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. Common Side effects typical of hypnotic benzodiazepines are related to CNS depression, and include somnolence, sedation, dizziness, fatigue, ataxia, headache, lethargy, impairment of memory and learning, longer reaction time and impairment of motor functions (including coordination problems), slurred speech, decreased physical performance, numbed emotions, reduced alertness, muscle weakness, blurred vision (in higher doses), and inattention. Euphoria was rarely reported with its use. According to the U.S. Food and Drug Administration,<unk>  had an incidence of euphoria of 1.5%, much more rarely reported than headaches and diarrhea. Anterograde amnesia may also develop, as may respiratory depression in higher doses. A 2009 meta-analysis found a 44% higher rate of mild infections, such as pharyngitis or sinusitis, in people taking<unk>  or other hypnotic drugs compared to those taking a placebo. Less common Hyperhydrosis, hypotension, burning eyes, increased appetite, changes in libido, hallucinations, faintness, nystagmus, vomiting, pruritus, gastrointestinal disturbances, nightmares, palpitation and paradoxical reactions including restlessness, aggression, violence, overstimulation and agitation have been reported, but are rare (less than 0.5%). Before taking<unk> , one should ensure that at least 8 hours are available to dedicate to sleep. Failing to do so can increase the side effects of the drug. Like all benzodiazepines, the use of this drug in combination with alcohol potentiates the side effects, and can lead to toxicity and death. Though rare, residual "hangover" effects after night-time administration of<unk>  occasionally occur. These include sleepiness, impaired psychomotor and cognitive functions which may persist into the next day, impaired driving ability, and possible increased risks of falls and hip fractures, especially in the elderly. Tolerance Chronic or excessive use of<unk>  may cause drug tolerance, which can develop rapidly, so this drug is not recommended for long-term use. In 1979, the Institute of Medicine (USA) and the National Institute on Drug Abuse stated that most hypnotics lose their sleep-inducing properties after about three to 14 days. In use longer than one to two weeks, tolerance will rapidly develop towards the ability of<unk>  to maintain sleep, resulting in a loss of effectiveness. Some studies have observed tolerance to<unk>  after as little as one week's use. Another study examined the short-term effects of the accumulation of<unk>  over seven days in elderly inpatients, and found little tolerance developed during the accumulation of the drug. Other studies examined the use of<unk>  over six days and saw no evidence of tolerance. A study in 11 young male subjects showed significant tolerance occurs to<unk> 's thermoregulatory effects and sleep inducing properties after one week of use of 30-mg<unk> . Body temperature is well correlated with the sleep-inducing or insomnia-promoting properties of drugs. In one study, the drug sensitivity of people who had used<unk>  for one to 20 years was no different from that of controls. An additional study, in which at least one of the authors is employed by multiple drug companies, examined the efficacy of<unk>  treatment on chronic insomnia over three months, and saw no drug tolerance, with the authors even suggesting the drug might become more effective over time. Establishing continued efficacy beyond a few weeks can be complicated by the difficulty in distinguishing between the return of the original insomnia complaint and withdrawal or rebound related insomnia. Sleep EEG studies on hypnotic benzodiazepines show tolerance tends to occur completely after one to four weeks with sleep EEG returning to pretreatment levels. The paper concluded that due to concerns about long-term use involving toxicity, tolerance and dependence, as well as to controversy over long-term efficacy, wise prescribers should restrict benzodiazepines to a few weeks and avoid continuing prescriptions for months or years. A review of the literature found the nonpharmacological treatment options were a more effective treatment option for insomnia due to their sustained improvements in sleep quality. Physical dependence<unk> , like other benzodiazepine drugs, can cause physical dependence and addiction. Withdrawal from<unk>  or other benzodiazepines after regular use often leads to benzodiazepine withdrawal syndrome, which resembles symptoms during alcohol and barbiturate withdrawal. The higher the dose and the longer the drug is taken, the greater the risk of experiencing unpleasant withdrawal symptoms. Withdrawal symptoms can also occur from standard dosages and after short-term use. Abrupt withdrawal from therapeutic doses of<unk>  after long-term use may result in a severe benzodiazepine withdrawal syndrome. Gradual and careful reduction of the dosage, preferably with a long-acting benzodiazepine with long half-life active metabolites, such as chlordiazepoxide or diazepam, are recommended to prevent severe withdrawal syndromes from developing. Other hypnotic benzodiazepines are not recommended. A study in rats found<unk>  is cross tolerant with barbiturates and is able to effectively substitute for barbiturates and suppress barbiturate withdrawal signs. Rare cases are reported in the medical literature of psychotic states developing after abrupt withdrawal from benzodiazepines, even from therapeutic doses. Antipsychotics increase the severity of benzodiazepine withdrawal effects with an increase in the intensity and severity of convulsions. Patients who were treated in the hospital with<unk>  or nitrazepam have continued taking these after leaving the hospital. Hypnotic uses in the hospital were recommended to be limited to five nights' use only, to avoid the development of withdrawal symptoms such as insomnia.
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