Clorazepate
Clorazepate dipotassium
Also known as: Tranxene-SD · Gen-Xene · Tranxene T-tab · Abbott-35616 · AH-3232 · 4306-CB · clorazepic acid · dipotassium clorazepate · dikalii clorazepas
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Adjunctive medication in the treatment of seizures (in combination with phenobarbital) | 1-2 mg/kg PO q12h, but may need to divide q12h dose and give q8h to minimize adverse effects and maintain therapeutic levels | PO | q8-12h | — | 🌎 NA |
| Adjunctive medication in the treatment of seizures (in combination with phenobarbital) | 0.5-1 mg/kg PO q8h | PO | q8h | — | 🌎 NA |
| Adjunctive medication in the treatment of seizures | 1-2 mg/kg PO q12h | PO | q12h | — | 🌎 NA |
| Adjunctive medication in the treatment of seizures | 2-4 mg/kg PO twice daily, some dogs may require three times daily | PO | q8-12h | — | 🌎 NA |
| Third-line agent for seizures | 1-2 mg/kg PO q8-12h | PO | q8-12h | — | 🌎 NA |
| Management of cluster seizures | 0.5-2 mg/kg two to three times daily | PO | q8-12h | 48-96 hours | 🌎 NA |
| Adjunctive therapy for fears and phobias | 11.25-22.5 mg per dog PO once to twice daily | PO | q12-24h | — | 🌎 NA |
| Adjunctive therapy for fears and phobias | 22.5 mg for large dogs, 11.25 mg for medium dogs and 5.6 mg for small dogs PO | PO | prn | — | 🌎 NA |
| Adjunctive therapy for fears and phobias | 0.55-2.2 mg/kg PO as needed up to q8h | PO | up to q8h | — | 🌎 NA |
| Adjunctive therapy for fears and phobias | 0.2-1 mg/kg PO q12-24h | PO | q12-24h | — | 🌎 NA |
- Adjunctive medication in the treatment of seizures (in combination with phenobarbital): No advantage gained with using sustained release products. May affect phenobarb levels; monitor 2 and 4 weeks later.
- Management of cluster seizures: Give immediately after first seizure and stop after 48-96 hours. Used only during seizure activity, not as maintenance.
- Adjunctive therapy for fears and phobias: Recommends the sustained-delivery product (Tranxene-SD).
- Adjunctive therapy for fears and phobias: Using sustained delivery product. Adjust dosage according to dog's response.
- Adjunctive therapy for fears and phobias: Titrate to clinical sedation; dose may vary for individual dogs.
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Anxiolytic or for compulsive behaviors | 0.2-0.5 mg/kg PO q12-24h | PO | q12-24h | — | 🌎 NA |
| Alternative drug to phenobarbital for seizures | 3.75-7.5 mg (total dose per cat) PO once to twice daily | PO | q12-24h | — | 🌎 NA |
- Alternative drug to phenobarbital for seizures: Similar precautions are necessary as described for diazepam use in cats (risk of hepatic necrosis).
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Clorazepate is a benzodiazepine primarily used in veterinary medicine as an adjunctive anticonvulsant and for managing anxiety or phobia-related behavioral disorders.
- Clinical Pearl: Clorazepate is a prodrug. It requires the acidic environment of the stomach to be rapidly decarboxylated into its active metabolite, nordiazepam (desmethyldiazepam), before absorption.
- In dogs, it is frequently paired with phenobarbital for refractory seizures. While tolerance to its anticonvulsant effects can develop, it is reported to occur less rapidly than with clonazepam.
- In cats, it is utilized as an anxiolytic and occasionally as an alternative to phenobarbital for seizure management, though caution is required due to the risk of idiosyncratic hepatotoxicity associated with oral benzodiazepines in felines.
Mechanism of action
Benzodiazepines exert their effects by enhancing the inhibitory activity of gamma-aminobutyric acid (GABA) in the central nervous system.
- Mechanism: They bind to specific allosteric sites on the GABA-A receptor complex → increases the frequency of chloride channel opening → cellular hyperpolarization → decreased neuronal excitability.
- This depression of subcortical CNS levels (primarily limbic, thalamic, and hypothalamic) produces the characteristic anxiolytic, sedative, skeletal muscle relaxant, and anticonvulsant effects.
- Other postulated mechanisms include antagonism of serotonin and diminished release or turnover of acetylcholine in the CNS.
Safety & warnings
Contraindications
- Hypersensitivity to benzodiazepines
- Significant liver disease/dysfunction
- Acute narrow angle glaucoma
- Fear-induced aggression (relative contraindication; may disinhibit bite inhibition)
Adverse effects
- Sedation (most common)
- Ataxia
- Physical dependence (with chronic use)
- Acute hepatic necrosis (idiosyncratic in cats)
- Paradoxical excitation or disinhibition of aggression
Precautions
Use with extreme caution in aggressive animals, particularly those with fear-induced aggression, as benzodiazepines can disinhibit anxiety-based bite inhibition and provoke attacks. Benzodiazepines may exacerbate myasthenia gravis. Safe use during pregnancy is not established (FDA Category D in humans; teratogenic effects noted in lab animals). The active metabolite, nordiazepam, is distributed into milk and may affect nursing neonates. Abrupt withdrawal after chronic use can precipitate severe rebound seizures.
Drug interactions
May increase serum levels of benzodiazepines by inhibiting their metabolism.
May decrease the metabolism of benzodiazepines, leading to prolonged effects.
Additive CNS depression; may cause profound sedation or respiratory depression.
May decrease the metabolism of benzodiazepines.
Complex interaction: Clorazepate may initially increase phenobarbital serum levels. Over time, clorazepate levels may decrease, leading to decreased phenobarbital levels. Requires close monitoring.
May decrease clorazepate concentrations.
May induce hepatic microsomal enzymes and decrease the pharmacologic effects of benzodiazepines.
Monitoring
- Clinical efficacy (seizure frequency or behavioral improvement)
- Adverse effects (sedation, ataxia)
- Liver enzymes (especially critical in cats due to risk of acute hepatic necrosis)
- Phenobarbital serum levels (if used concurrently, monitor at 2 and 4 weeks after adding clorazepate)
Pharmacokinetics
Absorption
In dogs, peak serum levels generally occur within 1-2 hours.
Distribution
Volume of distribution is about 1.8 L/kg after multiple dosing in dogs. Nordiazepam is distributed into milk.
Metabolism
Clorazepate is a prodrug that is rapidly decarboxylated in the acidic environment of the stomach to nordiazepam (active) and other metabolites.
Elimination
Eliminated primarily via hepatic metabolism and subsequent renal excretion of metabolites.
Overdose
When used alone, clorazepate overdoses are generally limited to significant CNS depression (confusion, coma, decreased reflexes, profound sedation).
- Treatment: Consists of standard protocols for removing and/or binding the drug in the gut (e.g., emesis if asymptomatic and recent, activated charcoal) and supportive systemic measures.
- The use of analeptic agents (CNS stimulants such as caffeine, amphetamines) is generally not recommended.
- Flumazenil (a specific benzodiazepine reversal agent) may be considered for very serious, life-threatening overdoses.
Available products
Formulations
- Capsules
- Sustained-release tablets
Human-labeled
- Clorazepate Dipotassium Tablets: 3.75 mg, 7.5 mg, & 15 mg (Tranxene T-tab; generic)
Regulatory status
No regulatory data for: 🇺🇸 US · 🇪🇺 EU · 🇬🇧 UK · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Clorazepate dipotassium is unstable in the presence of water. Keep the desiccant packets in the original container of the capsules and tablets. Consider adding a desiccant packet to the prescription vial when dispensing large quantities.
Client information
CRITICAL WARNING: Do not stop giving this drug abruptly. Sudden withdrawal can trigger severe, life-threatening seizures. Always consult your veterinarian for a tapering schedule if the medication needs to be discontinued.
- Consistency is Key: A major factor in anticonvulsant therapy failure is missed doses. Give the medication at the same times every day.
- Cats: If your cat develops a lack of appetite, vomiting, or yellowish whites of the eyes/gums (jaundice), contact your veterinarian immediately, as this could indicate a severe liver reaction.
- Side Effects: Your pet may appear sleepy, uncoordinated, or clumsy, especially when first starting the medication. This often improves as their body adjusts.
- Storage: Keep the medication in its original container with the desiccant (moisture-absorbing) packet, as the drug degrades quickly when exposed to moisture.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.