Side effects from<unk>  Sedative drugs, including<unk> , have been associated with an increased risk of death. Possible side effects include: * Anterograde amnesia and concentration problems * Ataxia, slurred speech * Disinhibition * Drowsiness, dizziness, lightheadedness, fatigue, unsteadiness, and impaired coordination, vertigo * Dry mouth (infrequent) * Hallucinations (rare) * Jaundice (very rare) * Seizures (less common) * Skin rash, respiratory depression, constipation * Suicidal ideation or suicide * Urinary retention (infrequent) *Muscle weakness In September 2020, the U.S. Food and Drug Administration (FDA) required the boxed warning be updated for all benzodiazepine medicines to describe the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class. Paradoxical reactions Although unusual, the following paradoxical reactions have been shown to occur: * Aggression * Mania, agitation, hyperactivity, and restlessness * Rage, hostility * Twitches and tremor Food and drug interactions<unk>  is primarily metabolized via CYP3A4. Combining CYP3A4 inhibitors such as cimetidine, erythromycin, norfluoxetine, fluvoxamine, itraconazole, ketoconazole, nefazodone, propoxyphene, and ritonavir delay the hepatic clearance of<unk> , which may result in its accumulation and increased severity of its side effects. Imipramine and desipramine have been reported to increase an average of 31% and 20% respectively by the concomitant administration of<unk>  tablets. Combined oral contraceptive pills reduce the clearance of<unk> , which may lead to increased plasma levels of<unk>  and accumulation. Alcohol is one of the most common interactions; alcohol and<unk>  taken in combination have a synergistic effect on one another, which can cause severe sedation, behavioral changes, and intoxication. The more alcohol and<unk>  taken, the worse the interaction. Combination of<unk>  with the herb kava can result in the development of a semi-comatose state. Plants in the genus Hypericum (including St. John's wort) conversely can lower the plasma levels of<unk>  and reduce its therapeutic effect. Pregnancy and breastfeeding Benzodiazepines cross the placenta, enter the fetus, and are also excreted in breast milk. Chronic administration of diazepam, another benzodiazepine, to nursing mothers has been reported to cause their infants to become lethargic and to lose weight. The use of<unk>  during pregnancy is associated with congenital abnormalities, and use in the last trimester may cause fetal drug dependence and withdrawal symptoms in the post-natal period as well as neonatal flaccidity and respiratory problems. However, in long-term users of benzodiazepines, abrupt discontinuation due to concerns of teratogenesis has a high risk of causing extreme withdrawal symptoms and a severe rebound effect of the underlying mental health disorder. Spontaneous abortions may also result from abrupt withdrawal of psychotropic medications, including benzodiazepines. Overdose right The maximum recommended daily dose is 10 milligrams per day. Overdoses of<unk>  can be mild to severe depending on the quantity ingested and if other drugs are taken in combination.<unk>  overdoses cause excess central nervous system (CNS) depression and may include one or more of the following symptoms: * Coma and death if<unk>  is combined with other substances. * Fainting * Hypotension (low blood pressure) * Hypoventilation (shallow breathing) * Impaired motor functions * Dizziness * Impaired balance * Impaired or absent reflexes * Muscle weakness * Orthostatic hypotension (fainting while standing up too quickly) * Somnolence (drowsiness) Dependence and withdrawal The potential for misuse among those taking it for medical reasons is controversial, with some expert reviews stating that the risk is low and similar to that of other benzodiazepine drugs. Others state that there is a substantial risk of misuse and dependence in both patients and non-medical users and that the short half-life and rapid onset of action may increase the risk of misuse. Compared to the large number of prescriptions, relatively few individuals increase their dose on their own initiative or engage in drug-seeking behavior.<unk> , like other benzodiazepines, binds to specific sites on the GABAA (gamma-aminobutyric acid) receptor. When bound to these sites, which are referred to as benzodiazepine receptors, it modulates the effect of GABAA receptors and, thus, of GABAergic neurons. Long-term use causes adaptive changes in the benzodiazepine receptors, making them less sensitive to stimulation and thus making the drugs less potent. Withdrawal and rebound symptoms commonly occur and necessitate a gradual reduction in dosage to minimize withdrawal effects when discontinuing. Not all withdrawal effects are evidence of true dependence or withdrawal. Recurrence of symptoms such as anxiety may simply indicate that the drug was having its expected anti-anxiety effect and that, in the absence of the drug, the symptom has returned to pretreatment levels. If the symptoms are more severe or frequent, the person may be experiencing a rebound effect due to the removal of the drug. Either of these can occur without the person actually being drug dependent.<unk>  and other benzodiazepines may also cause the development of physical dependence, tolerance, and benzodiazepine withdrawal symptoms during rapid dose reduction or cessation of therapy after long-term treatment. There is a higher chance of withdrawal reactions if the drug is administered in a higher dosage than recommended, or if a person stops taking the medication altogether without slowly allowing the body to adjust to a lower-dosage regimen. In 1992, Romach and colleagues reported that dose escalation is not a characteristic of long-term<unk>  users and that the majority of long-term<unk>  users change their initial pattern of regular use to one of symptom control only when required. Some common symptoms of<unk>  discontinuation include malaise, weakness, insomnia, tachycardia, lightheadedness, and dizziness. Those taking more than 4 mg per day have an increased potential for dependence. This medication may cause withdrawal symptoms upon abrupt withdrawal or rapid tapering, which in some cases have been known to cause seizures, as well as marked delirium similar to that produced by the anticholinergic tropane alkaloids of Datura (scopolamine and atropine). The discontinuation of this medication may also cause a reaction called rebound anxiety. In a 1983 study, only 5% of patients who had abruptly stopped taking long-acting benzodiazepines after less than 8 months demonstrated withdrawal symptoms, but 43% of those who had been taking them for more than 8 months did. With<unk>  – a short-acting benzodiazepine – taken for 8 weeks, 65% of patients experienced significant rebound anxiety. To some degree, these older benzodiazepines are self-tapering. The benzodiazepines diazepam and oxazepam have been found to produce fewer withdrawal reactions than<unk> , temazepam, or lorazepam. Factors that determine the risk of psychological dependence or physical dependence and the severity of the benzodiazepine withdrawal symptoms during dose reduction of<unk>  include: dosage used, length of use, frequency of dosing, personality characteristics of the individual, previous use of cross-dependent/cross-tolerant drugs (alcohol or other sedative-hypnotic drugs), current use of cross-dependent/-tolerant drugs, use of other short-acting, high-potency benzodiazepines, and method of discontinuation.
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Medazepam
Pinazepam