[128] Clonazepam plasma levels are very unreliable amongst patients. Losses of 7-aminoclonazepam in urine averaging 43% have been reported under refrigerated conditions at 2 months.7 A 76% drop in clonazepam concentration has occurred in an oral fluid specimen stored at room temperature overnight.8 Complete loss of clonazepam in oral fluid has occurred in 7 days at room temperature.9 In oral fluid, losses of 7-aminoclonazepam up to 20% and 33% have been observed at room and refrigerated temperatures, respectively, over a week.10 Providers may consider these known issues particularly when evaluating unexpected negative clonazepam results. Moeller KE, Lee KC, Kissack JC. Development of an LC-MS/MS method for the simultaneous determination of 25 benzodiazepines and zolpidem in oral fluid and its application to authentic samples from regular drug users. At Aegis, we understand your concerns as you evaluate definitive drug testing results. Nihon Rinsho. Ther Drug Monit. 12% 38% 41% 1% 8% Fig. [118][119] Clonazepam decreases release of acetylcholine in the feline brain[120] and decreases prolactin release in rats. 2010 Mar 20;196(1-3):14-7. doi: 10.1016/j.forsciint.2009.12.037. Other drugs were present in all cases, with clonazepam judged to be the primary cause of death in five cases. Eight of the ten volunteers had measurable amounts of the metabolite 21 days after administration. Clonazepam can slow or stop your breathing, especially if you have recently used an opioid medication or alcohol. Kirsh KL, Heit HA, Huskey A, et al. eCollection 2019. 1B). Use caution to avoid falling or accidental injury. Get emergency medical help if you have signs of an allergic reaction to clonazepam: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Quantitation of clonazepam and its major metabolite 7-aminoclonazepam in hair. 2015 Aug;37(4):451-60. doi: 10.1097/FTD.0000000000000174. Tell your doctor right away if you have new or sudden changes in mood or behavior, including new or worse depression or anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, more active or talkative, or have thoughts about suicide or hurting yourself. Six of the volunteers had urine concentrations of 7-ACLO that peaked at 1 day after administration. [9], There is some medical evidence of various malformations (for example, cardiac or facial deformations when used in early pregnancy); however, the data is not conclusive. Clonazepam, marketed as Klonopin and Rivotril, is a long-acting benzodiazepine with anxiolytic, anticonvulsant, muscle relaxant, and hypnotic properties. Prolonged accumulation of diazepam in obesity. Clipboard, Search History, and several other advanced features are temporarily unavailable. Kempf J, Wuske T, Schubert R, Weinmann W. Pre-analytical stability of selected benzodiazepines on a polymeric oral fluid sampling device. Providers may also consider recent GI illness in the interpretation of unexpected negative results. This test measures the amount of clonazepam in your blood. Efavirenz treatment and false-positive results in benzodiazepine screening tests. Procedural Administration: Abenzodiazepine may be administered as an anxiolytic or sedative prior to medical procedures. Clonazepam was the second most frequently implicated benzodiazepine in ED visits. 0000007155 00000 n In addition, it is frequently used to treat drug addicts and is itself a popular drug of abuse. These values do not apply to results that are converted to other units of measure. Dosage forms: oral tablet (0.5 mg; 1 mg; 2 mg), oral tablet, disintegrating (0.125 mg; 0.25 mg; 0.5 mg; 1 mg; 2 mg) [9], The elderly are especially susceptible to increased risk of harm from motor impairments and drug accumulation side effects. Clonazepam (CLON) is not only frequently prescribed in addiction management but is also commonly abused. It differs from other anticonvulsant drugs it was compared to in a study. The https:// ensures that you are connecting to the 2013 Nov;5(22):2803-20. doi: 10.4155/bio.13.244. Detection of Nitrobenzodiazepines and Their 7-Amino Metabolites in Oral Fluid. confusion, paranoia, nightmares, hallucinations; Drowsiness or dizziness may last longer in older adults. It may also be used to treat panic attacks, insomnia, and generalized anxiety. A highly sensitive NCI-GC-MS method for the simultaneous quantitation of CLO and its major metabolite 7-ACLO in urine was developed and validated. trailer 215 0 obj <> endobj These data illustrate the limitations of using a 200 ng/ mL cutoff to monitor clonazepam compliance and suggest that a cutoff of 40 ng/mL or less is needed to reliably monitor use of this drug. . However, CLON and other benzodiazepines can be challenging to detect in OF due to their weakly acidic nature and their presence in low concentrations. Methods Find Exp Clin Pharmacol. 2002 Oct;26(7):471-8. doi: 10.1093/jat/26.7.471. Detection Times of Diazepam, Clonazepam, and Alprazolam in Oral Fluid Collected From Patients Admitted to Detoxification, After High and Repeated Drug Intake. In the case of unexpected positive benzodiazepine results, consider the following drug exposures:Chlordiazepoxide (Librax, Librium), Clorazepate (Gen-xene, Tranxene), Diazepam (Valium), Oxazepam, and/or Temazepam (Restoril). Physiological dependence was demonstrated by flumazenil-precipitated withdrawal. It can cause side effects such as drowsiness . J Opioid Manag. Management of sleep disorders in older people", "Benzodiazepine Equivalency Table: Benzodiazepine Equivalency", "Effects of commonly used benzodiazepines on the fetus, the neonate, and the nursing infant", "Solubilization of peripheral benzodiazepine-binding sites from rat kidney", "What are the equivalent doses of oral benzodiazepines? Your doctor may occasionally change your dose. -7-Aminoclonazepam (metabolite of clonazepam)-Diazepam (separate prescribable drug and . Using molecular similarity to highlight the challenges of routine immunoassay-based drug of abuse/toxicology screening in emergency medicine. Clonazepam is a medicine used to treat seizures. Blank A, Hellstern V, Shuster D, et al. Common clonazepam side effects may include: After you stop using clonazepam, get medical help right away if you have symptoms such as: unusual muscle movements, being more active or talkative, sudden and severe changes in mood or behavior, confusion, hallucinations, seizures, suicidal thoughts or actions. [131] The metabolites of clonazepam include 7-aminoclonazepam, 7-acetaminoclonazepam and 3-hydroxy clonazepam. Considerations for Interpreting Unexpected Results. 7-Aminoclonazepam | C15H12ClN3O - PubChem Apologies, we are having some trouble retrieving data from our servers. Drug monitoring of benzodiazepines is often performed in toxicology and pain management settings. Bioanalysis. Tell your doctor right away if you have any sudden changes in mood or behavior, or thoughts about suicide. Read the medication guide or patient instructions provided with each medication. J Anal Toxicol. Clipboard, Search History, and several other advanced features are temporarily unavailable. Please enable it to take advantage of the complete set of features! You should be aware if anyone is using it improperly or without a prescription. [125] Clonazepam is metabolized extensively via nitroreduction by cytochrome P450 enzymes, including CYP3A4. 2016 Mar;95(9):e2881. Figure 1. [14][15] In many areas of the world it is commonly used as a recreational drug. 2004 Dec;62 Suppl 12:360-3. The mechanism of tolerance includes receptor desensitization, down regulation, receptor decoupling, and alterations in subunit composition and in gene transcription coding. 2012;413(15-16):1199-202. Seal Beach, CA: Biomedical Publications; 2017.2. [117], Benzodiazepines, including clonazepam, bind to mouse glial cell membranes with high affinity. Clonazepam is used to treat certain seizure disorders (including absence seizures or Lennox-Gastaut syndrome) in adults and children. Possible adverse effects of use of benzodiazepines such as clonazepam during pregnancy include: miscarriage, malformation, intrauterine growth retardation, functional deficits, carcinogenesis, and mutagenesis. Forensic Sci Int. [85] The combination of clonazepam and certain barbiturates (for example, amobarbital), at prescribed doses has resulted in a synergistic potentiation of the effects of each drug, leading to serious respiratory depression. [16][17], Clonazepam is prescribed for short term management of epilepsy, anxiety, and panic disorder with or without agoraphobia.[18][19][20]. Our series on interpreting unexpected results concludes with a discussion on the interpretation of benzodiazepine results from Aegis Sciences Corporation. Ask your doctor before using opioid medication, a sleeping pill, a muscle relaxer, or medicine for anxiety or seizures. Feasibility of Using Oral Fluid for Therapeutic Drug Monitoring of Antiepileptic Drugs. Ask your healthcare provider what your test results mean for you. 0000001741 00000 n Click on the title Specimen Validity Testing and Specimen Tampering to download a copy of this chapter. 0000003040 00000 n The criteria for non-medical use in this study were purposefully broad, and include, for example, drug abuse, accidental or intentional overdose, or adverse reactions resulting from legitimate use of the medication.[134]. m@6lm -"`uX. You should not take clonazepam if you allergic to it or if you have: a history of allergic reaction to any benzodiazepine (including alprazolam, diazepam, lorazepam, Valium, Xanax, Versed, and others). [113] Because clonazepam is effective in low milligram doses (0.5mg clonazepam = 10mg diazepam),[114][115] it is said to be among the class of "highly potent" benzodiazepines. 0000004622 00000 n It may also be used to treat medicines that don't need a prescription and any illegal drugs you may use. Copyright and Disclaimer, Department of Laboratory Medicine & Pathology, ALPHA-HYDROXYALPRAZOLAM (Xanax metabolite), 7-AMINOCLONAZEPAM (Clonazepam metabolite), 7-AMINOFLUNITRAZEPAM (Flunitrazepam metabolite), 10, 11-CARBAMAZEPINE EPOXIDE (Carbamazepine metabolite), DESALKYLFLURAZEPAM (Flurazepam metabolite), DEXTRORPHAN (Dextromethorphan metabolite; see LEVORPHANOL), DIPHENHYDRAMINE / DIMENHYDRINATE (Benadryl/Dramamine), ECGONINE METHYL ESTER (Cocaine metabolite), LEVORPHANOL/DEXTRORPHAN (optical isomers). [110], Clonazepam's primary mechanism of action is the modulation of GABA function in the brain, by the benzodiazepine receptor, located on GABAA receptors, which, in turn, leads to enhanced GABAergic inhibition of neuronal firing. Clonazepam pregnancy and breastfeeding warnings. This syndrome can develop between three days to three weeks after birth and can have a duration of up to several months. Only two studies have reported detection times of 7-AC in urine after a single dose of clonazepam, and no previous studies have reported detection times after repeated . The information provided here is intended to assist providers with deciphering benzodiazepine results from Aegis, which have undergone definitive testing by liquid chromatography/tandem mass spectrometry prior to reporting as positive. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances. Both the parent drug and 7-aminoclonazepam are unstable in biofluids, and therefore specimens should be preserved with sodium fluoride, stored at the lowest possible temperature and analyzed quickly to minimize losses. Please see below for a list of drugs which may cause a false positive for benzodiazepines on POCT.6,11-15 Please refer to the package insert that came with the POCT device being used or contact the manufacturer for more information regarding which drugs may cause false positive results as this information may differ among devices and manufacturers. [24], Abrupt or over-rapid withdrawal from clonazepam may result in the development of the benzodiazepine withdrawal syndrome, causing psychosis characterised by dysphoric manifestations, irritability, aggressiveness, anxiety, and hallucinations. 7AC should be the analyte measured in OF for the detection of CLON use. Tell your doctor if you feel an increased urge to use more of this medicine. government site. Follow the directions on your prescription label and read all medication guides. Application to forensic cases of drug facilitated crimes. MeSH Test results may vary depending on your age, gender, health history, and other things. High dosage and long-term use increase the risk and severity of dependence and withdrawal symptoms. Some commonly prescribed benzodiazepines have unique metabolites, which make identification more straightforward: Alprazolam (Xanax): Metabolizes to alpha-hydroxyalprazolam; reported as AlprazolamClonazepam (Klonopin): Metabolizes to 7-aminoclonazepam; reported as ClonazepamFlurazepam: Metabolizes to 2-hydroxyethylflurazepam; reported as FlurazepamLorazepam (Ativan): Metabolizes to lorazepam glucuronide; reported as Lorazepam. Copyright 2023 Aegis Sciences Corporation, https://www.aegislabs.com/resources/clinical-reference-guide/, Parent drug may not be present in all results; only one marker is required for a positive result, If parent drug is present in urine with no alpha-OH-alprazolam present, please consult the Aegis Clinical Team as multiple clinical factors may be pertinent to result interpretation, and this does not always indicate aberrant patient behavior, Nordiazepam, Temazepam, and/or Oxazepam may be present, Only one marker is required for a positive result, Presence of other benzodiazepine markers may indicate ingestion of other benzodiazepines, Only Temazepam and/or Oxazepam should be present.