Butalbital

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.

SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

The CNS effects of butalbital may be enhanced by monoamine oxidase (MAO) inhibitors.

A 44-year-old woman was admitted to the psychiatric unit for exacerbation of her depressive disorder. Blood concentrations of her antidepressant, imipramine, were within normal range and consistent with past concentrations. Her medical history was significant for a chronic headache disorder for which she was given a prescription containing butalbital on admission. The patient's depressive disorder was quickly controlled but relapsed 2 weeks later. Concentrations of imipramine showed a decrease of approximately 50%. Imipramine is metabolized in the liver by the cytochrome P-450 (CYP 1A2) system, and barbiturates are known inducers of this enzyme subset.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 26(SRC), determined from a structure estimation method(2), indicates that butalbital is expected to have very high mobility in soil(SRC). Volatilization of butalbital from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 6.3X10-13 atm-cu m/mole(SRC), using a fragment constant estimation method(3)). Butalbital is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.6X10-10 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). Biodegradation data in soil were not available(SRC, 2011).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 26(SRC), determined from a structure estimation method(2), indicates that butalbital is not 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 6.3X10-13 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(6), an estimated BCF of 8(SRC), from an estimated log Kow of 1.87(7) and a regression-derived equation(8), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2011).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), butalbital, which has an estimated vapor pressure of 1.5X10-10 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase butalbital may be removed from the air by wet or dry deposition(SRC). Butalbital contains chromophores that absorb at wavelengths >290 nm(4), and therefore may be susceptible to direct photolysis by sunlight(SRC).

Butalbital was detected in three wastewater treatment plant effluents associated with facilities involved in the manufacture of pharmaceuticals in New York; 35-38 samples were collected from each plant between 2004 and 2009. The maximum concentrations of butalbital were 0.9 (78% detection); 50 ug/L (97% detection) and 30 ug/L (100% detection) in the three New York samples, respectively; the latter receives 20% of its discharge from a pharmaceutical formulation facility. It was detected in 83% of samples (maximum concentration = 0.08 ug/L) from twenty-three plants across the US that were analyzed once between 2004 and 2009 as part of a National Survey; more than half of these plants receive hospital discharge. Detection limit = 0.011 ug/L. These findings suggest that current manufacturing practices at pharmaceutical formulation facilities can result in pharmaceuticals concentrations from 10 to 1000 times higher than those typically found in wastewater treatment plant effluents(1).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of butalbital can be estimated to be 26(SRC). According to a classification scheme(2), this estimated Koc value suggests that butalbital is expected to have very high mobility in soil.

/SIGNS AND SYMPTOMS/ Barbiturates may be habit-forming: Tolerance, psychological dependence, and physical dependence may occur especially following prolonged use of high doses of barbiturates. The average daily dose for the barbiturate addict is usually about 1500 mg. As tolerance to barbiturates develops, the amount needed to maintain the same level of intoxication increases; tolerance to a fatal dosage, however, does not increase more than two-fold. As this occurs, the margin between an intoxication dosage and fatal dosage becomes smaller. The lethal dose of a barbiturate is far less if alcohol is also ingested. Major withdrawal symptoms (convulsions and delirium) may occur within 16 hours and last up to 5 days after abrupt cessation of these drugs. Intensity of withdrawal symptoms gradually declines over a period of approximately 15 days. Treatment of barbiturate dependence consists of cautious and gradual withdrawal of the drug. Barbiturate-dependent patients can be withdrawn by using a number of different withdrawal regimens. One method involves initiating treatment at the patient's regular dosage level and gradually decreasing the daily dosage as tolerated by the patient.

/SIGNS AND SYMPTOMS/ Toxicity from barbiturate poisoning include drowsiness, confusion, and coma; respiratory depression; hypotension; and hypovolemic shock.

/CASE REPORTS/ ... The case of a 54-year-old woman who developed a barbiturate abstinence syndrome when she suspended self-administration of a drug containing butalbital /is reported/. The patient had been using barbiturates, 900 mg/day, for 2+ years for persistent headache. She was admitted to the hospital because of seizures, hallucinations and delirium not controlled by benzodiazepine and phenothiazine administration. Her symptoms resolved after parenteral phenobarbital administration.

/CASE REPORTS/ The patient was a 37-year-old woman with a history of depression and migraine headaches but not drug abuse. She developed a florid withdrawal delirium following the discontinuation of a drug she purchased online. The medication, which contained butalbital, was self-administered in escalating doses for the treatment of chronic headaches. Daily doses of up to 750 mg to 1000 mg were reported. The patient was admitted to the hospital for the treatment of unexplained seizures that were followed by several days of an intense withdrawal syndrome. Little improvement was noted after the administration of benzodiazepines and phenothiazine. After parenteral phenobarbital administration, her symptoms resolved. The withdrawal state from barbiturates is similar to that from ethanol. Tolerance can develop with prolonged abuse, leading to escalating drug doses to achieve the desired effect.

For more Human Toxicity Excerpts (Complete) data for Butalbital (6 total), please visit the HSDB record page.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

Butalbital

DILI Negative

Oral

DOI:10.1016/j.drudis.2019.09.022

An estimated BCF of 8 was calculated in fish for butalbital(SRC), using an estimated log Kow of 1.87(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Henry's Law constant for butalbital is estimated as 6.3X10-13 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that butalbital is expected to be essentially nonvolatile from water and moist soil surfaces(2). Butalbital is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.6X10-10 mm Hg(SRC), determined from a fragment constant method(3).

Butalbital is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Butalbital contains chromophores that absorb at wavelengths >290 nm(1), and therefore may be susceptible to direct photolysis by sunlight(SRC).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 284 workers (144 of these were female) were potentially exposed to butalbital in the US(1). Occupational exposure to butalbital may occur through inhalation and dermal contact with this compound at workplaces where butalbital is produced or used. Limited monitoring data indicate that the general population may be exposed to butalbital via ingestion of contaminated drinking water. Exposure to butalbital among the general population may be limited to those administered the analgesic drugs containing this compound(SRC).

Butalbital's production and use as a component in some analgesics may result in its release to the environment through various waste streams. If released to air,an estimated vapor pressure of 2.6X10-10 mm Hg at 25 °C indicates butalbital will exist solely in the particulate phase in the atmosphere. Particulate-phase butalbital will be removed from the atmosphere by wet or dry deposition. Butalbital does contains chromophores that absorb at wavelengths >290 nm, and therefore may be susceptible to direct photolysis by sunlight. If released to soil, butalbital is expected to have very high mobility based upon an estimated Koc of 26. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 6.3X10-13 atm-cu m/mole. Boidegradation data were not available. If released into water, butalbital is not expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's estimated Henry's Law constant. An estimated BCF of 8 suggests the potential for bioconcentration in aquatic organisms is low. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions. Occupational exposure to butalbital may occur through inhalation and dermal contact with this compound at workplaces where butalbital is produced or used. Limited monitoring data indicate that the general population may be exposed to butalbital via ingestion of contaminated drinking water. Exposure to butalbital among the general population may be limited to those administered the analgesic drugs containing this compound. (SRC)

The compounds, mixtures, or preparations that contain a nonnarcotic controlled substance listed in part 1308.12(e) or in part1308.13(b) or (c) or in part 1308.14 or in part 1308.15 listed in the Table of Exempted Prescription Products have been exempted by the Administrator from the application of sections 302 through 305, 307 through 309, and 1002 through 1004 of the Act (21 U.S.C. 822-825, 827-829, and 952-954) and parts 1301.13, 1301.22, and parts 1301.71 through 1301.76 of this chapter for administrative purposes only. An exception to the above is that those products containing butalbital shall not be exempt from the requirement of 21 U.S.C. 952-954 concerning importation, exportation, transshipment and in-transit shipment of controlled substances. Any deviation from the quantitative composition of any of the listed drugs shall require a petition of exemption in order for the product to be exempted. A listing of the Exempted Prescription Products may be obtained by submitting a written request to the Drug and Chemical Evaluation Section, Drug Enforcement Administration.

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

MEDICATION

Use (kg) in USA (2002): 13500