Alprazolam

Q: Is Alprazolam available over the counter?

Alprazolam is a prescription medication. You will need a valid prescription from a licensed healthcare provider.

Prescription

الأسماء التجارية: Alprazolam

الشكل الصيدلاني

Tablet

طريق الإعطاء

ORAL

الشركة المصنِّعة

NuCare Pharmaceuticals,Inc.

About This Medication

11 DESCRIPTION Alprazolam tablets, USP contain alprazolam which is a triazolo analog of the 1,4 benzodiazepine class of central nervous system-active compounds. The chemical name of alprazolam is 8-Chloro-1-methyl-6-phenyl-4H-s-triazolo [4,3-α] [1,4] benzodiazepine. The structural formula is: Alprazolam USP is a white to off-white, crystalline powder, which is soluble in methanol or ethanol but which has no appreciable solubility in water at physiological pH. Each alprazolam tablet USP, for oral administration, contains 0.25 mg, 0.5 mg, 1 mg, or 2 mg of alprazolam USP. Inactive ingredients: colloidal silicon dioxide, corn starch, docusate sodium 85% with sodium benzoate 15%, lactose monohydrate, magnesium stearate, and microcrystalline cellulose. In addition, the 0.5 mg tablet contains FD&C Yellow # 6 aluminum lake and the 1 mg tablet contains FD&C Blue No. 2 lake. Chemical Structure

المواد الفعالة

المادة الفعالة	التركيز
Alprazolam	-

المؤشرات العلاجية والاستخدام

1 INDICATIONS AND USAGE Alprazolam tablets are indicated for the: acute treatment of generalized anxiety disorder (GAD) in adults. treatment of panic disorder (PD), with or without agoraphobia in adults. Alprazolam is a benzodiazepine indicated for the: Acute treatment of generalized anxiety disorder in adults. ( 1 ) Treatment of panic disorder with or without agoraphobia in adults. ( 1 )

آلية العمل

12.1 Mechanism of Action Alprazolam is a 1,4 benzodiazepine. Alprazolam exerts its effect for the acute treatment of generalized anxiety disorder and panic disorder through binding to the benzodiazepine site of gamma-aminobutyric acid-A (GABA A ) receptors in the brain and enhances GABA-mediated synaptic inhibition.

الجرعة وطريقة الإعطاء

2 DOSAGE AND ADMINISTRATION Generalized Anxiety Disorder : ( 2.1 ) Recommended starting oral dosage is 0.25 mg to 0.5 mg three times daily. Dosage may be increased, at intervals of every 3 to 4 days, to a maximum recommended daily dose of 4 mg, given in divided doses. Use the lowest possible effective dose and frequently assess the need for continued treatment. Panic Disorder : Recommended starting oral dosage is 0.5 mg three times daily. The dosage may be increased at intervals of every 3 to 4 days in increments of no more than 1 mg per day. ( 2.2 ) When tapering, decrease dosage by no more than 0.5 mg every 3 days. Some patients may require an even slower dosage reduction. ( 2.3 , 5.2 ) See the Full Prescribing Information for the recommended dosage in geriatric patients, patients with hepatic impairment, and with use with ritonavir. ( 2.4 , 2.5 , 2.6 ) 2.1 Dosage in Generalized Anxiety Disorder The recommended starting oral dosage of alprazolam tablets for the acute treatment of patients with GAD is 0.25 mg to 0.5 mg administered three times daily. Depending upon the response, the dosage may be adjusted at intervals of every 3 to 4 days. The maximum recommended dosage is 4 mg daily (in divided doses). Use the lowest possible effective dose and frequently assess the need for continued treatment [see Warnings and Precautions (5.2) ] . 2.2 Dosage in Panic Disorder The recommended starting oral dosage of alprazolam tablets for the treatment of PD is 0.5 mg three times daily. Depending on the response, the dosage may be increased at intervals of every 3 to 4 days in increments of no more than 1 mg per day. Controlled trials of alprazolam tablets in the treatment of panic disorder included dosages in the range of 1 mg to 10 mg daily. The mean dosage was approximately 5 mg to 6 mg daily. Occasional patients required as much as 10 mg per day. For patients receiving doses greater than 4 mg per day, periodic reassessment and consideration of dosage reduction is advised. In a controlled postmarketing dose-response study, patients treated with doses of alprazolam tablets greater than 4 mg per day for 3 months were able to taper to 50% of their total maintenance dose without apparent loss of clinical benefit. The necessary duration of treatment for PD in patients responding to alprazolam tablets are unknown. After a period of extended freedom from panic attacks, a carefully supervised tapered discontinuation may be attempted, but there is evidence that this may often be difficult to accomplish without recurrence of symptoms and/or the manifestation of withdrawal phenomena [see Dosage and Administration (2.3) ]. 2.3 Discontinuation or Dosage Reduction of Alprazolam Tablets To reduce the risk of withdrawal reactions, use a gradual taper to discontinue alprazolam tablets or reduce the dosage. If a patient develops withdrawal reactions, consider pausing the taper or increasing the dosage to the previous tapered dosage level. Subsequently decrease the dosage more slowly [see Warnings and Precautions (5.3) , Drug Abuse and Dependence (9.3) ]. Reduced the dosage by no more than 0.5 mg every 3 days. Some patients may benefit from an even more gradual discontinuation. Some patients may prove resistant to all discontinuation regimens. In a controlled postmarketing discontinuation study of panic disorder patients which compared the recommended taper schedule with a slower taper schedule, no difference was observed between the groups in the proportion of patients who tapered to zero dose; however, the slower schedule was associated with a reduction in symptoms associated with a withdrawal syndrome. 2.4 Dosage Recommendations in Geriatric Patients In geriatric patients, the recommended starting oral dosage of alprazolam tablets is 0.25 mg, given 2 or 3 times daily. This may be gradually increased if needed and tolerated. Geriatric patients may be especially sensitive to the effects of benzodiazepines. If adverse reactions occur at the recommended starting dosage, the dosage may be reduced [see Use in Specific Populations (8.5) , Clinical Pharmacology (12.3) ] . 2.5 Dosage Recommendations in Patients with Hepatic Impairment In patients with hepatic impairment, the recommended starting oral dosage of alprazolam tablets is 0.25 mg, given 2 or 3 times daily. This may be gradually increased if needed and tolerated. If adverse reactions occur at the recommended starting dose, the dosage may be reduced [see Use in Specific Populations (8.6) , Clinical Pharmacology (12.3) ] . 2.6 Dosage Modifications for Drug Interactions Alprazolam tablets should be reduced to half of the recommended dosage when a patient is started on ritonavir and alprazolam tablets together, or when ritonavir administered to a patient treated with alprazolam tablets. Increase the alprazolam tablets dosage to the target dose after 10 to 14 days of dosing ritonavir and alprazolam tablets together. It is not necessary to reduce alprazolam tablets dose in patients who have been taking ritonavir for more than 10 to 14 days. Alprazolam tablets are contraindicated with concomitant use of all strong CYP3A inhibitors, except ritonavir [see Contraindications (4) , Warnings and Precautions (5.5) ] .

Side Effects Overview

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Risks from Concomitant Use with Opioids [see Warnings and Precautions (5.1) ] Abuse, Misuse, and Addiction [see Warnings and Precautions (5.2) ] Dependence and Withdrawal Reactions [see Warnings and Precautions (5.3) ] Effects on Driving and Operating Machinery [see Warnings and Precautions (5.4) ] Patients with Depression [see Warnings and Precautions (5.6) ] Neonatal Sedation and Withdrawal Syndrome [see Warnings and Precautions (5.8) ] Risks in Patients with Impaired Respiratory Function [see Warnings and Precautions (5.9) ] The most common adverse reactions reported in clinical trials for generalized anxiety disorder and panic disorder (incidence > 5% and at least twice that of placebo) include: impaired coordination, hypotension, dysarthria, and increased libido. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data in the two tables below are estimates of adverse reaction incidence among adult patients who participated in: 4-week placebo-controlled clinical studies with alprazolam dosages up to 4 mg per day for the acute treatment of generalized anxiety disorder (Table 1) Short-term (up to 10 weeks) placebo-controlled clinical studies with alprazolam dosages up to 10 mg per day for panic disorder, with or without agoraphobia (Table 2). Table 1: Adverse Reactions Occurring in ≥1% in Alprazolam-treated Patients and Greater than Placebo-treated Patients in Placebo-Controlled Trials for Generalized Anxiety Alprazolam n=565 Placebo n=505 Nervous system disorders Drowsiness Light-headedness Dizziness Akathisia Gastrointestinal disorders Dry mouth Increased salivation 41% 21% 2% 2% 15% 4% 22% 19% 1% 1% 13% 2% Cardiovascular disorders Hypotension Skin and subcutaneous tissue disorders Dermatitis/allergy 5% 4% 2% 3% In addition to the adverse reactions (i.e., greater than 1%) enumerated in the table above for patients with generalized anxiety disorder, the following adverse reactions have been reported in association with the use of benzodiazepines: dystonia, irritability, concentration difficulties, anorexia, transient amnesia or memory impairment, loss of coordination, fatigue, seizures, sedation, slurred speech, jaundice, musculoskeletal weakness, pruritus, diplopia, dysarthria, changes in libido, menstrual irregularities, incontinence and urinary retention. Table 2: Adverse Reactions Occuring in ≥1% in Alprazolam-treated Patients and Greater than Placebo-treated Patients in Placebo-Controlled Trials (Up to 10 Weeks) for Panic Disorder Alprazolam n=1388 Placebo n=1231 Drowsiness Fatique and Tiredness Impaired Coordination Irritability Memory Impairment Cognitive Disorder Decreased Libido Dysartharia Confusional state Increased libido Change in libido (not specified) Disinhibition Talkativeness Derealization 77% 49% 40% 33% 33% 29% 14% 23% 10% 8% 7% 3% 2% 2% 43% 42% 18% 30% 22% 21% 8% 6% 8% 4% 6% 2% 1% 1% Gastrointestinal disorders Constipation Increased salivation 26% 6% 15% 4% Skin and subcutaneous tissue disorders Rash 11% 8% Other Increased appetite Decreased appetite Weight gain Weight loss Micturition difficulties Menstrual disorders Sexual dysfunction Incontinence 33% 28% 27% 23% 12% 11% 7% 2% 23% 24% 18% 17% 9% 9% 4% 1% In addition to the reactions (i.e., greater than 1%) enumerated in the table above for patients with panic disorder, the following adverse reactions have been reported in association with the use of alprazolam: seizures, hallucinations, depersonalization, taste alterations, diplopia, elevated bilirubin, elevated hepatic enzymes, and jaundice. Adverse Reactions Reported as Reasons for Discontinuation in Treatment of Panic Disorder in Placebo-Controlled Trials In a larger database comprised of both controlled and uncontrolled studies in which 641 patients received alprazolam, discontinuation-emergent symptoms which occurred at a rate of over 5% in patients treated with alprazolam and at a greater rate than the placebo-treated group are shown in Table 3. Table 3: Discontinuation-Emergent Symptom Incidence Reported in ≥5% of Alprazolam-treated Patients and > Placebo-treated Patients n=number of patients. Alprazolam-treated Patients n=641 Nervous system disorders Insomnia Light-headedness Abnormal involuntary movement Headache Muscular twitching Impaired coordination Muscle tone disorders Weakness 29.5% 19.3% 17.3% 17.0% 6.9% 6.6% 5.9% 5.8% Psychiatric disorders Anxiety Fatigue and Tiredness Irritability Cognitive disorder Memory impairment Depression Confusional state 19.2% 18.4% 10.5% 10.3% 5.5% 5.1% 5.0% Gastrointestinal disorders Nausea/Vomiting Diarrhea Decreased salivation 16.5% 13.6% 10.6% Metabolism and nutrition disorders Weight loss Decreased appetite 13.3% 12.8% Dermatological disorders Sweating 14.4% Cardiovascular disorders Tachycardia 12.2% Special Senses Blurred vision 10.0% There have also been reports of withdrawal seizures upon rapid decrease or abrupt discontinuation of alprazolam [see Warning and Precautions (5.2) and Drug Abuse and Dependence (9.3) ]. Paradoxical reactions such as stimulation, increased muscle spasticity, sleep disturbances, hallucinations, and other adverse behavioral effects such as agitation, rage, irritability, and aggressive or hostile behavior have been reported rarely. In many of the spontaneous case reports of adverse behavioral effects, patients were receiving other CNS drugs concomitantly and/or were described as having underlying psychiatric conditions. Should any of the above events occur, alprazolam should be discontinued. Isolated published reports involving small numbers of patients have suggested that patients who have borderline personality disorder, a prior history of violent or aggressive behavior, or alcohol or substance abuse may be at risk for such events. Instances of irritability, hostility, and intrusive thoughts have been reported during discontinuation of alprazolam in patients with posttraumatic stress disorder. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of alprazolam. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Endocrine disorders: Hyperprolactinemia General disorders and administration site conditions: Edema peripheral Hepatobiliary disorders: Hepatitis, hepatic failure Investigations: Liver enzyme elevations Psychiatric disorders: Hypomania, mania Reproductive system and breast disorders: Gynecomastia, galactorrhea Skin and subcutaneous tissue disorders: Photosensitivity reaction, angioedema, Stevens-Johnson syndrome

التحذيرات والاحتياطات

5 WARNINGS AND PRECAUTIONS Effects on Driving and Operating Machinery: Patients receiving alprazolam should be cautioned against operating machinery or driving a motor vehicle, as well as avoiding concomitant use of alcohol and other central nervous system (CNS) depressant drugs. ( 5.4 ) Patients with Depression: Exercise caution in patients with signs or symptoms of depression. Prescribe the least number of tablets feasible to avoid intentional overdosage. ( 5.6 ) Neonatal Sedation and Withdrawal Syndrome: Alprazolam use during pregnancy can result in neonatal sedation and/or neonatal withdrawal. ( 5.8 , 8.1 ) 5.1 Risks from Concomitant Use with Opioids Concomitant use of benzodiazepines, including alprazolam, and opioids may result in profound sedation, respiratory depression, coma, and death. Because of these risks, reserve concomitant prescribing of these drugs in patients for whom alternative treatment options are inadequate. Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. If a decision is made to prescribe alprazolam concomitantly with opioids, prescribe the lowest effective dosages and minimum durations of concomitant use, and follow patients closely for signs and symptoms of respiratory depression and sedation. In patients already receiving an opioid analgesic, prescribe a lower initial dose of alprazolam than indicated in the absence of an opioid and titrate based on clinical response. If an opioid is initiated in a patient already taking alprazolam, prescribe a lower initial dose of the opioid and titrate based upon clinical response. Advise both patients and caregivers about the risks of respiratory depression and sedation when alprazolam is used with opioids. Advise patients not to drive or operate heavy machinery until the effects of concomitant use with the opioid have been determined [see Drug Interactions (7.1) ] . 5.2 Abuse, Misuse, and Addiction The use of benzodiazepines, including alprazolam, exposes users to the risks of abuse, misuse, and addiction, which can lead to overdose or death. Abuse and misuse of benzodiazepines often (but not always) involve the 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 [see Drug Abuse and Dependence (9.2) ] . Before prescribing alprazolam and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction (e.g., using a standardized screening tool). Use of alprazolam, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of alprazolam along with monitoring for signs and symptoms of abuse, misuse, and addiction. Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. If a substance use disorder is suspected, evaluate the patient and institute (or refer them for) early treatment, as appropriate. 5.3 Dependence and Withdrawal Reactions To reduce the risk of withdrawal reactions, use a gradual taper to discontinue alprazolam or reduce the dosage (a patient-specific plan should be used to taper the dose) [see Dosage and Administration (2.3) ] . 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. Acute Withdrawal Reactions The continued use of benzodiazepines, including alprazolam, may lead to clinically significant physical dependence. Abrupt discontinuation or rapid dosage reduction of alprazolam after continued use, or administration of flumazenil (a benzodiazepine antagonist) may precipitate acute withdrawal reactions, which can be life-threatening (e.g., seizures) [see Drug Abuse and Dependence (9.3) ] . Protracted Withdrawal Syndrome In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months [see Drug Abuse and Dependence (9.3) ] . Certain adverse clinical events, some life-threatening, are a direct consequence of physical dependence to alprazolam. These include a spectrum of withdrawal symptoms; the most important is seizure [see Drug Abuse and Dependence (9.3) ] . Even after relatively short-term use at doses of < 4 mg/day, there is some risk of dependence. Spontaneous reporting system data suggest that the risk of dependence and its severity appear to be greater in patients treated with doses greater than 4 mg/day and for long periods (more than 12 weeks). However, in a controlled postmarketing discontinuation study of panic disorder patients who received alprazolam, the duration of treatment (3 months compared to 6 months) had no effect on the ability of patients to taper to zero dose. In contrast, patients treated with doses of alprazolam greater than 4 mg/day had more difficulty tapering to zero dose than those treated with less than 4 mg/day. In a controlled clinical trial in which 63 patients were randomized to alprazolam and where withdrawal symptoms were specifically sought, the following were identified as symptoms of withdrawal: heightened sensory perception, impaired concentration, dysosmia, clouded sensorium, paresthesias, muscle cramps, muscle twitch, diarrhea, blurred vision, appetite decrease, and weight loss. Other symptoms, such as anxiety and insomnia, were frequently seen during discontinuation, but it could not be determined if they were due to return of illness, rebound, or withdrawal. Interdose Symptoms Early morning anxiety and emergence of anxiety symptoms between doses of alprazolam have been reported in patients with panic disorder taking prescribed maintenance doses. These symptoms may reflect the development of tolerance or a time interval between doses which is longer than the duration of clinical action of the administered dose. In either case, it is presumed that the prescribed dose is not sufficient to maintain plasma levels above those needed to prevent relapse, rebound, or withdrawal symptoms over the entire course of the interdosing interval. 5.4 Effects on Driving and Operating Machinery Because of its CNS depressant effects, patients receiving alprazolam should be cautioned against engaging in hazardous occupations or activities requiring complete mental alertness such as operating machinery or driving a motor vehicle. For the same reason, patients should be cautioned about the concomitant use of alcohol and other CNS depressant drugs during treatment with alprazolam [see Drug Interactions (7.1) ] . 5.5 Interaction with Drugs that Inhibit Metabolism via Cytochrome P450 3A The initial step in alprazolam metabolism is hydroxylation catalyzed by cytochrome P450 3A (CYP3A). Drugs that inhibit this metabolic pathway may have a profound effect on the clearance of alprazolam. Strong CYP3A Inhibitors Alprazolam is contraindicated in patients receiving strong inhibitors of CYP3A (such as azole antifungal agents), except ritonavir [see Contraindications (4) ]. Ketoconazole and itraconazole have been shown in vivo to increase plasma alprazolam concentrations 3.98 fold and 2.70 fold, respectively. Dosage adjustment is necessary when alprazolam and ritonavir are initiated concomitantly or when ritonavir is added to a stable dosage of alprazolam [see Dosage and Administration (2.6) , Drug Interactions (7.1) ]. Drugs demonstrated to be CYP3A inhibitors on the basis of clinical studies involving alprazolam: nefazodone, fluvoxamine, and cimetidine [see Drug Interaction (7.1), Clinical Pharmacology (12.3)]. Use caution and consider dose reduction of alprazolam, as appropriate, during co-administration with these drugs. 5.6 Patients with Depression Benzodiazepines may worsen depression. Panic disorder has been associated with primary and secondary major depressive disorders and increased reports of suicide among untreated patients. Consequently, appropriate precautions (e.g., limiting the total prescription size and increased monitoring for suicidal ideation) should be considered in patients with depression. 5.7 Mania Episodes of hypomania and mania have been reported in association with the use of alprazolam in patients with depression [see Adverse Reactions (6.2) ] . 5.8 Neonatal Sedation and Withdrawal Syndrome Use of alprazolam late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in the neonate [see Use in Specific Populations (8.1) ] . Monitor neonates exposedtoalprazolam during pregnancy or labor for signs of sedation and monitor neonates exposed to alprazolam during pregnancy for signs of withdrawal; manage these neonates accordingly. 5.9 Risk in Patients with Impaired Respiratory Function There have been reports of death in patients with severe pulmonary disease shortly after the initiation of treatment with alprazolam. Closely monitor patients with impaired respiratory function. If signs and symptoms of respiratory depression, hypoventilation, or apnea occur, discontinue alprazolam.

موانع الاستعمال

4 CONTRAINDICATIONS Alprazolam tablets are contraindicated in patients: with known hypersensitivity to alprazolam or other benzodiazepines. Angioedema has been reported [see Adverse Reactions (6.2) ] . taking strong cytochrome P450 3A (CYP3A) inhibitors (e.g., ketoconazole, itraconazole), except ritonavir [see Dosage and Administration (2.6) , Warnings and Precautions (5.5) , Drug Interactions (7.1) ] Known hypersensitivity to alprazolam or other benzodiazepines. ( 4 ) Concomitant use with strong cytochrome P450 3A (CYP3A) inhibitors, except ritonavir. ( 4 , 5.5 , 7.1 )

الحرائك الدوائية

12.3 Pharmacokinetics Plasma levels of alprazolam increase proportionally to the dose over the range of 0.5 to 3 mg. Absorption Following oral administration, peak plasma concentration of alprazolam (C max ) occurs in 1 to 2 hours post dose. Distribution Alprazolam is 80% bound to human serum protein, and albumin accounts for the majority of the binding. Elimination The mean plasma elimination half-life (T 1/2 ) of alprazolam is approximately 11.2 hours (range: 6.3 to 26.9 hours) in healthy adults. Metabolism Alprazolam is extensively metabolized in humans, primarily by cytochrome P450 3A4 (CYP3A4), to 2 major active metabolites in the plasma: 4-hydroxyalprazolam and α-hydroxyalprazolam. The plasma circulation levels of the two active metabolites are less than 4% of the parent. The reported relative potencies in benzodiazepine receptor binding experiments and in animal models of induced seizure inhibition are 0.20 and 0.66, respectively, for 4-hydroxyalprazolam and α-hydroxyalprazolam. The low concentrations and low potencies of 4-hydroxyalprazolam and α-hydroxyalprazolam indicate that they unlikely contribute much to the effects of alprazolam. A benzophenone derived from alprazolam is also found in humans. Their half-lives appear to be similar to that of alprazolam. Excretion Alprazolam and its metabolites are excreted primarily in the urine. Specific Populations Geriatric Patients The mean T 1/2 of alprazolam was 16.3 hours (range: 9.0 to 26.9 hours) in healthy elderly subjects compared to 11.0 hours (range: 6.3 to 15.8 hours, n=16) in healthy younger adult subjects. Obese Patients The mean T 1/2 of alprazolam was 21.8 hours (range: 9.9 to 40.4 hours) in a group of obese subjects. Patients with Hepatic Impairment The mean T 1/2 of alprazolam was 19.7 hours (range: 5.8 to 65.3 hours) in patients with alcoholic liver disease. Racial or Ethnic Groups Maximal concentrations and T 1/2 of alprazolam are approximately 15% and 25% higher in Asians compared to Caucasians. Smoking Alprazolam concentrations may be reduced by up to 50% in smokers compared to non-smokers. Drug Interaction Studies In Vivo Studies Most of the interactions that have been documented with alprazolam are with drugs that modulate CYP3A4 activity. Compounds that are inhibitors or inducers of CYP3A would be expected to increase or decrease plasma alprazolam concentrations, respectively. Drug products that have been studied in vivo , along with their effect on increasing alprazolam AUC, are as follows: ketoconazole, 3.98 fold; itraconazole, 2.66 fold; nefazodone, 1.98 fold; fluvoxamine, 1.96 fold; and erythromycin, 1.61 fold [see Contraindications (4) , Warnings and Precautions (5.5) , Drug Interactions (7.2) ] . Other studied drugs include: Cimetidine : Coadministration of cimetidine increased the maximum plasma concentration of alprazolam by 82%, decreased clearance by 42%, and increased T 1/2 by 16%. Fluoxetine : Coadministration of fluoxetine with alprazolam increased the maximum plasma concentration of alprazolam by 46%, decreased clearance by 21%, increased T 1/2 by 17%, and decreased measured psychomotor performance. Oral Contraceptives : Coadministration of oral contraceptives increased the maximum plasma concentration of alprazolam by 18%, decreased clearance by 22%, and increased T 1/2 by 29%. Carbamazepine : The oral clearance of alprazolam (given in a 0.8 mg single dose) was increased from 0.90±0.21 mL/min/kg to 2.13±0.54 mL/min/kg and the elimination T 1/2 was shortened (from 17.1±4.9 to 7.7±1.7 hour) following administration of 300 mg per day carbamazepine for 10 days [see Drug Interactions (7.2) ] . However, the carbamazepine dose used in this study was fairly low compared to the recommended doses (1000 to 1200 mg per day); the effect at usual carbamazepine doses is unknown. Ritonavir : Interactions involving HIV protease inhibitors (e.g., ritonavir) and alprazolam are complex and time dependent. Short-term low doses of ritonavir (4 doses of 200 mg) increased mean AUC of alprazolam by about 2.5-fold, and did not significantly affect C max of alprazolam. The elimination T 1/2 was prolonged (30 hours versus 13 hours). However, upon extended exposure to ritonavir (500 mg, twice daily for 10 days), CYP3A induction offset this inhibition. Alprazolam AUC and C max was reduced by 12% and 16%, respectively, in the presence of ritonavir. The elimination T 1/2 of alprazolam was not significantly changed [see Warnings and Precautions (5.5) ] . Sertraline : A single dose of alprazolam 1 mg and steady state dose of sertraline (50 mg to 150 mg per day) did not reveal any clinically significant changes in the pharmacokinetics of alprazolam. Imipramine and Desipramine : The steady state plasma concentrations of imipramine and desipramine have been reported to be increased an average of 31% and 20%, respectively, by the concomitant administration of alprazolam in doses up to 4 mg per day. Warfarin : Alprazolam did not affect the prothrombin or plasma warfarin levels in male volunteers administered sodium warfarin orally. In Vitro Studies Data from in vitro studies of alprazolam suggest a possible drug interaction of alprazolam with paroxetine. The ability of alprazolam to induce human hepatic enzyme systems has not yet been determined.

Frequently Asked Questions

1 INDICATIONS AND USAGE Alprazolam tablets are indicated for the: acute treatment of generalized anxiety disorder (GAD) in adults. treatment of panic disorder (PD), with or without agoraphobia in adults. Alprazolam is a benzodiazepine indicated for the: Acute treatment of generalized anxiety disorder in adults. ( 1 ) Treatment of panic disorder with or without agoraphobia in adults. ( 1 )

2 DOSAGE AND ADMINISTRATION Generalized Anxiety Disorder : ( 2.1 ) Recommended starting oral dosage is 0.25 mg to 0.5 mg three times daily. Dosage may be increased, at intervals of every 3 to 4 days, to a maximum recommended daily dose of 4 mg, given in divided doses. Use the lowest possible effective dose and frequently assess the need for continued treatment. Panic Disorder : Recommended starting oral dosage is 0.5 mg three times daily. The dosage may be …

5 WARNINGS AND PRECAUTIONS Effects on Driving and Operating Machinery: Patients receiving alprazolam should be cautioned against operating machinery or driving a motor vehicle, as well as avoiding concomitant use of alcohol and other central nervous system (CNS) depressant drugs. ( 5.4 ) Patients with Depression: Exercise caution in patients with signs or symptoms of depression. Prescribe the least number of tablets feasible to avoid intentional overdosage. ( 5.6 ) Neonatal Sedation and Withdrawal Syndrome: Alprazolam use during pregnancy can …

4 CONTRAINDICATIONS Alprazolam tablets are contraindicated in patients: with known hypersensitivity to alprazolam or other benzodiazepines. Angioedema has been reported [see Adverse Reactions (6.2) ] . taking strong cytochrome P450 3A (CYP3A) inhibitors (e.g., ketoconazole, itraconazole), except ritonavir [see Dosage and Administration (2.6) , Warnings and Precautions (5.5) , Drug Interactions (7.1) ] Known hypersensitivity to alprazolam or other benzodiazepines. ( 4 ) Concomitant use with strong cytochrome P450 3A (CYP3A) inhibitors, except ritonavir. ( 4 , 5.5 , 7.1 …

Alprazolam is a prescription medication. You will need a valid prescription from a licensed healthcare provider.

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References & Data Sources

• DailyMed — Alprazolam drug label (National Library of Medicine)
• openFDA — Alprazolam label data (U.S. Food & Drug Administration)
• RxNorm — RXCUI 308047 (NLM Normalized Drug Names)
• NDC Directory — Alprazolam (FDA National Drug Code)

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