Alprazolam, Xanax®, Xanax TS®

Brand name

  • Xanax®
  • Xanax TS®

Drug Class

  • Anxiolytic
  • Anti-panic

Preparations

  • Tablet: 0.25 mg, 0.5 mg, 1 mg, 2 mg

Indications

  • Management of Anxiety Disorders
  • Short-term symptomatic relief of excessive anxiety

Pharmacology

  • Alprazolam, a triazolo 1,4 benzodiazepine analog, binds with high affinity to the GABA benzodiazepine receptor complex.

Metabolism

  • Alprazolam is extensively metabolized in humans, primarily by cytochrome P450 3A4 (CYP3A4)

Dosing

Anxiety Disorders

Adults:

  • The initial adult dosage of alprazolam is 0.25 mg given 2 or 3 times daily.
  • If required, increases may be made in 0.25 mg increments according to the severity of symptoms and patient response.
  • It is recommended that the evening dose be increased before the daytime doses.
  • Very severe manifestations of anxiety may require larger initial daily doses.
  • Exceptionally, it may be necessary to increase dosage to a maximum of 3.0 mg daily, given in divided

 

Elderly or Debilitated Patients:

  • Provide the lowest effective dose to elderly or debilitated patients to preclude the development of ataxia or oversedation
  • The initial dosage is 0.125 mg given 2 or 3 times daily

Hepatic or Renal Impairment:

  • In patients with advanced liver or renal disease, the usual dose is 0.125 to 0.25 mg, given two or three times daily.

 

Panic Disorders

  • The usual starting dose is 0.5 mg to 1.0 mg at bedtime or 0.5 mg three times daily.
  • The dose should be adjusted until the patient is free of panic attacks.
  • Dosage adjustments should be in increments no greater than 1 mg every three to four days.
  • The mean dosage employed was approximately 5 to 6 mg daily.

Discontinuation:

  • To discontinue treatment in patients taking alprazolam, the dosage should be reduced slowly in keeping with good medical practice.
  • It is suggested that the daily dosage of alprazolam be decreased by no more than 0.5 mg every 3 days. Some patients may require an even slower dosage reduction.
  • A decrease of 0.5 mg every 2 to 3 weeks is more appropriate when a dose of 6 mg daily or more has been administered even for only a few months. Once a dose of 2 mg daily is achieved, the dose should be decreased by 0.25 mg per 2 to 3 weeks.

Drug Interactions

CNS – acting drugs

  • Benzodiazepines, including alprazolam, may potentiate or produce additive central nervous system depressant effects when combined with other psychotropic medication, alcohol, narcotics, barbiturates, antihistamines or anticonvulsants.

CYP3A Inhibitors

  • Compounds which inhibit certain hepatic enzymes (particularly cytochrome P450 3A4) may increase the concentration of alprazolam and enhance its activity.

 

Antifungal agents

  • Ketoconazole and itraconazole are potent inhibitors of CYP3A. The co-administration of alprazolam with ketoconazole, itraconazole, or other azole-type antifungals is not recommended

 

Other medications:

  • Caution and consideration of dose reduction is recommended when alprazolam is co-administered with nefazodone, fluvoxamine, and cimetidine.

 

Oral contraceptives

  • Alprazolam clearance is lower in subjects taking oral contraceptives. Caution is recommended when alprazolam is co-administered with oral contraceptives.

 

HIV Protease Inhibitors

  • Low doses of ritonavir results in a large impairment of alprazolam clearance, prolongs its elimination half-life and enhances its clinical effects.

 

Carbamazepine (CYP3A Inducers)

  • Significant reductions in alprazolam concentration have been noted after carbamazepine treatment has been initiated.
  • Pharmacokinetic interactions between alprazolam and phenytoin have not been observed.

Adverse Effects

Respiratory (panic disorders):

  • Nasal Congestion
  • Tachycardia
  • Chest Pain
  • Hyperventilation
  • Upper Respiratory Infection

 

Nervous System (panic disorders):

  • Drowsiness
  • Fatigue & Tiredness
  • Impaired Coordination
  • Irritability
  • Memory Impairment
  • Lightheadedness/Dizziness
  • Insomnia
  • Headache
  • Cognitive Disorder
  • Dysarthria
  • Anxiety
  • Abnormal Involuntary Movement
  • Decreased Libido
  • Increased Libido
  • Depression
  • Confusional State
  • Muscular Twitching
  • Weakness
  • Muscle Tone Disorders
  • Syncope
  • Akathisia
  • Agitation
  • Disinhibition
  • Paresthesia
  • Talkativeness
  • Vasomotor Disturbances
  • Derealization
  • Dream Abnormalities
  • Fear
  • Feeling Warm

Gastrointestinal:

  • Decreased Salivation
  • Constipation
  • Nausea/vomiting
  • Diarrhea
  • Abdominal Distress
  • Dry mouth
  • Increased salivation

Cardiovascular:

  • Tachycardia/Palpitations
  • Hypotension

Genitourinary:

  • Micturition Difficulties
  • Menstrual Disorders
  • Sexual Dysfunction

Dermatologic:

  • Dermatitis/allergy
  • Sweating
  • Rash

Overdose:

  • Somnolence
  • Confusion
  • Drowsiness
  • Slurred speech
  • Impaired coordination
  • Diminished reflexes
  • Respiratory depression
  • Coma

Pregnancy and Breastfeeding

  • The safety has not been established. Therefore is not recommended for use during pregnancy.
  • Levels of benzodiazepines, including alprazolam, in breast milk are low. Therefore, nursing should not be undertaken while a patient is receiving alprazolam 

References

  • Glue P, Fang A, Gandelman K, Klee B. Pharmacokinetics of an extended release formulation of alprazolam (Xanax XR) in healthy normal adolescent and adult volunteers. Am J Ther. 2006 Sep-Oct;13(5):418-22.
  • Simeon JG, Ferguson HB. Alprazolam effects in children with anxiety disorders. Can J Psychiatry. 1987 Oct;32(7):570-4.
  • Crombez G, Kupers R, Adriaensen H. The effects of a single oral dose of lorazepam and alprazolam on reaction times in young healthy volunteers. Acta Anaesthesiol Belg. 1991;42(2):79-84.
  • Ware MR, DeVane CL, Hall KL. Panic disorder. Recognizing and managing the ‘real thing’. Postgrad Med. 1992 May 15;91(7):99-102, 105-8.
  • Mandrioli R, Mercolini L, Raggi MA. Metabolism of benzodiazepine and non-benzodiazepine anxiolytic-hypnotic drugs: an analytical point of view. Curr Drug Metab. 2010 Nov;11(9):815-29
  • Martin JL, Sainz-Pardo M, Furukawa TA, Martín-Sánchez E, Seoane T, Galán C. Benzodiazepines in generalized anxiety disorder: heterogeneity of outcomes based on a systematic review and meta-analysis of clinical trials. J Psychopharmacol. 2007 Sep;21(7):774-82.
  • Isbister GK, O’Regan L, Sibbritt D, Whyte IM. Alprazolam is relatively more toxic than other benzodiazepines in overdose. Br J Clin Pharmacol. 2004 Jul;58(1):88-95.
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