Class

• Benzodiazepine (anxiolytic)

LOFLAZEPATE commonly prescribed for

(Bold for FDA approved)

How LOFLAZEPATE 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 LOFLAZEPATE 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 LOFLAZEPATE 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

• 1 mg once or twice a day

Dosage Forms

• Tablet 1 mg, 2 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

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

Renal Impairment

• Drug should be used with caution

Hepatic Impairment

• Drug should be used with caution

Cardiac Impairment

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

Elderly

• Drug should be used with caution

• Should begin with lower starting dose

Children and Adolescents

• Safety and efficacy have not been established

• Benzodiazepines are often used in children and adolescents, especially short-term and at the lower end of the dosing scale

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

• Should generally receive lower doses and be more closely monitored

Pregnancy

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

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