontinued in such patients, it is recommended that dosage be gradually tapered. It is particularly important that the drugs not be discontinued abruptly in patients with a history of a seizure disorder since seizures may be precipitated.
Oral Dosage
Adult Dosage
For the management of anxiety or for adjunctive treatment of seizure disorders, the usual adult oral dosage of diazepam is 2-10 mg 2-4 times daily as tablets or oral solution.434,603
For adjunctive treatment of skeletal muscle spasticity, the usual adult oral dosage of diazepam is 2-10 mg 3 or 4 times daily as tablets or oral solution.434,603
For the management of acute alcohol withdrawal, the usual adult oral dosage of diazepam is 10 mg 3 or 4 times as tablets or oral solution during the first 24 hours, followed by 5 mg 3 or 4 times daily as needed.434,603
In adults with night terrors†, 5-20 mg of diazepam has been administered orally as tablets or oral solution at bedtime.
The initial oral dosage of diazepam for geriatric or debilitated patients should be 2-2.5 mg once or twice daily as tablets or oral solution.434,603 Dosage should be adjusted gradually according to response and tolerance.434,603
Pediatric Dosage
The manufacturers state that children 6 months of age or older may receive an initial oral diazepam dosage of 1-2.5 mg 3 or 4 times daily as tablets or oral solution.434,603 When used as a sedative or muscle relaxant in children, some clinicians recommend an oral diazepam dosage of 0.12-0.8 mg/kg daily in 3 or 4 divided doses.601 Dosage should be adjusted gradually according to response and tolerance.434,603
As an adjunct in the management of epilepsy in children, 6-15 mg daily (and occasionally up to 30 mg daily) in divided doses as tablets or oral solution has been used by some clinicians.
Parenteral Dosage
Adult Dosage
If diazepam injection is used for rapid relief of acute anxiety, the usual adult IV or IM dose is 2-5 mg for moderate anxiety or 5-10 mg for severe anxiety.713 The dose may be repeated in 3-4 hours if necessary.713 Some clinicians recommend that the adult dosage should not exceed 30 mg within an 8-hour period.
For the management of acute alcohol withdrawal, the manufacturer states that the usual adult dose of diazepam is 10 mg administered IM or IV initially;713 some clinicians recommend an initial dose of up to 20 mg. If necessary, the manufacturer states that an additional dose of 5-10 mg may be administered in 3-4 hours if necessary.713 For acute alcohol withdrawal, some clinicians recommend 10 mg of diazepam IV initially, followed by 10 mg at 20- to 30-minute intervals until the patient is calm.
To relieve anxiety and stress and produce amnesia in adults undergoing cardioversion, 5-15 mg of diazepam may be given IV within 5-10 minutes prior to the procedure.713
To reduce anxiety prior to endoscopy, diazepam is administered slowly IV immediately before the procedure; dosage is titrated to obtain the desired sedative response, such as slurring of speech. Generally, IV administration of up to 10 mg is adequate in adults, but up to 20 mg may be required especially if opiates are not given concomitantly. If IV administration is not feasible, 5-10 mg of diazepam may be given IM approximately 30 minutes prior to endoscopy in adults.
For preoperative sedation in adults, 10 mg of diazepam may be administered parenterally 1-2 hours prior to surgery. IM administration is preferred.713 Some clinicians have recommended a dose of up to 20 mg preoperatively.
For the treatment of skeletal muscle spasticity in adults, 5-10 mg may be administered IM or IV initially, and 3-4 hours later if necessary.713 For tetanus in adults, larger doses may be required;713 up to 20 mg has been given every 2-8 hours.
For the treatment of status epilepticus or severe recurrent convulsive seizures, the usual initial adult dose of diazepam is 5-10 mg administered IV.713 The initial dose may be repeated at 10- to 15-minute intervals, if necessary, until a maximum total dose of 30 mg has been given.713 If necessary, therapy with diazepam may be repeated in 2-4 hours, with consideration that residual active metabolites may persist following readministration.713 Although IV administration is preferred, diazepam may be given IM if IV administration is not possible.713
To reduce the requirements for opiate analgesics and produce anterograde amnesia during labor and delivery†, the usual parenteral dosage of diazepam is 10-20 mg.
If diazepam is used for sedation in intubated and mechanically ventilated adults in critical care settings†, an IV loading dose of 5-10 mg, followed by intermittent diazepam injections of 0.03-0.1 mg/kg every 0.5-6 hours as needed is recommended by some experts.801 Dosage should be titrated to the desired level of sedation; in most cases, a light rather than deep level of sedation is recommended in critically ill, mechanically ventilated adults.800,801 The depth and quality of sedation should be assessed frequently using a validated and reliable assessment tool.800,801
In geriatric or debilitated patients or in patients receiving other sedative drugs, lower parenteral diazepam doses (usually 2-5 mg) should be used, and dosage should be slowly increased if needed.713
Pediatric Dosage
In pediatric patients, IV diazepam should be given slowly over a 3-minute period.713 The manufacturers recommend that the initial dose not exceed 0.25 mg/kg.713 The dose may be repeated after 15-30 minutes; if relief of symptoms is not obtained after a third dose, adjunctive therapy appropriate to the condition being treated is recommended.713
For the treatment of status epilepticus or severe recurrent convulsant seizures in children 30 days to less than 5 years of age, the usual initial dose of diazepam is 0.2-0.5 mg administered slowly IV; this dose may be repeated every 2-5 minutes up to a maximum total dose of 5 mg.713,767 In children 5 years of age or older, the initial dose for the management of seizures is 1 mg administered slowly IV; this dose may be repeated every 2-5 minutes up to a maximum total dose of 10 mg.713 If necessary, the initial dose of diazepam may be repeated in 2-4 hours.713 Although IV administration is preferred, diazepam may be given IM if IV administration is not possible.713 Some clinicians prefer IV lorazepam because of its more prolonged duration of effect.545 If seizures continue with either diazepam or lorazepam, an additional long-acting anticonvulsant (e.g., IV phenytoin or fosphenytoin) generally is initiated.545
For tetanus in children, the manufacturers recommend 1-2 mg of diazepam for infants older than 30 days to 5 years of age and 5-10 mg for children older than 5 years of age administered slowly IV or by IM injection. This dose may be repeated every 3-4 hours as needed.
In painful musculoskeletal conditions and spasticity including tetanus in children, some clinicians recommend diazepam 0.04-0.3 mg/kg IV every 2-4 hours; however, dosage generally should not exceed 0.6 mg/kg in an 8-hour period.
Although the manufacturers have not established pediatric dosage recommendations for preoperative sedation, some clinicians have recommended IM administration of 0.4 mg/kg of diazepam in children older than 2 years of age 1-2 hours prior to surgery.
For acute anxiety reactions in children, some clinicians recommend 0.04-0.2 mg/kg of diazepam IV; this dose may be repeated in 3-4 hours, but dosage should not exceed 0.6 mg/kg in an 8-hour period.
Although the safety and efficacy of parenteral diazepam in infants 30 days of age or younger have not been established, neonates with agitation due to opiate withdrawal have received 0.5-2 mg IM every 8 hours followed by gradual reduction in dosage.
Rectal Dosage
When diazepam is administered rectally as the commercially available gel for the management of acute repetitive seizures, the dose should be individualized for maximum benefit.538 Children 2-5 years of age should receive 0.5 mg/kg and those 6-11 years of age should receive 0.3 mg/kg; adults and children 12 years of age and older should receive 0.2 mg/kg.538,540,544 These age-adjusted doses were based on the observation that diazepam clearance in children declines with age until about 12 years of age, at which time adult values are reached.540 The actual dose to be administered is determined by rounding up to the nearest commercially available dose (i.e., the next multiple of 2.5 mg).538,540,544 Using this method of rounded dosing, patients will receive 90-180% of the dose calculated on a weight and age basis.538,544 The safety of this dosing method has been established in clinical studies in adults and children 2 years of age and older.538,540,544 For geriatric or debilitated patients, the dose of the rectal gel should be adjusted downward to reduce the likelihood of ataxia and oversedation.538 The 2.5-mg applicator also may be used to provide a partial replacement dose (supplemental dose) for patients who partially expel the recommended dose538,540 within 5 minutes after administration.540
If necessary for adequate seizure control, the usual age- and weight-adjusted dose of diazepam rectal gel may be repeated 4-12 hours after the initial dose.538,540 Although the usual dose was repeated a third time 8 hours after the second dose in adults in one clinical study, the additional dose resulted in increased sedation and appeared to negatively affect global caregiver assessment of treatment outcome;540 therefore, a third dose currently is not recommended by the manufacturer.538 Dosage should be adjusted periodically by the clinician to reflect changes in the patient's age and/or weight; the manufacturer recommends dosage reevaluation at 6-month intervals.538
The manufacturer states that diazepam rectal gel is intended for use solely on an intermittent basis and therefore should be administered by caregivers outside the hospital no more frequently than one treatment course every 5 days nor more frequently than 5 treatment courses per month.538 In addition, chronic daily use of the rectal gel is not recommended because of the potential for development of tolerance to diazepam; chronic daily use may increase the frequency and/or severity of tonic-clonic seizures, requiring an increase in the dosage of concomitant chronic anticonvulsant therapy.538 In such cases, abrupt withdrawal of chronic diazepam also may be associated with a temporary increase in the frequency and/or severity of seizures.538
Because caregivers will be responsible for recognizing seizure episodes suitable for treatment, making the decision to initiate treatment, administering the drug, monitoring the patient, and assessing the adequacy of response, a major component of the prescribing process is the careful instruction of these individuals.538 The clinician and caregiver must share a common explicit understanding of what constitutes a seizure episode (and/or the events, which may be nonconvulsive, presumed to herald their onset) that is appropriate for treatment, the timing of administration in relation to the onset of the episode, the mechanics of competently administering the drug, how and what to observe following administration, when to repeat a dose, and what would constitute an outcome requiring immediate and direct medical attention.538
The caregiver should be instructed to contact the patient's clinician or seek other medical assistance if the seizure episode persists for longer than 15 minutes after administering the rectal gel (or as otherwise instructed), if the seizure behavior differs from other episodes, if the seizure frequency or severity or patient color or breathing is alarming, or if the patient is experiencing unusual or serious problems.538
The patient's underlying seizure disorder should be stabilized with a standard chronic anticonvulsant drug regimen, and rectal diazepam should be used only as an adjunct to this regimen for characteristic breakthrough bouts of repetitive seizures.538
When using the parenteral solution† of diazepam for rectal administration in the treatment of status epilepticus, a dose of 0.5 mg/kg (up to 20 mg) has been used in adults and children.545,546,547,549,601 Some clinicians state that a second dose of 0.25 mg/kg may be administered after 10 minutes if needed.601
Cautions ⬆ ⬇
Drowsiness, fatigue, muscle weakness, and ataxia are the most common adverse effects of diazepam.434,713 With parenteral therapy, local reactions (venous thrombosis, phlebitis) at the injection site are the most common adverse effects of the drug.713 For further information on adverse effects reported with benzodiazepines, see Cautions in the Benzodiazepines General Statement 28:24.08
Precautions and Contraindications
Diazepam shares the toxic potentials of the benzodiazepines, and the usual precautions of benzodiazepine administration should be observed. (See Cautions in the Benzodiazepines General Statement 28:24.08.)
A boxed warning has been included in the prescribing information for all benzodiazepines describing the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions associated with all drugs in this class.900 Abuse and misuse can result in overdose or death, especially when benzodiazepines are combined with other medicines, such as opioid pain relievers, alcohol, or illicit drugs.900 Frequent follow-up with patients receiving benzodiazepines is important.900 Reassess patients regularly to manage their medical conditions and any withdrawal symptoms.900 Clinicians should assess a patient's risk of abuse, misuse, and addiction. Standardized screening tools are available ([Web]).900 To reduce the risk of acute withdrawal reactions, use a gradual dose taper when reducing the dosage or discontinuing benzodiazepines.900 Take precautions when benzodiazepines are used in combination with opioid addiction medications.900
Parenterally administered diazepam may cause hypotension and/or respiratory depression, particularly if the drug is administered too rapidly IV. The drug should be administered slowly IV at a rate not exceeding 5 mg/minute in adults and over a 3-minute period in children; facilities and equipment for respiratory or cardiovascular assistance should be readily available.
The possibility that respiratory depression could occur with rectal administration of diazepam also should be considered, although the risk of its development probably is less than that with IV administration.538,540,544,546,547,550,551,554 The drug should be used with caution in patients with compromised respiratory function secondary to an underlying disease (e.g., asthma, pneumonia) or neurologic damage.538 Repeated rectal therapy at relatively short intervals by out-of-hospital caregivers should be avoided because of the possibility of life-threatening respiratory depression;547 the manufacturer recommends that out-of-hospital rectal diazepam therapy be repeated no more frequently than once during a 5-day period or 5 times monthly and that dosing be limited to 2 doses per treatment course.538 (See Dosage: Rectal Dosage, in Dosage and Administration.)
Diazepam is contraindicated in patients with known hypersensitivity to the drug.434,538 The manufacturers state that the drug is contraindicated in patients with acute angle-closure glaucoma but may be used with caution in patients with open-angle glaucoma who are receiving appropriate therapy.434,538 However, the clinical rationale for this contraindication has been questioned.
Pediatric Precautions
Safety and efficacy of oral diazepam in infants younger than 6 months of age have not been established. Safety and efficacy of parenteral diazepam in infants 30 days of age or younger have not been established. Safety and efficacy of rectal diazepam have not been established via clinical studies in children younger than 2 years of age, and the manufacturer states that the rectal gel is not recommended for use in infants younger than 6 months of age.538
Other Information ⬆ ⬇
Chemistry and Stability
Chemistry
Diazepam is a benzodiazepine. Diazepam occurs as an off-white to yellow, practically odorless, crystalline powder. The drug is sparingly soluble in propylene glycol and has solubilities of approximately 3 mg/mL in water and 62.5 mg/mL in alcohol at 25°C. Diazepam has a pKa of 3.4. Sodium benzoate and benzoic acid are added to the commercially available injection to adjust the pH to 6.2-6.9.
Diazepam rectal gel is commercially available as a nonsterile viscous gel formulated in an aqueous base that contains propylene glycol, alcohol (10%), hydroxypropyl methylcellulose, sodium benzoate, benzyl alcohol (1.5%), and benzoic acid.538,539 The rectal gel is clear to slightly yellow538 and has a pH of 6.5-7.2.538,539
Stability
Diazepam injection should be protected from light and stored at 15-30°C; freezing should be avoided. Diazepam tablets and extended-release capsules should be stored in tight, light-resistant containers at 15-30°C. Diazepam oral solution and oral concentrate solution should be stored at 20-25°C.603
The manufacturers state that diazepam injection should not be mixed with other drugs or IV fluids. Although some studies indicate that diazepam injection may be compatible with various drugs and IV fluids (e.g., diluted to a concentration of 5 mg/50 mL to 5 mg/100 mL with 0.9% sodium chloride, 5% dextrose, Ringer's, or lactated Ringer's injection), compatibility may depend on several factors (e.g., the concentration of the drugs, resulting pH, temperature). Specialized references should be consulted for more specific compatibility information. The addition of diazepam injection to an IV infusion solution or plastic syringes may result in adsorption of diazepam to the plastic container and tubing.
Diazepam rectal gel should be stored at a controlled room temperature of 25° but may be exposed to temperatures ranging from 15-30°C.538
Additional Information
For further information on chemistry, pharmacology, pharmacokinetics, uses, cautions, chronic toxicity, acute toxicity, drug interactions, laboratory test interferences, and dosage and administration of diazepam, see the Benzodiazepines General Statement 28:24.08.
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.
Diazepam is subject to control under the Federal Controlled Substances Act of 1970 as a schedule IV (C-IV) drug.
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) | |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Copyright ⬆ ⬇
AHFS® Drug Information. © Copyright, 1959-2024, Selected Revisions September 28, 2022. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
References ⬆
Please see the general statement for a list of references.
Only references cited for selected revisions after 1984 are available electronically.
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