ALPRAZOLAM

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Alprazolam

 

Generic name: alprazolam (al PRAY zoe lam)
Brand name: Xanax, Xanax XR, Niravam
Dosage forms: oral concentrate (1 mg/mL); oral tablet (0.25 mg; 0.5 mg; 1 mg; 2 mg); oral tablet, disintegrating (0.25 mg; 0.5 mg; 1 mg; 2 mg); oral tablet, extended release (0.5 mg; 1 mg; 2 mg; 3 mg)
Drug class: Benzodiazepines





What is alprazolam?

Alprazolam is a benzodiazepine (ben-zoe-dye-AZE-eh-peen). It is thought that it works by enhancing the activity of certain neurotransmitters in the brain.

Alprazolam is used to treat anxiety disorders, panic disorders, and anxiety caused by depression.

It is dangerous to purchase alprazolam on the Internet or outside the United States. The sale and distribution of medicines outside the U.S. does not comply with safe-use regulations of the Food and Drug Administration (FDA). These medications may contain dangerous ingredients, or may not be distributed by a licensed pharmacy.

Alprazolam (Xanax) is a benzodiazepine class of medicine. It is one of the most commonly used benzodiazepine that has got a very high potential for misuse.

It is also one of the most commonly misused drug that has got the most emergency department visits.

What does Xanax treat?

It is indicated for the treatment of the following conditions:

    1. Generalized anxiety disorder
    2. symptoms of anxiety
    3. panic disorders, with or without agoraphobia and,
    4. anxiety associated with depression.
    5. Adjustment disorder

Alprazolam has also been studied in the treatment of neuroleptic resistant symptoms in a subgroup of patients with chronic schizophrenia .

Alprazolam for sleep (Insomnia):

Xanax (alprazolam) is used primarily to treat symptoms of anxiety, however, because of its hypnotic effects, it is commonly used for sleep-related disorders.

Hypnotic drugs are primarily used for insomnia. Other drugs that may be used for insomnia include zolpidem, barbiturates, zopiclone, and eszopiclone.

Certain antihistamines like chlorpheniramine can also cause excessive sleep. Atypical antidepressants like trazodone ((Deprel) also cause excessive sleepiness.

Is Xanax good for depression?

Alprazolam (Xanax) is primarily used for the treatment of anxiety and panic attacks. In mild cases of depression, Xanax may be used as a temporary measurement.

Since chronic use of Alprazolam can result in dependence, addiction, and tolerance, it is usually given for a short period of time.

When used for depression, its use should not exceed two weeks. This is the time when most of the SSRIs (like escitalopram and Effexor) become effective.

It is used in depression associated with anxiety and in patients with depressive psychosis. It is considered unintelligent to combine CNS stimulants like modafinil and Xanax.

In a review of 25 studies, alprazolam was more effective than placebo and as effective as  amitriptyline, clomipramine, desipramine, dothiepin, doxepin, and imipramine, for the treatment of “neurotic” or moderate depression [Ref].

However, in severe depression, it was inferior to these medicines.

When given concomitant with alcohol, the toxicity of Xanax is increased as alcohol inhibits the enzyme CYP3A4 [Ref].

Alprazolam (Xanax) dose in Anxiety (Generalized anxiety disorder with or without agoraphobia):

  • Immediate-release Xanax tablets:

    • 0.25-0.5 mg orally thrice daily initially;
    • The dose should be titrated upwards every third or fourth day by no more than 1 mg/day
    • The usual maximum dose is 4 mg/day.
    • Patients requiring doses greater than 4 mg/day should be increased cautiously.

Alprazolam (Xanax) dose in Panic disorder:

  • Immediate-release Xanax tablets:

    • 0.5 mg orally thrice daily
    • The dose may be increased every third or fourth day in increments less than 1 mg/day.
    • The mean effective dosage is 5-6 mg daily. The patients may occasionally require up to 10 mg of alprazolam per day.
  • Extended-release Xanax tablets:

    • 0.5 mg to 1 mg orally initially once a day.
    • The extended-release tablets should be preferably taken in the morning
    • Lean and thin patients should be given the lowest possible dose initially and increased every third or fourth day by nor more than 1 mg.
    • Up to 10 mg/day has been required in occasional patients.

Xanax tablets dose in Pre-operative anxiety:

  • 0.5 mg tablets 60-90 minutes before the procedure.

Xanax dose in elderly patients:

  • Immediate-release tablets:

    • 0.25 mg twice or thrice daily initially.
  • Extended-release tablets:

    • 0.5 mg once a day.

Start with a lower initial dose and increase the dose gradually, if required.

The maximum adult dosage is 4 mg/day.

The elderly may be more sensitive to the effects of benzodiazepines. If discontinuation becomes necessary, the manufacturer suggests that the daily dose be decreased by no more than 0.5 mg every 3 days.

Alprazolam dose for the treatment of anxiety and mood-symptoms associated with premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD) that is unresponsive to non-pharmacologic therapy.

Immediate-release oral tablets or solution:

  • Adult females
    • 0.25 mg orally three times daily administered during the luteal phase through the second day of menses.
    • A maximum dose of up to 4 mg per day is recommended.
    • The dose should be tapered by 25% per day through menses.

Maximum dose of Xanax:

  • Adults:

    • 10 mg/day PO.
  • Geriatric:

    • 10 mg/day PO.
  • Adolescents:

    • Safety and efficacy have not been established; 0.06 mg/kg/day orally
  • Children

    • 7 years and older:
      • Safety and efficacy have not been established
      • 0.06 mg/kg/day orally
    • Less than 7 years:
      • Safety and efficacy have not been established.

Tapering off Xanax:

Abrupt discontinuation should be avoided.

The daily dose may be decreased by 0.5 mg every third day. Patients on long term use alprazolam should be tapered the drug very slowly.

The previous dose should be resumed if withdrawal symptoms start while reducing the dose.

 

Alprazolam (Xanax) dose in Children for anxiety:

  • Oral Immediate-release formulation:
    • 0.005 mg/kg/dose or 0.125 mg/dose thrice daily initially;
    • Increase the dose in increments of 0.125-0.25 mg to the maximum dose 0.02 mg/kg/dose.

Note: Treatment of more than 4 months should be re-evaluated to determine the patient’s continued need for the drug.

 

What happens if I miss a dose?

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of alprazolam can be fatal.

Overdose symptoms may include extreme drowsiness, confusion, muscle weakness, loss of balance or coordination, feeling light-headed, and fainting.

What to avoid

Avoid drinking alcohol. Dangerous side effects or death could occur.

Avoid driving or hazardous activity until you know how alprazolam will affect you. Dizziness or drowsiness can cause falls, accidents, or severe injuries.

Grapefruit may interact with alprazolam and lead to unwanted side effects. Avoid the use of grapefruit products.

Alprazolam dose in renal disease:

Dosage adjustment in renal disease has not been provided in the manufacturer’s labeling

 

Alprazolam dose in advanced liver disease:

Immediate release:

0.25 mg twice or thrice daily.

Extended-release tablets:

0.5 mg once daily. Titrate the dose gradually if needed and tolerated.

It should be administered cautiously to patients with severe hepatic disease because the elimination half-life of the drug can be prolonged, possibly resulting in toxicity.

 

How and when to take Xanax (Alprazolam)?

The Immediate-release preparations can be taken orally or sublingually at bedtime.

The Extended-release tablet should be taken once daily in the morning. The extended-release tablet should not be broken, crushed or chewed.

 

Xanax Pregnancy Risk Factor D

Benzodiazepines can cross the placental boundary and cause harm to the fetus. It has been associated with premature births, low birthweights, neonatal withdrawal syndrome and floppy infant syndromes in the third trimester.

Breastfeeding is not advised as alprazolam can enter breast milk. Alprazolam may cause sleepiness and lethargic in babies if it is given to their mothers.

 

Severe Side effects of Alprazolam (Xanax):

Rapid:

  • Angioedema

Delayed:

  • Seizures
  • Stevens-Johnson syndrome
  • Hepatic failure
  • Teratogenesis

Moderately severe side effects of Xanax:

Rapid:

    • Sinus Tachycardia
    • Hypotension

Early:

    • Withdrawal
    • Impaired cognition
    • Confusion
    • Hot flashes
    • Euphoria
    • Mania
    • Urinary Incontinence
    • Dysuria
    • Photophobia
    • Dyspnea
    • Hallucinations
    • Blurred vision
    • Palpitation
    • Chest pain
    • Hostility

Delayed:

    • memory impairment
    • Constipation
    • Dysarthria
    • Depression
    • Ataxia
    • Edema
    • Akathisia
    • Dyskinesia
    • Amnesia
    • Dysphonia
    • Hypotonia
    • Tolerance
    • Psychological dependence
    • Physiological dependence
    • Peripheral edema
    • Jaundice
    • Hyperbilirubinemia
    • Elevated hepatic enzymes
    • Hyperprolactinemia
    • Hepatitis
    • Galactorrhea

Mild side effects of Xanax:

Rapid:
      • Pruritis
      • Urticaria

Early:

    • Drowsiness
    • Fatigue
    • Dizziness
    • Nausea
    • Xerostomia
    • Hypersalivation
    • Syncope
    • Lethargy
    • Myalgia
    • Psychomotor impairment
    • Rhinorrhea
    • Rash
    • Mydriasis
    • Fever
    • Agitation
    • Nightmares
    • Tremors
    • Malaise
    • Vertigo
    • Insomnia
    • Weakness
    • Headache
    • Hyperventilation
    • Diaphoresis
    • Nasal congestion
    • Rhinitis
    • Diarrhea
    • Dyspepsia
    • Abdominal pain
    • Vomiting
    • Diplopia

Delayed:

    • Appetite stimulation
    • Weight gain
    • Weight loss
    • Anxiety
    • Libido decrease
    • Menstrual irregularity
    • Libido increase
    • Infection
    • Dysmenorrhea
    • Paresthesias
    • Arthralgia
    • Influenza
    • Anorexia
    • Asthenia
    • Tinnitus
    • Epistaxis
    • Irritability
    • Back pain
    • Muscle cramps
    • Gynecomastia

 

Contraindications to alprazolam (Xanax) include:

    1. Alprazolam allergy (cross-sensitivity may exist with other benzodiazepines)
    2. Narrow-angle Glaucoma
    3. Patients with Myasthenia Gravis, Guillain Barre Syndrome, Chronic Obstructive Airway Disease, and all others at risk for developing respiratory failure.
    4. Patients receiving itraconazole or ketoconazole.
    5. Patients who have had seizures in the past should not be prescribed benzodiazepines. Withdrawal of the drug could cause seizures. There have been reports of patients falling into epilepticus after benzodiazepines were stopped. It is the first 24 to 72 hours after stopping taking drugs that you are most at risk for seizures.
    6. Alprazolam can cause psychological and physical dependence, especially if taken in high doses for longer than 12 weeks.
    7. Alprazolam’s short duration has been linked to reports of anxiety that worsens daily.
    8. Alprazolam should not be prescribed to patients with hypomania, mania, bipolar disorder, mania and suicidal thoughts.
    9. Patients in shock and patients taking ethanol may experience CNS depression and low blood pressure. Alprazolam should not be prescribed to heavy machinery operators, especially drivers.
    10. Patients with Parkinson’s should avoid it as it can worsen symptoms, impair cognition, and cause psychosis.
    11. Patients with porphyria should avoid it.

Alprazolam (Xanax), Boxed Warning

§  Chronic obstructive pulmonary disease (COAD)
§  Coadministration with CNS depressants
§  Other chronic pulmonary diseases
§  Respiratory depression is a condition that can lead to and
§  Sleep apnea

Alprazolam should not be used in these conditions because it can cause respiratory depression, low blood pressure, or even death.

Patients at high risk for ventilatory failures, such as patients with Guillain Barre Syndrome, Opioid overdose and myasthenia should not use it.

Warnings and precautions

§  Anterograde amnesia:

        • Memory impairment may be caused by benzodiazepines

§  Depression in the CNS:

        • Drivers and operators of heavy machinery should avoid it as it can cause CNS depression.

§  Paradoxical reactions:

        • Teens and young adults can become aggressive and hyperactive, particularly in the case of patients.

Concerns about diseases:

§  Depression:

        • Patients with hypomania and suicidal tendencies should not take benzodiazepines.

§  Use of drugs:

        • It can cause psychological and physical dependence if it is used for a prolonged period.

§  Hepatic impairment

        • Patients suffering from liver disease should be cautious when using the drug.

§  Renal impairment

        • Patients with kidney disease may develop urate-nephropathy.

§  Respiratory disease:

        • It can cause depression in the respiratory system.

Special populations

§  Patients with disabilities:

        • Patients who are thin, slim and emaciated should be used with caution.

§  For the elderly:

        • It can increase the risk of motor vehicle accidents, impaired cognition, falls, fractures, and delirium in older patients.

§  Patients at high risk for falls and obese patients are advised to use the drug with caution.

Additional warnings and precautions

§  Use only when appropriate:

        • Alprazolam has no antidepressant, anti-analgesic or antipsychotic properties.

§  Breakthrough anxiety

        • After the last dose, breakthrough anxiety can occur.

 

Alprazolam (Xanax) MOA (Mechanism of action):

Alprazolam (Xanax), binds to receptors in the central nervous system at the postsynaptic GABA nerven. This results in membrane permeability for chloride ions, which causes hyperpolarization and stabilization.

The beginning of action: Instant release and extended-release formulations available in 1 hour

Time: Immediate-release – 5.1 +-1.7 hours; Extended – Release – 11.3 +-4.2 hours

AbsorptionExtended-release: Longer-lasting formulations are slower than immediate-release formulations. This means that the concentration is maintained for 5-11 hours after each dose

Protein binding: 80% of the protein is bound to albumin, primarily proteins

MetabolismCYP3A4 is the pathway that it is metabolized in your liver
BioavailabilityIt is bioavailable at about 90%.

Half-life elimination:

Adults: 11.2 Hours (Immediate Release Range: 6.3-26.9 Hours; Extended-release Range: 10.7-15.8 Hours); Orally-disintegrating Tablet Range: 7.9-19.2 Stunden

Seniors: 16.3 hours (range 9-26.9hrs)

Alcoholic liver disease: 19.7 hours (range 5.8-65.3 hours).

Obesity: 21.8 hours (range 9.9-40.4hrs)

Race: Asians have a higher rate of incarceration than Caucasians.

Time to reach peak serum concentrations:

Released immediately: Within 1-2 hours

Extended-release: approximately 9 hours

When administered at night, peak serum concentrations are reduced by an hour (as opposed to morning administration), and decrease by 33% when combined with high-fat meals (increased 33% if administered more than one hour after high-fat meals).

Orally disintegrating tablet takes 1.5-2 hours

When administered with water, the time to peak serum concentration takes approximately 15 minutes. It is reduced by two hours when taken with high-fat meals.

Excretion: Urine (as an unchanged drug or metabolite)




Alprazolam Brand Names (International):

  • Aceprax
  • Actazolam
  • Alcelam
  • Alnax
  • Alpaz
  • Alplax
  • Alpralid
  • Alpraline
  • Alpranax
  • Alprax
  • Alpraz
  • Alprocontin
  • Alprox
  • Altrox
  • Alviz
  • Alzam
  • Alzax
  • Alzolam
  • Anpress
  • Ansiolit
  • Apo-Alpraz
  • Apraz
  • Aprazo
  • Asolan
  • Axal
  • Azor
  • Cassadan
  • Constan
  • Dixin
  • Farmapram
  • Feprax
  • Frontal
  • Frontin
  • Helex
  • Irizz.
  • Kalma
  • Kinax
  • Marzolam
  • Neupax
  • Pacyl
  • Pharnax
  • Prazol
  • Prazovex
  • Prinox
  • Solanax
  • Soxietas
  • Tafil
  • Tafil D
  • Tazun
  • Trankimazin Retard
  • Tranquinal
  • Tricalma
  • Valeans
  • Xanacine
  • Xanagis
  • Xanax
  • Xanax SR
  • Xanax XR
  • Xanor
  • Xanor XR
  • Zacetin
  • Zanapam
  • Zolam
  • Zolarem
  • Zolastin
  • Zoldac
  • Zopax
  • Zotran
  • Zypraz
  • Zyren
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