diazepam (Valium, Diastat, Diastat AcuDial)

Dosing and uses of Valium, Diastat (diazepam)

• Adult
• Pediatric
• Geriatric

 

Adult dosage forms and strengths

tablet: Schedule IV

• 2mg
• 5mg
• 10mg

oral solution: Schedule IV

• 1mg/1mL
• 5mg/mL

rectal gel: Schedule IV

• 2.5mg
• 10mg
• 20mg

injectable solution: Schedule IV

• 5mg/mL

intramuscular device: Schedule IV

• 5mg/mL

 

Anxiety

2-10 mg PO q6-12hr, OR 2-10 mg IV/IM q6-12hr; no more than 30 mg/8 hours

 

Alcohol Withdrawal

10 mg PO q6-8hr during first 24hr; reduce to 5 mg PO q6-8hr PRn

Initial: 10 mg IV/IM, may give additional doses of 5-10 mg IV q6-8hr as needed

 

Endoscopy

IV: Titrate dose to 10 mg or less immediately before procedure, not to exceed cumulative dose of 20 mg; reduce dose of narcotic by one third or omit, Or

IM: 5-10 mg 30 minutes before procedure

 

Preoperative Sedation

10 mg IM before surgery

 

Sedation in the ICU

5-10 mg IV 1-2 hours before surgery; 0.03-0.1 mg/kg q30min to 6hr

 

Muscle Spasm

2-10 mg PO q6-8hr PRN, OR 5-10 mg IV/IM initially; THEN q3-4hr if necessary

 

Seizure Disorder

2-10 mg PO q6-12hr as adjunct, Or

0.2 mg/kg PR, repeat after 4-12 hours PRn

 

Status Epilepticus

5-10 mg IV/IM q5-10min; not to exceed 30 mg, Or

0.5 mg/kg PR (using parenteral solution), THEN 0.25 mg/kg in 10 minutes PRn

 

Dosage modifications

Renal impairment: No dose adjustment recommended unless administered for prolonged period; decrease dose in prolonged periods

Hepatic impairment: 50% of maintenance dose

 

Acute Repetitive Seizures (Orphan)

Orphan indication for management of acute repetitive seizures as intranasal or SC administration

Sponsors

• Intranasal: Neurelis Pharmaceuticals, Inc; 1042-B N. El Camino Real, Suite 430; Encinitas, California 92024
• SC (Diazepen [Tm]): Xeris Pharmaceuticals, Inc; 3208 Red River Street, Suite 300; Austin, Texas 78705

 

Pediatric dosage forms and strengths

tablet: Schedule IV

• 2mg
• 5mg
• 10mg

oral solution: Schedule IV

• 1mg/1mL
• 5mg/mL

rectal gel: Schedule IV

• 2.5mg
• 10mg
• 20mg

injectable solution: Schedule IV

• 5mg/mL

intramuscular device: Schedule IV

• 5mg/mL

 

Sedative/Muscle Relaxant

Potentially toxic dose in patients <6 years: >0.5 mg/kg

<6 months: Not recommended

>12 years

• 0.12-0.8 mg/kg/day PO divided q6-8hr, OR
• 0.04-0.2 mg/kg IV/IM q2-4hr; no more than 0.6 mg/kg within 8 hours

 

Status Epilepticus

Potentially toxic dose in patients <6 years: >0.5 mg/kg

Pr

• 2-6 years: 0.5 mg/kg; may repeat in 4-12 hours PRN
• 6-12 years: 0.3 mg/kg; may repeat in 4-12 hours PRN
• >12 years: 0.2 mg/kg; may repeat in 4-12 hours PRN

IV

• 6 months-5 years: 0.2-0.5 mg IV initially, repeat every 2-5 minutes; do not exceed 5 mg; may repeat 2-4 hours later PRN
• >5 years: 1 mg IV given slowly every 2-5 min; not to exceed 10 mg total dose; may repeat in 2-4 hours if necessary

 

Geriatric dosage forms and strengths

2-2.5 mg PO qDay or q12hr initially; increase gradually PRn

Rectal gel: Use lower dose

 

Dosing Considerations

Due to long-acting metabolite, not considered a drug of choice in the elderly; associated with falls

 

Valium, Diastat (diazepam) adverse (side) effects

1-10%

Atax (3%)

Euphoria (3%, rectal gel)

Incoordination (3%, rectal gel)

Somnolence (>1%)

Rash (3%, rectal gel)

Diarrhea (4%, rectal gel)

 

Frequency not defined

Common

• Hypotension
• Fatigue
• Muscle weakness
• Respiratory depression
• Urinary retention
• Depression
• Incontinence
• Blurred vision
• Dysarthria
• Headache
• Skin rash
• Changes in salivation

Serious

• Neutropenia
• Jaundice
• Local effects: Pain, swelling, thrombophlebitis, carpal tunnel syndrome, tissue necrosis
• Phlebitis if too rapid IV push

 

Postmarketing Reports

Injury, poisoning and procedural complications: Falls and fractures; increased risk in those taking concomitant sedatives (including alcoholic beverages) and in the elderly

 

Warnings

Contraindications

Documented hypersensitivity

Acute alcohol intoxication

Myasthenia gravis (allowable in limited circumstances)

Acute narrow angle glaucoma and open angle glaucoma unless patients receiving appropriate therapy

Severe respiratory depression

IV use in shock, coma, depressed respiration, patients who recently received other respiratory depressants

Sleep apnea

Children <6 months

 

Cautions

Use caution in COPD, sleep apnea, renal/hepatic disease, open-angle glaucoma (questionable), depression, suicide ideation, impaired gag reflex, history of drug abuse, or obese patients (prolonged action when discontinued)

May impair ability to perform hazardous tasks

Use with caution in patients with a history of drug abuse or acute alcoholism; tolerance, psychological, and physical dependence may occur with prolonged use (>10 days)

Anterograde amnesia reported with benzodiazepine use

Avoid extravasation with IV dosing

Paradoxical reactions may occur including hallucinations, aggressive behavior, and psychoses; dinscontinue use if reactions occur

Abrupt withdrawal may result in temporary increase of seizures

Reduce opiate dose one-third when diazepam is added

 

Pregnancy and lactation

Pregnancy category: d

Lactation: Enters breast milk; not recommended

Minor tranquilizers should be avoided in first trimester of pregnancy due to increased risk of congenital malformations

Maternal use shortly before delivery is associated with floppy infant syndrome (good and consistent evidence)

Prenatal benzodiazepine exposure slightly increased oral cleft risk (limited or inconsistent evidence)

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Valium, Diastat (diazepam)

Mechanism of action

Modulates postsynaptic effects of GABA-A transmission, resulting in an increase in presynaptic inhibition. Appears to act on part of the limbic system, as well as on the thalamus and hypothalamus, to induce a calming effect

 

Absorption

Bioavailability: 90% (PR)

Duration: Variable, dependent on dose and frequency (PO [hypnotic action]); 15-60 min (IV [sedative action])

Peak plasma time: 30-90 min (PO), 5-90 min (PR)

Peak plasma concentration: 373 ng/mL (initial at 45 min); 447 ng/mL (second peak at 70 min)

 

Distribution

Protein bound: 98%

Vd: 0.8-1 L/kg

 

Metabolism

Metabolized by hepatic P450 enzymes CYP2C19, CYP3A4

Metabolites: N-desmethyldiazepam, 3-hydroxdiazepam, oxazepam

 

Elimination

Half-life: 20-70 hr (active metabolite)

Renal clearance: 20-30 mL/min

Excretion: Urine

 

Administration

IV Incompatibilities

Solution: D5W(?), Ringer's(?), LR(?), NS(?) (See IV Preparation)

Additive: Bleomycin, dobutamine, doxorubicin, floxacillin, fluorouracil, furosemide

Syringe: Doxapram, glycopyrrolate, heparin, hydromorphone, ketorolac(?), nalbuphine(?), ranitidine(?), sufentaniL

Y-site: Amphotericin B cholesteryl SO4, atracurium, bivalirudin, cefepime, dexmedetomidine, diltiazem, fenoldopam, fluconazole, foscarnet, gatifloxacin, heparin, heparin/hydrocortisone, Hextend, hydromorphone, linezolid, meropenem, pancuronium, KCl, propofol, remifentanil(?), tirofiban, vecuronium, vitamin B/C

Not specified: Atropine, epinephrine, hydroxyzine, lidocaine, meperidine, morphine, norepinephrine, pentobarbital, Na bicarbonate

 

IV Compatibilities

Additive: Netilmicin, verapamiL

Syringe: Cimetidine

Y-site: Cisatracurium (may be incompatible at higher concentration), dobutamine, fentanyl, hydromorphone (may be incompatible at higher concentration), methadone, morphine sulfate, nafcillin, quinidine, remifentanil (may be incompatible at higher concentration), sufentaniL

Not specified: Aminophylline, cefazolin

 

IV Preparation

Compatibility with D5W, NS, and Ringer's controversial. If infusion is selected, adding the infusion solution to the diazepam injection (and not the other way around) may prevent precipitate formation

 

IV Administration

Administer over 3 min; no more than 5 mg/min

Monitor respiration q5-15min and before each IV dose

Have airway support ready until effects of IV administration are known

Thrombosis prevention

• Administer directly into a large vein to avoid thrombosis
• If this is not feasible, give drug into tubing of a flowing IV solution as close as possible to vein insertion
• Do not use small veins such as those of wrist or dorsum of hand

 

Oral Administration

Dilute oral concentrate with water/juice/carbonated beverages or mix with semisolid foods

 

Rectal Administration

Place patient on side facing you with upper leg bent forward, lubricate rectal applicator tip, gently insert syringe tip in rectum and slowly push plunger

Rectal gel should not be used more than 5 episodes/month and no more than one episode q5days

 

Storage

Store intact vials at room temperature; protect from light