Triclofos

Usage

• Triclofos sodium is prescribed for the short-term management of insomnia in adults and children. It is also used for sedation during diagnostic or therapeutic procedures.
• Pharmacological classification: Sedative-hypnotic.
• Mechanism of Action: Triclofos is a prodrug that is metabolized to trichloroethanol, which enhances the inhibitory effects of gamma-aminobutyric acid (GABA) in the central nervous system, leading to sedation and sleep induction.

Alternate Names

• Triclofos sodium
• Brand Names: Triclofos, Tricloryl, Pedicloryl, Hypnodil.

How It Works

• Pharmacodynamics: Triclofos is rapidly converted in the liver to its active metabolite, trichloroethanol. Trichloroethanol potentiates GABAergic neurotransmission by interacting with GABA_A receptors, the primary inhibitory neurotransmitter receptor in the CNS. This enhanced GABAergic activity results in neuronal hyperpolarization and decreased neuronal excitability, leading to sedation and sleep.

• Pharmacokinetics: Triclofos is administered orally and rapidly absorbed from the gastrointestinal tract. It is extensively metabolized in the liver to trichloroethanol, its active form. Peak plasma levels of trichloroethanol are typically reached within 30-60 minutes. Trichloroethanol is further metabolized to trichloroacetic acid, which is then conjugated with glycine and excreted in the urine. The elimination half-life of trichloroethanol is approximately 7-12 hours.

• Elimination pathways: Primarily renal excretion of trichloroacetic acid, conjugated with glycine. Hepatic metabolism via CYP enzymes is involved in the conversion of trichloroethanol to trichloroacetic acid.

Dosage

Standard Dosage

Adults:

• 1-2 g orally at bedtime. Maximum dosage 2 g daily.

Children:

• 20-50 mg/kg/dose orally as a single dose. The dose may be repeated once after 30 minutes if necessary. Maximum dosage 2 g daily.

Special Cases:

• Elderly Patients: Start with a lower dose (e.g., 500 mg) and titrate up based on response and tolerability due to potential for reduced metabolic clearance and increased sensitivity.
• Patients with Renal Impairment: Lower doses may be required based on the degree of impairment.
• Patients with Hepatic Dysfunction: Contraindicated in patients with marked hepatic impairment.
• Patients with Comorbid Conditions: Caution is advised in patients with respiratory disorders, severe cardiac disease, or a history of substance abuse.

Clinical Use Cases

• Intubation, Surgical Procedures, Mechanical Ventilation, ICU Use: 20-100 mg/kg as a single dose or multiple doses administered orally or via nasogastric tube. Dosage depends on patient factors, level of sedation required and type of procedure. Careful monitoring of respiratory status is mandatory.
• Emergency Situations: Not typically recommended.

Dosage Adjustments:

• Dosage adjustments are required based on patient factors (e.g., age, renal or hepatic function, and comorbid conditions) and level of sedation needed.

Side Effects

Common Side Effects

• Drowsiness, dizziness, nausea, vomiting, headache, gastrointestinal upset, confusion, paradoxical excitement, ataxia

Rare but Serious Side Effects

• Respiratory depression, allergic reactions (rash, itching, swelling), paradoxical agitation.

Long-Term Effects

• Potential for dependence with prolonged use.

Adverse Drug Reactions (ADR)

• Severe allergic reactions, including anaphylaxis, requiring immediate medical intervention.

Contraindications

• Hypersensitivity to triclofos or chloral hydrate.
• Severe respiratory insufficiency, sleep apnea.
• Marked hepatic or renal impairment.
• Porphyria.

Drug Interactions

• CNS depressants (e.g., alcohol, benzodiazepines, barbiturates, opioids): Increased sedation and respiratory depression.
• Anticoagulants (e.g., warfarin): Enhanced anticoagulant effect due to displacement from protein binding sites.
• CYP450 enzyme inducers or inhibitors: May alter the metabolism of triclofos and interacting medications.

Pregnancy and Breastfeeding

• Triclofos crosses the placenta and is excreted in breast milk. Use only if clearly needed and after careful consideration of potential risks to the fetus or infant. Consult a neonatologist or pediatrician for advice.

Drug Profile Summary

• Mechanism of Action: Enhances GABAergic neurotransmission leading to CNS depression.
• Side Effects: Drowsiness, dizziness, nausea, vomiting, headache, paradoxical excitement.
• Contraindications: Hypersensitivity, respiratory insufficiency, hepatic/renal impairment.
• Drug Interactions: CNS depressants, anticoagulants, CYP450 modulators.
• Pregnancy & Breastfeeding: Use with caution; potential fetal/neonatal risks.
• Dosage: Adults: 1-2 g orally at bedtime. Children: 20-50 mg/kg/dose orally. Special considerations for elderly and renal impairment.
• Monitoring Parameters: Respiratory rate, oxygen saturation, level of sedation.

Popular Combinations

• Not applicable as per included sources

Precautions

• General Precautions: Evaluate respiratory and hepatic function before starting therapy. Assess for history of substance abuse. Caution in elderly and patients with renal impairment. Monitor respiratory status during procedural sedation.
• Specific Populations: Use with caution in pregnancy and breastfeeding. Pediatric dosage based on weight. Lower initial doses in elderly.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Triclofos?

A: Adults: 1-2 g orally at bedtime. Children: 20-50 mg/kg/dose orally.

Q2: How does Triclofos work?

A: It is metabolized to trichloroethanol, which enhances GABAergic neurotransmission, causing sedation and sleep.

Q3: What are the common side effects of Triclofos?

A: Drowsiness, dizziness, nausea, vomiting, headache, paradoxical excitement.

Q4: Is Triclofos safe to use during pregnancy?

A: Use only if clearly needed and after careful consideration of potential risks to the fetus.

Q5: Can Triclofos be used in patients with liver disease?

A: Contraindicated in patients with marked hepatic impairment.

Q6: Does Triclofos interact with other medications?

A: Yes, it interacts with CNS depressants, anticoagulants, and CYP450 modulators.

Q7: What are the signs of Triclofos overdose?

A: Respiratory depression, excessive sedation, hypotension, coma.

Q8: Can Triclofos be used for procedural sedation in children?

A: Yes, it is commonly used for sedation in children undergoing diagnostic or therapeutic procedures at a dose of 20-100 mg/kg/dose, with appropriate monitoring.

Q9: Can Triclofos be used long-term for insomnia?

A: It is generally recommended for short-term use due to the potential for tolerance and dependence.