Alprazolam, Xanax®, Xanax TS®

• Xanax®
• Xanax TS®

• Anxiolytic
• Anti-panic

• Tablet: 0.25 mg, 0.5 mg, 1 mg, 2 mg

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

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

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

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.

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.

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

• 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 

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• 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
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• 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.