Alprazolam

From Drugs Prescribing Information
Jump to: navigation, search

Alprazolam is a tranquilliser. It belongs to one of a group of medicines called benzodiazepines. Benzodiazepines affect chemical activity in the brain to promote sleep and to reduce anxiety and worry.

Alprazolam is used to treat severe anxiety and severe anxiety associated with depression. Alprazolam should only be used for short-term treatment of anxiety. The overall duration of treatment should not be more than 12 weeks including a period where the dose is gradually reduced.

Alprazolam is not recommended for the treatment of depression.

Contents

[edit] BRAND NAMES

[edit] STRUCTURE

Alprazolam.jpg

[edit] MECHANISM OF ACTION

Alprazolam, like other Benzodiazepines bind to specific sites on the gamma-aminobutyric acid-A (GABAA) receptors. This enhances the effects of GABA by increasing its affinity for the GABAA receptor.

Activation of the GABAA receptor, which is linked to a chloride channel (Cl-), results in an influx of Cl- into the neurone causing hyperpolarisation, which results in inhibitory effects on the central nervous system.

Benzodiazepines action on GABAA receptors appears to produce their anxiolytic, sedative, muscle relaxant, hypnotic and anticonvulsant actions.

Peak Alprazolam concentrations in the plasma occur in 1 to 2 hours following administration and its elimination half-life is about 11.2 hours (range: 6.3-26.9 hours) in healthy adults.

[edit] INDICATIONS

  • Regular tablets are indicated for the management of:
    • Anxiety disorders associated or not with depression or for the short-term relief of the symptoms of anxiety. Anxiety and tension associated with the stresses of everyday life usually do not require treatment with anxiolytic drugs.
    • Panic disorder
  • Extended-release tablet (XR Tablets) are indicated for the treatment of panic disorder.

[edit] DOSAGE

  • Anxiety Disorders: Starting dose is 0.25 to 0.5 mg given three times daily. The dose may be increased to achieve a maximum therapeutic effect, at intervals of 3 to 4 days, to a maximum daily dose of 4 mg, given in divided doses.


  • Panic Disorder:
    • Regular tablets: the successful treatment of many panic disorder patients has required the use of Alprazolam at doses greater than 4 mg daily. Treatment may be initiated with a dose of 0.5 mg three times daily. Depending on the response, the dose may be increased at intervals of 3 to 4 days in increments of no more than 1 mg per day. Average maintenance dose is 5 to 6 mg daily.
    • Extended-release tablets: Treatment may be initiated with a dose of 0.5 mg to 1 mg once daily.

Depending on the response, the dose may be increased at intervals of 3 to 4 days in increments of no more than 1 mg/day. Most patients showed efficacy in the dose range of 3 to 6 mg/day. Occasional patients required as much as 10 mg/day to achieve a successful response.

Dosage should be reduced gradually when discontinuing therapy

[edit] CONTRAINDICATIONS

  • Hypersensitivity to Alprazolam or to other benzodiazepines
  • Acute narrow angle glaucoma.
  • Pregnancy and lactation
  • Coadministration with ketoconazole and itraconazole, since these medications are strong CYP3A4 inhibitors and decrease the clearance of Alprazolam.

[edit] WARNINGS AND PRECAUTIONS

  • Do not drive or do other dangerous activities after taking Alprazolam until you feel fully awake.
  • Do not drink alcohol
  • Respiratory depression may occur in benzodiazepine overdose
  • Use of benzodiazepines can lead to dependence. This risk increases with dose and duration of treatment.
  • Seizures attributable to Alprazolam were seen after drug discontinuance. (discontinue gradually)
  • Withdrawal symptoms and Rebound effect, like heightened sensory perception, impaired concentration, dysosmia, clouded sensorium, paresthesias, muscle cramps, muscle twitch, diarrhea, blurred vision, appetite decrease, and weight loss, anxiety and insomnia were seen during discontinuation. Alprazolam should be reduced or discontinued gradually
  • Amnesia: Benzodiazepines may induce anterograde amnesia leading to a partial or complete inability to recall the recent past. Anterograde amnesia may occur using higher therapeutic dosages, the risk increasing at higher dosages.
  • Paradoxical reactions like restlessness, agitation, irritability, aggressiveness, delusion, rages, nightmares, hallucinations, psychoses, inappropriate behavior and other adverse behavioral effects are known to occur when using benzodiazepines. Should this occur, the use of the drug should be discontinued.
  • Risk of Fetal Harm: Benzodiazepines can potentially cause fetal harm when administered to pregnant women

[edit] METABOLISM

Alprazolam is extensively metabolized in humans, primarily by CYP3A4, to two major metabolites in the plasma: 4-hydroxyalprazolam and α-hydroxyalprazolam

[edit] INTERACTIONS

  • Benzodiazepines, including Alprazolam, produce additive CNS depressant effects when co-administered with other medications which themselves produce CNS depression (e.g. barbiturates, alcohol, sedatives, tricyclic antidepressants, antipsychotics, skeletal muscle relaxants, antihistamines or narcotic analgesics and anaesthetics).
  • Cigarette Smoking: Alprazolam concentrations may be reduced by up to 50% in smokers compared to non-smokers.
  • CYP3A4 inhibitors : Alprazolam is extensively metabolized in humans, primarily by CYP3A4. CYP3A inhibitors like Ketoconazole, Itraconazole, Nefazodone, erythromycin, Clarithromycin, Isoniazid, fluvoxamine, Fluoxetine, and Grapefruit juice increase the maximum plasma concentration of Alprazolam, decrease clearance, and increase half-life.
  • CYP3A4 inducers (e.g. carbamazepine) are expected to decrease alprazolam concentrations
  • Digoxin: Increased digoxin concentrations have been reported in patients receiving 1 mg alprazolam daily, and this increase was more pronounced in patients older than 65 years of age. Patients who receive alprazolam and digoxin should therefore be monitored for signs and symptoms related to digoxin toxicity. [1]

[edit] PREGNANCY AND LACTATION

  • Pregnancy Category D (US). It is assumed that alprazolam undergoes transplacental passage.
    Benzodiazepines can potentially cause fetal harm when administered to pregnant women. If Alprazolam is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Because of experience with other members of the benzodiazepine class, Alprazolam is assumed to be capable of causing an increased risk of congenital abnormalities when administered to a pregnant woman during the first trimester. Because use of these drugs is rarely a matter of urgency, their use during the first trimester should almost always be avoided.
  • Nursing mothers: Benzodiazepines are known to be excreted in human milk. It should be assumed that alprazolam is as well. Chronic administration of diazepam to nursing mothers has been reported to cause their infants to become lethargic and to lose weight. As a general rule, nursing should not be undertaken by mothers who must use Alprazolam

[edit] SIDE EFFECTS

The most common side effects are are likely to be an extension of the pharmacological activity, eg, somnolence and dizziness.

Other possible adverse effects include: decreased attention, fatigue, confusion, muscle weakness, tremor, irritability, insomnia, headache and blurred vision.

See also WARNINGS AND PRECAUTIONS section

[edit] RELATED LINKS

[edit] BIBLIOGRAPHY

[edit] REFERENCES

  1. http://www.ncbi.nlm.nih.gov/pubmed/8330464
Sedatives / Hypnotics / Anxiolytics
Benzodiazepines Benzodiazepines (Anxiolytics)‎ Alprazolam (Xanax)   Bromazepam (Lexotan, Lexotanil)   Chlordiazepoxide (Librium)   Clobazam (Frisium)   Clorazepate (Tranxene)   Clotiazepam (Rizen, Tienor)   Delorazepam (EN)   Diazepam (Valium)   Etizolam (Depas)   Ketazolam   Lorazepam (Ativan, Control, Lorans, Tavor, Temesta)   Lormetazepam (Noctamid)   Nordazepam (Nordaz)   Oxazepam (Serepax)   Prazepam (Demetrin, Lysanxia)
Benzodiazepines (Hypnotics) Brotizolam (Lendormin, Bondormin, Dormex, Sintonal, Noctilan)   Clobazam (Frisium)   Estazolam (Esilgan, ProSom)   Etizolam (Depas, Pasaden, Etilaam, Etizest)   Flunitrazepam (Rohypnol)   Flurazepam (Dalmadorm, Dalmane, Felison, Flunox, Valdorm)   Ketazolam (Anseren, Anxon)   Lorazepam (Ativan, Control, Lorans, Tavor, Temesta)   Lormetazepam (Loramet, Minias, Noctamid, Pronoctan, Evamyl)   Midazolam (Dormicum, Hypnovel)   Nitrazepam (Mogadon, Nitrados, Numbon, Radedorm, Alodorm)   Nordazepam (Madar, Nordaz, Stilny, Tranxilium N)   Temazepam (Normison, Restoril, Tenox, Temaze)   Triazolam (Halcion, Hypam, Rilamir)
Non-Benzodiazepine Hypnotics Eszopiclone (Lunesta)   Zolpidem (Ambien, Stilnox, Hypnogen, Sanval, Stilnoct, Zoldem, Zolsana)   Zopiclone (Imovane, Zimovane)
Melatonin agonists Melatonin (Circadin)   Ramelteon (Rozerem)
Orexin agonists Suvorexant (Belsomra)