ALPRAZOLAM

brands

Class

• Neuroscience-based Nomenclature: GABA positive allosteric modulator (GABA-PAM) Benzodiazepine (anxiolytic)

ALPRAZOLAM commonly prescribed for

(Bold for FDA approved)

How ALPRAZOLAM works

• Binds to benzodiazepine receptors at the GABA-A ligand-gated chloride channel complex

• Enhances the inhibitory effects of GABA

• Boosts chloride conductance through GABA-regulated channels

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

How long until ALPRAZOLAM 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

• Rare hallucinations, mania

• Rare hypotension

• Hypersalivation, dry mouth

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

not usual

What to do about ALPRAZOLAM side effects

• Wait

• Wait

• Wait

• Lower the dose

• Switch to alprazolam XR

• 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

• Anxiety: alprazolam IR: 1–4 mg/day

• Panic: alprazolam IR: 5–6 mg/day

• Panic: alprazolam XR: 3–6 mg/day

Dosage Forms

• Alprazolam IR tablet 0.25 mg scored, 0.5 mg scored, 0.8 mg, 1 mg scored, 2 mg multiscored

• Alprazolam IR orally disintegrating tablet 0.25 mg, 0.5 mg, 1 mg, 2 mg

• Alprazolam XR (extended-release) tablet 0.5 mg, 1 mg, 2 mg, 3 mg

long term use

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

habit forming

• Alprazolam is a Schedule IV drug

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

Renal Impairment

• Drug should be used with caution

Hepatic Impairment

• Should begin with lower starting dose (0.5–0.75 mg/day in 2 or 3 divided doses)

Cardiac Impairment

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

Elderly

• Should begin with lower starting dose (0.5–0.75 mg/day in 2 or 3 divided doses) and be monitored closely

Children and Adolescents

• Safety and efficacy not established but often used, especially short-term and at the lower end of the dosing scale

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

• Should generally receive lower doses and be more closely monitored

Pregnancy

• Risk Category D [positive evidence of risk to human fetus; potential benefits may still justify its use during pregnancy]

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

• Because of the potential risks, alprazolam 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 bottle feed

• Effects on infant have been observed and include feeding difficulties, sedation, and weight loss