DIAZEPAM

brands

Class

• Neuroscience-based Nomenclature: GABA positive allosteric modulator (GABA-PAM)
• Benzodiazepine (anxiolytic, muscle relaxant, anticonvulsant)

DIAZEPAM commonly prescribed for

(Bold for FDA approved)

How DIAZEPAM works

• Binds to benzodiazepine receptors at the GABA-A ligand-gated chloride channel complex</br>

• Enhances the inhibitory effects of GABA</br>

• Boosts chloride conductance through GABA-regulated channels</br>

• Inhibits neuronal activity presumably in amygdala-centered fear circuits to provide therapeutic benefits in anxiety disorders</br>

• Inhibiting actions in cerebral cortex may provide therapeutic benefits in seizure disorders</br>

• Inhibitory actions in spinal cord may provide therapeutic benefits for muscle spasms

How long until DIAZEPAM works

• Some immediate relief with first dosing is common; can take several weeks with daily dosing for maximal therapeutic benefit

Notable Side Effects

• Sedation

• Fatigue, depression

• Dizziness, ataxia, slurred speech, weakness

• Forgetfulness, confusion

• Hyperexcitability, nervousness

• Hypersalivation, dry mouth

• Pain at injection site

• Rare hallucinations, mania

• Rare hypotension

Life Threatening Side Effects

• Respiratory depression, especially when taken with CNS depressants in overdose

• Rare hepatic dysfunction, renal dysfunction, blood dyscrasias

weight gain

unusual

sedation

common

What to do about DIAZEPAM side effects

• Wait

• Wait

• Wait

• Lower the dose

• Take largest dose at bedtime to avoid sedative effects during the day

• Switch to another agent

• Administer flumazenil if side effects are severe or life-threatening

usual dosage range

• Oral: 4–40 mg/day in divided doses

• Intravenous (adults): 5 mg/minute

• Intravenous (children): 0.25 mg/kg every 3 minutes

Dosage Forms

• Tablet 2 mg, 5 mg, 10 mg

• Nasal 5 mg/spray, 7.5 mg/spray, 10 mg/ spray

• Concentrate 5 mg/mL

• Solution 5 mg/5 mL

• Injection 10 mg/2 mL, 50 mg/10 mL

• Rectal gel 2.5

long term use

• Evidence of efficacy up to 16 weeks

• Risk of dependence, particularly for treatment periods longer than 12 weeks and especially in patients with past or current polysubstance abuse

• Not recommended for long-term treatment of seizure disorders

habit forming

• Diazepam is a Schedule IV drug

• Patients may develop dependence and/or tolerance with long-term use

Renal Impairment

• Initial 2–2.5 mg, 1–2 times/day; increase gradually as needed

Hepatic Impairment

• Initial 2–2.5 mg, 1–2 times/day; increase gradually as needed

Cardiac Impairment

• Benzodiazepines have been used to treat anxiety associated with acute myocardial infarction

• Diazepam may be used as an adjunct during cardiovascular emergencies

Elderly

• Initial 2–2.5 mg, 1–2 times/day; increase gradually as needed

Children and Adolescents

• 6 months and up: initial 1–2.5 mg, 3–4 times/day; increase gradually as needed

• Parenteral: 30 days or older

• Rectal: 2 years or older

• Long-term effects of diazepam in children/ adolescents are unknown

• Should generally receive lower doses and be more closely monitored

Pregnancy

• Possible increased risk of birth defects when benzodiazepines taken during pregnancy

• Because of the potential risks, diazepam is not generally recommended as treatment for anxiety during pregnancy, especially during the first trimester

• Drug should be tapered if discontinued

• Infants whose mothers received a benzodiazepine late in pregnancy may experience withdrawal effects

• Neonatal flaccidity has been reported in infants whose mothers took a benzodiazepine during pregnancy

• Seizures, even mild seizures, may cause harm to the embryo/fetus

Breast Feeding

• Some drug is found in mother’s breast milk

• Recommended either to discontinue drug or formula feed

• Effects of benzodiazepines on nursing infants have been reported and include feeding difficulties, sedation, and weight loss