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.