Clonazepam
Clonazepam is a potent, long-acting **benzodiazepine** used in veterinary medicine primarily as an adjunctive anticonvulsant and anxiolytic. > **Clinical Pearl:** In dogs, its utility as a long-term maintenance anticonvulsant is severely limited because they rapidly develop tolerance to its antiepileptic effects (often within 1 to 4 weeks). This is due to receptor downregulation and altered pharmacokinetics. Therefore, it is much better suited for short-term pulse therapy or the management of cluster seizures. - In cats, it can be used for longer-term adjunctive treatment of epilepsy or anxiety. While idiosyncratic acute hepatic necrosis is a known risk with oral benzodiazepines in cats (most notably diazepam), it is generally considered less likely to occur with clonazepam, though monitoring is still required. - Clonazepam is a **Schedule IV (C-IV)** controlled substance due to its potential for human abuse and dependence.
Mechanism: Clonazepam acts as a positive allosteric modulator at the **GABA-A receptor** complex in the central nervous system. - It binds to specific benzodiazepine receptors (located primarily in the limbic, thalamic, and hypothalamic regions) โ enhances the affinity of the receptor for the inhibitory neurotransmitter **gamma-aminobutyric acid (GABA)**. - This increases the frequency of chloride channel opening โ influx of chloride ions โ cellular hyperpolarization โ decreased neuronal excitability. - Additional postulated mechanisms include antagonism of serotonin and diminished release or turnover of acetylcholine in the CNS.
Dosing by species
- Anxiolytic ยท 0.05-0.25 mg/kg PO q12-24h ยท PO ยท q12-24h
- Anxiolytic ยท 0.02-0.2 mg/kg PO once to two times a day ยท PO ยท q12-24h
- Anxiolytic ยท 0.1-0.2 mg/kg PO as needed or up to two times a day ยท PO ยท PRN or q12h
- Adjunctive medication in the treatment of seizures ยท Starting dose is 0.5 mg (total dose) PO q12-24h ยท PO ยท q12-24h
- Adjunctive medication in the treatment of seizures ยท 1/8th to 1/4 of a 0.5 mg tablet PO two to three times daily ยท PO ยท q8-12h ยท Anecdotally more effective for maintenance and to decrease cluster seizures; acute hepatic necrosis possible
- Anxiolytic / Hyperaesthesia / Epilepsy ยท 0.5 mg/cat ยท PO ยท q12-24h ยท Suggested starting dose but there is a wide range of recommendations.
- Adjunctive medication in the treatment of seizures ยท 1-2 mg/kg PO q12h ยท PO ยท q12h
- Adjunctive medication in the treatment of seizures ยท 0.5 mg/kg PO two to three times a day ยท PO ยท q8-12h ยท May need to lower phenobarbital dose by 10-20%
- Anxiolytic ยท 0.05-0.25 mg/kg PO q12-24h ยท PO ยท q12-24h
- Anxiolytic ยท 0.1-1 mg/kg PO two to three times a day ยท PO ยท q8-12h
Routes of administration
Contraindications
- Hypersensitivity to clonazepam or other benzodiazepines
- Significant liver disease or dysfunction
- Acute narrow-angle glaucoma
- Myasthenia gravis (may exacerbate weakness)
- Marked CNS depression
- Respiratory depression
- Severe muscle weakness
- Hepatic impairment (may worsen hepatic encephalopathy)
- Acute narrow angle glaucoma
Adverse effects
- Sedation and lethargy
- Ataxia (incoordination)
- Paradoxical excitement, hyperactivity, or vocalization
- Increased salivation
- Gastrointestinal upset (vomiting, diarrhea, constipation)
- Dogs: Rapid tolerance to anticonvulsant effects
- Cats: Polyphagia, potential for acute hepatic necrosis (rare)
- Sedation
- Respiratory suppression (at higher doses)
- Ataxia
- Acute hepatic necrosis (idiosyncratic in cats)
- Tolerance development
Drug interactions
- Azole Antifungals (itraconazole, ketoconazole) ยท May increase clonazepam levels by inhibiting its metabolism.
- Cimetidine ยท May decrease the metabolism of benzodiazepines, increasing their effects.
- CNS Depressants (barbiturates, narcotics, anesthetics) ยท Additive CNS depression; may cause profound sedation or respiratory depression.
- Erythromycin ยท May decrease the metabolism of benzodiazepines.
- Phenobarbital ยท May decrease clonazepam concentrations via hepatic enzyme induction. ยท moderate
- Phenytoin ยท May decrease clonazepam concentrations. ยท moderate
- Propantheline ยท May decrease clonazepam concentrations.
- Rifampin ยท May induce hepatic microsomal enzymes and decrease the pharmacologic effects of benzodiazepines.
- Antifungal imidazoles (e.g., Ketoconazole, Itraconazole) ยท Inhibition of CYP450 enzymes may decrease clonazepam clearance, increasing its plasma levels and risk of toxicity. ยท moderate
- Other CNS Depressants ยท Additive sedation and respiratory depression. ยท major
Monitoring
- Clinical efficacy (seizure frequency, anxiety levels)
- Adverse effects (sedation, ataxia, paradoxical excitement)
- Therapeutic blood levels (reported target: 0.015-0.07 mcg/mL)
- Cats: Baseline and periodic liver function tests
- Degree of sedation and ataxia
- Respiratory rate and effort
- Hepatic function panel (especially in cats)
- Clinical response (seizure frequency, muscle tone, or behavioral changes)
Overdose
Overdoses commonly cause profound **sedation, depression, and ataxia**. - **Paradoxical Reactions:** Some animals may exhibit paradoxical signs such as hyperactivity, disorientation, agitation, and vocalization. Paradoxical excitation can be treated with a mild sedative, such as diphenhydramine. - **Management:** Emesis is generally NOT indicated due to the risk of rapid CNS depression and aspiration. Mild to moderate overdoses can often be monitored at home if the animal is rousable and not showing paradoxical signs. Keep the animal confined and minimize stimulation. - **Severe Toxicity:** Massive overdoses can lead to respiratory depression or hypotension. **Flumazenil** (a specific benzodiazepine antagonist) can be used to reverse severe respiratory or CNS depression. Because flumazenil has a short half-life, multiple doses may be required.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.