even as prescribed Stopping abruptly or reducing dosage too quickly can result in withdrawal reactions, including seizures, which can be life-threatening Abuse and misuse of benzodiazepines commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes; before prescribing and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction Assess each patient’s risk prior to prescribing and monitor regularly for the development of these conditions Risks of dependence and withdrawal increase with longer treatment duration and higher daily dose; although injection is indicated only for intermittent use, if used more frequently than recommended, abrupt discontinuation or rapid dosage reduction may precipitate acute withdrawal reactions, including seizures, which can be life-threatening; use gradual taper when discontinuing therapy to reduce withdrawal reactions risk Contraindications Documented hypersensitivity Narrow-angle glaucoma Caution Benzodiazepines expose users to risks of abuse, misuse, and addiction, which can lead to overdose or death; abuse and misuse of benzodiazepines often (but not always) involve 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 Use of drug, particularly in patients at elevated risk of abuse, necessitates counseling about risks and proper use of drug along with monitoring for signs and symptoms of abuse, misuse, and addiction; do not exceed recommended dosing frequency Avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (eg, opioid analgesics, stimulants); advise patients on proper disposal of unused drug; if a substance use disorder is suspected, evaluate patient and institute (or refer them for) early treatment, as appropriate Therapy not recommended for use in depressive neuroses or psychotic reactions Patients receiving therapy should be cautioned against engaging in hazardous occupations requiring mental alertness, including heavy machinery Therapy has central nervous system (CNS) effect; avoid simultaneous use of other CNS depressant drug; effects of alcohol may be increased For patients treated more frequently than recommended, use a gradual taper to discontinue therapy (a patient-specific plan should be used to taper the dose), to reduce risk of withdrawal reactions 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 In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months Patients taking drug for prolonged periods should have blood counts and liver function tests done periodically; the usual precautions in treating patients with impaired renal or hepatic function should also be observed In elderly or debilitated patients, initial dose should be small, and increments should be made gradually, in accordance with response of patient, to preclude ataxia or excessive sedation Suicidal behavior and ideation Antiepileptic drugs (AEDs), increase risk of suicidal thoughts or behavior in patients taking drugs for any indication Monitor patients treated with any AED for any indication for emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior Increased risk of suicidal thoughts or behavior with AEDs reported as early as one week after starting drug treatment with AEDs; epilepsy and many other illnesses for which AEDs are prescribed are associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior Should suicidal thoughts and behavior emerge during treatment, prescriber needs to consider whether emergence of these symptoms in any given patient may be related to illness being treated Pregnancy There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to psychiatric medications, including TRANXENE, during pregnancy; healthcare providers are encouraged to register patients calling the National Pregnancy Registry for PsychiatricMedications at 1-866-961-2388 or visiting online athttps://womensmentalhealth.org/pregnancyregistry/ Neonates born to mothers using benzodiazepines late in pregnancy have reported experiencing symptoms of sedation and/or neonatal withdrawal Available data from published observational studies of pregnant women exposed to benzodiazepines do not report a clear association with benzodiazepines and major birth defects Benzodiazepines cross the placenta and may produce respiratory depression, hypotonia, and sedation in neonates; monitor neonates exposed during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems; monitor neonates exposed during pregnancy for signs of withdrawal; manage these neonates accordingly Lactation Clorazepate and its active metabolite, nordiazepam, are present in breast milk; there are reports of sedation, poor feeding, and poor weight gain in infants exposed to benzodiazepines through breast milk; the effects of clorazepate on milk production are unknown Because of potential for serious adverse reactions, including sedation and withdrawal symptoms ininfants, advise patients that breastfeeding is not recommended during treatmentPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Enhances the inhibitory effect of GABA on neuronal excitability by increasing neuronal membrane permeability to chloride ions Pharmacokinetics Half-Life: 50-70 hr Time to peak: ~ 1 hr Protein Bound: 97-98% Metabolism: Hydroxylation, glucuronic acid conjugation Metabolites: Desmethyldiazepam (nordiazepam), oxazepam Excretion: Urine Onset of action: 1-2 hr Duration: Variable 8-24 hr BRAND FORM. UNIT PRICE PILL IMAGE clorazepate dipotassium oral- 15 mg tabletclorazepate dipotassium oral- 7.5 mg tabletclorazepate dipotassium oral- 15 mg tabletclorazepate dipotassium oral- 3.75 mg tabletclorazepate dipotassium oral- 3.75 mg tabletclorazepate dipotassium oral- 15 mg tabletclorazepate dipotassium oral- 7.5 mg tabletCopyright © 2010 First DataBank, Inc.Print Patient Educationclorazepate dipotassium oral CLORAZEPATE - ORAL (klor-AZ-e-pate) COMMON BRAND NAME(S): Tranxene WARNING: Clorazepate has a risk for abuse and addiction, which can lead to overdose and death. Taking this medication with alcohol or other drugs that can cause drowsiness or breathing problems (especially opioid medications such as codeine, hydrocodone) may cause very serious side effects, including death. To lower your risk, your doctor should have you take the smallest dose of clorazepate that works, and take it for the shortest possible time. Be sure you know how to take clorazepate and what other drugs you should avoid taking with it. See also Drug Interactions section. Get medical help right away if any of these very serious side effects occur: slow/shallow breathing, unusual lightheadedness, severe drowsiness/dizziness, difficulty waking up.Suddenly stopping this medication may cause serious (possibly fatal) withdrawal, especially if you have used it for a long time or in high doses. To prevent withdrawal, your doctor may lower your dose slowly. Tell your doctor or pharmacist right away if you have any withdrawal symptoms such as headaches, trouble sleeping, restlessness, hallucinations/confusion, depression, nausea, or seizures. Withdrawal symptoms may sometimes last weeks to months. USES: Clorazepate is used to treat anxiety, acute alcohol withdrawal, and seizures. This medication belongs to a class of drugs called benzodiazepines which act on the brain and nerves (central nervous system) to produce a calming effect. It works by enhancing the effects of a certain natural chemical in the body (GABA). HOW TO USE: See also Warning section.Read the Medication Guide provided by your pharmacist before you start taking clorazepate and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth as directed by your doctor. The dosage is based on your age, medical condition, and response to therapy.When this medication is used for a long time, it may not work as well. Talk with your doctor if this medication stops working well.Though it helps many people, this medication may sometimes cause addiction. This risk may be higher if you have a substance use disorder (such as overuse of or addiction to drugs/alcohol). Take this medication exactly as prescribed to lower the risk of addiction. Ask your doctor or pharmacist for more details. SIDE EFFECTS: See also Warning section.Drowsiness, dizziness, fatigue, dry mouth, upset stomach, constipation, blurred vision, or headache may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: trouble speaking, clumsiness, trouble walking, decreased/increased interest in sex, tremor, trouble urinating, sleep disturbances, signs of liver disease (such as nausea/vomiting that doesn't stop, stomach/abdominal pain, yellowing eyes/skin, dark urine), sore throat or fever that doesn't go away.A small number of people who take anticonvulsants for any condition (such as seizure, bipolar disorder, pain) may experience depression, suicidal thoughts/attempts, or other mental/mood problems. Tell your doctor right away if you or your family/caregiver notice any unusual/sudden changes in your mood, thoughts, or behavior including signs of depression, suicidal thoughts/attempts, thoughts about harming yourself.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345. PRECAUTIONS: Before taking this medication, tell your doctor or pharmacist if you are allergic to it; or to other benzodiazepines (such as diazepam, lorazepam); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, kidney disease, lung/breathing problems (such as COPD, sleep apnea), drug or alcohol abuse.This drug may make you dizzy or drowsy or blur your vision. Alcohol or marijuana (cannabis) can make you more dizzy or drowsy. Do not drive, use machinery, or do anything that needs alertness or clear vision until you can do it safely. Avoid alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).Older adults may be more sensitive to the side effects of this drug, especially drowsiness, which can increase the risk of falling.During pregnancy, this medication should be used only when clearly needed. It may harm an unborn baby. Newborn babies of mothers who use this medication late in pregnancy may have symptoms such as slow/shallow breathing, nonstop crying, shaking, or trouble feeding. However, since untreated seizures are a serious condition that can harm both a pregnant woman and her unborn baby, do not stop using this medication unless directed by your doctor. If you are planning pregnancy, become pregnant, or think you may be pregnant, talk to your doctor right away about the risks and benefits of this medication.This drug passes into breast milk and may have undesirable effects on a nursing infant. Consult your doctor before breast-feeding. DRUG INTERACTIONS: See also Warning section.Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: antacids, certain anti-depressants (such as fluoxetine, fluvoxamine, nefazodone), cimetidine, clozapine, digoxin, disulfiram, kava, orlistat, sodium oxybate.The risk of serious side effects (such as slow/shallow breathing, severe drowsiness/dizziness) may be increased if this medication is taken with other products that may also cause drowsiness or breathing problems. Tell your doctor or pharmacist