Dextromethorphan

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

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

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

Lozenges: store between 15 and 30 degrees C in well closed containers. Syrup USP: Store between 15 and 30 degrees C in light, resistant container, protected from freezing.

Dextromethorphan preparations should be stored in tight containers, and solutions and liquid-filled capsules containing dextromethorphan should be stored in tight, light-resistant containers.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Avoid dust formation. Avoid breathing vapors, mist or gas. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Sweep up and shovel. Keep in suitable, closed containers for disposal. /Dextromethorphan hydrobromide/

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. /Dextromethorphan hydrobromide/

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Avoid dust formation. Avoid breathing vapors, mist or gas. Environmental precautions: Do not let product enter drains. /Dextromethorphan hydrobromide/

Precautions for safe handling: Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection. /Dextromethorphan hydrobromide/

Appropriate engineering controls: General industrial hygiene practice. /Dextromethorphan hydrobromide/

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. /Dextromethorphan hydrobromide/

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: Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU). /Dextromethorphan hydrobromide/

Skin protection: Handle with gloves. /Dextromethorphan hydrobromide/

Body Protection: Choose body protection in relation to its type, to the concentration and amount of dangerous substances, and to the specific work-place. /Dextromethorphan hydrobromide/

Respiratory protection: Respiratory protection is not required. Where protection from nuisance levels of dusts are desired, use type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). /Dextromethorphan hydrobromide/

Because cases of apparent serotonin syndrome, including 2 fatalities, have been reported in patients receiving dextromethorphan and monoamine oxidase (MAO) inhibitors concomitantly, dextromethorphan preparations should not be used in patients receiving these drugs or for 2 weeks after discontinuing them.

Alcohol and CNS depressants should be avoided with dextromethorphan.

Consistent with their antagonistic actions at N-methyl-D-aspartate type glutamate receptors, dextromethorphan and its metabolite, dextrorphan decrease the intensity of opioid withdrawal syndrome. Since quinidine affects CYP2D6-mediated metabolism and P-glycoprotein governed transport, we sought to determine whether co-treatment with quinidine would affect brain levels of dextromethorphan and dextrorphan as well as the effect of these compounds on opioid withdrawal syndrome in mice. /The investigators/ found that dextromethorphan dose dependently inhibited the intensity of opioid withdrawal syndrome and that there was a tendency for a further decrease when quinidine was co-administered with dextromethorphan. Administration of 30 mg/kg of dextromethorphan resulted in higher brain levels of dextromethorphan and dextrorphan than administration of 10 mg/kg of dextromethorphan, but much lower dextrorphan levels than that produced by 30 mg/kg of dextrorphan. Co-treatment with quinidine resulted in higher brain levels of dextromethorphan (but not dextrorphan) suggesting that quinidine produces an increase in the brain availability of dextromethorphan. In summary, brain levels of dextromethorphan were inversely correlated with the intensity of opioid withdrawal syndrome. Quinidine induced increased brain levels of dextromethorphan tend to attenuate the intensity of opioid withdrawal syndrome. /The investigators/ suggest that it is dextromethorphan, rather than dextrorphan, that is responsible for the attenuating effect on the intensity of opioid withdrawal syndrome, and that the beneficial action of quinidine on the effect of dextromethorphan should be more pronounced in humans.

The aim of this review was to describe a patient with serotonin toxicity after an overdose of dextromethorphan and chlorphenamine and to perform a systematic literature review exploring whether dextromethorphan and chlorphenamine may be equally contributory in the development of serotonin toxicity in overdose. A Medline literature review was undertaken to identify cases of serotonin toxicity due to dextromethorphan and/or chlorphenamine. Case reports were included if they included information on the ingested dose or plasma concentrations of dextromethorphan and/or chlorphenamine, information about co-ingestions and detailed clinical information to evaluate for serotonin toxicity. Cases were reviewed by two toxicologists and serotonin toxicity, defined by the Hunter criteria, was diagnosed when appropriate. The literature was then reviewed to evaluate whether chlorphenamine may be a serotonergic agent. One hundred and fifty-five articles of dextromethorphan or chlorphenamine poisoning were identified. There were 23 case reports of dextromethorphan, of which 18 were excluded for lack of serotonin toxicity. No cases were identified in which serotonin toxicity could be solely attributed to chlorphenamine. This left six cases of dextromethorphan and/or chlorphenamine overdose, including our own, in which serotonin toxicity could be diagnosed based on the presented clinical information. In three of the six eligible cases dextromethorphan and chlorphenamine were the only overdosed drugs. There is substantial evidence from the literature that chlorphenamine is a similarly potent serotonin re-uptake inhibitor when compared with dextrometorphan. Chlorphenamine is a serotonergic medication and combinations of chlorphenamine and dextromethorphan may be dangerous in overdose due to an increased risk of serotonin toxicity.

For more Interactions (Complete) data for Dextromethorphan (12 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 23,000(SRC), determined from a structure estimation method(2), indicates that dextromethorphan is expected to be immobile in soil(SRC). The estimated pKa of dextromethorphan is 9.8(3), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of the cation from moist soil is not expected because cations do not volatilize(SRC). Dextromethorphan is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.0X10-5 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2017).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 23,000(SRC), determined from a structure estimation method(2), indicates that dextromethorphan is expected to adsorb to suspended solids and sediment(SRC). An estimated pKa of 9.8(3) indicates dextromethorphan will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water surfaces and bioconcentration in aquatic organisms are not expected to be an important fate processes(SRC). Dextromethorphan is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(4). Biodegradation data in water were not available(SRC, 2017).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), dextromethorphan, which has an estimated vapor pressure of 1.0X10-5 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase dextromethorphan is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 3.3 hours(SRC), calculated from its rate constant of 1.2X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Particulate-phase dextromethorphan may be removed from the air by wet or dry deposition(SRC). Dextromethorphan contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, is expected to be susceptible to direct photolysis by sunlight(SRC).

IDENTIFICATION AND USE: Dextromethorphan is a white odorless solid crystal or powder. It is an opium alkaloid derivative, which is found in cough and cold preparations. HUMAN STUDIES: Dextromethorphan is a drug of abuse. The main risks associated with dextromethorphan are ataxia, central nervous system (CNS) stimulation, dizziness, lethargy and psychotic behavior. Less frequently with large doses seizures and respiratory depression can occur. Nausea, vomiting, constipation and tachycardia may also occur. CNS effects include ataxia, drowsiness, vertigo and rarely coma. CNS stimulation may be observed. Restlessness, increased muscle tone with body rigidity have been reported. With extremely large ingestions respiratory depression can occur. Gastrointestinal effects include nausea, vomiting, constipation and dry mouth. Urinary retention may be seen. Dextromethorphan abuse has been described and produces euphoria, CNS stimulation, visual and/or auditory hallucinations. Dextromethorphan hydrobromide is the drug form, thus the possibility of bromide poisoning should be considered in the long term abuser. Dextromethorphan enhances serotonin activity by inhibiting the reuptake of serotonin. Specific non-opioid dextromethorphan binding sites are present in the CNS which mediate the antitussive effects, separate from codeine and other opioids. Death has been reported after overdose in two cases but quantity was uncertain. In adults, it can cause intoxication with hyperexcitability, visual and/or auditory hallucinations. It has been reported that sniffing two to three times a day over 2 to 3 months produced euphoria and restlessness for up to 2 hours followed by dizziness, nausea, depression and fatigue. Toxicity may be variable in children. Some children have shown no symptoms while others have shown ataxia, stupor, transient fever, lethargy or nystagmus. Seizures have also been reported. Long-acting products may be more toxic in children, producing prolonged CNS depression. There was no association between dextromethorphan and malformations. Dextromethorphan is generally considered safe to use during pregnancy. Urticaria was reported in a child after acute overdose of a long-acting preparation. A cutaneous lesion consistent with a fixed-drug reaction was reported after ingestion over 2 to 3 weeks in therapeutic doses. ANIMAL STUDIES: Dextromethorphan is a weak noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. It is metabolized in vivo to dextrorphan, a more potent noncompetitive NMDA antagonist that is the dextrorotatory enantiomer of the opioid agonist levorphanol. Although in rats both dextromethorphan and dextrorphan increased plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone, the dextromethorphan-induced responses occurred more rapidly than the dextrorphan-induced responses. Three sets of zebrafish embryos/larvae were exposed to dextromethorphan at 24, 48 and 72 hr post fertilization (hpf), respectively, during the embryonic/larval development. Compared with the 48 and 72 hpf exposure sets, the embryos/larvae in the 24 hpf exposure set showed much higher mortality rates which increased in a dose-dependent manner. Bradycardia and reduced blood flow were observed for the embryos/larvae treated with increasing concentrations of dextromethorphan. Morphological effects of dextromethorphan exposure, including yolk sac and cardiac edema, craniofacial malformation, lordosis, non-inflated swim bladder and missing gill, were also more frequent and severe among zebrafish embryos/larvae exposed to dextromethorphan at 24 hpf. After treatment with a high-dose of dextromethorphan (40 mg/kg/day) for 2 weeks, rats showed increased depression-like behavior when compared to the control animals. Neurogenesis in the hippocampus was suppressed by dextromethorphan treatment, which was indicated by decreases in number of proliferative cells and immature neurons. Dextromethorphan was not genotoxic in mice.

Using a structure estimation method based on molecular connectivity indices(1), the Koc of dextromethorphan can be estimated to be 23,000(SRC). According to a classification scheme(2), this estimated Koc value suggests that dextromethorphan is expected to be immobile in soil. The estimated pKa of dextromethorphan is 9.8(3), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

/HUMAN EXPOSURE STUDIES/ Dextromethorphan (DXM) is abused most commonly among adolescents as a recreational drug to generate a dissociative experience. The objective of the study was to assess driving with and without DXM ingestion. The effects of one-time maximum daily doses of DXM 120 mg versus a guaifenesin 400 mg dose were compared among 40 healthy subjects using a crossover design. Subjects' ability to drive was assessed by their performance in a driving simulator (STISIM Drive driving simulator software) and by conducting a standardized field sobriety test (SFST) administered 1-hr postdrug administration. The one-time dose of DXM 120 mg did not demonstrate driving impairment on the STISIM Drive driving simulator or increase SFST failures compared to guaifenesin 400 mg. Doses greater than the currently recommended maximum daily dose of 120 mg are necessary to perturb driving behavior.

/HUMAN EXPOSURE STUDIES/ This study in humans evaluated the effects of supratherapeutic doses of dextromethorphan (DXM) and triazolam. Single, acute oral doses of DXM (100, 200, 300, 400, 500, 600, 700, and 800 mg/70 kg), triazolam (0.25 and 0.5 mg/70 kg), and placebo were administered to 12 healthy volunteers with histories of hallucinogen use, under double-blind conditions, using an ascending dose run-up design. Subjective, behavioral, and physiological effects were assessed repeatedly after drug administration for 6 hr. Triazolam produced dose-related increases in subject-rated sedation, observer-rated sedation, and behavioral impairment. DXM produced a profile of dose-related physiological and subjective effects differing from triazolam. DXM effects included increases in blood pressure, heart rate, and emesis; increases in observer-rated effects typical of classic hallucinogens (e.g., distance from reality, visual effects with eyes open and closed, joy, anxiety); and participant ratings of stimulation (e.g., jittery, nervous), somatic effects (e.g., tingling, headache), perceptual changes, end-of-session drug liking, and mystical-type experience. After 400 mg/70 kg DXM, 11 of 12 participants indicated on a pharmacological class questionnaire that they thought they had received a classic hallucinogen (e.g., psilocybin). Drug effects resolved without significant adverse effects by the end of the session. In a 1-month follow-up, volunteers attributed increased spirituality and positive changes in attitudes, moods, and behavior to the session experiences. High doses of DXM produced effects distinct from triazolam and had characteristics that were similar to the classic hallucinogen psilocybin.

/HUMAN EXPOSURE STUDIES/ Although concerns surrounding high-dose dextromethorphan (DXM) abuse have recently increased, few studies have examined the acute cognitive effects of high doses of DXM. The aim of this study was to compare the cognitive effects of DXM with those of triazolam and placebo. Single, acute, oral doses of DXM (100, 200, 300, 400, 500, 600, 700, 800 mg/70 kg), triazolam (0.25, 0.5mg/70 kg), and placebo were administered p.o. to twelve healthy volunteers with histories of hallucinogen use, under double-blind conditions, using an ascending dose run-up design. Effects on cognitive performance were examined at baseline and after drug administration for up to 6 hr. Both triazolam and DXM produced acute impairments in attention, working memory, episodic memory, and metacognition. Impairments observed following doses of 100-300 mg/70 kg DXM were generally smaller in magnitude than those observed after 0.5 mg/70 kg triazolam. Doses of DXM that impaired performance to the same extent as triazolam were in excess of 10-30 times the therapeutic dose of DXM. The magnitude of the doses required for these effects and the absence of effects on some tasks within the 100-300 mg/70 kg dose range of DXM, speak to the relatively broad therapeutic window of over-the-counter DXM preparations when used appropriately. However, the administration of supratherapeutic doses of DXM resulted in acute cognitive impairments on all tasks that were examined. These findings are likely relevant to cases of high-dose DXM abuse.

Antitussive active ingredients. The active ingredients of the product consist of the following when used within the dosage limits and in the dosage forms established for each ingredient in section 341.74(d): Dextromethorphan and dextromethorphan hydrobromide are included on this list.

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

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed over-the-counter drug products, including dextromethorphan hydrobromide, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Dextromethorphan hydrobromide/

Antitussive Agents; Excitatory Amino Acid Antagonists

Probe to determine cytochrome 450 phenotype

MEDICATION

Dextromethorphan (DXM) is an over-the-counter (OTC) cough suppressant commonly found in cold medications. DXM is often abused in high doses by adolescents to generate euphoria and visual and auditory hallucinations. Illicit use of DXM is referred to on the street as "Robo-tripping" or "skittling." These terms are derived from the most commonly abused products, Robitussin and Coricidin.

Use (kg; approx.) in Germany (2009): >1000

The primary use of dextromethorphan is as a cough suppressant, for the temporary relief of cough caused by minor throat and bronchial irritation (as commonly accompanies the common cold), as well as those resulting from inhaled irritants. In addition, a combination of dextromethorphan and quinidine has been shown to alleviate symptoms of easy laughing and crying (pseudobulbar affect) in patients with amyotrophic lateral sclerosis and multiple sclerosis.

Dextromethorphan is made by resolution of (+,-)-3-hydroxy-N-methylmorphinan ... with D-tartaric acid and subsequent O-methylation of the (+)-isomer with phenyltrimethylammonium hydroxide.

Dextromethorphan base (d-3-methoxy-N-methylmorphinan) is prepared from the corresponding d-3-hydroxy compound by methylation with phenyltrimethylammonium hydroxide.

Preparation: O. Schnider, A. Grussner ... United States of America patent 2676177 (1954 to Hoffmann-La Roche).

Dextromethorphan is a common antitussive agent found in many over-the-counter cough and cold preparations. Dextromethorphan is often found in combination products containing antihistamines, decongestants, ethanol, or acetaminophen. Common combination products containing dextromethorphan include Coricidin HBP Cough & Cold Tablets, Robitussin DM, and NyQuil Nighttime Cold Medicine.

Table: Dextromethorphan Hydrochloride Preparations [Table#4373]

Table: Dextromethorphan Hydrochloride Combinations Preparations [Table#4374]

Nuedexta, Each capsule contains: 20 mg of dextromethorphan hydrobromide and 10 mg of quinidine sulfate (Avanir Pharmaceuticals, Inc).

For more Formulations/Preparations (Complete) data for Dextromethorphan (7 total), please visit the HSDB record page.