Diazepam

Action

Produces anxiolytic effect and CNS depression by stimulating gamma-aminobutyric acid receptors. Relaxes skeletal muscles of spine by inhibiting polysynaptic afferent pathways. Controls seizures by enhancing presynaptic inhibition.

Availability

Injection: 5 mg/ml

Oral solution: 1 mg/ml, 5 mg/5 ml

Tablets: 2 mg, 5 mg, 10 mg

Indications and dosages

➣ Anxiety disorders

Adults: 2 to 10 mg P.O. two to four times daily, depending on symptom severity. Alternatively, for moderate anxiety, 2 to 5 mg I.V., repeated in 3 to 4 hours if needed. For severe anxiety, 5 to 10 mg I.V., repeated in 3 to 4 hours if needed.

Children age 6 months and older: 1 to 2.5 mg P.O. three to four times daily; may increase gradually as needed

➣ Before cardioversion

Adults: 5 to 15 mg I.V. 5 to 10 minutes before cardioversion

➣ Before endoscopy

Adults: Usually, 10 mg I.V. is sufficient; may be increased to 20 mg I.V. Alternatively, 5 to 10 mg I.M. 30 minutes before endoscopy.

➣ Status epilepticus and severe recurrent convulsive seizures

Adults: 5 to 10 mg I.V. slowly, repeated as needed q 10 to 15 minutes, to a maximum of 30 mg; may repeat regimen if needed in 2 to 4 hours. May give I.M. if I.V. delivery is impossible.

Children ages 5 and older: 1 mg I.V. slowly q 2 to 5 minutes, to a maximum of 10 mg; repeat in 2 to 4 hours if needed. May give I.M. if I.V. delivery is impossible.

Children over 1 month to 5 years: 0.2 to 0.5 mg I.V. slowly q 2 to 5 minutes, to a maximum of 5 mg I.V. May give I.M. if I.V. delivery is impossible.

➣ Muscle spasm associated with local pathology, cerebral palsy, athetosis, "stiff-man" syndrome, or tetanus

Adults: 2 to 10 mg P.O. three to four times daily. Or initially, 5 to 10 mg I.V. or I.M., repeated in 3 to 4 hours if needed. Tetanus may necessitate higher dosages.

Elderly or debilitated patients: Initially, 2 to 2.5 mg P.O. once or twice daily, increased gradually as needed and tolerated

Children ages 5 and older: 5 to 10 mg I.M. or I.V., repeated q 3 to 4 hours as needed to control tetanus spasm

Children over 1 month to 5 years: 1 to 2 mg I.M. or I.V. slowly, repeated q 3 to 4 hours as needed to control tetanus spasm

➣ Acute alcohol withdrawal

Adults: Initially, 10 mg P.O. three to four times during first 24 hours, decreased to 5 mg P.O. three to four times daily p.r.n. Or initially, 10 mg I.M. or I.V.; then 5 to 10 mg I.M. or I.V. in 3 to 4 hours p.r.n.

Off-label uses

• Panic attacks

• Adjunct to general anesthesia

Contraindications

• Hypersensitivity to drug, other benzodiazepines, alcohol, or tartrazine

• Coma or CNS depression

• Narrow-angle glaucoma

Precautions

Use cautiously in:

• hepatic dysfunction, severe renal impairment

• elderly patients

• pregnant or breastfeeding patients (use not recommended)

• children.

Administration

• Give P.O. dose with or without food.

☞ Administer I.V. infusion slowly into large vein, taking at least 1 minute for each 5 mg in adults or at least 3 minutes for each 0.25 mg/kg in children.

• Know that I.V. route is preferred over I.M. route because of slow or erratic I.M. absorption.

• Don't mix with other drugs or solutions in syringe or container.

• Enforce bed rest for at least 3 hours after I.V. injection.

• Give I.M. injection deeply and slowly into large muscle mass.

• If desired, mix oral solution with liquid or soft food.

Adverse reactions

CNS: dizziness, drowsiness, lethargy, depression, light-headedness, disorientation, anger, manic or hypomanic episodes, restlessness, paresthesia, headache, slurred speech, dysarthria, stupor, tremor, dystonia, vivid dreams, extrapyramidal reactions, mild paradoxical excitation

CV: bradycardia, tachycardia, hypertension, hypotension, palpitations, cardiovascular collapse

EENT: blurred vision, diplopia, nystagmus, nasal congestion

GI: nausea, vomiting, diarrhea, constipation, gastric disorders, difficulty swallowing, increased salivation

GU: urinary retention or incontinence, menstrual irregularities, gynecomastia, libido changes

Hematologic: blood dyscrasias including eosinophilia, leukopenia, agranulocytosis, and thrombocytopenia

Hepatic: hepatic dysfunction

Musculoskeletal: muscle rigidity, muscular disturbances

Respiratory: respiratory depression

Skin: dermatitis, rash, pruritus, urticaria, diaphoresis

Other: weight gain or loss, decreased appetite, edema, hiccups, fever, physical or psychological drug dependence or tolerance

Interactions

Drug-drug. Antidepressants, antihistamines, barbiturates, opioids: additive CNS depression

Cimetidine, disulfiram, fluoxetine, hormonal contraceptives, isoniazid, ketoconazole, metoprolol, propoxyphene, propranolol, valproic acid: decreased metabolism and enhanced action of diazepam

Digoxin: increased digoxin blood level, possible toxicity

Levodopa: decreased levodopa efficacy

Rifampin: increased metabolism and decreased efficacy of diazepam

Theophylline: decreased sedative effect of diazepam

Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase: increased levels

Neutrophils, platelets: decreased counts

Drug-herbs. Chamomile, hops, kava, skullcap, valerian: increased CNS depression

Drug-behaviors. Alcohol use: increased CNS depression

Patient monitoring

• Monitor vital signs and respiratory and neurologic status.

• Supervise ambulation, especially in elderly patients.

• Monitor CBC and kidney and liver function test results.

☞ Avoid sudden drug withdrawal. Taper dosage gradually to termination of therapy.

Patient teaching

• Inform patient he may take drug with or without food; recommend taking it with food if it causes stomach upset.

• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.

☞ Tell patient to notify prescriber immediately if easy bruising or bleeding occurs.

• Instruct patient to move slowly when sitting up or standing, to avoid dizziness from blood pressure decrease. Advise him to dangle legs briefly before getting out of bed.

☞ Advise patient not to stop taking drug abruptly.

• Advise patient to avoid alcohol and other depressants such as sedatives while taking drug.

• Tell female patient not to take drug if she is pregnant or plans to breastfeed.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, herbs, and behaviors mentioned above.