Diazepam

Generic Name: diazepam

Brand Names: Apo-Diazepam (CAN), Diastat, Diazemuls (CAN), Diazepam Intensol, Valium

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 seizure 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 renal function; and in patients with a history of substance abuse.

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 give 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: Use 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 PATIENTS 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

Route	Onset	Peak	Duration
Oral	30–60 min	1–2 hr	3 hr
IM	15–30 min	30–45 min	3 hr
IV	1–5 min	30 min	15–60 min
Rectal	Rapid	1.5 hr	3 hr

Metabolism: Hepatic; T_1/2: 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.

Adverse effects

CNS: Transient, mild drowsiness initially; sedation, depression, lethargy, apathy, fatigue, light-headedness, disorientation, restlessness, confusion,crying, delirium, headache, slurred speech, dysarthria, stupor, rigidity, tremor, dystonia, vertigo, euphoria, nervousness, difficulty in concentration, vivid dreams, psychomotor retardation, extrapyramidal symptoms; mild paradoxical excitatory reactions, during first 2 wk of treatment, visual and auditory disturbances, diplopia, nystagmus, depressed hearing, nasal congestion
CV: Bradycardia, tachycardia, CV collapse, hypertension and hypotension, palpitations, edema
Dependence: Drug dependence with withdrawal syndrome when drug is discontinued (common with abrupt discontinuation of higher dosage used for longer than 4 mo); IV diazepam: 1.7% incidence of fatalities; oral benzodiazepines ingested alone; no well-documented fatal overdoses
Dermatologic: Urticaria, pruritus, skin rash, dermatitis
GI: Constipation; diarrhea, dry mouth; salivation; nausea; anorexia; vomiting; difficulty in swallowing; gastric disorders; elevations of blood enzymes—LDH, alkaline phosphatase, AST, ALT; hepatic impairment; jaundice
GU: Incontinence, urinary retention, changes in libido, menstrual irregularities
Hematologic: Decreased hematocrit, blood dyscrasias
Other: Phlebitis and thrombosis at IV injection sites, hiccups, fever, diaphoresis, paresthesias, muscular disturbances, gynecomastia; pain, burning, and redness after IM injection

Interactions

Drug-drug

Increased CNS depression with alcohol, omeprazole
Increased pharmacologic effects of diazepam if combined with cimetidine, disulfiram, hormonal contraceptives
Decreased effects of diazepam with theophyllines, ranitidine

Nursing considerations

Assessment

History: Hypersensitivity to benzodiazepines; psychoses, acute narrow-angle glaucoma, shock, coma, acute alcoholic intoxication; elderly or debilitated patients; impaired liver or renal function; pregnancy, lactation
Physical: Weight; skin color, lesions; orientation, affect, reflexes, sensory nerve function, ophthalmologic examination; P, BP; R, adventitious sounds; bowel sounds, normal output, liver evaluation; normal output; LFTs, renal function tests, CBC

Interventions

WARNING: Do not administer intra-arterially; may produce arteriospasm, gangrene.
Change from IV therapy to oral therapy as soon as possible.
Do not use small veins (dorsum of hand or wrist) for IV injection.
Reduce dose of opioid analgesics with IV diazepam; dose should be reduced by at least one-third or eliminated.
Carefully monitor P, BP, respiration during IV administration.
WARNING: Maintain patients receiving parenteral benzodiazepines in bed for 3 hr; do not permit ambulatory patients to operate a vehicle following an injection.
Monitor EEG in patients treated for status epilepticus; seizures may recur after initial control, presumably because of short duration of drug effect.
Monitor liver and renal function, CBC during long-term therapy.
Taper dosage gradually after long-term therapy, especially in epileptic patients.
Arrange for epileptic patients to wear medical alert ID indicating that they are epileptics taking this medication.
Discuss risk of fetal abnormalities with patients desiring to become pregnant.

Teaching points

Take this drug exactly as prescribed. Do not stop taking this drug (long-term therapy, antiepileptic therapy) without consulting your health care provider.
Caregiver should learn to assess seizures, administer rectal form, and monitor patient.
Use of barrier contraceptives is advised while using this drug; if you become or wish to become pregnant, consult with your health care provider.
It is advisable to wear a medical alert ID indicating your diagnosis and treatment (as antiepileptic).
You may experience these side effects: Drowsiness, dizziness (may lessen; avoid driving or engaging in other dangerous activities); GI upset (take drug with food); dreams, difficulty concentrating, fatigue, nervousness, crying (reversible).
Report severe dizziness, weakness, drowsiness that persists, rash or skin lesions, palpitations, swelling of the ankles, visual or hearing disturbances, difficulty voiding.

Adverse effects in Italic are most common; those in Bold are life-threatening.

Source (1)