CLONAZEPAM

brands

Class

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

CLONAZEPAM commonly prescribed for

(Bold for FDA approved)

How CLONAZEPAM 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

• Inhibitory actions in cerebral cortex may provide therapeutic benefits in seizure disorders

How long until CLONAZEPAM 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

• Grand mal seizure

weight gain

unusual

sedation

not usual

What to do about CLONAZEPAM 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

• Seizures: dependent on individual response of patient, up to 20 mg/day

• Panic: 0.5–2 mg/day either as divided doses or once at bedtime

Dosage Forms

• Tablet 0.5 mg scored, 1 mg, 2 mg

• Disintegrating (wafer) 0.125 mg, 0.25 mg, 0.5 mg, 1 mg, 2 mg

long term use

• May lose efficacy for seizures; dose increase may restore efficacy

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

habit forming

• Clonazepam is a Schedule IV drug

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

Renal Impairment

• Dose should be reduced

Hepatic Impairment

• Dose should be reduced

Cardiac Impairment

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

Elderly

• Should receive lower doses and be monitored

Children and Adolescents

• Seizures – up to 10 years or 30 kg – 0.01–0.03 mg/kg per day divided into 2–3 doses; maximum dose 0.05 mg/kg per day

• Safety and efficacy not established in panic disorder

• For anxiety, children and adolescents should generally receive lower doses and be more closely monitored

• Long-term effects of clonazepam in children/adolescents are unknow

Pregnancy

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

• Because of the potential risks, clonazepam 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