ALPRAZolam (Lexi-Drugs)

ALERT: US Boxed Warning
  Risks from concomitant use with opioids
Pronunciation

(al PRAY zoe lam)

Brand Names: US

ALPRAZolam Intensol; ALPRAZolam XR; Xanax; Xanax XR

Brand Names: Canada

ALPRAZolam TS; ALPRAZolam-1; APO-Alpraz; APO-Alpraz TS; JAMP-Alprazolam; MYLAN-ALPRAZolam [DSC]; NAT-ALPRAZolam [DSC]; NTP-ALPRAZolam [DSC]; NU-Alpraz [DSC]; RIVA-ALPRAZolam [DSC]; TEVA-Alprazolam; Xanax; Xanax TS

Pharmacologic Category

Benzodiazepine

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.

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

Level of Evidence Definitions
  Level of Evidence Scale
Administration: Oral

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.

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

• 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 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), severe fatigue, shortness of breath, severe dizziness, passing out, change in balance, confusion, memory impairment, difficulty speaking, menstrual changes, 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 health care 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.

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.

Geriatric Considerations

Refer to Medication Safety Issues for Beers Criteria information.

Pregnancy Risk Factor

D

Pregnancy Considerations

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%)

Frequency not defined:

Central nervous system: Drug dependence, drug withdrawal

<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

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 

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

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. 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. Risk D: Consider therapy modification

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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 patches (Butrans brand) at 5 mcg/hr in adults when used with other 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

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

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

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

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone 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

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

Indinavir: May increase the serum concentration of ALPRAZolam. 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

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

Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. 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

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. 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: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. 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

Pitolisant: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. Risk D: Consider therapy modification

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. 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

St John’s Wort: May decrease the serum concentration 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

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

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol 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

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 D: Consider therapy modification

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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.

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)]

Generic: 0.5 mg, 1 mg, 2 mg, 3 mg

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

Tablet, 24-hour (ALPRAZolam ER Oral)

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): $9.71

1 mg (per each): $12.09

2 mg (per each): $16.04

3 mg (per each): $24.06

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): $0.07 – $0.70

0.5 mg (per each): $0.07 – $0.96

1 mg (per each): $0.08 – $1.16

2 mg (per each): $1.69 – $2.14

Tablets (Xanax Oral)

0.25 mg (per each): $5.04

0.5 mg (per each): $6.28

1 mg (per each): $8.38

2 mg (per each): $14.25

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.

Mechanism of Action

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)

FDA Approval Date
October 16, 1981
References

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Alprazolam Intensol oral solution (concentrate) [prescribing information]. Eatontown, NJ: West-Ward Pharmaceuticals; March 2017.

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Anderson PO, McGuire GG. Neonatal alprazolam withdrawal–possible effects of breast feeding. DICP. 1989;23(7-8):614.[PubMed 2763587]

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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]

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Kelly LE, Poon S, Madadi P, Koren G. Neonatal benzodiazepines exposure during breastfeeding. J Pediatr. 2012;161(3):448-451.[PubMed 22504099]

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]

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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]

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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 Inc.; January 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 (MX, 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 (MX); 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, CR, CU, DO, EC, GT, HN, NI, PA, PY, SV, 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)

Alprazolam (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(al PRAY zoe lam)

Brand Names: US

ALPRAZolam Intensol; ALPRAZolam XR; Xanax; Xanax XR

Brand Names: Canada

Xanax; Xanax TS

Warning
  • This drug is a benzodiazepine. The use of a benzodiazepine drug along with opioid drugs has led to very bad side effects. Side effects that have happened include slowed or trouble breathing and death. Opioid drugs include drugs like codeine, oxycodone, and morphine. Opioid drugs are used to treat pain and some are used to treat cough. Talk with the doctor.
  • If you are taking this drug with an opioid drug, get medical help right away if you feel very sleepy or dizzy; if you have slow, shallow, or trouble breathing; or if you pass out. Caregivers or others need to get medical help right away if the patient does not respond, does not answer or react like normal, or will not wake up.
What is this drug used for?
  • It is used to treat anxiety.
  • It is used to treat panic attacks.
What do I need to tell my doctor BEFORE I take this drug?
  • If you have an allergy to alprazolam or any other part of this drug.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have glaucoma.
  • If you are taking any of these drugs: Itraconazole or ketoconazole.
  • If you are breast-feeding. Do not breast-feed while you take this drug.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • All products:
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • This drug may be habit-forming with long-term use.
  • If you have been taking this drug for a long time or at high doses, it may not work as well and you may need higher doses to get the same effect. This is known as tolerance. Call your doctor if this drug stops working well. Do not take more than ordered.
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how this drug affects you.
  • Avoid drinking alcohol while taking this drug.
  • Talk with your doctor before you use other drugs and natural products that slow your actions.
  • Have your blood work checked if you are on this drug for a long time. Talk with your doctor.
  • If you drink grapefruit juice or eat grapefruit often, talk with your doctor.
  • If you start or stop smoking, talk with your doctor. How much drug you take may need to be changed.
  • If you are taking digoxin, talk with your doctor. You may need to have your blood work checked more closely while you are taking it with this drug.
  • If you are 65 or older, use this drug with care. You could have more side effects.
  • This drug may cause harm to the unborn baby if you take it while you are pregnant, especially in the first trimester.
  • If you are pregnant or you get pregnant while taking this drug, call your doctor right away.
  • Extended-release tablets:
  • Do not stop taking this drug all of a sudden without calling your doctor. You may have a greater risk of signs of withdrawal. This includes seizures. If you need to stop this drug, you will want to slowly stop it as ordered by your doctor.
  • All other products:
  • If you have been taking this drug on a regular basis and you stop it all of a sudden, you may have signs of withdrawal. This includes seizures. Do not stop taking this drug all of a sudden without calling your doctor. Tell your doctor if you have any bad effects.
  • Oral-disintegrating tablet:
  • If you have phenylketonuria (PKU), talk with your doctor. Some products have phenylalanine.
What are some side effects that I need to call my doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of low mood (depression), thoughts of killing yourself, nervousness, emotional ups and downs, thinking that is not normal, anxiety, or lack of interest in life.
  • Change in balance.
  • Feeling very sleepy.
  • Shortness of breath.
  • Very bad dizziness or passing out.
  • Feeling confused.
  • Memory problems or loss.
  • Trouble speaking.
  • Trouble passing urine.
  • Period (menstrual) changes.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
  • Feeling sleepy.
  • Dizziness.
  • Dry mouth.
  • Feeling more or less hungry.
  • Upset stomach.
  • Constipation.
  • Change in sex interest.
  • Sex problems.
  • Feeling tired or weak.
  • Weight gain or loss.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • Take with or without food. Take with food if it causes an upset stomach.
  • Liquid (solution):
  • Use the dropper that comes with this drug to measure the drug.
  • Mix the liquid with water, juice, soda, applesauce, or pudding before taking it.
  • Swallow the mixture right away. Do not store for use at a later time.
  • Oral-disintegrating tablet:
  • If the tablets come in a foil blister, do not push the tablet out of the foil when opening. Use dry hands to take it from the foil.
  • Place on your tongue and let it dissolve. Water is not needed. Do not swallow it whole. Do not chew, break, or crush it.
  • Extended-release tablets:
  • Swallow whole. Do not chew, break, or crush.
What do I do if I miss a dose?
  • Extended-release tablets:
  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
  • All other products:
  • If you take this drug on a regular basis, take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
  • Many times this drug is taken on an as needed basis. Do not take more often than told by the doctor.
How do I store and/or throw out this drug?
  • All products:
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
  • Liquid (solution):
  • Protect from light.
  • Throw away any part not used 90 days after opening.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.
Alprazolam (Patient Education – Pediatric Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(al PRAY zoe lam)

Brand Names: US

ALPRAZolam Intensol; ALPRAZolam XR; Xanax; Xanax XR

Brand Names: Canada

Xanax; Xanax TS

Warning
  • This drug is a benzodiazepine. The use of a benzodiazepine drug along with opioid drugs has led to very bad side effects. Side effects that have happened include slowed or trouble breathing and death. Opioid drugs include drugs like codeine, oxycodone, and morphine. Opioid drugs are used to treat pain and some are used to treat cough. Talk with the doctor.
  • If your child is taking this drug with an opioid drug, get medical help right away if your child feels very sleepy or dizzy; if your child has slow, shallow, or trouble breathing; or if your child passes out. Get medical help right away if your child does not respond, does not answer or react like normal, or will not wake up.
What is this drug used for?
  • It is used to treat anxiety.
  • It is used to treat panic attacks.
What do I need to tell the doctor BEFORE my child takes this drug?
  • If your child has an allergy to this drug or any part of this drug.
  • If your child is allergic to any drugs like this one or any other drugs, foods, or other substances. Tell the doctor about the allergy and what signs your child had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If your child has glaucoma.
  • If your child is taking any of these drugs: Itraconazole or ketoconazole.
  • If your child is breast-feeding a baby:
  • Be sure your child does not breast-feed a baby while taking this drug.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell the doctor and pharmacist about all of your child’s drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for your child to take this drug with all of his/her drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.
What are some things I need to know or do while my child takes this drug?
  • All products:
  • Tell all of your child’s health care providers that your child is taking this drug. This includes your child’s doctors, nurses, pharmacists, and dentists.
  • This drug may be habit-forming with long-term use.
  • Have your child avoid tasks or actions that call for alertness until you see how this drug affects your child. These are things like riding a bike, playing sports, or using items such as scissors, lawnmowers, electric scooters, toy cars, or motorized vehicles.
  • Alcohol may interact with this drug. Be sure your child does not drink alcohol.
  • Talk with your child’s doctor before giving your child other drugs and natural products that may slow your child’s actions.
  • Have your child’s blood work checked if he/she is on this drug for a long time. Talk with your child’s doctor.
  • If your child drinks grapefruit juice or eats grapefruit often, talk with your child’s doctor.
  • If your child stops or starts smoking, talk with the doctor. How much drug your child takes may need to be changed.
  • If your child is taking digoxin, talk with your child’s doctor. Your child may need to have blood work checked more closely while taking it with this drug.
  • This drug may cause harm to the unborn baby if your child takes it during pregnancy, especially in the first trimester.
  • If your child is pregnant or gets pregnant while taking this drug, call the doctor right away.
  • Extended-release tablets:
  • Do not stop giving this drug to your child all of a sudden without calling the doctor. Your child may have a greater risk of signs of withdrawal. This includes seizures. If your child needs to stop this drug, you will want to slowly stop it as ordered by the doctor.
  • All other products:
  • If your child has been taking this drug on a regular basis and stops taking it all of a sudden, your child may have signs of withdrawal. This includes seizures. Do not stop giving this drug all of a sudden without calling the doctor. Tell the doctor if your child has any bad effects.
  • Oral-disintegrating tablet:
  • If your child has phenylketonuria (PKU), talk with your child’s doctor. Some products have phenylalanine.
What are some side effects that I need to call my child’s doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child’s doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • If your child shows signs of low mood (depression), thoughts of killing him/herself, nervousness, emotional ups and downs, thinking that is not normal, anxiety, or lack of interest in life.
  • Change in balance.
  • Feeling very sleepy.
  • Feeling confused.
  • Shortness of breath.
  • Very bad dizziness or passing out.
  • Memory problems or loss.
  • Trouble speaking.
  • Trouble passing urine.
  • Period (menstrual) changes.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child’s doctor or get medical help if any of these side effects or any other side effects bother your child or do not go away:
  • Feeling sleepy.
  • Dizziness.
  • Dry mouth.
  • Feeling more or less hungry.
  • Upset stomach.
  • Constipation.
  • Feeling tired or weak.
  • Weight gain or loss.
  • If your child is or may be sexually active:
  • Change in sex interest.
  • Sex problems.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your child’s doctor. Call your child’s doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best given?
  • Give this drug as ordered by your child’s doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • Give this drug with or without food. Give with food if it causes an upset stomach.
  • Liquid (solution):
  • Use the dropper that comes with this drug to measure the drug.
  • Oral-disintegrating tablet:
  • If the tablets come in a foil blister, do not push the tablet out of the foil when opening. Use dry hands to take it from the foil.
  • Place on your child’s tongue and let it dissolve. Water is not needed. Do not let your child swallow it whole. Do not let your child chew, break, or crush it.
  • Extended-release tablets:
  • Have your child swallow whole. Do not let your child chew, break, or crush.
What do I do if my child misses a dose?
  • Extended-release tablets:
  • Give a missed dose as soon as you think about it.
  • If it is close to the time for your child’s next dose, skip the missed dose and go back to your child’s normal time.
  • Do not give 2 doses at the same time or extra doses.
  • All other products:
  • If your child takes this drug on a regular basis, give a missed dose as soon as you think about it.
  • If it is close to the time for your child’s next dose, skip the missed dose and go back to your child’s normal time.
  • Do not give 2 doses at the same time or extra doses.
  • Many times this drug is given on an as needed basis. Do not give to your child more often than told by the doctor.
How do I store and/or throw out this drug?
  • All products:
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
  • Liquid (solution):
  • Protect from light.
  • Throw away any part not used 90 days after opening.
General drug facts
  • If your child’s symptoms or health problems do not get better or if they become worse, call your child’s doctor.
  • Do not share your child’s drug with others and do not give anyone else’s drug to your child.
  • Keep a list of all your child’s drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your child’s doctor.
  • Talk with your child’s doctor before giving your child any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your child’s doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.