Indications
Adjunct in the management of: Anxiety Disorder, Athetosis,
Anxiety relief prior to cardioversion (injection),
Stiffman Syndrome, Preoperative sedation, Conscious
sedation (provides light anesthesia and anterograde
amnesia). Treatment of status epilepticus/uncontrolled
seizures (injection). Skeletal muscle relaxant. Management
of the symptoms of alcohol withdrawal. Unlabeled
Use: Anxiety associated with acute myocardial
infarction, insomnia.
Action
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.
Pharmacokinetics
Absorption: Rapidly absorbed from the GI tract. Absorption
from IM sites may be slow and unpredictable.
Well absorbed (90%) from rectal mucosa.
Distribution: Widely distributed. Crosses the bloodbrain
barrier. Crosses the placenta; enters breast milk.
Metabolism and Excretion: Highly metabolized
by the hepatic P450 enzymes (CYP2C19 and CYP3A4);
the CYP2C19 enzyme system exhibits genetic polymorphism;
15–20% of Asian patients and 3–5% of Caucasian
and Black patients may be poor metabolizers
and may have significantlyqdiazepam concentrations
and anqrisk 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).
TIME/ACTION PROFILE (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.
Contraindications/Precautions
Contraindicated in: Hypersensitivity; Cross-sensitivity
with other benzodiazepines may occur; Comatose
patients; Myasthenia gravis; Severe pulmonary impairment;
Sleep apnea; Severe hepatic dysfunction; Pre-existing
CNS depression; Uncontrolled severe pain; Angleclosure
glaucoma; Some products contain alcohol,
propylene glycol, or tartrazine and should be avoided
in patients with known hypersensitivity or intolerance;
OB:qrisk of congenital malformations; Pedi: Children
6 mo (for oral; safety not established); Lactation:
Recommend to discontinue drug or bottle-feed.
Use Cautiously in: Severe renal impairment; History
of suicide attempt or drug dependence; Debilitated
patients (doseprequired); Patients with low albumin;
Pedi: Metabolites can accumulate in neonates. Injection
contains benzyl alcohol which can cause potentially fatal
gasping syndrome in neonates; Geri: Long-acting
benzodiazepines cause prolonged sedation in the elderly.
Appears on Beers list and is associated withq
risk of falls (pdose required or consider short-acting
benzodiazepine).
Adverse Reactions/Side Effects
CNS: dizziness, drowsiness, lethargy, depression,
hangover, ataxia, slurred speech, headache, paradoxical
excitation. EENT: blurred vision. Resp: RESPIRATORY
DEPRESSION. CV: hypotension (IV only). GI: constipation,
diarrhea (may be caused by propylene glycol
content in oral solution), nausea, vomiting, weight gain.
Derm: rashes. Local: pain (IM), phlebitis (IV), venous thrombosis. Misc: physical dependence, psychological
dependence, tolerance.
Interactions
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 mayp
the metabolism of diazepam, enhancing its actions. May
pthe efficacy of levodopa. Rifampin or barbiturates
mayqthe metabolism andpeffectiveness of diazepam.
Sedative effects may bepby theophylline. Concurrent
use of ritonavir is not recommended.
Drug-Natural Products: Concomitant use of
kava-kava, valerian, or chamomile canqCNS depression.
Route/Dosage
Antianxiety
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 1mo): 0.04–0.3 mg/kg/dose q
2–4 hr to a maximum of 0.6 mg/kg within an 8 hr period
if necessary.
Precardioversion
IV (Adults): 5–15 mg 5–10 min precardioversion.
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
IV (Adults): 5–10 mg, may repeat q 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 q 15–30 min to a total dose of 10 mg,
repeat q 2–4 hr.
IM, IV (Children 1 mo–5 yr ): 0.05–0.3 mg/kg/
dose given over 3–5 min q 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 q 15–30 min to maximum dose of 2 mg.
Rect (Adults and Children 12 yr): 0.2 mg/kg; may
repeat 4–12 hr later.
Rect (Children 6–11 yr): 0.3 mg/kg; may repeat 4–
12 hr later.
Rect (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 q 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 q 3–
4 hr.
IM, IV (Children 1mo): Tetanus—1–2 mg q 3–
4 hr.
Alcohol Withdrawal
PO (Adults): 10 mg 3–4 times in first 24 hr,pto 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.
Psychoneurotic Reactions
IM, IV (Adults): 2–10 mg, may be repeated in 3–4
hr.
Availability (generic available)
Tablets: 2 mg, 5 mg, 10 mg. Cost: Generic—2 mg
$7.51/100, 5 mg $10.74/100, 10 mg $10.84/100. Oral
solution: 1 mg/mL, 5 mg/mL (Intensol). Cost: Generic—
1 mg/mL $2.44/5 mL, 5 mg/mL $33.98/30 mL.
Injection: 5 mg/mL (contains 10% alcohol and 40%
propylene glycol). Rectal gel delivery system: 2.5
mg, 10 mg, 20 mg.
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