Adjunct in the management of nausea and vomiting associated with emetogenic cancer chemotherapy† (including cisplatin); currently not recommended as monotherapy.
May be useful in the management of anticipatory emesis†.
Dosage and Administration
General
Periodically reassess usefulness of the drug.
When discontinuing therapy or reducing daily dosage, reduce dosage gradually under close supervision. If significant withdrawal symptoms develop, reinstitute the previous dosage schedule; attempt a less-rapid schedule of dosage tapering only after stabilization. Some patients may be resistant to all discontinuance regimens.
The manufacturers recommend that dosage be decreased by ≤0.5 mg every 3 days; some patients may require slower reduction.
Some clinicians recommend decreasing the dosage by ≤0.25 mg every 3–7 days.
Administration
Oral Administration
Immediate-release Preparations
Administer conventional and orally disintegrating tablets and oral concentrate daily in divided doses.
Dilute oral concentrate in ≥30 mL of diluent (e.g., water, juice, carbonated or soda-like beverages) or mix with semisolid foods (e.g., applesauce, pudding) just prior to administration.
Remove orally disintegrating tablet from protective container with dry hands immediately prior to administration. Immediately place tablet on tongue, allow it to disintegrate (within a few seconds), then swallow with or without water. If a half tablet is used, discard the remaining portion because it may not remain stable.
Extended-release Tablets
Administer extended-release tablets daily as a single dose, preferably in the morning.
Swallow extended-release tablets whole; do not chew, crush, or break.
Patients with panic disorder may be switched from conventional tablets to extended-release tablets at the same total daily dosage. If the response is not sufficient, titrate dosage in a similar manner to initial therapy until an acceptable therapeutic response is achieved.
Dosage
Adults
Anxiety Disorders
Therapy with Conventional or Orally Disintegrating Tablets or Oral Concentrate
Oral
Initially, 0.25–0.5 mg 3 times daily. Increase dosage gradually at intervals of 3 or 4 days according to individual requirements and response; maximum dosage of 4 mg daily given in divided doses.
Panic Disorder
Therapy with Conventional or Orally Disintegrating Tablets
Oral
Dosages >4 mg daily have been required; dosage generally has averaged 5–6 mg daily but has ranged from 1–10 mg daily.
Initiate at low dosage; increase dosage gradually until an acceptable therapeutic response is achieved, intolerable adverse effects occur, or a maximum dosage of 10 mg daily is achieved.
Initially, 0.5 mg 3 times daily. Increase dosage as necessary at 3- or 4-day intervals in increments of ≤1 mg daily; slower titration to dosages ≥4 mg daily may be advisable so that full effects of a given dosage can be expressed.
Periodic reassessment and consideration of dosage reduction recommended in patients receiving dosages >4 mg daily.
To minimize risk of symptom emergence between doses, distribute doses evenly 3–4 times daily (while awake).
Therapy with Extended-release Tablets
Oral
Dosage of 3–6 mg daily recommended, but dosage has ranged from 1–10 mg daily.
Initiate at low dosage; increase dosage gradually until an acceptable therapeutic response is achieved, intolerable adverse effects occur, or a maximum dosage of 10 mg daily is achieved.
Initially, 0.5–1 mg daily. Increase dosage as necessary (based on response) at 3- or 4-day intervals in increments of ≤1 mg daily; slower titration may be advisable so that full effects of a given dosage can be expressed.
Prescribing Limits
Adults
Anxiety Disorders
Oral
Maximum 4 mg daily.
Panic Disorder
Oral
Maximum 10 mg daily.
Special Populations
Hepatic Impairment
Prolonged elimination. Use the smallest effective dosage.
Initially, 0.25 mg (as an immediate-release preparation) given 2 or 3 times daily or 0.5 mg (as extended-release tablets) once daily; adjust dosage according to individual tolerance and response.
Geriatric or Debilitated Patients
Possible increased sensitivity to benzodiazepines. Use the smallest effective dosage.
Initially, 0.25 mg (as an immediate-release preparation) given 2 or 3 times daily or 0.5 mg (as extended-release tablets) once daily; adjust dosage according to individual tolerance and response.
Manufacturers state that alprazolam is contraindicated in patients with acute angle-closure glaucoma but may be administered to patients with open-angle glaucoma who are receiving appropriate therapy; however, clinical rationale for this contraindication has been questioned.
Warnings/Precautions
Warnings
Withdrawal Effects
Rapid dosage reduction or abrupt discontinuance may result in seizures (including status epilepticus), delirium, or withdrawal symptoms.
Risk of seizures is greatest 24–72 hours after discontinuance.
Use of relatively higher dosages (e.g., those employed for panic disorder) may be associated with an increased frequency and severity of rebound and withdrawal symptoms.
Psychiatric Indications
Do not use in patients with depressive neuroses or psychotic reactions in which anxiety is not prominent.
Abuse Potential
Abuse potential similar to that of other benzodiazepines and related hypnotics.
Patients with a history of drug or alcohol dependence or abuse are at risk of habituation or dependence; use only with careful surveillance in such patients.
CNS Effects
Performance of activities requiring mental alertness and physical coordination may be impaired.
Concurrent use of other CNS depressants may cause additive or potentiated CNS depression. (See Specific Drugs and Foods under Interactions.)
Drug Interactions
Potential for marked increase in plasma alprazolam concentrations if used concomitantly with a CYP3A inhibitor. Avoid concomitant use of potent CYP3A inhibitors (e.g., delavirdine, itraconazole, ketoconazole); use of less potent CYP3A inhibitors requires caution and possible dosage reduction. (See Specific Drugs and Foods under Interactions.)
General Precautions
Suicide
Use with caution in depressed patients; potential for suicidal tendencies. Prescribe and dispense drug in the smallest feasible quantity.
Mania
Episodes of mania and hypomania reported in patients with depression.
Respiratory Effects
Rare reports of deaths following initiation of therapy in patients with severe pulmonary disease.
Use with caution in patients with compromised respiratory function.
Benzodiazepines generally are distributed into milk; discontinue nursing or the drug.
Pediatric Use
Safety and efficacy not established in children <18 years of age.
Geriatric Use
Potential increased sensitivity (increased risk of oversedation and ataxia). Initiate therapy at low dosage and adjust carefully. (See Geriatric or Debilitated Patients under Dosage and Administration.)
Hepatic Impairment
Prolonged elimination. Use with caution; use smallest effective dosage to avoid oversedation. (See Hepatic Impairment under Dosage and Administration.)
Extended-release tablets in patients with panic disorder: sedation, somnolence, memory impairment, dysarthria, fatigue, depression, dry mouth.
Interactions
Metabolized by CYP3A.
Drugs Affecting Hepatic Microsomal Enzymes
Potential pharmacokinetic interaction (altered serum concentrations of alprazolam) with drugs that induce or inhibit CYP3A. Avoid concomitant use with potent CYP3A inhibitors. Caution advised if alprazolam is used concomitantly with less potent CYP3A inhibitors; alprazolam dosage adjustment may be indicated. (See Specific Drugs and Foods under Interactions.)
Drugs Affecting Salivary Flow or Gastric pH
Possible pharmacokinetic interaction (decreased alprazolam absorption) with concomitant use of alprazolam orally disintegrating tablets and drugs that increase gastric pH or decrease salivary flow.
No effect on PT or plasma warfarin concentrations observed
Pharmacokinetics
Absorption
Bioavailability
Readily absorbed following oral administration as conventional or orally disintegrating tablets or oral solution, with peak plasma concentrations achieved within 1–2 hours.
When orally disintegrating tablets are taken with water, peak plasma concentrations occur 15 minutes sooner than when taken without water, but actual peak concentration and AUC are unaffected.
Rate of absorption of extended-release tablets is slower than that of conventional tablets, resulting in relatively constant plasma concentrations for 5–11 hours after a dose.
Absolute bioavailability of extended-release tablets is 90%; bioavailability is equivalent to that of conventional tablets.
Absorption rate for extended-release tablets is faster following nighttime versus morning administration.
Food
High-fat meal may alter the rate but not the extent of absorption of orally disintegrating or extended-release tablets.
Special Populations
In patients with conditions that increase gastric pH or cause dry mouth, absorption of orally disintegrating tablets may be slower or reduced.
Distribution
Extent
Benzodiazepines are widely distributed into body tissues and cross the blood-brain barrier.
Benzodiazepines generally cross the placenta and distribute into milk; because of its similarity to other benzodiazepines, alprazolam is presumed to cross the placenta and to distribute into milk.
Plasma Protein Binding
Approximately 80%, primarily to albumin.
Elimination
Metabolism
Extensively metabolized in the liver by CYP3A4 to metabolites that are inactive or have lower potency than alprazolam.
Elimination Route
Alprazolam and metabolites are excreted primarily in urine.
Half-life
Approximately 11–12.5 hours for immediate-release preparations; approximately 11–16 hours for extended-release tablets.
Special Populations
In geriatric patients, obese patients, and those with alcoholic liver disease, half-life is increased to approximately 16, 22, and 20 hours, respectively.
In Asians, half-life is about 25% greater than that in Caucasians.
Stability
Storage
Oral
Conventional Tablets
20–25°C.
Orally Disintegrating Tablets
20–25°C (may be exposed to 15–30°C). Protect from moisture. If a half tablet is used, discard remaining portion because it may not remain stable. Discard cotton after opening the container and reseal container tightly after each opening to prevent introduction of moisture.
Extended-release Tablets
25°C (may be exposed to 15–30°C).
Solution (Concentrate)
Tight, light-resistant containers at 15–30°C.
Actions
Effects appear to be mediated through the inhibitory neurotransmitter GABA; the site and mechanism of action within the CNS appear to involve a macromolecular complex (GABAA-receptor-chloride ionophore complex) that includes GABAA receptors, high-affinity benzodiazepine receptors, and chloride channels.
Advice to Patients
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and alcohol consumption. Importance of avoiding alcohol-containing beverages or products.
Importance of taking only as prescribed; do not increase dosage or duration of therapy unless otherwise instructed by a clinician.
For patients taking alprazolam orally disintegrating tablets, importance of not removing tablets from the container until just prior to administration; importance of removing tablet from container with dry hands and placing tablet on tongue to dissolve and be swallowed with saliva or water. Importance of discarding any cotton included in the container and of resealing the container tightly after each opening to prevent introduction of moisture.
For patients taking one-half of an orally disintegrating tablet, importance of immediately discarding the unused portion because of possible instability.
Importance of not abruptly discontinuing therapy; consult clinician about discontinuing use.
Potential for drug to impair mental alertness or physical coordination; avoid driving or operating machinery until effects on individual are known.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing clinicians of any behavioral or mental changes, memory impairment, tolerance, or dependence/withdrawal symptoms.
Potential for severe emotional and physical dependence in some patients receiving increased dosages for the management of panic disorder. Discontinuance of the drug may be difficult, with increased risk of withdrawal symptoms, including seizures.
Importance of informing clinicians about any concomitant illnesses, particularly depression.
Importance of informing patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Subject to control under the Federal Controlled Substances Act of 1970 as a schedule IV (C-IV) drug.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Comparative Pricing
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 09/2009. For the most current and up-to-date pricing information, please visit www.drugstore.com. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
Remember, keep this and all other medicines out of the reach of children,
never share your medicines with others, and use this medication only for the indication prescribed.
Sign up with Facebook
