Triazolam – TRIAZOLAM®

Brand name

  • TRIAZOLAM®

Drug Class

  • Benzodiazepine Hypnotic

Preparations

  • Triazolam Tablets USP125 mg and 0.25 mg

Indications

  • Symptomatic relief of transient and short-term insomnia in patients who have difficulty falling asleep.

Pharmacology

  • Pharmacokinetics:
    • Half-life: 1.5-5.5 hours
    • Peak plasma time: 2 hours
    • Onset of action: 15-30 min
    • Duration of action: 6-7 hours
    • Metabolism: metabolized via hepatic microsomal oxidation
    • Excretion: primarily in the urine

Metabolism

  • Depresses all level of CNS possibly by increasing membrane permeability to chloride ions, which in turn increase the inhibitory activity of GABA on neuronal excitability.

Dosing

  • Dosage in all patients:
    1. Initial dose: 0.125 mg (immediately before retiring)
    2. Duration: should usually not exceed 7-10 consecutive days.
    3. Max dose: Should not be exceeded 0.25 mg (0.5mg is used only for exceptional patients who do not respond to a trial of the lower dose.)
  • Dosage in elderly or debilitated patients and patients with disturbed liver/kidney function:
    1. Should not exceed 0.125 mg before retiring (0.25 mg is used only for exceptional patients who do not respond to a trial of the lower dose.)

Drug Interactions

  1. alcohol, antihistamines, anticonvulsants, or psychotropic medications: co-administration produces additive CNS depressant effects
  2. Cimetidine, erythromycin: interfere with triazolam metabolism

Adverse Effects

  • Most frequent:
    • Sedation (morning drowsiness, somnolence), dizziness, nervousness, irritability and impaired coordination.
  • Most serious:
    • memory impairment, abnormal thinking, abnormal behavior, confusion, anxiety, and depression
  • Rare:
    • Dysesthesia, paresthesia, dream abnormalities, drug abuse/habituation, drug withdrawal symptoms, hallucinations, muscle tone disorder, tremor, tinnitus, hearing impairment, eye irritation/redness, edema, chest pain, hot/cold flashes, hypertension, syncope, dyspnea, constipation, flatulence, oral irritation, micturition difficulties, dermatitis, diaphoresis, muscular cramps, muscular weakness, malaise, sexual dysfunction, Elevated levels of SGOT, bilirubin, and alkaline phosphatase

Contraindications

  1. Hypersensitivity to this drug or other benzodiazepines.
  2. Paradoxical reactions to alcohol or sedative medications, and history of substance or alcohol abuse.
  3. Pregnancy
  4. Myasthenia Gravis
  5. Uncorrected narrow-angle glaucoma.

Pregnancy and Breastfeeding

  • Pregnancy: category X
  • Lactation: not recommended in nursing mothers

Precautions

  1. Rebound” Insomnia:
    1. On the first or second night after drug discontinuance, total time asleep, and percentage of time spent sleeping frequently might significantly decrease.
  2. Treatment with triazolam should usually not exceed 7-10 consecutive days.
  3. Use in elderly:
    1. Degree of sedation and impairment of psychomotor performance are more pronounced in the elderly.
  4. Use in patients with severe liver disease:
    1. Greater psychomotor impairment than with minimal liver dysfunction.
  5. Over-dosage:
    1. Manifestations: somnolence, confusion, impaired coordination, slurred speech, coma, respiratory depression and apnea.
    2. Treatment: supportive care
    3. Antidote: flumazenil (‘Anexate’), a benzodiazepine antagonist.
  6. Failure of insomnia to remit after 7-10 days of treatment:
    1. Indicate the presence of a primary psychiatric or medical illness.
  7. Worsening of insomnia or the emergence of new abnormalities of thinking or behavior:
    1. Indicate consequence of an unrecognized psychiatric or physical disorder.
  8. Memory disturbance
    1. Anterograde amnesia:
      1. varying severity
      2. dose-related phenomenon
      3. Elderly subjects at a particular risk.
    2. Transient global amnesia and “traveler’s amnesia”:
      1. Unpredictable
      2. Not necessarily dose-related phenomena.
  9. Abnormal thinking and psychotic behavioral changes:
    1. Characterized by decreased inhibition, e.g., aggressiveness or extroversion
    2. Particular caution in patients with a history of violent behavior.
    3. Psychotic behavioral include:
    4. Bizarre behavior, hallucinations, and depersonalization.
    5. Abnormal behaviors are more with chronic use or high doses.
  10. Confusion:
    1. Triazolam affect mental efficiency, e.g., concentration, attention and vigilance.
    2. The risk of confusion is greater in elderly and patients with cerebral impairment.
  11. Anxiety, restlessness:
    1. Increase in daytime anxiety (interdose rebound anxiety) and restlessness
  12. Depression:
    1. Caution in patients with signs or symptoms of depression >>> because Suicidal tendencies e.g., intentional overdose, is more common in these patients,
  13. Complex sleep-related behaviors:
    1. Caution patients about dangerous sleep-related behaviors such as “sleep- driving – patients usually do not remember these events.
    2. Caution in concomitant use with alcohol and other CNS-depressants increase the risk of such behaviors
  14. Severe Anaphylactic and Anaphylactoid Reactions:
    1. Patients should be informed about angioedema
    2. Patients who develop angioedema after treatment with Triazolam should not be re-challenged with the drug.
  15. Drug abuse, dependence and withdrawal:
    1. Withdrawal symptoms:
      1. convulsions, tremor, abdominal and muscle cramps, vomiting, sweating, dysphoria, perceptual disturbances and insomnia
    2. Abrupt discontinuation should be avoided.
    3. Gradual dosage tapering is recommended in any patient taking more than the lowest dose for more than a few weeks.
    4. High risk of dependence:
      1. in patients with a history of alcoholism, drug abuse, or in patients with marked personality disorders
  16. caution in Patients with specific conditions:
    1. Impaired hepatic function,
    2. Impaired renal function,
    3. severe pulmonary insufficiency,
    4. Sleep apnea.
  17. Patients requiring mental alertness:
    1. Patients should be cautioned about:
    2. Engaging in hazardous occupations such as operating machinery or driving a motor vehicle.
    3. Concomitant ingestion of triazolam and alcohol or CNS depressant drugs.
  18. Use in children:
    1. Not recommended in children below the age of 18.
  19. Use in the elderly:
    1. Lowest possible dose should be used >>> elderly patients are susceptible to dose-related adverse effects

Warning

Section

This document is prepared by the “Mental Health for All” team. This document is provided for information purposes only and does not necessarily represent endorsement by or an official position of the Essentials of Medicine. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient’s medical history.

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