Pronunciation: DIE-aze-uh-pam
Class: Benzodiazepine, Centrally acting muscle relaxant

Trade Names

Diastat
- Gel, rectal 2.5 mg (pediatric)
- Gel, rectal 10 mg
- Gel, rectal 15 mg (adult)
- Gel, rectal 20 mg (adult)

Diazepam
- Solution, oral 1 mg/mL
- Injection 5 mg/mL

Diazepam Intensol
- Solution (intensol) 5 mg/mL

Valium
- Tablets 2 mg
- Tablets 5 mg
- Tablets 10 mg

Apo-Diazepam (Canada)
Diazemuls (Canada)
Valium Roche Oral (Canada)

Pharmacology

Potentiates action of GABA, inhibitory neurotransmitter, resulting in increased neural inhibition and CNS depression, especially in limbic system and reticular formation.

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Pharmacokinetics

Absorption

IM

Slow and erratic absorption unless administered in the deltoid muscle; C _max is lower than oral or IV administration.

Rectal

T _max is 1.5 h. Bioavailability is 90%.

Oral

T _max is 0.5 to 2 h.

Distribution

95% to 98% protein bound. Highly lipophilic. Crosses the placenta and is excreted in breast milk.

Metabolism

Metabolized in the liver (involving CYP2C19 and CYP3A4) to desmethyldiazepam (active) and 2 minor active metabolites.

Elimination

The t _½ is 20 to 80 h.

Onset

Rapid.

Special Populations

Hepatic Function Impairment

The t _½ is prolonged and Cl decreased in those with alcoholic cirrhosis.

Elderly

The t _½ is increased and Cl is decreased.

Children

The t _½ is longer in neonates and children younger than 2 yr of age; t _½ is shorter in children 2 to 16 yr of age.

Indications and Usage

Management of anxiety disorders; relief of acute alcohol withdrawal symptoms; relief of preoperative apprehension and anxiety and reduction of memory recall; treatment of muscle spasms, convulsive disorders (used adjunctively), and status epilepticus.

Unlabeled Uses

Treatment of irritable bowel syndrome; relief of panic attack.

Contraindications

Hypersensitivity to benzodiazepines; psychoses; acute narrow-angle glaucoma; use in children younger than 6 mo of age; lactation.

Dosage and Administration

Individualize dosage; increase cautiously.

Adults and Children

Usual recommended dose IM/IV 2 to 20 mg, depending on indication and severity. In acute conditions injection may be repeated within 1 h, but every 3 to 4 h is usually satisfactory. Dosage and route vary with indication and age.

Children 6 mo of age and older

Usual daily dose PO 1 to 2.5 mg 3 or 4 times daily initially; increase gradually as needed and tolerated.

Acute Alcohol Withdrawal
Adults

PO 10 mg 3 to 4 times daily first 24 h, then 5 mg 3 to 4 times daily as needed. IM/IV 10 mg initially, then 5 to 10 mg in 3 to 4 h if needed.

Anticonvulsant Adjunct
Adults

PO 2 to 10 mg 2 to 4 times daily.

Elderly or Debilitated Patients

PO Initial dose 2 to 2.5 mg once to twice daily; increase gradually.

Anxiety
Adults

PO 2 to 10 mg 2 to 4 times daily. IM/IV 2 to 10 mg; repeat in 3 to 4 h if needed.

Cardioversion (Anxiety and Tension)
Adults

IM/IV 5 to 15 mg 5 to 10  min before procedure.

Endoscopic Procedures

IM/IV 10 to 20 mg IV or 5 to 10 mg IM approximately 30 min prior to procedure.

Preoperative (Anxiety and Tension)
Adults

IM 10 mg before surgery.

Sedation/Muscle Relaxation
Adults

IM/IV 2 to 10 mg/dose every 3 to 4 h as needed.

Children 6 mo of age and older

PO 0.12 to 0.8 mg/kg/day in divided doses. IM/IV 0.04 to 0.2 mg/kg/dose every 2 to 4 h (max, 0.6 mg/kg in 8-h period).

Skeletal Muscle Spasm
Adults

PO 2 to 10 mg 3 to 4 times daily. IM/IV 5 to 10 mg initially, then 5 to 10 mg in 3 to 4 h if needed. Larger doses may be necessary in tetanus.

Status Epilepticus and Severe Recurrent Convulsive Disorders
Adults

IM/IV (IV preferred) 5 to 10 mg initially; then 5 to 10 mg at 10 to 15 min intervals (max total dose, 30 mg). If needed, repeat in 2 to 4 h.

Children 5 yr of age and older

IM/IV 1 mg every 2 to 5 min (max total dose, 10 mg). If needed, repeat in 2 to 4 h.

Infants and Children 1 mo to 5 yr of age

IM/IV 0.2 to 0.5 mg slowly every 2 to 5 min (max total dose, 5 mg).

Tetanus
Children 5 yr of age and older

IM/IV 5 to 10 mg; repeat every 3 to 4 h as needed.

Infants and Children 1 mo to 5 yr of age

IM/IV 1 to 2 mg slowly; repeat every 3 to 4 h as needed.

Rectal Gel
Children 2 to 5 yr of age

Rectal 0.5 mg/kg.

Children 6 to 11 yr of age

Rectal 0.3 mg/kg.

Adults and Children 12 yr of age and older

Rectal 0.2 mg/kg.

A second dose, when required, may be given 4 to 12 h after the first dose.

General Advice

• Oral Solution
• Use calibrated dropper to measure prescribed dose of concentrated oral solution. Add prescribed dose to a liquid (eg, juice, water, soda) or semisolid food (eg, applesauce, pudding); stir for a few seconds then immediately administer entire amount of mixture. Do not prepare and store doses for future use.

• Injection
• For IM or IV administration only.
• Do not administer if particulate matter, cloudiness, or discoloration is noted.
• For IM administration, inject deeply into muscle.
• To reduce risk of IV injection-site reactions (eg, venous thrombosis, phlebitis, local irritation) administer IV injection slowly (no more than 5 mg/min) directly into large vein. Do not administer using small veins (eg, dorsum of hand, wrist).
• To reduce risk of apnea and hypersomnolence in children, administer prescribed IV dose over 3 min.

Storage/Stability

Store tablets, oral solution, and injection at controlled room temperature (59° to 86°F). Protect from light. Protect tablets from moisture.

Drug Interactions

Azole antifungal agents (eg, itraconazole, ketoconazole), diltiazem, fluvoxamine, isoniazid, macrolide antibiotics (eg, erythromycin), nefazodone, non-nucleoside reverse transcriptase inhibitors (eg, delavirdine, efavirenz), protease inhibitors (eg, indinavir)

May increase diazepam plasma concentrations.

Cimetidine, oral contraceptives, disulfiram

May increase effects of diazepam with excessive sedation and impaired psychomotor function.

Digoxin

May increase serum digoxin concentrations.

Omeprazole

May increase diazepam levels and enhance effects.

Rifamycins

May decrease diazepam plasma concentrations.

Theophyllines

May antagonize sedative effects of diazepam.

Incompatibility

Diazepam interacts with plastic containers and IV tubing, significantly decreasing availability of drug delivered. Do not mix or dilute with other solutions or drugs in a syringe or infusion container.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

CV collapse; bradycardia; tachycardia; hypertension; palpitations; edema; hypotension; phlebitis or thrombosis at IV sites.

CNS

Drowsiness; confusion; ataxia; dizziness; lethargy; fatigue; apathy; memory impairment; disorientation; anterograde amnesia; restlessness; headache; slurred speech; loss of voice; stupor; coma; euphoria; irritability; vivid dreams; psychomotor retardation; paradoxical reactions (eg, anger, hostility, mania, insomnia, muscle spasms); depression; dysarthria; hypoactivity; tremor; vertigo.

Dermatologic

Urticaria; skin rash.

EENT

Visual or auditory disturbances; depressed hearing; blurred vision; diplopia; nystagmus.

GI

Constipation; diarrhea; dry mouth; coated tongue; nausea; anorexia; vomiting.

Genitourinary

Incontinence; changes in libido; urinary retention.

Hematologic

Blood dyscrasias including agranulocytosis, anemia, thrombocytopenia, leukopenia, neutropenia.

Hepatic

Hepatic dysfunction including hepatitis and jaundice; abnormal LFTs.

Miscellaneous

Dependency/withdrawal symptoms.

Precautions

Monitor Ensure that CBC with differential and liver enzymes are evaluated periodically in patient on prolonged therapy.

Pregnancy

Category D . Avoid drug especially during first trimester because of possible increased risk of congenital malformations.

Lactation

Excreted in breast milk.

Children

Oral form not recommended in patients younger than 6 mo of age; parenteral form not recommended in infants younger than 30 days of age.

Elderly

Initial dose should be small and gradually increased. Give with extreme care to elderly patients with limited pulmonary reserve.

Renal Function

Observe caution to avoid accumulation of drug.

Hepatic Function

Observe caution to avoid accumulation of drug.

Dependency

Prolonged use can lead to dependency. Withdrawal syndrome has occurred within 4 to 6 wk of treatment, especially if abruptly discontinued. For discontinuation after long-term treatment, use caution and taper dosage.

Parenteral administration

Reserved primarily for acute states.

Psychiatric disorders

Not intended for use in patients with primary depressive disorder, psychosis, or disorders in which anxiety is not prominent.

Seizures

Tonic status epilepticus has been precipitated in patients treated with IV for petit mal or variant status.

Suicide

Use drug with caution in patients with suicidal tendencies; do not allow access to large quantities of drug.

Overdosage

Symptoms

Hypotension, respiratory or cardiac arrest, drowsiness, confusion, somnolence, impaired coordination, diminished reflexes, lethargy, ataxia, hypotonia, hypnosis, coma, death.

Patient Information

• Advise patient or caregiver to read the patient information leaflet before starting therapy and with each refill.
• Advise patient that medication is usually started at a low dose and then gradually increased until maximum benefit is obtained.
• Caution patient that medication may be habit forming, to take as prescribed, and not to stop taking or change the dose unless advised by health care provider.
• Advise patient to take each dose without regard to meals but to take with food if stomach upset occurs.
• Advise patient or caregiver using concentrated oral solution to measure prescribed dose using calibrated dropper and then add solution to a liquid (eg, juice, water, soda) or semisolid food (eg, applesauce, pudding); stir for a few seconds then immediately take (give) the entire mixture. Caution patient or caregiver not to prepare mixtures ahead of time and store.
• Advise patient that if a dose is missed to skip that dose and take the next dose at the regularly scheduled time. Caution patient to never take 2 doses at the same time.
• Advise patient if medication needs to be discontinued, it will be slowly withdrawn unless safety concerns (eg, rash) require a more rapid withdrawal.
• Instruct patient to avoid alcoholic beverages and other depressants while taking this medication.
• Advise patient with anxiety to take medication as needed and to seek alternative methods for controlling or preventing anxiety (eg, stress reduction, counseling).
• Instruct patient to contact health care provider if symptoms (eg, anxiety, panic attacks, seizures) do not appear to be getting better, are getting worse, or if bothersome adverse reactions (eg, drowsiness, memory impairment) occur.
• Advise patient that drug may cause drowsiness or impair judgment, thinking, or reflexes and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
• Encourage patient with seizure disorder to carry identification (eg, card, bracelet) indicating condition and medication being used to treat.

• Injection
• Advise patient or caregiver that medication will be prepared by a health care provider and administered in a health care setting under close observation, when oral therapy is not feasible.
• Caution patient who receives parenteral therapy as an outpatient (eg, outpatient surgery) to use caution while ambulating, avoid ingestion of alcohol or other sedatives, and avoid driving or other hazardous activities for 24 to 48 h.

Copyright © 2009 Wolters Kluwer Health.