(al PRAY zoe lam)
Treatment of anxiety disorder (GAD); short-term relief of symptoms of anxiety; panic disorder, with or without agoraphobia; anxiety associated with depression
Hypersensitivity to alprazolam or any component of the formulation (cross-sensitivity with other benzodiazepines may exist); narrow-angle glaucoma; concurrent use with ketoconazole or itraconazole
Note: Treatment >4 months should be re-evaluated to determine the patients continued need for the drug
Anxiety: Oral: Immediate release: Initial: 0.25-0.5 mg 3 times/day; titrate dose upward every 3-4 days; usual maximum: 4 mg/day. Patients requiring doses >4 mg/day should be increased cautiously. Periodic reassessment and consideration of dosage reduction is recommended.
Panic disorder: Oral:
Immediate release: Initial: 0.5 mg 3 times/day; dose may be increased every 3-4 days in increments ≤1 mg/day. Mean effective dosage: 5-6 mg/day; some patients may require as much as 10 mg/day
Extended release: 0.5-1 mg once daily; may increase dose every 3-4 days in increments ≤1 mg/day (range: 3-6 mg/day)
Switching from immediate release to extended release: Patients may be switched to extended release tablets by taking the total daily dose of the immediate release tablets and giving it once daily using the extended release preparation.
Preoperative anxiety (off-label use): Oral: 0.5 mg 60-90 minutes before procedure (De Witte, 2002)
Dose reduction: Abrupt discontinuation should be avoided. Daily dose may be decreased by 0.5 mg every 3 days; however, some patients may require a slower reduction. If withdrawal symptoms occur, resume previous dose and discontinue on a less rapid schedule.
Note: Titrate gradually, if needed and tolerated.
Immediate release: Initial 0.25 mg 2 to 3 times/day
Extended release: Initial: 0.5 mg once daily
Anxiety (off-label use): Oral: Immediate release: Initial: 0.005 mg/kg/dose or 0.125 mg/dose 3 times/day; increase in increments of 0.125-0.25 mg, up to a maximum of 0.02 mg/kg/dose or 0.06 mg/kg/day (range of doses reported in one study: 0.375-3 mg/day) (Pfefferbaum, 1987). See Dose Reduction" comment in adult dosing.
Note: Treatment >4 months should be re-evaluated to determine the patients continued need for the drug.
No dosage adjustment provided in manufacturers labeling; however, use caution.
Advanced liver disease:
Immediate release: 0.25 mg 2-3 times/day; titrate gradually if needed and tolerated.
Extended release: 0.5 mg once daily; titrate gradually if needed and tolerate
Immediate release preparations: Can be administered sublingually if oral administration is not possible; absorption and onset of effect are comparable to oral administration (Scavone,1987; Scavone, 1992)
Extended release tablet: Should be taken once daily in the morning; do not crush, break, or chew.
Orally-disintegrating tablets: Using dry hands, place tablet on top of tongue and allow to disintegrate. If using one-half of tablet, immediately discard remaining half (may not remain stable). Administration with water is not necessary.
Extended release tablet should be taken once daily in the morning.
Immediate release tablets: Store at 20 � �C to 25 � �C (68 � �F to 77 � �F).
Extended release tablets: Store at 25 � �C (77 � �F); excursions permitted to 15 � �C to 30 � �C (59 � �F to 86 � �F).
Orally-disintegrating tablet: Store at room temperature of 20 � �C to 25 � �C (68 � �F to 77 � �F). Protect from moisture. Seal bottle tightly and discard any cotton packaged inside bottle.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Concentrate, Oral:
ALPRAZolam Intensol: 1 mg/mL (30 mL) [unflavored flavor]
Tablet, Oral:
Xanax: 0.25 mg [scored]
Xanax: 0.5 mg [scored; contains fd&c yellow #6 (sunset yellow)]
Xanax: 1 mg [scored; contains fd&c blue #2 (indigotine)]
Xanax: 2 mg [scored]
Generic: 0.25 mg, 0.5 mg, 1 mg, 2 mg
Tablet Dispersible, Oral:
Niravam: 0.25 mg [DSC], 0.5 mg [DSC], 1 mg [DSC], 2 mg [DSC] [scored; orange flavor]
Generic: 0.25 mg, 0.5 mg, 1 mg, 2 mg
Tablet Extended Release 24 Hour, Oral:
ALPRAZolam XR: 0.5 mg
ALPRAZolam XR: 1 mg [contains fd&c yellow #10 (quinoline yellow)]
ALPRAZolam XR: 2 mg [contains fd&c blue #2 (indigotine)]
ALPRAZolam XR: 3 mg [contains fd&c blue #2 (indigotine), fd&c yellow #10 (quinoline yellow)]
Xanax XR: 0.5 mg
Xanax XR: 1 mg [contains fd&c yellow #10 (quinoline yellow)]
Xanax XR: 2 mg [contains fd&c blue #2 (indigotine)]
Xanax XR: 3 mg [contains fd&c blue #2 (indigotine), fd&c yellow #10 (quinoline yellow)]
Generic: 0.5 mg, 1 mg, 2 mg, 3 mg
Note: Commercial oral solution is available (Alprazolam Intensol � � �: 1 mg/mL [dye free, ethanol free, sugar free; contains propylene glycol])
A 1 mg/mL oral suspension may be made with tablets and one of three different vehicles (a 1:1 mixture of Ora-Sweet � � and Ora-Plus � �, a 1:1 mixture of Ora-Sweet � � SF and Ora-Plus � �, or a 1:4 mixture of cherry syrup with Simple Syrup, NF). Crush sixty 2 mg tablets in a mortar and reduce to a fine powder. Add 40 mL of vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add a quantity of vehicle sufficient to make 120 mL. Label shake well" and "refrigerate". Stable for 60 days.
Nahata MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy
Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy
Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification
Boceprevir: May increase the serum concentration of ALPRAZolam. Management: In patients receiving boceprevir, consider lower alprazolam doses and monitor closely for symptoms of toxicity (including prolonged sedation and respiratory depression). Consider therapy modification
Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification
Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
CloZAPine: Benzodiazepines may enhance the adverse/toxic effect of CloZAPine. Management: Consider decreasing the dose of (or possibly discontinuing) benzodiazepines prior to initiating clozapine. Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Consider therapy modification
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Dimethindene: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Monitor therapy
Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy
Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification
Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification
Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Monitor therapy
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification
FluvoxaMINE: May increase the serum concentration of ALPRAZolam. Monitor therapy
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination
HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Indinavir: May increase the serum concentration of ALPRAZolam. Avoid combination
Itraconazole: May increase the serum concentration of ALPRAZolam. Avoid combination
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy
Ketoconazole (Systemic): May increase the serum concentration of ALPRAZolam. Avoid combination
Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Consider therapy modification
Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Macrolide Antibiotics: May increase the serum concentration of ALPRAZolam. Management: Consider an alternative less likely to interact. Azithromycin is likely a lower-risk macrolide, and benzodiazepines less dependent on CYP3A metabolism (e.g., lorazepam, oxazepam) are similarly less likely to interact. Exceptions: Azithromycin (Systemic); Fidaxomicin; Roxithromycin; Spiramycin. Consider therapy modification
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Methadone: Benzodiazepines may enhance the CNS depressant effect of Methadone. Avoid combination
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy
MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification
Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy
Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Monitor therapy
OLANZapine: May enhance the adverse/toxic effect of Benzodiazepines. Management: Avoid concomitant use of parenteral benzodiazepines and IM olanzapine due to risks of additive adverse events (e.g., cardiorespiratory depression). Olanzapine prescribing information provides no specific recommendations regarding oral administration. Avoid combination
Ombitasvir, Paritaprevir, and Ritonavir: May increase the serum concentration of ALPRAZolam. Monitor therapy
Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir: May increase the serum concentration of ALPRAZolam. Monitor therapy
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination
Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: When oxycodone is combined with another CNS depressant, a dose reduction of one or both agents should be considered. The extended release oxycodone starting dose should be reduced 50% to 67% when initiated in patients already receiving CNS depressants. Consider therapy modification
Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination
Piribedil [INT]: CNS Depressants may enhance the CNS depressant effect of Piribedil [INT]. Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy
Protease Inhibitors: May increase the serum concentration of ALPRAZolam. Management: Seek alternatives to alprazolam in patients treated with HIV protease inhibitors. Concurrent use of alprazolam with indinavir is contraindicated. All patients receiving such a combination should be monitored closely for excessive response to alprazolam. Consider therapy modification
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Sodium Oxybate: Benzodiazepines may enhance the CNS depressant effect of Sodium Oxybate. Avoid combination
St Johns Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification
Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Start tapentadol at a dose of one-third to one-half of the normal dose if being initiated in a patient who is taking another drug with CNS depressant effects. Monitor closely for evidence of excessive CNS depression. Consider therapy modification
Teduglutide: May increase the serum concentration of Benzodiazepines. Monitor therapy
Telaprevir: May increase the serum concentration of ALPRAZolam. Monitor therapy
Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination
Theophylline Derivatives: May diminish the therapeutic effect of Benzodiazepines. Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Yohimbine: May diminish the therapeutic effect of Antianxiety Agents. Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification
Respiratory and cardiovascular status
>10%:
Central nervous system: Drowsiness (immediate-release: 41% to 77%; extended-release: 23%), fatigue (immediate-release: 49%; extended-release: 14%), sedation (extended-release: 45%), ataxia (immediate-release: 40%; extended-release: 7% to 9%), memory impairment (immediate-release: 33%; extended-release: 15%), irritability (immediate-release: 33%; extended-release: ≥1%), cognitive dysfunction (immediate-release: 29%), dysarthria (immediate-release: 23%; extended-release: 11%), dizziness (immediate-release: 2% to 21%; extended-release: ≥1%), depression (extended-release: 1% to 12%)
Dermatologic: Skin rash (immediate-release: 11%; extended-release: <1%)
Endocrine & metabolic: Weight gain (immediate-release: 27%; extended-release: 5%), weight loss (immediate-release: 23%), decreased libido (6% to 14%)
Gastrointestinal: Increased appetite (immediate-release: 33%; extended-release: 7%), decreased appetite (immediate-release: 28%), constipation (immediate-release: 26%; extended-release: 8%), xerostomia (immediate-release: 15%)
Genitourinary: Difficulty in micturition (immediate-release: 12%; extended-release: ≥1%)
1% to 10%:
Cardiovascular: Hypotension (immediate-release: 5%; extended-release: <1%), chest pain (extended-release: ≥1%), palpitations (extended-release: ≥1%)
Central nervous system: Confusion (immediate-release: 10%; extended-release: 2%), altered mental status (extended-release: 7%), disinhibition (immediate-release: 3%), disturbance in attention (extended-release: 3%), equilibrium disturbance (extended-release: 3%), akathisia (immediate-release: 2%), disorientation (extended-release: 2%), lethargy (extended-release: 2%), talkativeness (immediate-release: 2%), derealization ( ≥1% to 2%), agitation (extended-release: ≥1%), depersonalization (extended-release: ≥1%), headache (extended-release: ≥1%), insomnia (extended-release: ≥1%), malaise (extended-release: ≥1%), nervousness (extended-release: ≥1%), nightmares (extended-release: ≥1%), restlessness ( ≥1%), vertigo (extended-release: ≥1%), anxiety (extended-release: 1%), feeling hot (immediate-release: 1%; extended-release: <1%), hypersomnia (extended-release: 1%), hypoesthesia (extended-release: 1%), dystonia
Dermatologic: Allergic skin reaction ( ≤4%), dermatitis (immediate-release: ≤4%), diaphoresis (extended-release: ≥1%), pruritus (extended-release: 1%)
Endocrine & metabolic: Menstrual disease (immediate-release: 10%; extended-release: 2%), increased libido (immediate-release: 8%; extended-release: ≥1%), change in libido (immediate-release: 7%), hot flash (extended-release: 2%)
Gastrointestinal: Nausea (extended-release: 6%), sialorrhea (immediate-release: 4% to 6%; extended-release: ≥1%), anorexia (extended-release: 2%), abdominal pain (extended-release: ≥1%), diarrhea (extended-release: ≥1%), dyspepsia (extended-release: ≥1%), vomiting (extended-release: ≥1%)
Genitourinary: Sexual disorder (immediate-release: 7%; extended-release: 2%), dysmenorrhea (extended-release: 4%), urinary incontinence (immediate-release: 2%; extended-release: <1%)
Neuromuscular & skeletal: Arthralgia (extended-release: 2%), dyskinesia (extended-release: 2%), myalgia (extended-release: 2%), back pain (extended-release: ≥1%), muscle cramps (extended-release: ≥1%), muscle twitching (extended-release: ≥1%), tremor (extended-release: ≥1%), weakness (extended-release: ≥1%), limb pain (extended-release: 1%)
Ophthalmic: Blurred vision (extended-release: ≥1%)
Respiratory: Dyspnea (extended-release: 2%), hyperventilation (extended-release: ≥1%), nasal congestion (extended-release: ≥1%), allergic rhinitis (extended-release: 1%)
Frequency not defined:
Central nervous system: Drug dependence, drug withdrawal
<1% (Limited to important or life-threatening): Abnormal dreams, aggressive behavior, amnesia, angioedema, apathy, bradyphrenia, chest tightness, choking sensation, clammy skin, clumsiness, diplopia, dysgeusia, dysphagia, edema, emotional lability, epistaxis, euphoria, falling, feeling drunk, fever, galactorrhea, gastrointestinal disease, gynecomastia, hallucination, hangover effect, hepatic failure, hepatitis, homicidal ideation, hyperprolactinemia, hypomania, hypotonia, impaired consciousness, impulse control disorder, increased energy, increased liver enzymes, increased serum bilirubin, increased thirst, jaundice, jitteriness, loss of control of legs, mania, mydriasis, otalgia, outbursts of anger, peripheral edema, photophobia, psychomotor retardation, relaxation, rhinorrhea, rigors, seizure, sensation of cold, sinus tachycardia, skin photosensitivity, sleep apnea, sleep talking, Stevens-Johnson syndrome, stupor, suicidal ideation, syncope, tinnitus, urinary frequency, urticaria, voice disorder
Maximal concentrations and half-life are approximately 15% and 25% higher in Asians.
Cigarette smoking: Concentrations may be reduced by up to 50% in smokers.
Concerns related to adverse effects:
- Anterograde amnesia: Benzodiazepines have been associated with anterograde amnesia.
- CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
- Paradoxical reactions: Paradoxical reactions, including hyperactive or aggressive behavior, have been reported with benzodiazepines, particularly in adolescent/pediatric or psychiatric patients.
Disease-related concerns:
- Depression: Use caution in patients with depression, particularly if suicidal risk may be present; episodes of mania or hypomania have occurred in depressed patients treated with alprazolam.
- Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use (generally >10 days).
- Hepatic impairment: Use with caution in patients with hepatic impairment.
- Renal impairment: Use with caution in patients with renal impairment or predisposition to urate nephropathy; has weak uricosuric properties.
- Respiratory disease: Use with caution in patients with respiratory disease.
Concurrent drug therapy issues:
- CNS depressants/psychoactive medications: Use with caution in patients receiving other CNS depressants or psychoactive medication; effects with other sedative drugs or ethanol may be potentiated.
- High potential for interactions: Use with caution in patients taking strong CYP3A4 inhibitors, moderate or strong CYP3A4 inducers and major CYP3A4 substrates (see Drug Interactions); consider alternative agents that avoid or lessen the potential for CYP-mediated interactions.
Special populations:
- Debilitated patients: Use with caution in debilitated patients.
- Fall risk: Use with extreme caution in patients who are at risk of falls; benzodiazepines have been associated with falls and traumatic injury.
- Obese patients: Use with caution in obese patients; may have prolonged action when discontinued.
- Smokers: Cigarette smoking may decrease alprazolam concentrations up to 50%.
Other warnings/precautions:
- Appropriate use: Does not have analgesic, antidepressant, or antipsychotic properties.
- Breakthrough anxiety: At the end of dosing interval, breakthrough anxiety may occur.
- Tolerance: Alprazolam has a short half-life for a benzodiazepine and the duration of action after a single dose is determined by redistribution rather than metabolism. Tolerance does not develop to the anxiolytic effects (Vinkers, 2012). Chronic use of this agent may increase the perioperative benzodiazepine dose needed to achieve desired effect.
- Withdrawal: Rebound or withdrawal symptoms, including seizures, may occur following abrupt discontinuation or large decreases in dose (more common in adult patients receiving >4 mg/day or prolonged treatment); the risk of seizures appears to be greatest 24 to 72 hours following discontinuation of therapy. Use caution when reducing dose or withdrawing therapy; decrease slowly (eg, ≤0.5 mg every 3 days in adults) and monitor for withdrawal symptoms. Flumazenil may cause withdrawal in patients receiving long-term benzodiazepine therapy.
D
Benzodiazepines have the potential to cause harm to the fetus. Alprazolam and its metabolites cross the human placenta. Teratogenic effects have been observed with some benzodiazepines; however, additional studies are needed. The incidence of premature birth and low birth weights may be increased following maternal use of benzodiazepines; hypoglycemia and respiratory problems in the neonate may occur following exposure late in pregnancy. Neonatal withdrawal symptoms may occur within days to weeks after birth and "floppy infant syndrome " � (which also includes withdrawal symptoms) has been reported with some benzodiazepines (Bergman, 1992; Iqbal, 2002; Wikner, 2007).
Binds to stereospecific benzodiazepine receptors on the postsynaptic GABA neuron at several sites within the central nervous system, including the limbic system, reticular formation. Enhancement of the inhibitory effect of GABA on neuronal excitability results by increased neuronal membrane permeability to chloride ions. This shift in chloride ions results in hyperpolarization (a less excitable state) and stabilization. Benzodiazepine receptors and effects appear to be linked to the GABA-A receptors. Benzodiazepines do not bind to GABA-B receptors.
Readily absorbed; Extended release: Slower relative to immediate release formulation resulting in a concentration that is maintained 5 to 11 hours after dosing; rate increased following night time dosing (versus morning dosing)
Immediate release: Vd: 0.84 to 1.42 L/kg (Greenblatt 1993)
Hepatic via CYP3A4; forms two active metabolites (4-hydroxyalprazolam andα-hydroxyalprazolam [about half as active as alprazolam]) and an inactive metabolite benzophenone metabolite, however, the active metabolites are unlikely to contribute to much of the pharmacologic effects because of their low concentrations and lesser potencies.
Urine (as unchanged drug and metabolites)
Immediate release: 1 to 2 hours
Extended release: Adolescents and Adults: ~9 hours, relatively steady from 4 to 12 hours (Glue 2006); decreased by 1 hour when administered at bedtime (as compared to morning administration); decreased by 33% when administered with a high-fat meal; increased by 33% when administered ≥1 hour after a high-fat meal
Orally-disintegrating tablet: 1.5 to 2 hours; occurs ~15 minutes earlier when administered with water; increased to ~4 hours when administered with a high-fat meal
Adults: Mean: 11.2 hours (Immediate release range: 6.3 to 26.9 hours; Extended release range: 10.7 to 15.8 hours); Orally-disintegrating tablet: Mean: 12.5 hours (range: 7.9 to 19.2 hours)
Alcoholic liver disease: 19.7 hours (range: 5.8 to 65.3 hours)
Obesity: 21.8 hours (range: 9.9 to 40.4 hours)
Elderly: 16.3 hours (range: 9 to 26.9 hours)
80%; primarily to albumin
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience fatigue, dry mouth, increased hunger, lack of appetite, nausea, constipation, sexual dysfunction, decreased libido, or weight change. Have patient report immediately to prescriber signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), shortness of breath, burning or numbness feeling, angina, tachycardia, abnormal heartbeat, severe dizziness, passing out, change in balance, confusion, hallucinations, memory impairment, difficulty speaking, severe loss of strength and energy, twitching, tremors, dark urine, jaundice, blurred vision, or difficult urination (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.