Alprazolam

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.

Keep container tightly closed in a dry and well-ventilated place.

Commercially available alprazolam tablets should be stored in tight, light-resistant containers at 15-30 °C.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Avoid breathing dust. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company; Contaminated packaging: Dispose of as unused product.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Avoid breathing dust. Environmental precautions: Do not let product enter drains.

Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection.

Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

Eye/face protection: Safety glasses with side-shields conforming to EN166. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Skin protection: Handle with gloves.

Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator. For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

As in all cases of drug overdosage, respiration, pulse rate, and blood pressure should be monitored. General supportive measures should be employed, along with immediate gastric lavage. Intravenous fluids should be administered and an adequate airway maintained. If hypotension occurs, it may be combated by the use of vasopressors. Dialysis is of limited value. Flumazenil, a specific benzodiazepine receptor antagonist, is indicated for the complete or partial reversal of the sedative effects of benzodiazepines and may be used in situations when an overdose with a benzodiazepine is known or suspected. (L1712)

Concomitant use of HIV protease inhibitors (e.g., amprenavir, fosamprenavir, ritonavir, saquinavir) with certain other benzodiazepines (e.g., alprazolam, clorazepate, diazepam, flurazepam) also may result in increased concentrations of the benzodiazepine. While the clinical importance of the interaction is unknown, a reduction in dosage of the benzodiazepine may be needed.

Although specific drug interaction studies are not available, concomitant use of amiodarone with some benzodiazepines (e.g., alprazolam, triazolam) may result in decreased metabolism of the benzodiazepine; caution is advised.

Although specific drug interaction studies are not available, clinically important decreases in the metabolism and clearance of some benzodiazepines (e.g., alprazolam, estazolam, triazolam) may occur when these benzodiazepines are used concomitantly with nicardipine or nifedipine.

An elderly woman developed a high serum digoxin concentration resulting in toxicity when alprazolam was added to her digoxin therapy. The reduced renal clearance of digoxin is postulated as the mechanism for this interaction.

For more Interactions (Complete) data for ALPRAZOLAM (16 total), please visit the HSDB record page.

Alprazolam, like other benzodiazepines, is rarely associated with serum ALT or alkaline phosphatase elevations, and clinically apparent liver injury from alprazolam is extremely rare, considering the frequency of its use. There have been a few case reports of acute liver injury from alprazolam, and recurrence on reexposure has been reported. In alprazolam-related cases of acute liver injury, the latency has been within a few weeks and the typical pattern of liver enzyme elevations has been cholestatic or mixed (Case 1). The injury was usually mild-to-moderate in severity and self-limited in course. Fever and rash have not been described nor has autoantibody formation. Similar rare cases of self-limited, mild-to-moderate, cholestatic liver injury have been reported with other benzodiazepines including chlordiazepoxide, clonazepam, diazepam, flurazepam, lorazepam, and triazolam.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 9.8X10+4(SRC), determined from a structure estimation method(2), indicates that alprazolam is expected to be immobile in soil(SRC). Volatilization of alprazolam from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 9.8X10-12 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Alprazolam is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.7X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2016).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 9.8X10+4(SRC), determined from a structure estimation method(2), indicates that alprazolam is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 9.8X10-12 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 12(SRC), from its log Kow of 2.12(6) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2016).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), alprazolam, which has an estimated vapor pressure of 1.7X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist solely in the particulate phase in the ambient atmosphere. Particulate-phase alprazolam may be removed from the air by wet and dry deposition(SRC). Alprazolam contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

IDENTIFICATION AND USE: Alprazolam forms white to off-white, solid crystals. Classification: Psycholeptics, anxiolytics, and benzodiazepine derivatives. HUMAN EXPOSURE AND TOXICITY: Alprazolam, a widely used drug, has widespread, nonspecific depressant effects on the central nervous system, similar to other benzodiazepines. Alprazolam is used as an anxiolytic drug for generalized anxiety disorder and it has been reported to produce sedation and anterograde amnesia. Manifestations of alprazolam overdosage include somnolence, confusion, impaired coordination, diminished reflexes and coma. Death has been reported in association with overdoses of alprazolam by itself, as it has with other benzodiazepines. In addition, fatalities have been reported in patients who have overdosed with a combination of a single benzodiazepine, including alprazolam, and alcohol; alcohol levels seen in some of these patients have been lower than those usually associated with alcohol-induced fatality. Benzodiazepines can potentially cause fetal harm when administered to pregnant women. The newborn of a mother reporting alprazolam use during pregnancy presented with respiratory distress and clinical features consistent with neonatal withdrawal syndrome or neonatal sepsis of vertical transmission. Following ingestion of 10 mg of alprazolam, a 34 year old patient exhibited dangerous aggressive behavior. Five months later he presented with evidence of major depression. ANIMAL STUDIES: A retrospective study was conducted of 415 alprazolam ingestions in dogs: 238 suspected alprazolam toxicoses in dogs were evaluated. Clinical signs were ataxia/disorientation, depression, hyperactivity, vomiting, weakness, tremors, vocalization, tachycardia, tachypnea, hypothermia, diarrhea, and increased salivation that developed within 10-30 min post-ingestion. Other experiments in animals have indicated cardiopulmonary collapse can occur following massive intravenous doses of alprazolam. No evidence of carcinogenic potential was observed during 2 year bioassay studies of alprazolam in rats at doses up to 30 mg/kg/day and in mice at dose up to 10 mg/kg/day. Alprazolam produced no impairment of fertility in rats at doses up to 5 mg/kg/day. Altered behaviors in several mouse strains after prenatal exposure to alprazolam suggests a vulnerability of GABA-benzodiazepine receptor formation in fetal brain development. Mice offspring that were exposed prenatally to alprazolam demonstrated more individual rather than group activities, avoidance of open areas, and aggression in males. Alprazolam was not mutagenic in the rat micronucleus test at doses up to 100 mg/kg. Alprazolam also was not mutagenic in vitro in the DNA Damage/Alkaline Elution Assay or the Ames Assay. Alprazolam was also studied using Allium cepa test, where it induced chromosomal and cytological aberrations, especially nuclear alterations.

The continued use of alprazolam, like all benzodiazepines, may lead to clinically significant physical dependence. The risks of withdrawal and dependence increase with chronic treatment using alprazolam for a longer duration and in high daily doses. After long-term treatment, rapid dosage reduction and abrupt discontinuation of alprazolam may precipitate acute withdrawal. Therefore, it is recommended to taper to discontinue alprazolam gradually To reduce the risk of alprazolam withdrawals and reactions, which can be fatal.

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of October 28, 2016: http://actor.epa.gov/dashboard/]

Alprazolam was detected at an average concentration of 1.3 ng/L (maximum 33.0 ng/L) in 8% of 90 European wastewater treatment plant effluents sampled in 2010(1). Based on an annual consumption of 385.81 kg/yr, the estimated alprazolam elimination from primary and secondary treatment processes was 0.56 and 2.37%, respectively, from wastewater facilities in Spain in 2009, giving a predicted environmental occurrence of 1.29 ng/L(2). The compound was detected not quantified in 38% of 42 wastewater treatment plant effluents in the Spanish Mediterranean area of Valencia; sampling conducted in June 2008 and January 2009. Monitoring conducted in April and October 2009 resulted in detection of 0.1 ug/L in all 14 effluents tested(3).

Schedule IV shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. ... Depressants: Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation which contains any quantity of the following substances, including its salts, isomers, and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation: Alprazolam (DEA Code Number: 2882) is included on this list.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including alprazolam, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Alprazolam (DEA Code Number: 2882) is a Schedule IV controlled substance.

Schedule IV Controlled Substance: (A) The drug or other substance has a low potential for abuse relative to the drugs or other substances in schedule III. (B) The drug or other substance has a currently accepted medical use in treatment in the United States. (C) Abuse of the drug or other substance may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in schedule III.

MEDICATION (VET)

MEDICATION

Anti-Anxiety Agents; GABA Modulators; Hypnotics and Sedatives

Use (kg; approx.) in Germany (2009): >10