Clotiazepam: Indications, Pharmacokinetics, Side Effects, Administration, Warnings and Precautions

It is a thienodiazepine drug that is a benzodiazepine analog.

Clotiazepam is marketed under the brand names Clozan, Distensan, Trecalmo, Rize, Rizen, and Veratran.

The clotiazepam molecule differs from benzodiazepines in that the benzene ring has been replaced by a thiophene ring.

It has anxiolytic , skeletal muscle relaxant, anticonvulsant and sedative properties.

It is a short-acting drug with general properties similar to diazepam. Clotiazepam is also known as Y-6047.

Clotiazepamum is the derivative of clotiazepam. It is of synthetic origin. The Molecular Weight of clotiazepam is 318.80.

Indications

This medication has been tested and found to be effective in managing anxiety in the short term.

Clotiazepam is also used as a premedicant in minor surgery in France and Japan, where the drug is commercially available under the trade names Veratran and Rize, respectively.

It can also be administered in complementary therapy as an alternative drug of choice in irritability.

Pharmacokinetics

A crossover study was conducted in six healthy volunteers (median age 28 years) using a single dose pharmacokinetics of 5 mg of clotiazepam drops, oral tablets, and sublingual tablets.

The formulations had similar systemic availability. Compared to oral tablets, the sublingual route gave a lower peak concentration and a delayed peak time, while the drops gave a higher maximum concentration with a similar peak time.

The use of drops is suggested for a more marked initial effect and the sublingual route for an easier administration, especially in the elderly.

Pharmacology

Similar to other benzodiazepines, clotiazepam has anxiolytic, sedative, hypnotic, amnesic, anticonvulsant, and muscle relaxant pharmacological properties.

This drug binds to the benzodiazepine site of the GABA receptor where it acts as a full agonist; this action results in an enhanced GABA inhibitory effect at the GABA receptor resulting in the pharmacological effects of clotiazepam.

Clotiazepam has a relatively short elimination half-life and is less prone to accumulation after repeated dosing compared to longer-acting benzodiazepine agents. It is metabolized by oxidation.

Clotiazepam is metabolized to hydroxyclothiazepam and desmethylclothiazepam. Following oral ingestion of a single 5 mg dose of clotiazepam by three healthy volunteers, the drug was rapidly absorbed. The elimination half-life of the drug and its metabolites ranges from 6.5 hours to 18 hours.

Clotiazepam is 99 percent bound to plasma protein. In elderly men, the elimination half-life is longer and in elderly women the volume of distribution increases.

People with hepatic impairment have a reduced volume of distribution as well as a reduced total clearance of clotiazepam; Kidney failure does not affect the kinetics of clotiazepam.

Side effects

Serious or irreversible adverse effects of clotiazepam, leading to additional complications, include depression of respiration. There has also been a report of hepatitis caused by clotiazepam.

Signs and symptoms that occur after an acute overdose of this drug include:

  •  Hypotension
  •  Tachycardia.
  •  Coma.
  •  Urinary retention.
  •  Ataxia.
  • Respiratory faliure.
  • Drowsiness.

Symptomatic adverse reactions produced by clotiazepam are more or less tolerable and, if they become severe, can be treated symptomatically, such as:

  •  Headache.
  •  Drowsiness.
  •  Confusion.
  •  Asthenia.

Dosage

Dosage details for clotiazepam are as follows:

Adult dosage

5 a 15 mg.

Pediatric dose (20kg)

No data are available on the pediatric dose details of clotiazepam.

Neonatal dose (3kg)

No data are available on the neonatal dose details of clotiazepam.

High risk groups

The drug should not be administered to pediatric patients.

If the prescribing authority justifies the benefits of the drug against possible harm, it should reassess them and consult the reference material and previous studies.

Warning / Precautions

The elderly, respiratory diseases, a history of alcohol and drug dependence can produce tolerance, physical and psychological dependence, rebound in somania and anxiety induce anterograde amnesia,

Abuse

Clotiazepam is a recognized drug of abuse.

Storage

  • Store in its packaging in a cool place.
  • Keep out of the reach of children.