Embedded Files
Pharmacologic Category
Dosing: Adult
Note: Titrate dose gradually as needed and tolerated. Periodic reassessment and consideration of dosage reduction is recommended.
Anxiety disorders: Oral: Immediate release tablet, oral concentrate, orally-disintegrating tablet: Initial: 0.25 to 0.5 mg 3 times daily; titrate dose every 3 to 4 days; usual maximum: 4 mg/day. Patients requiring doses >4 mg/day should be increased cautiously.
Panic disorder: Oral:
Immediate release tablet, oral concentrate, orally-disintegrating tablet: Initial: 0.5 mg 3 times daily; titrate dose every 3 to 4 days in increments ≤1 mg/day. Mean effective dosage: 5 to 6 mg/day, in 3 or 4 divided doses; some patients may require as much as 10 mg/day.
Extended release: 0.5 to 1 mg once daily; titrate dose every 3 to 4 days in increments ≤1 mg/day (range: 3 to 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.
* See Dosage and Administration in AHFS Essentials for additional information.
Dosing: Geriatric
Note: Titrate gradually, if needed and tolerated. Periodic reassessment and consideration of dosage reduction is recommended.
Immediate release: Initial 0.25 mg 2 to 3 times/day
Extended release: Initial: 0.5 mg once daily
Dose reduction: Refer to adult dosing.
Dosing: Renal Impairment: Adult
There are no dosage adjustments provided in the manufacturer's labeling; use caution.
Dosing: Hepatic Impairment: Adult
Advanced liver disease:
Immediate release tablet, oral concentrate, orally-disintegrating tablet: 0.25 mg 2 to 3 times daily.
Extended release: 0.5 mg once daily
Dosing: Pediatric
Note: Titrate dose to effect; use lowest effective dose. The usefulness of this medication should be periodically reassessed.
Anxiety:
Children ≥7 years and Adolescents <18 years: Limited data available: Oral: Immediate release: Initial: 0.005 to 0.02 mg/kg/dose 3 times daily (Kliegman 2007); dosing based on a trial in patients 7 to 16 years of age (n=13), initial doses of 0.005 mg/kg or 0.125 mg/dose were given 3 times/day for situational anxiety and increments of 0.125 to 0.25 mg/dose were used to increase doses to maximum of 0.02 mg/kg/dose or 0.06 mg/kg/day; a range of 0.375 to 3 mg/day was needed (Pfefferbaum 1987). Another study in 17 children (8 to 17 years of age) with overanxious disorder or avoidant disorders used initial daily doses of 0.25 mg for children <40 kg and 0.5 mg for those >40 kg. The dose was titrated at 2-day intervals to a maximum of 0.04 mg/kg/day. Required doses ranged from 0.5 to 3.5 mg/day with a mean of 1.6 mg/day. Based on clinical global ratings, alprazolam appeared to be better than placebo; however, this difference was not statistically significant (Simeon 1992).
Adolescents ≥18 years: Oral: Immediate release: Initial: 0.25 to 0.5 mg 3 times daily; titrate dose upward as needed every 3 to 4 days; usual maximum daily dose: 4 mg/day. Patients requiring doses >4 mg/day should be increased cautiously. Periodic reassessment and consideration of dosage reduction is recommended.
Panic disorder: Adolescents ≥18 years: Oral:
Immediate release: Initial: 0.5 mg 3 times daily; titrate dose upward as needed every 3 to 4 days in increments ≤1 mg/day; mean dose used in controlled trials: 5 to 6 mg/day; maximum daily dose: 10 mg/day (rarely required)
Extended release: Initial: 0.5 to 1 mg once daily; titrate dose upward as needed every 3 to 4 days in increments ≤1 mg/day; usual dose: 3 to 6 mg/day; maximum daily dose: 10 mg/day (rarely required)
Switching from immediate release to extended release: Administer the same total daily dose, but give once daily; if effect is not adequate, titrate dose as above.
Premenstrual dysphoric disorder: Limited data available: Adolescents: Oral: Initial dose: 0.25 mg 3 times daily; titrate as needed. Usual daily dose: 1.25 to 2.25 mg/day (Kliegman 2011)
Discontinuation of therapy: Abrupt discontinuation should be avoided. Daily dose must be gradually decreased no more frequently than 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.
Dosing: Renal Impairment: Pediatric
There are no dosage adjustments provided in the manufacturer's labeling.
Use: Labeled Indications
Anxiety disorders (immediate release tablet, oral concentrate, orally-disintegrating tablets): Treatment of generalized anxiety disorder (GAD), short-term anxiety and anxiety association with depression
Panic disorder (extended-release tablets, oral solution, orally-disintegrating tablets, immediate-release tablets): Treatment of panic disorder, with or without agoraphobia
* See Uses in AHFS Essentials for additional information.
Class and Related Monographs
Administration: Oral
IR 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)
ER tablet: Should be taken once daily in the morning; do not crush, break, or chew.
Bariatric surgery: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Switch to IR formulation.
Oral concentrate: Use only the provided calibrated dropper to withdraw the prescribed dose. Mix the dose with ≥30 mL of juice or other liquid or semi-solid foods (eg, applesauce, pudding). The prepared mixture should be administered immediately.
Orally disintegrating tablets: Using dry hands, place tablet on top of tongue and allow to disintegrate. Administration with water is not necessary.
Administration: Pediatric
Oral:
Immediate-release tablet: Adults: May be administered sublingually if oral administration is not possible; absorption and onset of effect is comparable to oral administration (Scavone 1987; Scavone 1992)
Extended-release tablet: Administer once daily, preferably in the morning; do not crush, chew, or break; swallow whole
Oral concentrate: Use only the provided calibrated dropper to withdraw the prescribed dose. Mix the dose with ≥30 mL of juice or other liquid or semi-solid foods (eg, applesauce, pudding). The prepared mixture should be administered immediately.
Orally-disintegrating tablet: Do not remove tablets from bottle until right before dose; using dry hands, place tablet on top of tongue. If using one-half of tablet, immediately discard remaining half (half tablet may not remain stable). Administration with water is not necessary.
Dietary Considerations
Orally-disintegrating tablets may contain phenylalanine.
Storage/Stability
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).
Oral concentrate: Store at 20°C to 25°C (68°F to 77°F). Protect from moisture. Discard opened bottle after 90 days.
Orally disintegrating tablet: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture.
Extemporaneously Prepared
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.
Medication Patient Education with HCAHPS Considerations
What is this drug used for?
• It is used to treat anxiety.
• It is used to treat panic attacks.
Frequently reported side effects of this drug
• Dry mouth
• Increased hunger
• Lack of appetite
• Nausea
• Constipation
• Sexual dysfunction
• Decreased sex drive
• Weight change
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
• Depression like thoughts of suicide, anxiety, emotional instability, or confusion.
• Severe fatigue
• Shortness of breath
• Severe dizziness
• Passing out
• Change in balance
• Confusion
• Trouble with memory
• Difficulty speaking
• Menstrual changes
• Difficult urination
• Signs of a significant reaction like 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. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
Medication Safety Issues
Sound-alike/look-alike issues:
Geriatric Patients: High-Risk Medication:
Medication Guide and/or Vaccine Information Statement (VIS)
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Xanax: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018276s052lbl.pdf
Xanax XR: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021434s016lbl.pdf#page=24
Contraindications
Hypersensitivity to alprazolam or any component of the formulation (cross-sensitivity with other benzodiazepines may exist); acute narrow-angle glaucoma; concurrent use with ketoconazole, itraconazole, or other potent CYP3A4 inhibitors.
Canadian labeling: Additional contraindications (not in US labeling): Myasthenia gravis; severe hepatic insufficiency; severe respiratory insufficiency; sleep apnea.
Warnings/Precautions
Concerns related to adverse effects:
• Anterograde amnesia: Benzodiazepines have been associated with anterograde amnesia (Nelson 1999).
• 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; risk may be increased in adolescent/pediatric patients, geriatric patients, or patients with a history of alcohol use disorder or psychiatric/personality disorders (Mancuso 2004).
• Sleep-related activities: Hazardous sleep-related activities such as sleep-driving, cooking and eating food, and making phone calls while asleep have been noted with benzodiazepines (Dolder 2008).
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:
• Concomitant use with CYP inhibitors: 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.
• Concomitant use with opioids: [US Boxed warning]: Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
• Debilitated patients: Use with caution in debilitated patients; use lower starting dose.
• Elderly patients: Elderly patients may be at an increased risk of death with use; risk has been found highest within the first 4 months of use in elderly dementia patients (Jennum 2015; Saarelainen 2018).
• Fall risk: Use with extreme caution in patients who are at risk of falls; benzodiazepines have been associated with falls and traumatic injury (Nelson 1999).
• 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.
* See Cautions in AHFS Essentials for additional information.
Pregnancy Risk Factor
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). When treating pregnant females with panic disorder, psychosocial interventions should be considered prior to pharmacotherapy (APA 2009). If a benzodiazepine is needed in pregnancy, agents other than alprazolam are preferred (Larsen 2015).
Breast-Feeding Considerations
Alprazolam is present in breast milk.
The relative infant dose (RID) of alprazolam is 7.9% when calculated using a mean breast milk concentration and compared to a weight-adjusted maternal dose of 0.5 mg.
In general, breastfeeding is considered acceptable when an RID of a medication is <10% (Anderson 2016; Ito 2000). However, some sources note breastfeeding should only be considered if the RID is <5% for psychotropic agents (Larsen 2015).
The RID of alprazolam was calculated using a mean maximum milk concentration of 3.7 ng/mL, providing an estimated daily infant dose via breast milk of 0.555 mcg/kg/day. This milk concentration was obtained following administration of a single oral dose of alprazolam 0.5 mg to eight postpartum females. Peak breast milk concentrations of alprazolam occurred at ~1 hour and the half-life was ~14 hours; metabolites were not detected (Oo 1995).
Case reports have noted drowsiness (Ito 1993) or CNS depression (Kelly 2012) in infants exposed to alprazolam while breastfeeding. Symptoms of withdrawal were described in an infant following alprazolam exposure in utero and via breast milk (Anderson 1989).
Breastfeeding is not recommended by the manufacturer. If a benzodiazepine is needed in breastfeeding females, use of shorter acting agents is preferred (Larsen 2015; WHO 2002).
Briggs' Drugs in Pregnancy & Lactation
Adverse Reactions
>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%)
<1%, postmarketing, and/or case reports: Abnormal dreams, aggressive behavior, amnesia, angioedema, apathy, chest tightness, choking sensation, clumsiness, cold and clammy skin, diplopia, dysgeusia, dysphagia, edema, emotional lability, epistaxis, euphoria, falling, 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, intoxicated feeling, jaundice, jitteriness, mania, mydriasis, otalgia, outbursts of anger, paraplegia, 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
* See Cautions in AHFS Essentials for additional information.
Allergy and Idiosyncratic Reactions
Toxicology
Metabolism/Transport Effects
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP3A4 (weak)
Drug Interactions Open Interactions
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Risk X: Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
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 at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification
Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Cannabis: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: 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. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of ALPRAZolam. Management: Consider using an alternative agent that is less likely to interact. If combined, monitor for increased therapeutic/toxic effects of alprazolam if combined with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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). Risk D: Consider therapy modification
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Risk C: 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. Risk C: Monitor therapy
Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk D: Consider therapy modification
Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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. Risk D: Consider therapy modification
Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy
Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Erythromycin (Systemic): May increase the serum concentration of ALPRAZolam. Risk C: Monitor therapy
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Risk C: Monitor therapy
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Risk D: Consider therapy modification
FluvoxaMINE: May increase the serum concentration of ALPRAZolam. Risk C: Monitor therapy
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Itraconazole: May increase the serum concentration of ALPRAZolam. Risk X: Avoid combination
Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy
Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
Ketoconazole (Systemic): May increase the serum concentration of ALPRAZolam. Risk X: Avoid combination
Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider therapy modification
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk C: Monitor therapy
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. Risk D: Consider therapy modification
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Melatonin: May enhance the sedative effect of Benzodiazepines. Risk C: Monitor therapy
Methadone: Benzodiazepines may enhance the CNS depressant effect of Methadone. Management: Clinicians should generally avoid concurrent use of methadone and benzodiazepines when possible; any combined use should be undertaken with extra caution. Risk D: Consider therapy modification
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. Risk D: Consider therapy modification
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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. Risk D: Consider therapy modification
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Risk D: Consider therapy modification
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Risk C: 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. Risk X: Avoid combination
Ombitasvir, Paritaprevir, and Ritonavir: May increase the serum concentration of ALPRAZolam. Risk C: Monitor therapy
Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir: May increase the serum concentration of ALPRAZolam. Risk C: Monitor therapy
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: 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. Risk D: Consider therapy modification
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: 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. Risk C: Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy
Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Sodium Oxybate: Benzodiazepines may enhance the CNS depressant effect of Sodium Oxybate. Risk X: Avoid combination
Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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. Risk D: 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. Risk D: Consider therapy modification
Teduglutide: May increase the serum concentration of Benzodiazepines. Risk C: Monitor therapy
Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Theophylline Derivatives: May diminish the therapeutic effect of Benzodiazepines. Risk C: Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy
Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Management: Consider triazolam dose reduction in patients receiving concomitant weak CYP3A4 inhibitors. Risk D: Consider therapy modification
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (if needed) of ubrogepant should be limited to 50 mg. Risk D: Consider therapy modification
Yohimbine: May diminish the therapeutic effect of Antianxiety Agents. Risk C: 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. Risk D: Consider therapy modification
Food Interactions
The Cmax of the extended release formulation is increased by 25% when a high-fat meal is given 2 hours before dosing. Tmax is decreased 33% when food is given immediately prior to dose and increased by 33% when food is given ≥1 hour after dose. Management: Administer without regard to food.
Genes of Interest
Monitoring Parameters
Respiratory and cardiovascular status
Advanced Practitioners Physical Assessment/Monitoring
Assess for signs of CNS depression. Assess for history of addiction; long-term use can result in dependence, abuse, or tolerance; periodically evaluate need for continued use. For inpatient use, institute safety measures to prevent falls. Taper dosage slowly when discontinuing.
Nursing Physical Assessment/Monitoring
Assess for signs of CNS depression (sedation, dizziness, confusion, or ataxia). Assess for history of addiction; long-term use can result in dependence, abuse, or tolerance; periodically evaluate need for continued use. For inpatient use, institute safety measures to prevent falls. Taper dosage slowly when discontinuing.
Controlled Substance
C-IV
Dosage Forms: US
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
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 Disintegrating, Oral:
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)]
Dosage Forms: Canada
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Xanax: 0.25 mg, 0.5 mg, 1 mg
Xanax TS: 2 mg
Generic: 0.25 mg, 0.5 mg, 1 mg, 2 mg
Anatomic Therapeutic Chemical (ATC) Classification
- N05BA12
Generic Available (US)
May be product dependent
Pricing: US
Concentrate (ALPRAZolam Intensol Oral)
1 mg/mL (per mL): $3.66
0.5 mg (per each): $2.15 - $2.26
1 mg (per each): $2.67 - $2.81
2 mg (per each): $3.55 - $3.73
3 mg (per each): $5.32 - $5.59
Tablet, 24-hour (Xanax XR Oral)
0.5 mg (per each): $10.19
1 mg (per each): $12.68
2 mg (per each): $16.83
3 mg (per each): $25.24
Tablet, orally-disintegrating (ALPRAZolam Oral)
0.25 mg (per each): $1.52 - $2.18
0.5 mg (per each): $1.89 - $2.72
1 mg (per each): $2.52 - $3.63
2 mg (per each): $4.29 - $6.17
Tablets (ALPRAZolam Oral)
0.25 mg (per each): $0.60 - $0.76
0.5 mg (per each): $0.76 - $1.08
1 mg (per each): $0.90 - $1.16
2 mg (per each): $1.69 - $2.14
Tablets (Xanax Oral)
0.25 mg (per each): $5.29
0.5 mg (per each): $6.59
1 mg (per each): $8.79
2 mg (per each): $14.95
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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.
Pharmacodynamics/Kinetics
Absorption: 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)
Distribution: Immediate release: Vd: 0.84 to 1.42 L/kg (Greenblatt 1993)
Protein binding: 80%; primarily to albumin
Metabolism: Hepatic via CYP3A4; forms two active metabolites (4-hydroxyalprazolam and α-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.
Bioavailability: Immediate release: 84% to 92% (Greenblatt 1993); Extended release: 90%
Half-life elimination:
Adults: 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)
Time to peak, serum:
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
Excretion: Urine (as unchanged drug and metabolites)
Pharmacodynamics/Kinetics: Additional Considerations
Race: 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.
Dental Use
Preoperative anxiety
Local Anesthetic/Vasoconstrictor Precautions
No information available to require special precautions
Dental Health Professional Considerations
Patient should not drive themselves to and from the dental office. It is recommended an adult companion accompany the patient to their appointment.
Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Significant xerostomia and changes in salivation (normal salivary flow resumes upon discontinuation)
Effects on Bleeding
No information available to require special precautions
Dental Usual Dosing
Preoperative anxiety (off-label use) Adults: Oral: 0.5 mg 60-90 minutes before procedure (De Witte, 2002)
Related Information
- Beers Criteria 2019: Potentially Inappropriate Medication Use in Older Adults ≥65 Years of Age
- Benzodiazepine Comparison Table
- Oral Medications That Should Not Be Crushed or Altered
- Relative Infant Dose
Pharmacotherapy Pearls
Not intended for management of anxieties and minor distresses associated with everyday life. Treatment longer than 4 months should be re-evaluated to determine the patient's need for the drug. Patients who become physically dependent on alprazolam tend to have a difficult time discontinuing it; withdrawal symptoms may be severe. To minimize withdrawal symptoms, taper dosage slowly; do not discontinue abruptly. Abrupt discontinuation after sustained use (generally >10 days) may cause withdrawal symptoms.
FDA Approval Date
October 16, 1981
References
2019 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2019;67(4):674-694. doi: 10.1111/jgs.15767.[PubMed 30693946]
Alprazolam Intensol oral solution (concentrate) [prescribing information]. Eatontown, NJ: West-Ward Pharmaceuticals; March 2017.
Alprazolam orally disintegrating tablets [prescribing information]. Chestnut Ridge, NY: Par Pharmaceutical; March 2017.
American Academy of Pediatrics Committee on Drugs. "Inactive" ingredients in pharmaceutical products: update (subject review). Pediatrics. 1997;99(2):268-278.[PubMed 9024461]
American Psychiatric Association (APA). Practice guideline for the treatment of patients with panic disorder. 2009. Available at http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/panicdisorder.pdf. Published January 2009. Accessed May 24, 2017.
Anderson PO, Sauberan JB. Modeling drug passage into human milk. Clin Pharmacol Ther. 2016;100(1):42-52.[PubMed 27060684]
Anderson PO, McGuire GG. Neonatal alprazolam withdrawal--possible effects of breast feeding. DICP. 1989;23(7-8):614.[PubMed 2763587]
Bergman U, Rosa FW, Baum C, et al, "Effects of Exposure to Benzodiazepine During Fetal Life," Lancet, 1992, 340(8821):694-6.[PubMed 1355799]
Bernstein GA, Garfinkel BD, and Borchardt CM, “Comparative Studies of Pharmacotherapy for School Refusal,” J Am Acad Child Adolesc Psychiatry, 1990, 29(5):773-81.[PubMed 2228932]
Brunton LL, Chabner BA, Knollmann BC, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 12th ed. New York, NY: McGraw-Hill Medical; 2011.
De Witte JL, Alegret C, Sessler DI, et al, “Preoperative Alprazolam Reduces Anxiety in Ambulatory Surgery Patients: A Comparison With Oral Midazolam,” Anesth Analg, 2002, 95(6):1601-6.[PubMed 12456424]
Dolder CR, Nelson MH. Hypnosedative-induced complex behaviours: incidence, mechanisms and management. CNS Drugs. 2008;22(12):1021-1036. doi:10.2165/0023210-200822120-00005.[PubMed 18998740]
Glue P, Fang A, Gandelman K, et al, “Pharmacokinetics of an Extended Release Formulation of Alprazolam (Xanax XR) in Healthy Normal Adolescent and Adult Volunteers,” Am J Ther, 2006, 13(5):418-22.[PubMed 16988537]
Iqbal MM, Sobhan T, Ryals T, et al, "Effects of Commonly Used Benzodiazepines on the Fetus, the Neonate, and the Nursing Infant," Psychiatr Serv, 2002, 53(1):39-49.[PubMed 11773648]
Ito S, Blajchman A, Stephenson M, Eliopoulos C, Koren G. Prospective follow-up of adverse reactions in breast-fed infants exposed to maternal medication. Am J Obstet Gynecol. 1993;168(5):1393-1399.[PubMed 8498418]
Ito S. Drug therapy for breast-feeding women. N Engl J Med. 2000;343(2):118-126.[PubMed 10891521]
Jennum P, Baandrup L, Ibsen R, et al. Increased all-cause mortality with use of psychotropic medication in dementia patients and controls: A population-based register study. Eur Neuropsychopharmacol. 2015;25(11):1906-1913. doi: 10.1016/j.euroneuro.2015.08.014.[PubMed 26342397]
Kelly LE, Poon S, Madadi P, Koren G. Neonatal benzodiazepines exposure during breastfeeding. J Pediatr. 2012;161(3):448-451.[PubMed 22504099]
Kliegman RM, Behrman RE, Jenson HB, et al, eds. Nelson Textbook of Pediatrics. 18th ed. Philadelphia, PA: Saunders Elsevier; 2007.
Kliegman RM, Stanton BF, St. Gemell JW, et al, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, PA: Saunders Elsevier; 2011.
Larsen ER, Damkier P, Pedersen LH, et al. Use of psychotropic drugs during pregnancy and breast-feeding. Acta Psychiatr Scand Suppl. 2015;(445):1-28.[PubMed 26344706]
Mancuso CE, Tanzi MG, Gabay M. Paradoxical reactions to benzodiazepines: literature review and treatment options. Pharmacotherapy. 2004;24(9):1177-1185.[PubMed 15460178]
Mokhlesi B, Leikin JB, Murray P, et al, “Adult Toxicology in Critical Care: Part II: Specific Poisonings,” Chest, 2003, 123(3):897-922.[PubMed 12628894]
Moulin CH, Rolachon A, Cohard M, et al, “Fulminant Hepatitis Secondary to Alprazolam,” Therapie, 1994, 49(4):362-3.[PubMed 7878609]
Mumford GK, Evans SM, Fleishaker JC, et al, “Alprazolam Absorption Kinetics Affects Abuse Liability,” Clin Pharmacol Ther, 1995, 57(3):356-65.[PubMed 7697954]
Nelson J, Chouinard G. Guidelines for the clinical use of benzodiazepines: pharmacokinetics, dependency, rebound and withdrawal. Canadian Society forClinical Pharmacology. Can J Clin Pharmacol. 1999;6(2):69-83.[PubMed 10519733]
Niravam orally disintegrating tablets (alprazolam) [prescribing information]. Philadelphia, PA: Azur Pharma, Inc; January 2011.
Noyes R Jr, DuPont RL Jr, Pecknold JC, et al, “Alprazolam in Panic Disorder and Agoraphobia: Results From a Multicenter Trial. II. Patient Acceptance, Side Effects, and Safety,” Arch Gen Psychiatry, 1988, 45(5):423-8.[PubMed 3358644]
Oo CY, Kuhn RJ, Desai N, et al, "Pharmacokinetics in Lactating Women: Prediction of Alprazolam Transfer Into Milk," Br J Clin Pharmacol, 1995, 40(3):231-6.[PubMed 8527284]
Rickels K, “Alprazolam Extended-Release in Panic Disorder,” Expert Opin Pharmacother, 2004, 5(7):1599-611.[PubMed 15212610]
Saarelainen L, Tolppanen AM, Koponen M, et al. Risk of death associated with new benzodiazepine use among persons with Alzheimer disease: A matched cohort study. Int J Geriatr Psychiatry. 2018;33(4):583-590. doi: 10.1002/gps.4821.[PubMed 29143367]
Scavone JM, Greenblatt DJ, Goddard JE, Friedman H, Harmatz JS, Shader RI. The pharmacokinetics and pharmacodynamics of sublingual and oral alprazolam in the post-prandial state. Eur J Clin Pharmacol. 1992;42(4):439-443.[PubMed 1516609]
Scavone JM, Greenblatt DJ, Shader RI. Alprazolam kinetics following sublingual and oral administration. J Clin Psychopharmacol. 1987;7(5):332-334.[PubMed 3680603]
Sheehan DV, Sheehan KH, and Raj BA, “The Speed of Onset of Action of Alprazolam-XR Compared to Alprazolam-CT in Panic Disorder,” Psychopharmacol Bull, 2007, 40(2):63-81.[PubMed 17514187]
Shehab N, Lewis CL, Streetman DD, Donn SM. Exposure to the pharmaceutical excipients benzyl alcohol and propylene glycol among critically ill neonates. Pediatr Crit Care Med. 2009;10(2):256-259.[PubMed 19188870]
Simeon JG, Ferguson HB, Knott V, et al, “Clinical, Cognitive, and Neurophysiological Effects of Alprazolam in Children and Adolescents With Overanxious and Avoidant Disorders,” J Am Acad Child Adolesc Psychiatry, 1992, 31(1):29-33.[PubMed 1537778]
Vinkers CH, Olivier B. Mechanisms Underlying Tolerance after Long-Term Benzodiazepine Use: A Future for Subtype-Selective (A) Receptor Modulators? Adv Pharmacol Sci. 2012;2012:416864.[PubMed 22536226]
Wikner BN, Stiller CO, Bergman U, et al, "Use of Benzodiazepines and Benzodiazepine Receptor Agonists During Pregnancy: Neonatal Outcome and Congenital Malformations," Pharmacoepidemiol Drug Saf, 2007, 16(11):1203-10.[PubMed 17894421]
World Health Organization (WHO). Breastfeeding and maternal medication, recommendations for drugs in the eleventh WHO model list of essential drugs. 2002. Available at http://www.who.int/maternal_child_adolescent/documents/55732/en/
Xanax concentrate (alprazolam) [prescribing information]. Eatontown, NJ: West-Ward Phamaceuticals Corp; June 2016.
Xanax (alprazolam) [prescribing information]. New York, NY: Pharmacia and Upjohn Co; December 2016.
Xanax and Xanax TS (alprazolam) [product monograph]. Kirkland, Quebec, Canada: Pfizer Canada ULC; April 2019.
Xanax XR (alprazolam) [prescribing information]. New York, NY: Pharmazia and Upjohn Co; December 2016.
Brand Names: International
Aceprax (PY, UY); Actazolam (ID); Adax (CL, EC); Adax Retard (EC); Alcelam (TH); Alnax (TH); Alpax (LK); Alpaz (PE); Alplax (AR); Alpralid (IL); Alpraline (MY); Alpranax (JO, KR, MY); Alpratop (BE); Alprax (AU, EG, HK, IN, TH); Alpraz (BE, LU); Alprocontin (IN); Alprox (HU, LB, TW); Altrox (PH); Alviz (ID); Alzam (CR, DO, GT, HN, MX, NI, PA, SV, ZA); Alzax (KR); Alzolam (IN, SG); Ansiolit (EC); Antonil (BD); Apo-Alpraz (SG); Apraz (BR); Aprazo (TW); Asolan (MY); Axal (PH); Azor (ZA); Cassadan (DE); Constan (JP); Dixin (CO); Farmapram (MX); Feprax (ID); Frontal (BR); Frontin (HU, LV, RO); Gerax (IE); Getzpraz (VN); Helex (HR, LV); Helex SR (LV); Helix SR (HU); Irizz. (MX); Kalma (AU); Kinax (TW); Manorest (LK); Marzolam (TH); Misar (HR); Moderex (PY); Nalion (TR); Neupax (CR, DO, GT, HN, MX, NI, PA, SV); Opizolam (ID); Pacyl (IN); Pazolam (LB); Pharnax (TH); Prazin (JO); Prazol (AE, BH, CY, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Prazovex (MY); Prinox (AR); Renax (TR); Sedalam (LK); Solanax (JP); Soxietas (ID); Stressnor (EG); Sublimex (CR, DO, GT, HN, NI, PA, SV); Tafil (CR, DE, DK, DO, GT, HN, IS, MX, NI, PA, SV, VE); Tafil D (MU); Tazun (MX); Toranax (VN); Trankimazin Retard (ES); Tranquinal (BR, CU, EC, PY, UY); Tricalma (CL); Valeans (IT); Xanacine (TH); Xanagis (IL); Xanax (AE, AR, BB, BD, BE, BF, BG, BH, BJ, BM, BS, BZ, CH, CI, CO, CY, CZ, DE, EE, EG, ET, FR, GB, GH, GM, GN, GR, GY, HK, HR, HU, IE, IQ, IR, IT, JM, JO, KE, KW, LB, LR, LT, LU, LV, LY, MA, ML, MR, MT, MU, MW, MY, NE, NG, NL, NZ, OM, PE, PK, PL, PT, QA, RO, RU, SA, SC, SD, SI, SK, SL, SN, SR, SY, TH, TN, TR, TT, TW, TZ, UG, VN, YE, ZM, ZW); Xanax Retard (BE, LU); Xanax SR (BG, SG); Xanax XR (BB, IL, KW, LT, LV, RO, TH, TW); Xanor (AT, FI, NO, PH, SE, ZA); Xanor Depot (NO); Xanor XR (PH); Xiety (BD); Xolam (BD); Zacetin (KR); Zanapam (AE, BH, CY, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Zolam (IN, JO); Zolapar (EG); Zolaram (LK, TR); Zolarem (AE, BF, BH, BJ, CI, CY, ET, GH, GM, GN, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MT, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Zolastin (ID); Zoldac (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM, ZW); Zolgen (PH); Zopax (ZA); Zotran (CL); Zypraz (ID); Zyren (KR)
Last Updated 5/2/20
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