Alprazolam (Systemic)Introductory InformationBenzodiazepine; anxiolytic.b, cClass: 28:24.08 Benzodiazepines; cn302 (VA primary)

Brands*: Niravam, Xanax

*also available genericallyGeneric Name: AlprazolamCAS Number: 28981-97-7Chemical Name: 8-Chloro-1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepineMolecular Formula: C17H13ClN4Investigational Drug Number: U-31,889

UsesAnxiety DisordersManagement of anxiety disorders or short-term relief of anxiety or anxiety associated with depressive symptoms.b, cPanic DisorderManagement of panic disorder, with or without agoraphobia.Cancer Chemotherapy-induced Nausea and VomitingAdjunct in the management of nausea and vomiting associated with emetogenic cancer chemotherapyb (including cisplatin); b currently not recommended as monotherapy.bMay be useful in the management of anticipatory emesis.cDosage and AdministrationGeneral 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.107, 108, 109

AdministrationOral AdministrationImmediate-release PreparationsAdminister conventional and orally disintegrating tablets and oral concentrate daily in divided doses.cDilute 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.cRemove 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 TabletsAdminister 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.DosageAdultsAnxiety Disorders>Therapy with Conventional or Orally Disintegrating Tablets or Oral ConcentrateOral: Initially, 0.25-0.5 mg 3 times daily.c 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.cPanic Disorder>Therapy with Conventional or Orally Disintegrating TabletsOral: 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 TabletsOral: 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 LimitsAdultsAnxiety DisordersOral: Maximum 4 mg daily.cPanic DisorderOral: Maximum 10 mg daily.Special PopulationsHepatic ImpairmentProlonged elimination. Use the smallest effective dosage.cInitially, 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 PatientsPossible increased sensitivity to benzodiazepines.b Use the smallest effective dosage.cInitially, 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.cCautionsContraindications Known hypersensitivity to alprazolam or other benzodiazepines.b Concurrent ketoconazole, itraconazole, or delavirdine therapy. (See Specific Drugs and Foods under Interactions.) 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;b however, clinical rationale for this contraindication has been questioned.b

Warnings/PrecautionsWarningsWithdrawal EffectsRapid dosage reduction or abrupt discontinuance may result in seizures (including status epilepticus),102, 103 delirium,102, 104 or withdrawal symptoms.101, 104Risk 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 IndicationsDo not use in patients with depressive neuroses or psychotic reactions in which anxiety is not prominent.bAbuse PotentialAbuse 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 EffectsPerformance of activities requiring mental alertness and physical coordination may be impaired.b, cConcurrent use of other CNS depressants may cause additive or potentiated CNS depression. (See Specific Drugs and Foods under Interactions.)Drug InteractionsPotential 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 PrecautionsSuicideUse with caution in depressed patients; potential for suicidal tendencies.b Prescribe and dispense drug in the smallest feasible quantity.bManiaEpisodes of mania and hypomania reported in patients with depression.Respiratory EffectsRare reports of deaths following initiation of therapy in patients with severe pulmonary disease.Use with caution in patients with compromised respiratory function.bRenal EffectsWeak uricosuric effect; however, no reports of acute renal failure.Specific PopulationsPregnancyCategory D.LactationBenzodiazepines generally are distributed into milk; discontinue nursing or the drug.bPediatric UseSafety and efficacy not established in children