diazepam

Therapeutic Classification: antianxiety agents, anticonvulsants, sedative/hypnotics, skeletal muscle relaxants (centrally acting)

Pharmacologic Classification: benzodiazepines

BEERS REMS

Anxiety disorders.
Preoperative sedation.
Conscious sedation (provides light anesthesia and anterograde amnesia).
Status epilepticus/uncontrolled seizures.
Acute treatment of intermittent, stereotypic episodes of frequent seizure activity that are distinct from a patient’s usual seizure pattern (not status epilepticus) (nasal spray or buccal film).
Skeletal muscle spasms.
Alcohol withdrawal.

Depresses the CNS, probably by potentiating GABA, an inhibitory neurotransmitter.
Produces skeletal muscle relaxation by inhibiting spinal polysynaptic afferent pathways.
Has anticonvulsant properties due to enhanced presynaptic inhibition.

Therapeutic effects:

Relief of anxiety.
Sedation.
Amnesia.
Skeletal muscle relaxation.
Decreased seizure activity.

Absorption: Rapidly absorbed from the GI tract. Absorption from IM sites may be slow and unpredictable. Well absorbed from rectal mucosa (90%) and nasal mucosa (97%). IV administration results in complete bioavailability.

Distribution: Widely distributed. Crosses the blood-brain barrier.

Metabolism/Excretion: Primarily metabolized in the liver via the CYP2C19 and CYP3A4 isoenzymes; the CYP2C19 isoenzyme exhibits genetic polymorphism; 5–20% of Asian patients and 3–5% of Caucasian and Black patients may be poor metabolizers and may have significantly ↑ diazepam concentrations and an ↑ risk of adverse effects. Some products of metabolism are active as CNS depressants.

Half-Life: Neonates: 50–95 hr; Infants (1 mo–2 yr): 40–50 hr; Children 2–12 yr: 15–21 hr; Children 12–16 yr: 18–20 hr; Adults: 20–50 hr (up to 100 hr for metabolites).

(sedation)

ROUTE	ONSET	PEAK	DURATION
PO	30–60 min	1–2 hr	up to 24 hr
IM	within 20 min	0.5–1.5 hr	unknown
IV	1–5 min	15–30 min	15–60 min‡
Rectal	2–10 min	1–2 hr	4–12 hr

‡In status epilepticus, anticonvulsant duration is 15–20 min.

Contraindicated in:

Hypersensitivity;
Cross-sensitivity with other benzodiazepines may occur;
Comatose patients;
Myasthenia gravis;
Severe pulmonary impairment;
Sleep apnea;
Severe hepatic impairment;
Pre-existing CNS depression;
Uncontrolled severe pain;
Angle-closure glaucoma;
Some products contain alcohol, propylene glycol, or tartrazine and should be avoided in patients with known hypersensitivity or intolerance;
Lactation: Lactation;
Pedi: Children 6 mo (for oral; safety not established).

Use Cautiously in:

Severe renal impairment;
History of suicide attempt or drug dependence;
Debilitated patients (dose ↓ required);
Patients with low albumin;
OB: Use late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in neonates;
Pedi: Metabolites can accumulate in neonates. Injection contains benzyl alcohol, which can cause potentially fatal gasping syndrome in neonates;
Geri: Appears on Beers list. risk of cognitive impairment, delirium, falls, fractures, and motor vehicle accidents. If possible, avoid use in older adults.

CV: hypotension (IV only)

Derm: rash

EENT: ↑intraocular pressure, blurred vision, epistaxis (nasal spray only), nasal congestion (nasal spray only), nasal discomfort (nasal spray only)

GI: constipation, diarrhea (may be caused by propylene glycol content in oral solution), nausea, vomiting

Local: pain (IM), phlebitis (IV)

Metab: weight gain

Neuro: dizziness, drowsiness, lethargy, ataxia, depression, dysgeusia (nasal spray only), hangover, headache, paradoxical excitation, slurred speech

Resp: RESPIRATORY DEPRESSION

Misc: physical dependence, psychological dependence, tolerance

Drug-drug:

Use with opioids or other CNS depressants, including other benzodiazepines, nonbenzodiazepine sedative/hypnotics, anxiolytics, general anesthetics, muscle relaxants, antipsychotics, and alcohol, may cause profound sedation, respiratory depression, coma, and death; reserve concurrent use for when alternative treatment options are inadequate.
Cimetidine, hormonal contraceptives, disulfiram, fluoxetine, isoniazid, ketoconazole, metoprolol, propranolol, or valproic acid may ↓ the metabolism of diazepam, enhancing its actions.
May ↓ the efficacy of levodopa.
Rifampin or barbiturates may ↑ the metabolism and ↓ effectiveness of diazepam.
Sedative effects may be ↓ by theophylline.
Concurrent use of ritonavir is not recommended.

Drug-Natural Products:

Concomitant use of kava-kava, valerian, or chamomile can ↑ CNS depression.

Anxiety

PO (Adults ): 2–10 mg 2–4 times daily.
IM IV (Adults ): 2–10 mg; may repeat in 3–4 hr as needed.
PO (Children >6 mo): 1–2.5 mg 3–4 times daily.
IM IV (Children >1 mo): 0.04–0.3 mg/kg/dose every 2–4 hr to a maximum of 0.6 mg/kg within an 8-hr period if necessary.

Pre-Endoscopy

IV (Adults ): 2.5–20 mg.
IM (Adults ): 5–10 mg 30 min pre-endoscopy.

Pediatric Conscious Sedation for Procedures

PO (Children >6 mo): 0.2–0.3 mg/kg (not to exceed 10 mg/dose) 45–60 min prior to procedure.

Status Epilepticus/Acute Seizure Activity

(Children 2–5 yr and 26–30 kg): 15 mg as single dose. May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode)
(Children 2–5 yr and 21–25 kg): 12.5 mg as single dose. May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode)
(Children 2–5 yr and 16–20 kg): 10 mg as single dose. May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode)
(Children 2–5 yr and 11–15 kg): 7.5 mg as single dose. May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode)
(Children 2–5 yr and 6–10 kg): 5 mg as single dose. May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode)
IV (Adults ): 5–10 mg, may repeat every 10–15 min to a total of 30 mg, may repeat regimen again in 2–4 hr (IM route may be used if IV route unavailable); larger doses may be required.
IM IV (Children ≥5 yr): 0.05–0.3 mg/kg/dose given over 3–5 min every 15–30 min to a total dose of 10 mg, repeat every 2–4 hr.
IM IV (Children 1 mo–5 yr ): 0.05–0.3 mg/kg/dose given over 3–5 min every 15–30 min to maximum dose of 5 mg, repeat in 2–4 hr if needed.
IV (Neonates ): 0.1–0.3 mg/kg/dose given over 3–5 min every 15–30 min to maximum dose of 2 mg.
(Adults and Children ≥12 yr and ≥76 kg): 0.2 mg/kg as single dose (total dose = 20 mg; administered using two 10-mg spray devices, with one spray [10 mg] from each device administered into each nostril). May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode)
(Adults and Children ≥12 yr and 51–75 kg): 0.2 mg/kg as single dose (total dose = 15 mg; administered using two 7.5-mg spray devices, with one spray [7.5 mg] from each device administered into each nostril). May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode).
(Adults and Children ≥12 yr and 28–50 kg): 0.2 mg/kg as single dose (total dose = 10 mg; administered using one 10-mg spray device, with one spray [10 mg] from device administered into one nostril). May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode).
(Adults and Children ≥12 yr and 14–27 kg): 0.2 mg/kg as single dose (total dose = 5 mg; administered using one 5-mg spray device, with one spray [5 mg] from device administered into one nostril). May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode).
(Children 6–11 yr and 56–74 kg): 0.3 mg/kg as single dose (total dose = 20 mg; administered using two 10-mg spray devices, with one spray [10 mg] from each device administered into each nostril). May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode).
(Children 6–11 yr and 38–55 kg): 0.3 mg/kg as single dose (total dose = 15 mg; administered using two 7.5-mg spray devices, with one spray [7.5 mg] from each device administered into each nostril). May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode).
(Children 6–11 yr and 19–37 kg): 0.3 mg/kg as single dose (total dose = 10 mg; administered using one 10-mg spray device, with one spray [10 mg] from device administered into one nostril). May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode).
(Children 6–11 yr and 10–18 kg): 0.3 mg/kg as single dose (total dose = 5 mg; administered using one 5-mg spray device, with one spray [5 mg] from device administered into one nostril). May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode).
(Adults and Children >12 yr): 0.2 mg/kg; may repeat 4–12 hr later.
(Children 6–11 yr): 0.3 mg/kg; may repeat 4–12 hr later.
(Children 2–5 yr): 0.5 mg/kg; may repeat 4–12 hr later.

Febrile Seizure Prophylaxis

PO (Children >1 mo): 1 mg/kg/day divided every 8 hr at first sign of fever and continue for 24 hr after fever is gone.

Skeletal Muscle Relaxation

PO (Adults ): 2–10 mg 3–4 times daily.
PO Geriatric Patients or Debilitated Patients): 2–2.5 mg 1–2 times daily initially.
PO (Children >6 mo): 1–2.5 mg 3–4 times daily.
IM IV (Adults ): 5–10 mg; may repeat in 2–4 hr (larger doses may be required for tetanus).
IM IV Geriatric Patients or Debilitated Patients): 2–5 mg; may repeat in 2–4 hr (larger doses may be required for tetanus).
IM IV (Children ≥5 yr): Tetanus: 5–10 mg every 3–4 hr.
IM IV (Children >1 mo): Tetanus: 1–2 mg every 3–4 hr.

Alcohol Withdrawal

PO (Adults ): 10 mg 3–4 times in first 24 hr, ↓ to 5 mg 3–4 times daily.
IM IV (Adults ): 10 mg initially, then 5–10 mg in 3–4 hr as needed; larger or more frequent doses have been used.

(Generic available)

Tablets: 2 mg; 5 mg; 10 mg
Oral solution: 1 mg/mL; 5 mg/mL (Intensol)
Buccal film (Libervant): 5 mg; 7.5 mg; 10 mg; 12.5 mg; 15 mg
Rectal gel delivery system: 2.5 mg; 10 mg; 20 mg
Nasal spray (Valtoco): 5 mg/device; 7.5 mg/device; 10 mg/device
Solution for injection: 5 mg/mL (contains 10% alcohol and 40% propylene glycol)

Monitor BP, pulse, and respiratory rate prior to and periodically during therapy and frequently during IV therapy.
- Assess IV site frequently during administration; diazepam may cause phlebitis and venous thrombosis.
- Prolonged high-dose therapy may lead to psychological or physical dependence. Restrict amount of drug available to patient. Observe depressed patients closely for suicidal tendencies.
- Assess risk for addiction, abuse, or misuse prior to administration.
Conduct regular assessment of continued need for treatment.
Geri: Assess risk of falls and institute fall prevention strategies.
Anxiety: Assess mental status (orientation, mood, behavior) and degree of anxiety.
Assess level of sedation (ataxia, dizziness, slurred speech) prior to and periodically throughout therapy.
Seizures: Observe and record intensity, duration, and location of seizure activity. The initial dose of diazepam offers seizure control for 15–20 min after administration. Institute seizure precautions.
Muscle Spasms: Assess muscle spasm, associated pain, and limitation of movement prior to and during therapy.
Alcohol Withdrawal: Assess patient experiencing alcohol withdrawal for tremors, agitation, delirium, and hallucinations. Protect patient from injury.

Lab Test Considerations:

Evaluate hepatic and renal function and CBC periodically during prolonged therapy. May cause ↑ AST, ALT, and alkaline phosphatase.

Toxicity and Overdose:

Flumazenil is an adjunct in the management of toxicity or overdose. Flumazenil may induce seizures in patients with a history of seizures disorder or who are on tricyclic antidepressants.

Do not confuse diazepam with diltiazem.
Patient should be kept on bedrest and observed for at least 3 hr following parenteral administration.
- If opioid analgesics are used concurrently with parenteral diazepam, decrease opioid dose by ⅓ and titrate dose to effect.
Use lowest effective dose. Taper by 2 mg every 3 days to decrease withdrawal symptoms. Some patients may require longer taper periods (mo).
PO: Tablets may be crushed and taken with food or water if patient has difficulty swallowing.
Libervant: Open pouch by tearing along perforation. Remove film from foil pouch. Place film flat against inside of cheek; do not place against the teeth. Do not rub the film into the cheek. Mouth can remain open or closed while medication dissolves. If film is accidentally swallowed or chewed, do not administer a replacement dose. Do not administer film with liquids.
IM: IM injections are painful and erratically absorbed. If IM route is used, inject deeply into deltoid muscle for maximum absorption.
Do not prime before use. Only used for seizure clusters. Ensure caregiver is able to distinguish cluster seizures from patient's usual seizure activity. A 2nd dose, when required, may be administered >4 hr after initial dose; use a new blister pack. Do not use >2 doses to treat a single episode and no more than one episode every 5 days and no more than 5 episodes per mo.
Only used for seizure clusters. Ensure caregiver is able to distinguish cluster seizures from patient's usual seizure activity; have been instructed to administer rectal dose; understands explicitly which seizure manifestations may or may not be treated with diazepam rectal gel; and are able to monitor the clinical response and recognize when that response is such that immediate professional medical evaluation is required.

IV Administration:

IV: Resuscitation equipment should be available when diazepam is administered IV.
Diluent: For IV administration do not dilute or mix with any other drug. If IV push is not feasible, administer IV push into tubing as close to insertion site as possible. Continuous infusion is not recommended due to precipitation in IV fluids and absorption of diazepam into infusion bags and tubing. Injection may cause burning and venous irritation; avoid small veins.Concentration: 5 mg/mL.
Rate: Administer slowly at a rate of 5 mg/min in adults. Infants and children should receive 1–2 mg/min. Rapid injection may cause apnea, hypotension, bradycardia, or cardiac arrest.

Instruct patient to take medication as directed and not to take more than prescribed or increase dose if less effective after a few wk without checking with health care professional. Review Medication Guide for Valtoco and Diastat rectal gel with patient/caregiver prior to administration. Abrupt withdrawal of diazepam may cause insomnia, unusual irritability or nervousness, and seizures. Advise patient that sharing of this medication may be dangerous.
- Advise patient that diazepam is a drug with known abuse potential. Protect it from theft, and never give to anyone other than the individual for whom it was prescribed. Store out of sight and reach of children, and in a location not accessible by others.
- Medication may cause drowsiness, clumsiness, or unsteadiness. Advise patient to avoid driving or other activities requiring alertness until response to medication is known. Advise geriatric patients of increased risk for CNS effects and potential for falls.
- Caution patient to avoid taking alcohol or other CNS depressants, including opioids, concurrently with this medication; may cause an overdose.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
- May cause fetal harm. Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Use in late pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in the neonate. Monitor neonates exposed to diazepam during pregnancy or labor for signs of sedation and monitor neonates exposed to diazepam during pregnancy for signs of withdrawal. Monitor infants exposed to diazepam through breast milk for sedation, poor feeding, and poor weight gain. Encourage women who take diazepam during pregnancy to enroll in the North American Antiepileptic Drug Pregnancy Registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org to monitor pregnancy outcomes in women exposed to antiepileptic drugs.
- Emphasize the importance of follow-up examinations to determine effectiveness of the medication.
Instruct caregiver in correct technique for administration and how to monitor patient after dose. Stay with patient and monitor for changes in resting breathing rate, changes in color, and side effects. A second dose, if prescribed, may be given at least 4 hr after the first dose, when required. Instruct caregiver that any films spit out or not used after opening should be flushed down the toilet or placed in the sink and rinsed with water until film is no longer visible.
Instruct caregiver in correct technique for administration and how to monitor patient after dose.
Instruct caregiver in correct technique for administration and monitoring. Turn patient on side and administer rectal gel. Stay with patient and monitor for changes in resting breathing rate, changes in color, and side effects. A second dose, if prescribed, may be given 4–12 hr after the first dose, when required.
Seizures: Patients on anticonvulsant therapy should carry identification describing disease process and medication regimen at all times.

Decrease in anxiety level. Full therapeutic antianxiety effects occur after 1–2 wk of therapy.
Decreased recall of surgical or diagnostic procedures.
Control of seizures.
Decrease in muscle spasms.
Decreased tremulousness and more rational ideation when used for alcohol withdrawal.

Diastat, Libervant, Valium, Valtoco

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆ ⬇

Contr. Subst. Schedule ⬆