diazepam

Therapeutic Classification: antianxiety agents, anticonvulsants, sedative/hypnotics, skeletal muscle relaxants (centrally acting)

Pharmacologic Classification: benzodiazepines

BEERS REMS

Anxiety disorders.
Preoperative sedation.
Conscious sedation (provides light anesthesia and anterograde amnesia).
Status epilepticus/uncontrolled seizures.
Acute treatment of intermittent, stereotypic episodes of frequent seizure activity that are distinct from a patient’s usual seizure pattern (not status epilepticus) (nasal spray or buccal film).
Skeletal muscle spasms.
Alcohol withdrawal.

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.

Absorption: Rapidly absorbed from the GI tract. Absorption from IM sites may be slow and unpredictable. Well absorbed from rectal mucosa (90%) and nasal mucosa (97%). IV administration results in complete bioavailability.

Distribution: Widely distributed. Crosses the blood-brain barrier.

Metabolism/Excretion: Primarily metabolized in the liver via the CYP2C19 and CYP3A4 isoenzymes; the CYP2C19 isoenzyme exhibits genetic polymorphism; 5–20% of Asian patients and 3–5% of White and Black patients may be poor metabolizers and may have significantly ↑ diazepam concentrations and an ↑ risk 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).

(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.

Contraindicated in:

Hypersensitivity;
Cross-sensitivity with other benzodiazepines may occur;
Comatose patients;
Myasthenia gravis;
Severe pulmonary impairment;
Sleep apnea;
Severe hepatic impairment;
Pre-existing CNS depression;
Uncontrolled severe pain;
Angle-closure glaucoma;
Some products contain alcohol, propylene glycol, or tartrazine and should be avoided in patients with known hypersensitivity or intolerance;
Lactation: Lactation;
Pedi: Children <6 mo (for oral; safety not established).

Use Cautiously in:

History of suicide attempt or drug dependence;
Debilitated patients (↓ dose);
Hypoalbuminemia;
Severe renal impairment;
OB: Use late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, feeding difficulties) in neonates;
Pedi: Metabolites can accumulate in neonates. Injection contains benzyl alcohol, which can cause potentially fatal gasping syndrome in neonates;
Geri: Appears on Beers list. ↑ risk of cognitive impairment, delirium, falls, fractures, and motor vehicle accidents. If possible, avoid use in older adults.

CV: hypotension(IV)

Derm: rash

EENT: ↑intraocular pressure, blurred vision, epistaxis(nasal spray), nasal congestion (nasal spray), nasal discomfort (nasal spray)

GI: constipation, diarrhea(may be caused by propylene glycol content in oral solution), nausea, vomiting

Local: pain (IM), phlebitis(IV)

Metab: weight gain

Neuro: dizziness, drowsiness, lethargy, ataxia, depression, dysgeusia (nasal spray), hangover, headache, paradoxical excitation, slurred speech

Resp: RESPIRATORY DEPRESSION

Misc: physical dependence, psychological dependence, tolerance

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 may ↑ levels and risk of toxicity.
May ↓ the effectiveness of levodopa.
Rifampin or barbiturates may ↓ levels and effectiveness.
Sedative effects may be ↓ by theophylline.
Concurrent use of ritonavir is not recommended.

Drug-Natural Products:

Kava-kava, valerian, or chamomile can ↑ risk of CNS depression.

Anxiety

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 >1 mo): 0.04–0.3 mg/kg/dose every 2–4 hr to a maximum of 0.6 mg/kg within an 8-hr period if necessary.

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

(Children 2–5 yr and 26–30 kg): 15 mg as a single dose. May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode).
(Children 2–5 yr and 21–25 kg): 12.5 mg as a single dose. May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode).
(Children 2–5 yr and 16–20 kg): 10 mg as a single dose. May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode).
(Children 2–5 yr and 11–15 kg): 7.5 mg as a single dose. May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode).
(Children 2–5 yr and 6–10 kg): 5 mg as a single dose. May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode).
IV (Adults ): 5–10 mg; may repeat every 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 every 15–30 min to a total dose of 10 mg; repeat every 2–4 hr.
IM IV (Children 1 mo–5 yr ): 0.05–0.3 mg/kg/dose given over 3–5 min every 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 every 15–30 min to maximum dose of 2 mg.
(Adults and Children ≥12 yr and ≥76 kg): 0.2 mg/kg as a single dose (total dose = 20 mg; administered using two 10-mg spray devices, with one spray [10 mg] from each device administered into each nostril). May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode).
(Adults and Children ≥12 yr and 51–75 kg): 0.2 mg/kg as a single dose (total dose = 15 mg; administered using two 7.5-mg spray devices, with one spray [7.5 mg] from each device administered into each nostril). May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode).
(Adults and Children ≥12 yr and 28–50 kg): 0.2 mg/kg as a single dose (total dose = 10 mg; administered using one 10-mg spray device, with one spray [10 mg] from device administered into one nostril). May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode).
(Adults and Children ≥12 yr and 14–27 kg): 0.2 mg/kg as a single dose (total dose = 5 mg; administered using one 5-mg spray device, with one spray [5 mg] from device administered into one nostril). May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode).
(Children 6–11 yr and 56–74 kg): 0.3 mg/kg as a single dose (total dose = 20 mg; administered using two 10-mg spray devices, with one spray [10 mg] from each device administered into each nostril). May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode).
(Children 6–11 yr and 38–55 kg): 0.3 mg/kg as a single dose (total dose = 15 mg; administered using two 7.5-mg spray devices, with one spray [7.5 mg] from each device administered into each nostril). May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode).
(Children 6–11 yr and 19–37 kg): 0.3 mg/kg as a single dose (total dose = 10 mg; administered using one 10-mg spray device, with one spray [10 mg] from device administered into one nostril). May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode).
(Children 6–11 yr and 10–18 kg): 0.3 mg/kg as a single dose (total dose = 5 mg; administered using one 5-mg spray device, with one spray [5 mg] from device administered into one nostril). May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode).
(Children 2–5 yr and 23–33 kg): 0.5 mg/kg as a single dose (total dose = 15 mg; administered using two 7.5-mg spray devices, with one spray [7.5 mg] from each device administered into each nostril). May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode).
(Children 2–5 yr and 12–22 kg): 0.5 mg/kg as a single dose (total dose = 10 mg; administered using one 10-mg spray device, with one spray [10 mg] from device administered into one nostril). May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode).
(Children 2–5 yr and 6–11 kg): 0.5 mg/kg as a single dose (total dose = 5 mg; administered using one 5-mg spray device, with one spray [5 mg] from device administered into one nostril). May administer another dose, if needed, ≥4 hr after initial dose (max = 2 doses/seizure episode).
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 every 8 hr at 1st 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 every 3–4 hr.
IM IV (Children >1 mo): Tetanus: 1–2 mg every 3–4 hr.

Alcohol Withdrawal

PO (Adults ): 10 mg 3–4 times in first 24 hr; ↓ to 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.

(Generic available)

Tablets: 2 mg; 5 mg; 10 mg
Oral solution: 1 mg/mL; 5 mg/mL (Intensol)
Buccal film (Libervant): 5 mg; 7.5 mg; 10 mg; 12.5 mg; 15 mg
Rectal gel delivery system: 2.5 mg; 10 mg; 20 mg
Nasal spray (Valtoco): 5 mg/device; 7.5 mg/device; 10 mg/device
Solution for injection: 5 mg/mL (contains 10% alcohol and 40% propylene glycol)

Monitor BP, HR, respiratory rate, and level of sedation (ataxia, dizziness, slurred speech) before and periodically during therapy and frequently during IV therapy.
- Assess IV site frequently during administration; may cause phlebitis.
- Assess risk for addiction, abuse, or misuse prior to administration. Prolonged high-dose therapy may lead to psychological or physical dependence. Restrict amount of drug available to patient. Observe depressed patients closely for suicidal tendencies.
Pedi: Monitor neonates exposed to diazepam during pregnancy or labor for signs of sedation and withdrawal; manage as indicated.
Geri: Assess risk of falls and institute fall prevention strategies.
Anxiety: Assess orientation, mood, behavior, and degree of anxiety.
Seizures: Observe and record intensity, duration, and location of seizure activity. The initial dose offers seizure control for 15–20 min after administration. Institute seizure precautions.
Muscle Spasms: Assess muscle spasm, associated pain, and limitation of movement prior to and during therapy.
Alcohol Withdrawal: Assess for tremor, agitation, delirium, and hallucinations.

Lab Test Considerations:

Evaluate hepatic and renal function and CBC periodically during prolonged therapy. May ↑ AST, ALT, and alkaline phosphatase.

Toxicity and Overdose:

Flumazenil is an adjunct in the management of toxicity or overdose. Flumazenil may induce seizures in patients with a history of seizure disorder or who are on tricyclic antidepressants.

Do not confuse diazepam with diltiazem.
Patient should be kept on bedrest and observed for ≥3 hr following parenteral administration.
- If opioid analgesics are used concurrently with parenteral diazepam, ↓ opioid dose by ⅓ and titrate to effect.
Use lowest effective dose. Taper by 2 mg every 3 days to ↓ withdrawal symptoms. Some patients may require longer taper periods.
PO: Tablets may be crushed and taken with food or water.
Buccal: Libervant: Open pouch by tearing along perforation. Remove film from foil pouch. Place film flat against inside of cheek; do not place against teeth or rub into cheek. Mouth can be open or closed while medication dissolves. If film is accidentally swallowed or chewed, do not administer a replacement dose. Do not administer with liquids.
Device delivers entire contents upon activation. Do not prime or use device for more than one dose. A 2nd dose may be administered >4 hr after initial dose; use a new blister pack. Do not use >2 doses to treat a single episode and no more than one episode every 5 days and no more than 5 episodes per month.
IM: IM injections are painful and erratically absorbed. If IM route is used, inject deeply into deltoid muscle for maximum absorption.
Upon receipt of syringe, confirm correct prescribed dose is visible in display window, and the green “ready” band is visible prior to rectal administration.

IV Administration:

IV diazepam is a vesicant. Administer into a large vein. If extravasation occurs, immediately stop infusion. Leave needle/cannula in place temporarily but do not flush the line. Gently aspirate extravasated solution; then remove needle/cannula. Elevate patient's extremity and apply dry cold or warm compresses.
IV: Resuscitation equipment should be available when diazepam is administered IV.
IV Push: Diluent: Do not dilute or mix with any other drug. If IV push is not feasible, administer into tubing as close to insertion site as possible. Continuous infusion is not recommended due to precipitation in IV fluids and absorption into infusion bags and tubing. Concentration: 5 mg/mL.
Rate: Administer slowly at 5 mg/min in adults and 1–2 mg/min in infants and children. Rapid injection may cause apnea, hypotension, bradycardia, or cardiac arrest.
Y-Site Compatibility:
- docetaxel
- methadone
- piperacillin/tazobactam
Y-Site Incompatibility:
- acetaminophen
- acyclovir
- alemtuzumab
- amikacin
- aminocaproic acid
- aminophylline
- amiodarone
- amphotericin B deoxycholate
- amphotericin B liposomal
- ampicillin
- ampicillin/sulbactam
- anidulafungin
- argatroban
- arsenic trioxide
- ascorbic acid
- atracurium
- atropine
- azathioprine
- azithromycin
- aztreonam
- benztropine
- bivalirudin
- bleomycin
- bumetanide
- buprenorphine
- butorphanol
- calcium chloride
- calcium gluconate
- cangrelor
- carboplatin
- carmustine
- caspofungin
- cefazolin
- cefepime
- cefotaxime
- cefotetan
- cefoxitin
- ceftaroline
- ceftazidime
- ceftobiprole
- ceftriaxone
- cefuroxime
- chloramphenicol
- chlorpromazine
- cisplatin
- clindamycin
- cyanocobalamin
- cyclophosphamide
- cyclosporine
- cytarabine
- dacarbazine
- dactinomycin
- dantrolene
- daunorubicin
- dexamethasone
- dexmedetomidine
- dexrazoxane
- diazoxide
- digoxin
- diltiazem
- dimenhydrinate
- diphenhydramine
- dopamine
- doxorubicin hydrochloride
- doxorubicin liposomal
- doxycycline
- enalaprilat
- ephedrine
- epinephrine
- epirubicin
- epoetin alfa
- eptifibatide
- ertapenem
- erythromycin
- esmolol
- etoposide
- etoposide phosphate
- famotidine
- fluconazole
- fludarabine
- fluorouracil
- folic acid
- foscarnet
- fosphenytoin
- furosemide
- ganciclovir
- gemcitabine
- gemtuzumab ozogamicin
- gentamicin
- glycopyrrolate
- granisetron
- haloperidol
- heparin
- hetastarch
- hydralazine
- hydrocortisone
- idarubicin
- ifosfamide
- imipenem/cilastatin
- indomethacin
- insulin, regular
- irinotecan
- isoproterenol
- ketorolac
- labetalol
- leucovorin
- levofloxacin
- lidocaine
- linezolid
- magnesium sulfate
- mannitol
- meperidine
- meropenem
- mesna
- methotrexate
- methylprednisolone
- metoclopramide
- metoprolol
- metronidazole
- midazolam
- milrinone
- minocycline
- mitomycin
- mitoxantrone
- multivitamins
- mycophenolate
- nalbuphine
- naloxone
- nicardipine
- nitroglycerin
- nitroprusside
- norepinephrine
- octreotide
- oxacillin
- oxaliplatin
- oxytocin
- paclitaxel
- palonosetron
- pamidronate
- pantoprazole
- papaverine
- pemetrexed
- penicillin G
- pentamidine
- pentobarbital
- phenobarbital
- phentolamine
- phenylephrine
- phenytoin
- phytonadione
- potassium acetate
- potassium chloride
- procainamide
- prochlorperazine
- promethazine
- propofol
- propranolol
- protamine
- pyridoxine
- rocuronium
- sodium acetate
- sodium bicarbonate
- succinylcholine
- tacrolimus
- theophylline
- thiamine
- thiotepa
- tigecycline
- tirofiban
- tobramycin
- topotecan
- trimethoprim/sulfamethoxazole
- vancomycin
- vasopressin
- vecuronium
- verapamil
- vinblastine
- vincristine
- vinorelbine
- voriconazole
- zoledronic acid

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
- Instruct patient and caregiver on appropriate steps for administration technique, disposal of equipment, and monitoring of patient for buccal, intranasal, and rectal preparations, if appropriate. Instruct patient not to ↑ dose if less effective after a few weeks without checking with health care provider.
- Caution patient not to stop taking diazepam without consulting health care provider. Abrupt withdrawal may cause sweating, vomiting, muscle cramps, tremors, and seizures; may be life-threatening.
- Advise patient that diazepam is a drug with known abuse potential. Protect it from theft, and never give to anyone other than the individual for whom it was prescribed. Store out of sight and reach of children and in a location not accessible by others.
- Advise patient to avoid driving or other activities requiring alertness until response to medication is known. Advise older adults of ↑ risk for CNS effects and potential for falls.
- Advise patient to avoid the use of alcohol or other CNS depressants, including opioids, concurrently with diazepam; may cause respiratory depression and overdose.
- Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other medications.
- May cause fetal harm. Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding. Use in late pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, feeding difficulties) in the neonate. Monitor neonates exposed to diazepam during pregnancy or labor for signs of sedation or withdrawal. Monitor infants exposed to diazepam through breast milk for sedation, poor feeding, and poor weight gain. Encourage pregnant patient to enroll in the North American Antiepileptic Drug Pregnancy Registry to monitor outcomes of diazepam exposure: 1-888-233-2334; https://www.aedpregnancyregistry.org.
- Emphasize the importance of follow-up examinations to determine effectiveness of therapy.
Seizures: Patients on anticonvulsant therapy should carry identification describing disease process and medication regimen at all times.

Decrease in anxiety level. Full therapeutic antianxiety effects occur after 1–2 wk of therapy.
Decreased recall of surgical or diagnostic procedures.
Control of seizures.
Decreased muscle spasm.
Decreased tremulousness and more rational ideation when used for alcohol withdrawal.

Diastat, Libervant, Valium, Valtoco

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆ ⬇

Contr. Subst. Schedule ⬆