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remedyrepack inc. - diazepam (unii: q3jtx2q7tu) (diazepam - unii:q3jtx2q7tu) - diazepam tablets are indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety. anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. in acute alcohol withdrawal, diazepam tablets may be useful in the symptomatic relief of acute agitation, tremor, impending or acute delirium tremens and hallucinosis. diazepam is a useful adjunct for the relief of skeletal muscle spasm due to reflex spasm to local pathology (such as inflammation of the muscles or joints, or secondary to trauma), spasticity caused by upper motor neuron disorders (such as cerebral palsy and paraplegia), athetosis, and stiff-man syndrome. oral diazepam may be used adjunctively in convulsive disorders, although it has not proved useful as the sole therapy. the effectiveness of diazepam in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies. the physician should periodically reassess the usefulness of the drug for the individual patient. diazepam tablets are contraindicated in patients with a known hypersensitivity to diazepam and, because of lack of sufficient clinical experience, in pediatric patients under 6 months of age. diazepam tablets are also contraindicated in patients with myasthenia gravis, severe respiratory insufficiency, severe hepatic insufficiency, and sleep apnea syndrome. they may be used in patients with open-angle glaucoma who are receiving appropriate therapy, but are contraindicated in acute narrow-angle glaucoma. diazepam tablets contain diazepam, a schedule iv controlled substance. diazepam is a benzodiazepine and a cns depressant with a potential for abuse and addiction. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. even taking benzodiazepines as prescribed may put patients at risk for abuse and misuse of their medication. abuse and misuse of benzodiazepines may lead to addiction. abuse and misuse of benzodiazepines often (but not always) involve the 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. benzodiazepines are often sought by individuals who abuse drugs and other substances, and by individuals with addictive disorders (see warnings: abuse, misuse, and addiction ). the following adverse reactions have occurred with benzodiazepine abuse and/or misuse: abdominal pain, amnesia, anorexia, anxiety, aggression, ataxia, blurred vision, confusion, depression, disinhibition, disorientation, dizziness, euphoria, impaired concentration and memory, indigestion, irritability, muscle pain, slurred speech, tremors, and vertigo. the following severe adverse reactions have occurred with benzodiazepine abuse and/or misuse: delirium, paranoia, suicidal ideation and behavior, seizures, coma, breathing difficulty, and death. death is more often associated with polysubstance use (especially benzodiazepines with other cns depressants such as opioids and alcohol). diazepam may produce physical dependence from continued therapy. physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. abrupt discontinuation or rapid dosage reduction of benzodiazepines or administration of flumazenil, a benzodiazepine antagonist, may precipitate acute withdrawal reactions, including seizures, which can be life-threatening. patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages (i.e., higher and/or more frequent doses), those who have had longer durations of use (see warnings: dependence and withdrawal reactions ). to reduce the risk of withdrawal reactions, use a gradual taper to discontinue diazepam tablets or reduce the dosage (see dosage and administration: discontinuation or dosage reduction of diazepam tablets and warnings: dependence and withdrawal reactions ). acute withdrawal signs and symptoms associated with benzodiazepines have included abnormal involuntary movements, anxiety, blurred vision, depersonalization, depression, derealization, dizziness, fatigue, gastrointestinal adverse reactions (e.g., nausea, vomiting, diarrhea, weight loss, decreased appetite), headache, hyperacusis, hypertension, irritability, insomnia, memory impairment, muscle pain and stiffness, panic attacks, photophobia, restlessness, tachycardia, and tremor. more severe acute withdrawal signs and symptoms, including life-threatening reactions, have included catatonia, convulsions, delirium tremens, depression, hallucinations, mania, psychosis, seizures, and suicidality. protracted withdrawal syndrome associated with benzodiazepines is characterized by anxiety, cognitive impairment, depression, insomnia, formication, motor symptoms (e.g., weakness, tremor, muscle twitches), paresthesia, and tinnitus that persists beyond 4 to 6 weeks after initial benzodiazepine withdrawal. protracted withdrawal symptoms may last weeks to more than 12 months. as a result, there may be difficulty in differentiating withdrawal symptoms from potential re-emergence or continuation of symptoms for which the benzodiazepine was being used. tolerance to diazepam may develop from continued therapy. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). tolerance to the therapeutic effect of diazepam may develop; however, little tolerance develops to the amnestic reactions and other cognitive impairments caused by benzodiazepines.

United States - English - NLM (National Library of Medicine)

diazepam tablet

a-s medication solutions - diazepam (unii: q3jtx2q7tu) (diazepam - unii:q3jtx2q7tu) - diazepam tablets are indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety. anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. in acute alcohol withdrawal, diazepam tablets may be useful in the symptomatic relief of acute agitation, tremor, impending or acute delirium tremens and hallucinosis. diazepam is a useful adjunct for the relief of skeletal muscle spasm due to reflex spasm to local pathology (such as inflammation of the muscles or joints, or secondary to trauma), spasticity caused by upper motor neuron disorders (such as cerebral palsy and paraplegia), athetosis, and stiff-man syndrome. oral diazepam may be used adjunctively in convulsive disorders, although it has not proved useful as the sole therapy. the effectiveness of diazepam in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies. the physician should periodically reassess the usefulness of the drug for the individual patient. diazepam tablets are contraindicated in patients with a known hypersensitivity to diazepam and, because of lack of sufficient clinical experience, in pediatric patients under 6 months of age. diazepam tablets are also contraindicated in patients with myasthenia gravis, severe respiratory insufficiency, severe hepatic insufficiency, and sleep apnea syndrome. they may be used in patients with open-angle glaucoma who are receiving appropriate therapy, but are contraindicated in acute narrow-angle glaucoma. diazepam tablets contain diazepam, a schedule iv controlled substance. diazepam is a benzodiazepine and a cns depressant with a potential for abuse and addiction. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. even taking benzodiazepines as prescribed may put patients at risk for abuse and misuse of their medication. abuse and misuse of benzodiazepines may lead to addiction. abuse and misuse of benzodiazepines often (but not always) involve the 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. benzodiazepines are often sought by individuals who abuse drugs and other substances, and by individuals with addictive disorders (see warnings: abuse, misuse, and addiction ). the following adverse reactions have occurred with benzodiazepine abuse and/or misuse: abdominal pain, amnesia, anorexia, anxiety, aggression, ataxia, blurred vision, confusion, depression, disinhibition, disorientation, dizziness, euphoria, impaired concentration and memory, indigestion, irritability, muscle pain, slurred speech, tremors, and vertigo. the following severe adverse reactions have occurred with benzodiazepine abuse and/or misuse: delirium, paranoia, suicidal ideation and behavior, seizures, coma, breathing difficulty, and death. death is more often associated with polysubstance use (especially benzodiazepines with other cns depressants such as opioids and alcohol). diazepam may produce physical dependence from continued therapy. physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. abrupt discontinuation or rapid dosage reduction of benzodiazepines or administration of flumazenil, a benzodiazepine antagonist, may precipitate acute withdrawal reactions, including seizures, which can be life-threatening. patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages (i.e., higher and/or more frequent doses), those who have had longer durations of use (see warnings: dependence and withdrawal reactions ). to reduce the risk of withdrawal reactions, use a gradual taper to discontinue diazepam tablets or reduce the dosage (see dosage and administration: discontinuation or dosage reduction of diazepam tablets and warnings: dependence and withdrawal reactions ). acute withdrawal signs and symptoms associated with benzodiazepines have included abnormal involuntary movements, anxiety, blurred vision, depersonalization, depression, derealization, dizziness, fatigue, gastrointestinal adverse reactions (e.g., nausea, vomiting, diarrhea, weight loss, decreased appetite), headache, hyperacusis, hypertension, irritability, insomnia, memory impairment, muscle pain and stiffness, panic attacks, photophobia, restlessness, tachycardia, and tremor. more severe acute withdrawal signs and symptoms, including life-threatening reactions, have included catatonia, convulsions, delirium tremens, depression, hallucinations, mania, psychosis, seizures, and suicidality. protracted withdrawal syndrome associated with benzodiazepines is characterized by anxiety, cognitive impairment, depression, insomnia, formication, motor symptoms (e.g., weakness, tremor, muscle twitches), paresthesia, and tinnitus that persists beyond 4 to 6 weeks after initial benzodiazepine withdrawal. protracted withdrawal symptoms may last weeks to more than 12 months. as a result, there may be difficulty in differentiating withdrawal symptoms from potential re-emergence or continuation of symptoms for which the benzodiazepine was being used. tolerance to diazepam may develop from continued therapy. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). tolerance to the therapeutic effect of diazepam may develop; however, little tolerance develops to the amnestic reactions and other cognitive impairments caused by benzodiazepines.

United States - English - NLM (National Library of Medicine)

clobazam suspension

bionpharma inc. - clobazam (unii: 2mro291b4u) (clobazam - unii:2mro291b4u) - clobazam oral suspension is indicated for the adjunctive treatment of seizures associated with lennox-gastaut syndrome (lgs) in patients 2 years of age or older. clobazam oral suspension is contraindicated in patients with a history of hypersensitivity to the drug or its ingredients. hypersensitivity reactions have included serious dermatological reactions [see warnings and precautions ( 5.6)] . pregnancy registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to aeds, such as clobazam, during pregnancy. healthcare providers are encouraged to recommend that pregnant women taking clobazam enroll in the north american antiepileptic drug (naaed) pregnancy registry by calling 1-888-233-2334 or online at http://www.aedpregnancyregistry.org/. risk summary neonates born to mothers using benzodiazepines late in pregnancy have been reported to experience symptoms of sedation and/or neonatal withdrawal [see warnings and precautions ( 5.8) and clinical considerations] . available data from published observational studies of pregnant women exposed to benzodiazepines do not report a clear association with benzodiazepines and major birth defects ( see data ). administration of clobazam to pregnant rats and rabbits during the period of organogenesis or to rats throughout pregnancy and lactation resulted in developmental toxicity, including increased incidences of fetal malformations and mortality, at plasma exposures for clobazam and its major active metabolite, n-desmethylclobazam, below those expected at therapeutic doses in patients [see animal data] . data for other benzodiazepines suggest the possibility of long-term effects on neurobehavioral and immunological function in animals following prenatal exposure to benzodiazepines at clinically relevant doses. clobazam should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. advise a pregnant woman and women of childbearing age of the potential risk to a fetus. the background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations fetal/neonatal adverse reactions benzodiazepines cross the placenta and may produce respiratory depression, hypotonia, and sedation in neonates. monitor neonates exposed to clobazam during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems. monitor neonates exposed to clobazam during pregnancy for signs of withdrawal. manage these neonates accordingly [see warnings and precautions ( 5.8)]. data human data published data from observational studies on the use of benzodiazepines during pregnancy do not report a clear association with benzodiazepines and major birth defects. although early studies reported an increased risk of congenital malformations with diazepam and chlordiazepoxide, there was no consistent pattern noted. in addition, the majority of more recent case-control and cohort studies of benzodiazepine use during pregnancy, which were adjusted for confounding exposures to alcohol, tobacco and other medications, have not confirmed these findings. animal data in a study in which clobazam (0 mg/kg/day, 150 mg/kg/day, 450 mg/kg/day, or 750 mg/kg/day) was orally administered to pregnant rats throughout the period of organogenesis, embryofetal mortality and incidences of fetal skeletal variations were increased at all doses. the low-effect dose for embryofetal developmental toxicity in rats (150 mg/kg/day) was associated with plasma exposures (auc) for clobazam and its major active metabolite, n-desmethylclobazam, lower than those in humans at the maximum recommended human dose (mrhd) of 40 mg/day. oral administration of clobazam (0 mg/kg/day, 10 mg/kg/day, 30 mg/kg/day, or 75 mg/kg/day) to pregnant rabbits throughout the period of organogenesis resulted in decreased fetal body weights, and increased incidences of fetal malformations (visceral and skeletal) at the mid and high doses, and an increase in embryofetal mortality at the high dose. incidences of fetal variations were increased at all doses. the highest dose tested was associated with maternal toxicity (ataxia and decreased activity). the low-effect dose for embryofetal developmental toxicity in rabbits (10 mg/kg/day) was associated with plasma exposures for clobazam and n-desmethylclobazam lower than those in humans at the mrhd. oral administration of clobazam (0 mg/kg/day, 50 mg/kg/day, 350 mg/kg/day, or 750 mg/kg/day) to rats throughout pregnancy and lactation resulted in increased embryofetal mortality at the high dose, decreased pup survival at the mid and high doses and alterations in offspring behavior (locomotor activity) at all doses. the low-effect dose for adverse effects on pre- and postnatal development in rats (50 mg/kg/day) was associated with plasma exposures for clobazam and n-desmethylclobazam lower than those in humans at the mrhd. risk summary clobazam is excreted in human milk ( see data ). there are reports of sedation, poor feeding and poor weight gain in infants exposed to benzodiazepines through breast milk. there are no data on the effects of clobazam on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for clobazam and any potential adverse effects on the breastfed infant from clobazam or from the underlying maternal condition. clinical considerations adverse reactions such as somnolence and difficulty feeding have been reported in infants during breastfeeding in postmarketing experience with clobazam. infants exposed to clobazam through breast milk should be monitored for sedation, poor feeding and poor weight gain. data scientific literature on clobazam use during lactation is limited. after short-term administration, clobazam and n-desmethylclobazam are transferred into breast milk. administration of clobazam to rats prior to and during mating and early gestation resulted in adverse effects on fertility and early embryonic development at plasma exposures for clobazam and its major active metabolite, n-desmethylclobazam, below those in humans at the mrhd [see nonclinical toxicology ( 13.1)] . safety and effectiveness in patients less than 2 years of age have not been established. in a study in which clobazam (0 mg/kg/day, 4 mg/kg/day, 36 mg/kg/day, or 120 mg/kg/day) was orally administered to rats during the juvenile period of development (postnatal days 14 to days 48), adverse effects on growth (decreased bone density and bone length) and behavior (altered motor activity and auditory startle response; learning deficit) were observed at the high dose. the effect on bone density, but not on behavior, was reversible when drug was discontinued. the no-effect level for juvenile toxicity (36 mg/kg/day) was associated with plasma exposures (auc) to clobazam and its major active metabolite, n-desmethylclobazam, less than those expected at therapeutic doses in pediatric patients. clinical studies of clobazam did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. however, elderly subjects appear to eliminate clobazam more slowly than younger subjects based on population pharmacokinetic analysis. for these reasons, the initial dose in elderly patients should be 5 mg/day. patients should be titrated initially to 10 mg/day to 20 mg/day. patients may be titrated further to a maximum daily dose of 40 mg if tolerated [see dosage and administration ( 2.4), clinical pharmacology ( 12.3)] . concentrations of clobazam's active metabolite, n-desmethylclobazam, are higher in cyp2c19 poor metabolizers than in extensive metabolizers. for this reason, dosage modification is recommended [see dosage and administration ( 2.5), clinical pharmacology ( 12.3)] . the pharmacokinetics of clobazam were evaluated in patients with mild and moderate renal impairment. there were no significant differences in systemic exposure (auc and c max ) between patients with mild or moderate renal impairment and healthy subjects. no dose adjustment is required for patients with mild and moderate renal impairment. there is essentially no experience with clobazam in patients with severe renal impairment or esrd. it is not known if clobazam or its active metabolite, n-desmethylclobazam, is dialyzable [see dosage and administration ( 2.6), clinical pharmacology ( 12.3)] . clobazam is hepatically metabolized; however, there are limited data to characterize the effect of hepatic impairment on the pharmacokinetics of clobazam. for this reason, dosage adjustment is recommended in patients with mild to moderate hepatic impairment (child-pugh score 5-9). there is inadequate information about metabolism of clobazam in patients with severe hepatic impairment [see dosage and administration ( 2.7), clinical pharmacology ( 12.3)] . clobazam oral suspension contains clobazam, a schedule iv controlled substance. clobazam is a benzodiazepine and a cns depressant with a potential for abuse and addiction. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. even taking benzodiazepines as prescribed may put patients at risk for abuse and misuse of their medication. abuse and misuse of benzodiazepines may lead to addiction. abuse and misuse of benzodiazepines often (but not always) involve the 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. benzodiazepines are often sought by individuals who abuse drugs and other substances, and by individuals with addictive disorders [see warnings and precautions ( 5.2)] . the following adverse reactions have occurred with benzodiazepine abuse and/or misuse: abdominal pain, amnesia, anorexia, anxiety, aggression, ataxia, blurred vision, confusion, depression, disinhibition, disorientation, dizziness, euphoria, impaired concentration and memory, indigestion, irritability, muscle pain, slurred speech, tremors, and vertigo. the following severe adverse reactions have occurred with benzodiazepine abuse and/or misuse: delirium, paranoia, suicidal ideation and behavior, seizures, coma, breathing difficulty, and death. death is more often associated with polysubstance use (especially benzodiazepines with other cns depressants such as opioids and alcohol) . the world health organization epidemiology database contains reports of drug abuse, misuse, and overdoses associated with clobazam. physical dependence clobazam may produce physical dependence from continued therapy. physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. abrupt discontinuation or rapid dosage reduction of benzodiazepines or administration of flumazenil, a benzodiazepine antagonist, may precipitate acute withdrawal reactions, including seizures, which can be life-threatening. patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages (i.e., higher and/or more frequent doses) and those who have had longer durations of use [see warnings and precautions ( 5.3)]. in clinical trials, cases of dependency were reported following abrupt discontinuation of clobazam. to reduce the risk of withdrawal reactions, use a gradual taper to discontinue clobazam or reduce the dosage [see dosage and administration ( 2.2) and warnings and precautions ( 5.3)]. acute withdrawal signs and symptoms acute withdrawal signs and symptoms associated with benzodiazepines have included abnormal involuntary movements, anxiety, blurred vision, depersonalization, depression, derealization, dizziness, fatigue, gastrointestinal adverse reactions (e.g., nausea, vomiting, diarrhea, weight loss, decreased appetite), headache, hyperacusis, hypertension, irritability, insomnia, memory impairment, muscle pain and stiffness, panic attacks, photophobia, restlessness, tachycardia, and tremor. more severe acute withdrawal signs and symptoms, including life-threatening reactions, have included catatonia, convulsions, delirium tremens, depression, hallucinations, mania, psychosis, seizures, and suicidality. protracted withdrawal syndrome protracted withdrawal syndrome associated with benzodiazepines is characterized by anxiety, cognitive impairment, depression, insomnia, formication, motor symptoms (e.g., weakness, tremor, muscle twitches), paresthesia, and tinnitus that persists beyond 4 to 6 weeks after initial benzodiazepine withdrawal. protracted withdrawal symptoms may last weeks to more than 12 months. as a result, there may be difficulty in differentiating withdrawal symptoms from potential re-emergence or continuation of symptoms for which the benzodiazepine was being used. tolerance tolerance to clobazam may develop from continued therapy. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). tolerance to the therapeutic effect of clobazam may develop; however, little tolerance develops to the amnestic reactions and other cognitive impairments caused by benzodiazepines.

United States - English - NLM (National Library of Medicine)

lorazepam tablet

remedyrepack inc. - lorazepam (unii: o26fzp769l) (lorazepam - unii:o26fzp769l) - lorazepam is indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety or anxiety associated with depressive symptoms. anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. the effectiveness of lorazepam in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies. the physician should periodically reassess the usefulness of the drug for the individual patient. lorazepam is contraindicated in patients with: - hypersensitivity to benzodiazepines or to any components of the formulation - acute narrow-angle glaucoma. lorazepam contains lorazepam, a schedule iv controlled substance. lorazepam is a benzodiazepine and a cns depressant with a potential for abuse and addiction. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. even taking benzodiazepines as prescribed may put patients at risk for abuse and misuse of their medication. abuse and misuse of benzodiazepines may lead to addiction. abuse and misuse of benzodiazepines often (but not always) involve the 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. benzodiazepines are often sought by individuals who abuse drugs and other substances, and by individuals with addictive disorders (see warnings: abuse, misuse, and addiction ) the following adverse reactions have occurred with benzodiazepine abuse and/or misuse: abdominal pain, amnesia, anorexia, anxiety, aggression, ataxia, blurred vision, confusion, depression, disinhibition, disorientation, dizziness, euphoria, impaired concentration and memory, indigestion, irritability, muscle pain, slurred speech, tremors, and vertigo. the following severe adverse reactions have occurred with benzodiazepine abuse and/or misuse: delirium, paranoia, suicidal ideation and behavior, seizures, coma, breathing difficulty, and death. death is more often associated with polysubstance use (especially benzodiazepines with other cns depressants such as opioids and alcohol). physical dependence lorazepam may produce physical dependence from continued therapy. physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. abrupt discontinuation or rapid dosage reduction of benzodiazepines or administration of flumazenil, a benzodiazepine antagonist, may precipitate acute withdrawal reactions, including seizures, which can be life-threatening. patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages (i.e., higher and/or more frequent doses) and those who have had longer durations of use (see warnings: dependence and withdrawal reactions ). to reduce the risk of withdrawal reactions, use a gradual taper to discontinue lorazepam or reduce the dosage (see dosage and administration: discontinuation or dosage reduction of lorazepamand warnings ). acute withdrawal signs and symptom acute withdrawal signs and symptoms associated with benzodiazepines have included abnormal involuntary movements, anxiety, blurred vision, depersonalization, depression, derealization, dizziness, fatigue, gastrointestinal adverse reactions (e.g., nausea, vomiting, diarrhea, weight loss, decreased appetite), headache, hyperacusis, hypertension, irritability, insomnia, memory impairment, muscle pain and stiffness, panic attacks, photophobia, restlessness, tachycardia, and tremor. more severe acute withdrawal signs and symptoms, including life-threatening reactions, have included catatonia, convulsions, delirium tremens, depression, hallucinations, mania, psychosis, seizures and suicidality. protracted withdrawal syndrome protracted withdrawal syndrome associated with benzodiazepines is characterized by anxiety, cognitive impairment, depression, insomnia, formication, motor symptoms (e.g., weakness, tremor, muscle twitches), paresthesia, and tinnitus that persists beyond 4 to 6 weeks after initial benzodiazepine withdrawal. protracted withdrawal symptoms may last weeks to more than 12 months. as a result, there may be difficulty in differentiating withdrawal symptoms from potential reemergence or continuation of symptoms for which the benzodiazepine was being used. tolerance tolerance to lorazepam may develop from continued therapy. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). tolerance to the therapeutic effect of lorazepam may develop; however, little tolerance develops to the amnestic reactions and other cognitive impairments caused by benzodiazepines.