diazepam

General

Pronunciation
dye-AZ-e-pam [Pronunciation]

Trade Name(s)

• Diastat

• Diazemuls [Canada]

• Valium

Genetic Implications

Controlled Substance Schedule
IV

Pregnancy Category
Category D

Ther. class.
antianxiety agents
anticonvulsants
sedative/hypnotics
skeletal muscle relaxants
(centrally acting)

Pharm. class.
benzodiazepines

Indications

• Adjunct in the management of:

» Anxiety Disorder,

» Athetosis,

» Anxiety relief prior to cardioversion (injection),

» Stiffman Syndrome,

» Preoperative sedation,

» Conscious sedation (provides light anesthesia and anterograde amnesia).

• Treatment of status epilepticus/uncontrolled seizures (injection).

• Skeletal muscle relaxant.

• Management of the symptoms of alcohol withdrawal.

Unlabelled Use(s):
Anxiety associated with acute myocardial infarction, insomnia.

Action

• 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 Effect(s):

• Relief of anxiety.

• Sedation.

• Amnesia.

• Skeletal muscle relaxation.

• Decreased seizure activity.

Pharmacokinetics

Absorption: Rapidly absorbed from the GI tract. Absorption from IM sites may be slow and unpredictable. Well absorbed (90%) from rectal mucosa.

Distribution: Widely distributed. Crosses the blood-brain barrier. Crosses the placenta; enters breast milk.

Metabolism and Excretion: Highly metabolized by the hepatic P450 enzymes (CYP2C19 and CYP3A4); the CYP2C19 enzyme system exhibits genetic polymorphism; 15–20% of Asian patients and 3–5% of Caucasian 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).

TIME/ACTION PROFILE (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

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity;

• Cross-sensitivity with other benzodiazepines may occur;

• Comatose patients;

• Myasthenia gravis;

• Severe pulmonary impairment;

• Sleep apnea;

• Severe hepatic dysfunction;

• 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;

• OB: ↑ risk of congenital malformations;

• Pedi: Children <6 mo (for oral; safety not established);

• Lactation: Recommend to discontinue drug or bottle-feed.

Use Cautiously in:

• Severe renal impairment;

• History of suicide attempt or drug dependence;

• Debilitated patients (dose ↓ required);

• Patients with low albumin;

• Pedi: Metabolites can accumulate in neonates. Injection contains benzyl alcohol which can cause potentially fatal gasping syndrome in neonates;

• Geri: Long-acting benzodiazepines cause prolonged sedation in the elderly. Appears on Beers list and is associated with ↑ risk of falls (↓ dose required or consider short-acting benzodiazepine).

Adverse Reactions/Side Effects

CNS: dizziness, drowsiness, lethargy, depression, hangover, ataxia, slurred speech, headache, paradoxical excitation.

EENT: blurred vision.

Resp: respiratory depression.

CV: hypotension (IV only).

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

Derm: rashes.

Local: pain (IM), phlebitis (IV), venous thrombosis.

Misc: physical dependence, psychological dependence, tolerance.

*CAPITALS indicates life-threatening.
*italic indicates most frequent.

Interactions

Drug-Drug

• Alcohol , antidepressants , antihistamines , and opioid analgesics —concurrent use results in additive CNS depression.

• Cimetidine , hormonal contraceptives , disulfiram , fluoxetine , isoniazid , ketoconazole , metoprolol , propoxyphene , propranolol , or valproic acid may ↓ the metabolism of diazepam, enhancing its actions.

• May ↓ the efficacy of levodopa .

• Rifampin or barbiturates may ↑ the metabolism and ↓ effectiveness of diazepam.

• Sedative effects may be ↓ by theophylline .

• Concurrent use of ritonavir is not recommended.

Drug-Natural Products
Concomitant use of kava-kava , valerian , or chamomile can ↑ CNS depression.

Route/Dosage

Antianxiety

• 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 q 2–4 hr to a maximum of 0.6 mg/kg within an 8 hr period if necessary..

Precardioversion

• IV (Adults): 5–15 mg 5–10 min precardioversion..

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

• IV (Adults): 5–10 mg, may repeat q 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 q 15–30 min to a total dose of 10 mg, repeat q 2–4 hr..

• IM, IV (Children 1 mo–5 yr ): 0.05–0.3 mg/kg/dose given over 3–5 min q 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 q 15–30 min to maximum dose of 2 mg..

• 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 q 8 hr at first 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 q 3–4 hr..

• IM, IV (Children >1 mo): Tetanus—1–2 mg q 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..

Psychoneurotic Reactions

• IM, IV (Adults): 2–10 mg, may be repeated in 3–4 hr..

Availability

• Tablets: 2 mg, 5 mg, 10 mg

» Cost:
Generic: 2 mg $13.99/30, 5 mg $11.99/30, 10 mg $12.99/30.

• Oral solution: 1 mg/mL, 5 mg/mL (Intensol)

» Cost:
Generic: 1 mg/mL $16.47/60 mL, 5 mg/mL $32.99/30 mL.

• Injection: 5 mg/mL (contains 10% alcohol and 40% propylene glycol)

• Rectal gel delivery system: 2.5 mg, 10 mg, 20 mg

Assessment

• Monitor BP, pulse, and respiratory rate prior to and periodically throughout therapy and frequently during IV therapy.

» Assess IV site frequently during administration; diazepam may cause phlebitis and venous thrombosis.

» 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.

• Conduct regular assessment of continued need for treatment.

• Geri: Assess risk of falls and institute fall prevention strategies.

Anxiety

• Assess mental status (orientation, mood, behavior) and degree of anxiety.

• Assess level of sedation (ataxia, dizziness, slurred speech) prior to and periodically throughout therapy.

Seizures

• Observe and record intensity, duration, and location of seizure activity. The initial dose of diazepam 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 patient experiencing alcohol withdrawal for tremors, agitation, delirium, and hallucinations. Protect patient from injury.

Lab Test Considerations

• Evaluate hepatic and renal function and CBC periodically during prolonged therapy.

Toxicity and Overdose

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

Potential Nursing Diagnoses

• Anxiety (Indications)

• Impaired physical mobility (Indications)

• Risk for injury (Side Effects)

Implementation

• Patient should be kept on bedrest and observed for at least 3 hr following parenteral administration.

» If opioid analgesics are used concurrently with parenteral diazepam, decrease opioid dose by 1/3 and titrate dose to effect.

• Use lowest effective dose. Taper by 2 mg every 3 days to decrease withdrawal symptoms. Some patients may require longer taper periods (mos).

• PO: Tablets may be crushed and taken with food or water if patient has difficulty swallowing.

» Mix Intensol preparation with liquid or semisolid food such as water, juices, soda, applesauce, or pudding. Administer entire amount immediately. Do not store.

• IM: IM injections are painful and erratically absorbed. If IM route is used, inject deeply into deltoid muscle for maximum absorption.

IV Adminstration:

• pH:
6.2–6.9.

• IV:
Resuscitation equipment should be available when diazepam is administered IV.

• Direct IV:

Diluent: For IV administration do not dilute or mix with any other drug. If direct IV push is not feasible, administer IV push into tubing as close to insertion site as possible. Continuous infusion is not recommended due to precipitation in IV fluids and absorption of diazepam into infusion bags and tubing. Injection may cause burning and venous irritation; avoid small veins.
Concentration: 5 mg/mL.

• Rate:
Administer slowly at a rate of 5 mg/min in adults. Infants and children should receive 1–2 mg/min. Rapid injection may cause apnea, hypotension, bradycardia, or cardiac arrest.

• Y-Site Compatibility:

» daptomycin

» docetaxel

» methadone

» piperacillin/tazobactam

» teniposide

• Y-Site Incompatibility:

» acetaminophen

» acyclovir

» alemtuzumab

» alfentanil

» amikacin

» aminocaproic acid

» aminophylline

» amphotericin B cholesteryl

» amphotericin B colloidal

» amphotericin B lipid complex

» amphotericin B liposome

» ampicillin

» ampicillin/sulbactam

» anidulafungin

» argatroban

» ascorbic acid

» atracurium

» atropine

» azathioprine

» aztreonam

» benztropine

» bivalirudin

» bleomycin

» bumetanide

» buprenorphine

» butorphanol

» calcium chloride

» calcium gluconate

» carboplatin

» carmustine

» caspofungin

» cefazolin

» cefepime

» cefonocid

» cefoperazone

» cefotaxime

» cefotetan

» cefoxitin

» ceftaroline

» ceftazidime

» ceftriaxone

» cefuroxime

» chloramphenicol

» chlorpromazine

» cisplatin

» clindamycin

» cyanocobalamin

» cyclophosphamide

» cyclosporine

» cytarabine

» dactinomycin

» dantrolene

» dexamethasone

» dexmedetomidine

» diazoxide

» digoxin

» diltiazem

» diphenhydramine

» dopamine

» doripenem

» doxacurium

» doxorubicin

» doxycycline

» enalaprilat

» ephedrine

» epinephrine

» epirubicin

» epoetin alfa

» eptifibatide

» erythromycin

» esmolol

» etoposide

» etoposide phosphate

» famotidine

» fenoldopam

» fluconazole

» fludarabine

» fluorouracil

» folic acid

» foscarnet

» furosemide

» ganciclovir

» gemcitabine

» gentamicin

» glycopyrrolate

» granisetron

» haloperidol

» heparin

» hetastarch

» hydralazine

» hydrocortisone

» hydroxycobalamin

» hydroxyzine

» idarubicin

» ifosfamide

» imipenem/cilastatin

» indomethacin

» insulin

» irinotecan

» isoproterenol

» ketorolac

» labetalol

» levofloxacin

» lidocaine

» linezolid

» magnesium chloride

» mannitol

» mechlorethamine

» meperidine

» meropenem

» metaraminol

» methotrexate

» methoxamine

» methyldopate

» methylprednisolone

» metoclopramide

» metoprolol

» metronidazole

» midazolam

» milrinone

» mitoxantrone

» multivitamin

» mycophenolate

» nalbuphine

» naloxone

» nesiritide

» nitroglycerin

» nitroprusside

» norepinephrine

» octreotide

» oxacillin

» oxaliplatin

» oxytocin

» paclitaxel

» palonosetron

» pancuronium

» pantoprazole

» papaverine

» pemetrexed

» penicillin G

» pentamidine

» pentazocine

» pentobarbital

» phenobarbital

» phentolamine

» phenylephrine

» phenytoin

» phytonadione

» potassium acetate

» potassium chloride

» procainamide

» prochlorperazine

» promethazine

» propofol

» propranolol

» protamine

» pyridoxime

» quinupristin/dalfopristin

» ranitidine

» rocuronium

» sodium acetate

» sodium bicarbonate

» streptokinase

» succinylcholine

» tacrolimus

» theophylline

» thiamine

» thiotepa

» ticarcillin/clavulanate

» tigecycline

» tirofiban

» tobramycin

» tolazoline

» trimetaphan

» trimethoprim/sulfamethoxazole

» vancomycin

» vasopressin

» vecuronium

» verapamil

» vincristine

» vinorelbine

» vitamin B complex with C

» voriconazole

» zolendronic acid

• Rect: Do not repeat Diastat rectal dose more than 5 times/mo or 1 episode every 5 days. Round dose up to next available dose unit.

» Diazepam injection has been used for rectal administration. Instill via catheter or cannula fitted to the syringe or directly from a 1-mL syringe inserted 4–5 cm into the rectum. A dilution of diazepam injection with propylene glycol containing 1 mg/mL has also been used.

» Do not dilute with other solutions, IV fluids, or medications.

Patient/Family Teaching

• Instruct patient to take medication as directed and not to take more than prescribed or increase dose if less effective after a few weeks without checking with health care professional. Review package insert for Diastat rectal gel with patient/caregiver prior to administration. Abrupt withdrawal of diazepam may cause insomnia, unusual irritability or nervousness, and seizures. Advise patient that sharing of this medication may be dangerous.

» Medication may cause drowsiness, clumsiness, or unsteadiness. Advise patient to avoid driving or other activities requiring alertness until response to medication is known. Geri: Advise geriatric patients of increased risk for CNS effects and potential for falls.

» Caution patient to avoid taking alcohol or other CNS depressants concurrently with this medication.

» Advise patient to notify health care professional if pregnancy is planned or suspected.

» Emphasize the importance of follow-up examinations to determine effectiveness of the medication.

• Seizures: Patients on anticonvulsant therapy should carry identification describing disease process and medication regimen at all times.

Evaluation/Desired Outcomes

• 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.

• Decrease in muscle spasms.

• Decreased tremulousness and more rational ideation when used for alcohol withdrawal.