estazolam

Estazolam is a medication used for short-term management of insomnia characterized by difficulty in falling asleep, frequent awakening in the night and/or waking up extremely early in the morning. Estazolam is a sedative-hypnotic medication that belongs to the class of benzodiazepines, which induce sleep by depressing the central nervous system (CNS).

Like other benzodiazepines, estazolam has effects on the limbic system that regulates emotion and behavior and reticular formation that regulates arousal and consciousness. Estazolam suppresses the CNS by enhancing the effect of gamma-aminobutyric acid (GABA), the primary inhibitory chemical (neurotransmitter) in the central nervous system. GABA inhibits excitatory signals in the brain, relieving anxiety and producing calmness and drowsiness.

Estazolam binds to benzodiazepine receptors which are found on the nerve cell (neuron) membrane in close association with GABA-A receptors, the protein particles that transmit inhibitory signals when stimulated by GABA. This enhances GABA’s affinity and binding to the GABA-A receptors, which opens up the chloride channels on the neuronal membrane, resulting in hyperpolarization and reduced excitability of the neurons.

• Do not use in patients with documented hypersensitivity to estazolam, other benzodiazepines or any of the components in the formulation.
• Do not use estazolam in pregnant or breastfeeding women. Screen premenopausal women for pregnancy before prescribing estazolam, and caution patients about fetal risks if pregnancy occurs during therapy. Advise patients to discontinue drug before getting pregnant.
• Do not use estazolam concurrently with ketoconazole or itraconazole because these drugs inhibit CYP3A enzyme which metabolizes estazolam. Use with caution and adjust dose as necessary when concurrently using with other drugs that inhibit CYP3A to a lesser extent.
• Concomitant use of estazolam with opioid drugs can cause profound sedation, respiratory depression, coma and death.
  • If concurrent use cannot be avoided, prescribe the lowest effective dose of estazolam for minimum possible duration.
  • Caution patients and caregivers of the risks of concomitant use of estazolam and opioids and to be alert for symptoms of sedation and respiratory depression.
• Do not prescribe estazolam with other CNS depressant drugs and advise patients to avoid alcohol.
• Estazolam, like all benzodiazepines, has a high potential for misuse, abuse and addiction, which can result in overdose and death. Apprise patients and caregivers of the risks for addiction. Prescribe after carefully assessing the patient’s risk, and regularly monitor patients at high risk for addiction.
• Estazolam can cause physical dependence. Abrupt discontinuation can cause acute withdrawal symptoms that can be life-threatening. Taper dose and discontinue the drug gradually.
• Withdrawal of drug may cause rebound insomnia, restlessness, anxiety and mood changes. Some patients may experience withdrawal symptoms lasting over 12 months.
• Estazolam treatment should be initiated only after evaluating for any underlying physical and/or psychiatric disorder that may cause sleep disturbances. Insomnia that does not remit after 7 to 10 days of treatment may indicate the presence of a disorder and should be investigated.
• There have been reports of complex behaviors such as sleep-driving and performing other activities while half asleep, with no recall of the events afterwards. Discontinue estazolam in such patients.
• Estazolam can affect physical and mental abilities. Advise patients to avoid hazardous tasks during treatment.
• Estazolam may impair the ability to form new memories (anterograde amnesia).
• Use the smallest possible dose with caution in elderly or debilitated patients. CNS effects are more pronounced in elderly patients, as are risks of falls and injury.
• There have been reports of severe allergic reactions (anaphylaxis) after taking first or subsequent doses of estazolam. Discontinue the drug and initiate appropriate treatment for hypersensitivity immediately. Do not rechallenge patients with a history of such reactions.
• Estazolam may cause paradoxical reactions, including hyperactive or aggressive behavior. The risk may be higher in adolescent/pediatric patients, geriatric patients, or patients with a history of alcohol use disorder or psychiatric/personality disorders.
• Avoid use of estazolam in patients with depression, it may worsen symptoms.
• Use with caution in patients with kidney or liver function impairment.
• Use with caution in patients with respiratory disease or sleep apnea because of the risk for significant respiratory depression.

Common side effects of estazolam include:

• Drowsiness (somnolence)
• Diminished body movement (hypokinesia)
• Dizziness
• Abnormal coordination
• Nervousness
• Hangover
• Confusion
• Anxiety
• Depression
• Abnormal thinking
• Abnormal dreams
• Headache
• Weakness (asthenia)
• Feeling unwell (malaise)
• Lower extremity pain
• Body pain
• Back pain
• Chest pain
• Stiffness
• Abdominal pain
• Nausea
• Indigestion (dyspepsia)
• Constipation
• Dry mouth
• Cold symptoms
• Throat inflammation (pharyngitis)
• Itching (pruritus)

Less common side effects of estazolam include:

• Agitation
• Apathy
• Mood swings (emotional lability)
• Euphoria
• Hostility
• Amnesia
• Sleep disorder
• Stupor
• Twitch
• Numbness and tingling (paresthesia)
• Seizure
• Muscle spasm
• Muscle pain (myalgia)
• Joint inflammation (arthritis)
• Chills
• Fever
• Neck pain
• Upper extremity pain
• Allergic reaction
• Rash
• Hives (urticaria)
• Sweating
• Flushing
• Palpitation
• Increase or decrease in appetite
• Gas (flatulence)
• Vomiting
• Gastritis
• Thirst
• Asthma
• Cough
• Shortness of breath (dyspnea)
• Nasal inflammation (rhinitis)
• Sinus inflammation (sinusitis)
• Abnormal vision
• Eye irritation
• Eye pain
• Eye swelling
• Light sensitivity (photophobia)
• Ear pain
• Ringing in the ears (tinnitus)
• Taste perversion
• Urinary hesitancy
• Urinary urgency
• Frequent urination
• Menstrual cramps
• Vaginal discharge and itching

Rare side effects of estazolam include:

• Impaired balance, coordination and speech (ataxia)
• Tingling and numbness around the mouth (circumoral paresthesia)
• Decreased reflexes
• Tremor
• Nerve inflammation (neuritis)
• Rapid, repetitive, uncontrolled eye movements (nystagmus)
• Hallucinations
• Reduced libido
• Minor changes in EEG patterns
• Joint pain (arthralgia)
• Jaw pain
• Swollen breast
• Swelling (edema)
• Dry skin
• Acne
• Photosensitivity
• Severe drug-induced skin reaction (Stevens-Johnson syndrome)
• Irregular heart rhythm (arrhythmia)
• Fainting (syncope)
• Intestinal inflammation (enterocolitis)
• Dark tarry stools (melena)
• Ulceration of the mouth
• Weight gain or loss
• Increase in liver enzyme SGOT
• Thyroid nodule
• Low count of leukocyte immune cells in blood (leukopenia)
• Low count of granulocyte immune cells in blood (agranulocytosis)
• Bruising (purpura)
• Swollen lymph nodes
• Nasal bleeding (epistaxis)
• Voice box inflammation (laryngitis)
• Rapid breathing (hyperventilation)
• Blind spot in the visual field (scotomata)
• Double vision (diplopia)
• Decreased hearing
• Urinary incontinence
• Reduce urine output (oliguria)
• Frequent nighttime urination (nocturia)
• Blood in urine (hematuria)
• Penile discharge

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Tablet: Schedule IV

• 1 mg
• 2 mg

Adult:

Insomnia

• 1-2 mg orally at night

Dosing considerations

Hepatic Impairment

• Specific guidelines for dosage adjustments in hepatic impairment are not available; however, dosage adjustments may be needed due to a prolonged half-life of estazolam in patients with hepatic dysfunction.

Renal Impairment

• Specific guidelines for dosage adjustments in renal impairment are not available. For patients with severe renal impairment (creatinine clearance less than 10 mL/min), a dosage reduction of up to 50% may be needed; patients should be closely monitored.

Geriatric:

• Initial dose: 0.5 mg orally at bedtime in small or debilitated elderly patients; healthy patients may receive 1 mg

Pediatric:

• Safety and efficacy not established

• Benzodiazepines, including estazolam have a high potential for abuse, misuse, and addiction which can lead to tolerance, dependence, and withdrawal symptoms upon discontinuation. Addiction and abuse can result in overdose and death. 
• Estazolam overdose symptoms include confusion, lack of coordination, slurred speech, respiratory depression, and drowsiness progressing to coma and death.
• Treatment for estazolam overdose is supportive and symptomatic care including:
  • Gastric lavage to eliminate any undigested drug in the gastrointestinal tract
  • Maintenance of airway and respiratory support
  • Intravenous fluids and medications
  • Administration of flumazenil, an antidote to benzodiazepines (flumazenil can cause withdrawal symptoms including seizures in chronic benzodiazepine users and must be used with caution)
  • Monitoring vital signs for an appropriate period after treatment, for residual benzodiazepine effects
• Up-to-date information on the management of hypnotic drug product overdose is available at Poison Control.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe interactions of estazolam include:
  • calcium/magnesium/potassium/sodium oxybates
  • itraconazole
  • sodium oxybate
• Serious interactions of estazolam include:
  • benzhydrocodone/acetaminophen
  • fentanyl
  • fentanyl intranasal
  • fentanyl transdermal
  • fentanyl transmucosal
  • hydrocodone
  • lemborexant
  • metoclopramide intranasal
  • selinexor
  • sufentanil SL
  • valerian
• Estazolam has moderate interactions with at least 187 different drugs.
• Mild interactions of estazolam include:
  • brimonidine
  • ciprofloxacin
  • esomeprazole
  • eucalyptus
  • fleroxacin
  • gemifloxacin
  • levofloxacin
  • moxifloxacin
  • ofloxacin
  • omeprazole
  • rifabutin
  • sage
  • vinpocetine
  • zolpidem

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or healthcare provider about all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or healthcare provider if you have any questions about the medication.

• Do not use estazolam to treat insomnia in pregnant women. Estazolam can cause fetal harm and withdrawal symptoms in the newborn if used during pregnancy. 
• Women with pregnancy potential should practice effective contraception during estazolam therapy and discontinue the drug before becoming pregnant.
• It is not known if estazolam is present in breast milk, however, all benzodiazepines are expected to be excreted in breast milk. Do not use estazolam to treat nursing mothers.

• Take estazolam exactly as prescribed. Do not take a higher or more frequent dosage.
• Estazolam has a high potential for misuse, abuse, addiction, and dependence, even with prescribed doses, and can lead to fatal overdose. Use with extreme caution.
• In case of known or suspected overdose, seek immediate medical help or contact Poison Control.
• Do not take concurrently with opioid drugs unless administered by the healthcare provider under medical supervision. Concurrent use can cause profound sedation, respiratory depression and coma.
• Do not drink alcohol or take other drugs that can depress the central nervous system, while taking estazolam. It increases the risk for sedation, respiratory depression, coma and death.
• Estazolam should be tapered gradually, do not abruptly discontinue. Report to the physician if you experience withdrawal symptoms.
• Report to your physician immediately if you experience hypersensitivity reactions such as difficulty breathing, face, tongue and/or throat swelling, nausea or vomiting.
• Estazolam can impair mental and physical abilities. Avoid driving, operating heavy machinery or performing other potentially hazardous tasks while on estazolam therapy.
• Store estazolam out of reach of children in a safe location not accessible to others.