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Generic Name: diazepam

Brands: Apo-Diazepam (CAN), Diastat, Diazemuls (CAN), Diazepam Intensol, Valium, Vivol (CAN)

Pregnancy Category D
Controlled Substance C-IV

Drug classes
Benzodiazepine
Anxiolytic
Antiepileptic
Skeletal muscle relaxant (centrally acting)

Therapeutic actions
Exact mechanisms of action not understood; acts mainly at the limbic system and reticular formation; may act in spinal cord and at supraspinal sites to produce skeletal muscle relaxation; potentiates the effects of GABA, an inhibitory neurotransmitter; anxiolytic effects occur at doses well below those necessary to cause sedation, ataxia; has little effect on cortical function.

Indications
• Management of anxiety disorders or for short-term relief of symptoms of anxiety
• Acute alcohol withdrawal; may be useful in symptomatic relief of acute agitation, tremor, delirium tremens, hallucinosis
• Muscle relaxant: Adjunct for relief of reflex skeletal muscle spasm due to local pathology (inflammation of muscles or joints) or secondary to trauma; spasticity caused by upper motoneuron disorders (cerebral palsy and paraplegia); athetosis, stiff-man syndrome
• Parenteral: Treatment of tetanus
• Antiepileptic: Adjunct in status epilepticus and severe recurrent convulsive seizures (parenteral); adjunct in convulsive disorders (oral)
• Preoperative (parenteral): Relief of anxiety and tension and to lessen recall in patients prior to surgical procedures, cardioversion, and endoscopic procedures
• Rectal: Management of selected, refractory patients with epilepsy who require intermittent use to control bouts of increased seizure activity
• Unlabeled use: Treatment of panic attacks

Contraindications and cautions
• Contraindicated with hypersensitivity to benzodiazepines; psychoses, acute narrow-angle glaucoma, shock, coma, acute alcoholic intoxication; pregnancy (cleft lip or palate, inguinal hernia, cardiac defects, microcephaly, pyloric stenosis when used in first trimester; neonatal withdrawal syndrome reported in newborns); lactation.
• Use cautiously with elderly or debilitated patients; impaired liver or kidney function.

Available forms
Tablets—2, 5, 10 mg; SR capsule—15 mg; oral solution—1 mg/mL, 5 mg/5 mL; rectal pediatric gel—2.5, 5, 10 mg; rectal adult gel—10, 15, 20 mg; injection—5 mg/mL

Dosages
Individualize dosage; increase dosage cautiously to avoid adverse effects.
ADULTS
Oral
• Anxiety disorders, skeletal muscle spasm, seizure disorders: 2–10 mg bid–qid.
• Alcohol withdrawal: 10 mg tid–qid first 24 hr; reduce to 5 mg tid–qid, as needed.
Oral sustained release
• Anxiety disorders: 15–30 mg/day.
• Alcohol withdrawal: 30 mg first 24 hr; reduce to 15 mg/day as needed.
Rectal
0.2 mg/kg PR; treat no more than one episode q 5 days. May be given a second dose in 4–12 hr.
Parenteral
Usual dose is 2–20 mg IM or IV. Larger doses may be required for some indications (tetanus). Injection may be repeated in 1 hr.
• Anxiety: 2–10 mg IM or IV; repeat in 3–4 hr if necessary.
• Alcohol withdrawal: 10 mg IM or IV initially, then 5–10 mg in 3–4 hr if necessary.
• Endoscopic procedures: 10 mg or less, up to 20 mg IV just before procedure or 5–10 mg IM 30 min prior to procedure. Reduce or omit dosage of opioids.
• Muscle spasm: 5–10 mg IM or IV initially, then 5–10 mg in 3–4 hr if necessary.
• Status epilepticus: 5–10 mg, preferably by slow IV. May repeat q 5–10 min up to total dose of 30 mg. If necessary, repeat therapy in 2–4 hr; other drugs are preferable for long-term control.
• Preoperative: 10 mg IM.
• Cardioversion: 5–15 mg IV 5–10 min before procedure.
PEDIATRIC PATIENTS
Oral
6 mo: 1–2.5 mg PO tid–qid initially. Gradually increase as needed and tolerated. Can be given rectally if needed.
Rectal
< 2 yr: Not recommended.
2–5 yr: 0.5 mg/kg.
6–11 yr: 0.3 mg/kg.
>12 yr: Adult dose; may give a second dose in 4–12 hr.
Parenteral
Maximum dose of 0.25 mg/kg IV administered over 3 min; may repeat after 15–30 min. If no relief of symptoms after three doses, adjunctive therapy is recommended.
• Tetanus (> 1 mo): 1–2 mg IM or IV slowly q 3–4 hr as necessary.
• Tetanus (> 5 yr): 5–10 mg q 3–4 hr.
• Status epilepticus (> 1 mo–< 5 yr): 0.2–0.5 mg slowly IV q 2–5 min up to a maximum of 5 mg.
• Status epilepticus (> 5 yr): 1 mg IV q 2–5 min up to a maximum of 10 mg; repeat in 2–4 hr if necessary.
GERIATRIC PATIENTS OR THOSE WITH DEBILITATING DISEASE
2–2.5 mg PO daily–bid or 2–5 mg parenteral initially; reduce rectal dose. Gradually increase as needed and tolerated; use cautiously.

Pharmacokinetics

Metabolism: Hepatic; T1/2: 20–80 hr
Distribution: Crosses placenta; enters breast milk
Excretion: Urine

IV facts
Preparation: Do not mix with other solutions; do not mix in plastic bags or tubing.
Infusion: Inject slowly into large vein, 1 mL/min at most; for children do not exceed 3 min; do not inject intra-arterially; if injected into IV tubing, inject as close to vein insertion as possible.
Incompatibilities: Do not mix with other solutions; do not mix with any other drugs.
Y-site Incompatibilities: Atracurium, heparin, foscarnet, pancuronium, potassium, vecuronium.