Estazolam is an intermediate-acting benzodiazepine drug that has anxiolytic, hypnotic, anticonvulsant, and muscle-relaxing properties. It is commonly used in patients with problems related to sleep such as difficulty falling asleep and frequent nocturnal awakenings.

Estazolam Uses:

• Insomnia:

  • It is indicated for the management of patients who have difficulty falling asleep, or have frequent awakenings while asleep and early morning awakening.

Read:

• Xanax (Alprazolam) for Sleep and Anxiety
• Bromazepam for the short-term treatment of anxiety.

Estazolam Dose in Adults

Estazolam Dose in the treatment of Insomnia:

• 1 mg orally at bedtime.
• A dose of 2 mg may be required by some patients.

Dose in Children:

Not indicated.

Pregnancy Risk Factor X

• All benzodiazepines are capable of crossing the placental barrier. They have been linked to teratogenic effects.
• Pregnancy with benzodiazepines can lead to an increase in premature births and low birth weight.
• If taken during the third trimester and before delivery, there may be hypoglycemia or respiratory problems in the neonate.
• Within days or weeks of birth, neonates can experience withdrawal symptoms known as "floppy infant syndrome".
• It is not advised to use estazolam when pregnant.

Use while breastfeeding

• It is unknown if the drug will be excreted into breastmilk. However, benzodiazepines may cross the placental boundary.
• Breastfeeding infants can experience drowsiness, lethargy and weight loss after the mother uses benzodiazepines.
• Manufacturer recommends that you avoid breastfeeding.

Dose in Kidney Disease:

It has not been studied in patients with kidney disease. The manufacturer has not recommended any adjustment in the dose, however, it should be used with caution.

Dose in Liver disease:

It has not been studied in patients with kidney disease. The manufacturer has not recommended any adjustment in the dose, however, it should be used with caution.

Common Side Effects of Estazolam:

• Central nervous system:

  • Drowsiness

Less Common Side Effects of Estazolam:

• Central Nervous System:

  • Dizziness
  • Ataxia
  • Hangover Effect
  • Abnormality In Thinking
  • Confusion
  • Anxiety

• Dermatologic:

  • Pruritus

• Gastrointestinal:

  • Constipation
  • Xerostomia

• Neuromuscular & Skeletal:

  • Hypokinesia
  • Leg Pain
  • Stiffness

Contraindications to Estazolam:

• Itraconazole and ketoconazole concurrently
• Pregnancy

Warnings and precautions

• Anterograde amnesia

  • Patients may experience anterograde amnesia, as with all benzodiazepines.

• Depression in the CNS:

  • Side effects of benzodiazepines include CNS depression and drowsiness.
  • Patients who are required to be alert or who use heavy machinery should be aware of the dangers.

• Hypersensitivity reactions

  • It is possible to experience severe allergic reactions, including angioedema or anaphylaxis, after its use. Hypersensitivity reactions can be severe and should not be repeated.

• Paradoxical reactions

  • There have been paradoxical effects associated with benzodiazepines, such as aggression or hyperactivity.
  • Paradoxical behavior is more common in patients with personality disorders, older patients, and children with a history with alcohol abuse.

• Activities that are sleep-related:

  • There have been reports of dangerous sleep-related activities associated with the use of benzodiazepines.
  • These include sleeping, cooking, making calls and driving.

• Depression

  • Patients with depression have been shown to be at greater risk for suicidal tendencies when taking benzodiazepines.
  • It may cause depression symptoms to return.

• Use of drugs:

  • Some patients taking benzodiazepines can develop tolerance and may need to take higher doses.
  • Patients can also develop psychological and physical dependence.
  • Patients who have a history of substance abuse or severe alcoholism should not use it.

• Hepatic impairment

  • Patients suffering from liver disease or hepatic impairment should be cautious when taking the drug.

• Renal impairment

  • Patients with impaired renal function should be cautious when taking the drug.

• Respiratory disease

  • Patients with chronic lung disease may experience respiratory depression from benzodiazepines.
  • These patients should use it with caution.

Estazolam: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Particularly in individuals with underlying organ failure, keep an eye on the patient's respiratory and cardiovascular health.
• CBC and urinalysis periodically
• Observe for daytime somnolence;
• Assess behavior profile

How to administer Estazolam?

• Administer the drug orally at bedtime preferably without a meal (on an empty stomach).
• It should be taken just prior to getting into bed or when in bed.

Mechanism of action of Estazolam:

• By interacting with the postsynaptic GABA Neuron's typical benzodiazepine receptors at various locations across the central nervous systems, it strengthens the inhibitory impact of GABA.
• These receptors are found mainly in the limbic and reticular activating systems.
• By increasing the permeability of neurons' membranes to chloride ions and resulting hyperpolarization, it amplifies the effects of GABA.

Duration of the effect:

• Variable The excitability of neurons decreases in hyperpolarized conditions.
• GABA A receptors are a binding site for benzos. They are not able to bind to GABA B receptors.

Protein binding:

• 93%

Metabolism:

• It is metabolized extensively in the liver to 11 inactive metabolites including 1-oxo-estazolam and 4-hydroxy-estazolam.
• Its metabolism to 4-hydroxy-estazolam is mediated by CYP3A4

Half-life elimination:

• 10 to 24 hours

Time to peak, serum:

• About two 2 hours (range: 0.5 to 6 hours)

Excretion:

• Urine (Less than 5% of the drug is excreted as unchanged drug and more than 70% is excreted as inactive metabolites);
• feces (4%)

International Brands of Estazolam:

• Domnamid
• Esilgan
• Eslam
• Estalin
• Estazolam
• Eszo 2
• Eurodin
• Kainever
• Kinzolam
• Noctal
• Nuctalon
• Sedarest
• Somnatrol
• Tasedan

Estazolam Brand Names in Pakistan: