therapeutic index; dose adjustment may be necessary.temazepamMonitor Closely (1)alprazolam and temazepam both increase sedation. Use Caution/Monitor.terbutalineMonitor Closely (1)alprazolam increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.thioridazineMonitor Closely (1)alprazolam and thioridazine both increase sedation. Use Caution/Monitor.thiothixeneMonitor Closely (1)alprazolam and thiothixene both increase sedation. Use Caution/Monitor.tipranavirContraindicated (1)tipranavir increases levels of alprazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Potential for increased toxicity. Tipranavir is used with ritonavir (boosted therapy) which is a potent CYP3A4 inhibitor.topiramateMonitor Closely (2)topiramate will decrease the level or effect of alprazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. alprazolam and topiramate both increase sedation. Modify Therapy/Monitor Closely.tramadolMonitor Closely (1)alprazolam and tramadol both increase sedation. Use Caution/Monitor.trazodoneMonitor Closely (1)alprazolam and trazodone both increase sedation. Use Caution/Monitor.triazolamMonitor Closely (1)alprazolam and triazolam both increase sedation. Use Caution/Monitor.triclofosMonitor Closely (1)alprazolam and triclofos both increase sedation. Use Caution/Monitor.trifluoperazineMonitor Closely (1)alprazolam and trifluoperazine both increase sedation. Use Caution/Monitor.trimipramineMonitor Closely (1)alprazolam and trimipramine both increase sedation. Use Caution/Monitor.triprolidineMonitor Closely (1)triprolidine and alprazolam both increase sedation. Use Caution/Monitor.valerianSerious - Use Alternative (1)valerian and alprazolam both increase sedation. Avoid or Use Alternate Drug.verapamilMonitor Closely (1)verapamil will increase the level or effect of alprazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.vinpocetineMinor (1)alprazolam increases effects of vinpocetine by unspecified interaction mechanism. Minor/Significance Unknown. Desirable interaction enhanced memory improvement (based on preliminary trial).voriconazoleMonitor Closely (1)voriconazole will increase the level or effect of alprazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.voxelotorSerious - Use Alternative (1)voxelotor will increase the level or effect of alprazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.xylometazolineMonitor Closely (1)alprazolam increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.yohimbineMonitor Closely (1)alprazolam increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.zafirlukastMonitor Closely (1)zafirlukast will increase the level or effect of alprazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.ziconotideMonitor Closely (1)alprazolam and ziconotide both increase sedation. Use Caution/Monitor.ziprasidoneMonitor Closely (1)alprazolam and ziprasidone both increase sedation. Use Caution/Monitor.zolpidemMinor (1)zolpidem, alprazolam. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive CNS depression.zotepineMonitor Closely (1)alprazolam and zotepine both increase sedation. Use Caution/Monitor. >10% (4 mg dose) Drowsiness (41%) Depression (10-15%) Headache (10-15%) Constipation (10-15%) Diarrhea (10-15%) Dry mouth (10-15%) >10% (10 mg dose) Drowsiness (77%) Impaired coordination (40-50%) Increased appetite (30-35%) Fatigue (30-35%) Memory impairment (30-35%) Irritability (30-35%) Decreased salivation (30-35%) Cognitive disorders (20-30%) Insomnia (20-30%) Dcreased appetite (20-30%) Headache (20-30%) Lightheadedness (20-30%) Dysarthria (20-30%) Diarrhea, constipation, and nausea/vomiting (20-30%) Weight change (20-30%) Nasal congestion (15-20%) Decreased or increased libido (10-15%) Menstrual disorder (10-15%) Difficult micturition (10-15%) 1-10% (4 mg dose) Tachycardia (5-10%) Confusion (5-10%) Insomnia (5-10%) Nausea/vomiting (5-10%) Blurred vision (5-10%) Nasal congestion (5-10%) Hypotension (1-5%) Syncope (1-5%) Akathisia (1-5%) Dizziness (1-5%) Increased salivation (1-5%) Nervousness (1-5%) Tremor (1-5%) Weight change (1-5%) 1-10% (10 mg dose) Increased salivation (5-10%) Talkativeness (1-5%) Incontinence (1-5%) Postmarketing Reports Gastrointestinal: Liver enzyme elevations, hepatitis, hepatic failure CNS: Hypomania, mania Immunologic: Stevens-Johnson syndrome, angioedema, peripheral edema Endocrine: Hyperprolactinemia, gynecomastia, galactorrhea Black Box Warnings Risks from concomitant use with opioids 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 Inform patients and caregivers that potentially fatal additive effects may occur if drug is used with opioids and that such drugs should not be used concomitantly unless supervised by a health care provider Prescribers should advise caregivers that they expect to be informed immediately if a patient develops any new findings which are not typical of the patient’s characteristic seizure episode Addiction, abuse, and misuse In September 2020, FDA addressed serious risks of benzodiazepine addiction, abuse, and misuse, which can lead to overdose and death Physical dependence can occur when taken steadily for several days to weeks, even as prescribed Stopping abruptly or reducing dosage too quickly can result in withdrawal reactions, including seizures, which can be life-threatening Abuse and misuse of benzodiazepines commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes; before prescribing and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction Assess each patient’s risk prior to prescribing and monitor regularly for the development of these conditions Risks of dependence and withdrawal increase with longer treatment duration and higher daily dose; although injection is indicated only for intermittent use, if used more frequently than recommended, abrupt discontinuation or rapid dosage reduction may precipitate acute withdrawal reactions, including seizures, which can be life-threatening; use gradual taper when discontinuing therapy to reduce withdrawal reactions risk Contraindications Documented hypersensitivity Acute narrow angle glaucoma Concomitant use with CYP3A4 inhibitors (itraconazole, ketoconazole) Cautions Anterograde amnesia reported with benzodiazepine use Use caution in elderly patients Use caution in debilitated patients Use caution in severe respiratory depression; if signs and symptoms of respiratory depression, hypoventilation, or apnea occur, discontinue Use caution in patients who recently received other respiratory depressants Use caution in patients who are at risk of falls May have prolonged effects in obese patients when discontinued; use caution Not for us in acute alcohol intoxication Use with caution in patients with hepatic or renal impairment Myasthenia gravis (allowable in limited circumstances) Use caution in cases of respiratory disease (COPD), sleep apnea, renal/hepatic disease, open-angle glaucoma (questionable), depression, suicide ideation, drug abuse CNS depressant; may impair ability to perform hazardous tasks Paradoxical reactions, including hyperactive or aggressive behavior reported Cigarette smoking may decrease alprazolam concentration up to 50% Mania and hypomania episodes reported in depressed patients Benzodiazepines expose users to risks of abuse, misuse, and addiction, which can lead to overdose or death; abuse and misuse of benzodiazepines often (but not always) involve use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death Use of drug, particularly in patients at elevated risk of abuse, necessitates counseling about risks and proper use of drug along with monitoring for signs and symptoms of abuse, misuse, and addiction; do not exceed recommended dosing frequency Avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (eg, opioid analgesics, stimulants); advise patients on proper disposal of unused drug; if a substance use disorder is suspected, evaluate patient and institute (or refer them for) early treatment, as appropriate For patients treated more frequently than recommended, use a gradual taper to discontinue therapy (a patient-specific plan should be used to taper the dose), to reduce risk of withdrawal reactions Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages, and those who have had longer durations of use In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months; symptoms may include heightened sensory perception, impaired concentration, dysosmia, clouded sensorium, paresthesias, muscle cramps, muscle twitch, diarrhea, blurred vision, appetite decrease, and weight loss Pregnancy There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to drug during pregnancy; healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Other Psychiatric Medications at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/othermedications/. Neonates born to mothers using benzodiazepines during later stages of pregnancy reported to experience symptoms of sedation and neonatal withdrawal; overall available data from published observational studies of pregnant women exposed to drug have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes Benzodiazepines cross the placenta and may produce respiratory depression and sedation in neonates; monitor neonates exposed to benzodiazepines during pregnancy and labor for signs of sedation, respiratory depression, withdrawal, and feeding problems and manage accordingly Lactation Limited data from published literature reports the presence of the drug in human breast milk; there are reports of sedation and withdrawal symptoms in breastfed neonates and infants exposed to alprazolam; effects of alprazolam on lactation are unknown Because of potential for serious adverse reactions, including sedation and withdrawal symptoms in breastfed neonates and infants, advise patients that breastfeeding is not recommended during treatment Pregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Binds receptors at several sites within the CNS, including the limbic system and reticular formation; effects may be mediated through GABA receptor system; increase in neuronal membrane permeability to chloride ions enhances the inhibitory effects of GABA; the shift in chloride ions causes hyperpolarization (less excitability) and stabilization of the neuronal membrane Absorption Bioavailability: 90% Peak serum time: 1-2 hr (immediate release); 9 hr (extended release); 1.5-2 hr (disintegrating tablet) Peak plasma concentration: 8-37 ng/mL (dose dependent) Distribution Protein bound: 80% Vd: 0.9-1.2 L/kg Metabolism Metabolized by hepatic P-450 enzyme CYP3A4 Elimination Half-life: 11 hr average for immediate release, 13 hr average for extended release, and 13 hr average for disintegrating tablets (adults); 16.3 hr (elderly); 21.8 hr (obesity) Excretion: Urine BRAND FORM. UNIT PRICE PILL IMAGE Xanax oral- 0.25 mg tabletXanax oral- 1 mg tabletXanax oral- 0.5 mg tabletXanax oral- 2 mg tabletAlprazolam Intensol oral- 1 mg/mL liquidalprazolam oral- 1 mg tabletalprazolam oral- 0.5 mg tabletalprazolam oral- 0.5 mg tabletalprazolam oral- 0.25 mg tabletalprazolam oral- 0.25 mg tabletalprazolam oral- 0.5 mg tabletalprazolam oral- 1 mg tabletalprazolam oral- 0.5 mg tabletalprazolam oral- 0.5 mg tabletalprazolam oral- 3 mg tabletalprazolam oral- 0.5 mg tabletalprazolam oral- 0.5 mg tabletalprazolam oral- 0.25 mg tabletalprazolam oral- 2 mg tabletalprazolam oral- 2 mg tabletalprazolam oral- 0.25 mg tabletalprazolam oral- 2 mg tabletalprazolam oral- 1 mg tabletalprazolam oral- 0.25 mg tabletalprazolam oral- 2 mg tabletalprazolam oral- 0.5 mg tabletalprazolam oral- 0.25 mg tabletalprazolam oral- 1 mg tabletalprazolam oral- 1 mg tabletalprazolam oral- 2 mg tabletalprazolam oral- 1 mg tabletalprazolam oral- 2 mg tabletalprazolam oral- 1 mg tabletalprazolam oral- 0.5 mg tabletalprazolam oral- 0.5 mg tabletalprazolam oral- 1 mg tabletalprazolam oral- 2 mg tabletalprazolam oral- 2 mg tabletalprazolam oral- 2 mg tabletalprazolam oral- 0.25 mg tabletalprazolam oral- 1 mg tabletalprazolam oral- 0.5 mg tabletalprazolam oral- 2 mg tabletalprazolam oral- 1 mg tabletalprazolam oral- 0.25 mg tabletalprazolam oral- 1 mg tabletalprazolam oral- 0.5 mg tabletalprazolam oral- 2 mg tabletalprazolam oral- 0.25 mg tabletalprazolam oral- 0.5 mg tabletalprazolam oral- 0.5 mg tabletalprazolam oral- 3 mg tabletalprazolam oral- 2 mg tabletalprazolam oral- 0.5 mg tabletalprazolam oral- 1 mg tabletalprazolam oral- 0.25 mg tabletalprazolam oral- 1 mg tabletalprazolam oral- 1 mg tabletalprazolam oral- 2 mg tabletalprazolam oral- 3 mg tabletalprazolam oral- 1 mg tabletXanax XR oral- 3 mg tabletXanax XR oral- 2 mg tabletXanax XR oral- 1 mg tabletXanax XR oral- 0.5 mg tabletCopyright © 2010 First DataBank, Inc.Print Patient Educationalprazolam oral ALPRAZOLAM EXTENDED-RELEASE - ORAL (al-PRA-zoe-lam) COMMON BRAND NAME(S): Xanax XR WARNING: Alprazolam has a risk for abuse and addiction, which can lead to overdose and death. Taking this medication with alcohol or other drugs that can cause drowsiness or breathing problems (especially opioid medications such as codeine, hydrocodone) may cause very serious side effects, including death. To lower your risk, your doctor should have you take the smallest dose of alprazolam that works, and take it for the shortest possible time. Be sure you know how to take alprazolam and what other drugs you should avoid taking with it. See also Drug Interactions section. Get medical help right away if