diazepam (Valium, Diastat, Diastat AcuDial)
Classes: Anticonvulsants, Other; Skeletal Muscle Relaxants; Antianxiety Agents; Anxiolytics, Benzodiazepines
Dosing and uses of Valium, Diastat (diazepam)
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