d according to labeling.

ribe a lower initial dose of the opioid and titrate based upon clinical response. advise both patients and caregivers about the risks of respiratory depression and sedation when restoril is used with opioids. advise patients not to drive or operate heavy machinery until the effects of concomitant use with the opioid have been determined ( see precautions, drug interactions ). abuse, misuse, and addiction the use of benzodiazepines, including restoril, exposes users to the risks of abuse, misuse, and addiction, which can lead to overdose or death. 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 ( see drug abuse and dependence, abuse ). before prescribing restoril and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction (e.g., using a standardized screening tool). use of restoril, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of restoril along with monitoring for signs and symptoms of abuse, misuse, and addiction. prescribe the lowest effective dosage; avoid or minimize concomitant use of cns depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. if a substance use disorder is suspected, evaluate the patient and institute (or refer them for) early treatment, as appropriate. dependence and withdrawal reactions to reduce the risk of withdrawal reactions, use a gradual taper to discontinue restoril or reduce the dosage (a patient-specific plan should be used to taper the dose) ( see dosage and administration, discontinuation or dosage reduction of restoril ). 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. acute withdrawal reactions the continued use of benzodiazepines, including restoril, may lead to clinically significant physical dependence. abrupt discontinuation or rapid dosage reduction of restoril after continued use, or administration of flumazenil (a benzodiazepine antagonist) may precipitate acute withdrawal reactions, which can be life-threatening (e.g., seizures) ( see drug abuse and dependence, dependence ). protracted withdrawal syndrome in some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months ( see drug abuse and dependence, dependence ). sleep disturbance may be the presenting manifestation of an underlying physical and/or psychiatric disorder. consequently, a decision to initiate symptomatic treatment of insomnia should only be made after the patient has been carefully evaluated. the failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness that should be evaluated. worsening of insomnia may be the consequence of an unrecognized psychiatric or physical disorder as may the emergence of new abnormalities of thinking or behavior. such abnormalities have also been reported to occur in association with the use of drugs with central nervous system depressant activity, including those of the benzodiazepine class. because some of the worrisome adverse effects of benzodiazepines, including restoril, appear to be dose related ( see precautions and dosage and administration ), it is important to use the lowest possible effective dose. elderly patients are especially at risk. some of these changes may be characterized by decreased inhibition, e.g., aggressiveness and extroversion that seem out of character, similar to that seen with alcohol. other kinds of behavioral changes can also occur, for example, bizarre behavior, agitation, hallucinations, and depersonalization. complex behaviors such as “sleep-driving” (i.e., driving while not fully awake after ingestion of a sedative-hypnotic, with amnesia for the event) have been reported. these events can occur in sedative-hypnotic-naïve as well as in sedative-hypnotic-experienced persons. although behaviors such as “sleep-driving” may occur with restoril alone at therapeutic doses, the use of alcohol and other cns depressants with restoril appears to increase the risk of such behaviors, as does the use of restoril at doses exceeding the maximum recommended dose. due to the risk to the patient and the community, discontinuation of restoril should be strongly considered for patients who report a “sleep-driving” episode. other complex behaviors (e.g., preparing and eating food, making phone calls, or having sex) have been reported in patients who are not fully awake after taking a sedative-hypnotic. as with “sleep-driving”, patients usually do not remember these events. amnesia and other neuro-psychiatric symptoms may occur unpredictably. in primarily depressed patients, worsening of depression, including suicidal thinking has been reported in association with the use of sedative/hypnotics. it can rarely be determined with certainty whether a particular instance of the abnormal behaviors listed above is drug induced, spontaneous in origin, or a result of an underlying psychiatric or physical disorder. nonetheless, the emergence of any new behavioral sign or symptom of concern requires careful and immediate evaluation. because restoril can cause drowsiness and a decreased level of consciousness, patients, particularly the elderly, are at higher risk of falls. severe anaphylactic and anaphylactoid reactions rare cases of angioedema involving the tongue, glottis or larynx have been reported in patients after taking the first or subsequent doses of sedative-hypnotics, including restoril. some patients have had additional symptoms such as dyspnea, throat closing, or nausea and vomiting that suggest anaphylaxis. some patients have required medical therapy in the emergency department. if angioedema involves the tongue, glottis or larynx, airway obstruction may occur and be fatal. patients who develop angioedema after treatment with restoril should not be rechallenged with the drug. neonatal sedation and withdrawal syndrome use of restoril late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in the neonate ( see precautions, pregnancy ). monitor neonates exposed to restoril during pregnancy or labor for signs of sedation and monitor neonates exposed to restoril during pregnancy for signs of withdrawal; manage these neonates accordingly.

egnant patient received restoril and diphenhydramine. a cause and effect relationship has not yet been determined ( see contraindications ).

rning eyes amnesia, hallucinations, horizontal nystagmus, and paradoxical reactions including restlessness, overstimulation and agitation were rare (less than 0.5%).

d according to labeling.

ss, or other adverse outcomes. in the u.s. general population, the estimated 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 restoril during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems. monitor neonates exposed to restoril during pregnancy for signs of withdrawal. manage these neonates accordingly ( see warnings, neonatal sedation and withdrawal syndrome ). 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 reproduction studies in animals with temazepam were performed in rats and rabbits. in a perinatal-postnatal study in rats, oral doses of 60 mg/kg/day resulted in increasing nursling mortality. teratology studies in rats demonstrated increased fetal resorptions at doses of 30 and 120 mg/kg in one study and increased occurrence of rudimentary ribs, which are considered skeletal variants, in a second study at doses of 240 mg/kg or higher. in rabbits, occasional abnormalities such as exencephaly and fusion or asymmetry of ribs were reported without dose relationship. although these abnormalities were not found in the concurrent control group, they have been reported to occur randomly in historical controls. at doses of 40 mg/kg or higher, there was an increased incidence of the 13th rib variant when compared to the incidence in concurrent and historical controls.

ime curve over the 15 to 30 mg dose range. temazepam was completely metabolized through conjugation prior to excretion; 80% to 90% of the dose appeared in the urine. the major metabolite was the o-conjugate of temazepam (90%); the o-conjugate of n-desmethyl temazepam was a minor metabolite (7%). bioavailability, induction, and plasma levels following ingestion of a 30 mg restoril capsule, measurable plasma concentrations were achieved 10 to 20 minutes after dosing with peak plasma levels ranging from 666 to 982 ng/ml (mean 865 ng/ml) occurring approximately 1.2 to 1.6 hours (mean 1.5 hours) after dosing. in a 7 day study, in which subjects were given a 30 mg restoril capsule 1 hour before retiring, steady-state (as measured by the attainment of maximal trough concentrations) was achieved by the third dose. mean plasma levels of temazepam (for days 2 to 7) were 260±210 ng/ml at 9 hours and 75±80 ng/ml at 24 hours after dosing. a slight trend toward declining 24 hour plasma levels was seen after day 4 in the study, however, the 24 hour plasma levels were quite variable. at a dose of 30 mg once-a-day for 8 weeks, no evidence of enzyme induction was found in man. elimination rate of benzodiazepine hypnotics and profile of common untoward effects the type and duration of hypnotic effects and the profile of unwanted effects during administration of benzodiazepine hypnotics may be influenced by the biologic half-life of the administered drug and for some hypnotics, the half-life of any active metabolites formed. benzodiazepine hypnotics have a spectrum of half-lives from short (<4 hours) to long (>20 hours). when half-lives are long, drug (and for some drugs their active metabolites) may accumulate during periods of nightly administration and be associated with impairments of cognitive and/or motor performance during waking hours; the possibility of interaction with other psychoactive drugs or alcohol will be enhanced. in contrast, if half-lives are shorter, drug (and, where appropriate, its active metabolites) will be cleared before the next dose is ingested, and carry-over effects related to excessive sedation or cns depression should be minimal or absent. however, during nightly use for an extended period, pharmacodynamic tolerance or adaptation to some effects of benzodiazepine hypnotics may develop. if the drug has a short elimination half-life, it is possible that a relative deficiency of the drug, or, if appropriate, its active metabolites (i.e., in relationship to the receptor site) may occur at some point in the interval between each night's use. this sequence of events may account for 2 clinical findings reported to occur after several weeks of nightly use of rapidly eliminated benzodiazepine hypnotics, namely, increased wakefulness during the last third of the night, and the appearance of increased signs of daytime anxiety. controlled trials supporting efficacy restoril improved sleep parameters in clinical studies. residual medication effects (“hangover”) were essentially absent. early morning awakening, a particular problem in the geriatric patient, was significantly reduced. patients with chronic insomnia were evaluated in 2 week, placebo controlled sleep laboratory studies with restoril at doses of 7.5 mg, 15 mg, and 30 mg, given 30 minutes prior to bedtime. there was a linear dose-response improvement in total sleep time and sleep latency, with significant drug-placebo differences at 2 weeks occurring only for total sleep time at the 2 higher doses, and for sleep latency only at the highest dose. in these sleep laboratory studies, rem sleep was essentially unchanged and slow wave sleep was decreased. no measurable effects on daytime alertness or performance occurred following restoril treatment or during the withdrawal period, even though a transient sleep disturbance in some sleep parameters was observed following withdrawal of the higher doses. there was no evidence of tolerance development in the sleep laboratory parameters when patients were given restoril nightly for at least 2 weeks. in addition, normal subjects with transient insomnia associated with first night adaptation to the sleep laboratory were evaluated in 24 hour, placebo controlled sleep laboratory studies with restoril at doses of 7.5 mg, 15 mg, and 30 mg, given 30 minutes prior to bedtime. there was a linear dose-response improvement in total sleep time, sleep latency and number of awakenings, with significant drug-placebo differences occurring for sleep latency at all doses, for total sleep time at the 2 higher doses and for number of awakenings only at the 30 mg dose.

in red, and a maroon cap imprinted “restoril 30 mg” twice in white. bottle of 100 . . . . . . . . .ndc 0406-9917-01 dispense in a well-closed, light-resistant container with a child-resistant closure. storage: store at 20° to 25°c (68° to 77°f) [see usp controlled room temperature]. mallinckrodt, the “m” brand mark, the mallinckrodt pharmaceuticals logo, and other brands are trademarks of a mallinckrodt company. © 2023 mallinckrodt. rev 01/2023 mallinckrodt™ pharmaceuticals an electronic copy of this medication guide can be obtained from www.mallinckrodt.com/medguide/l20r02.pdf or by calling 1-800-778-7898 for alternate delivery options. boxed m boxed m

diction; to seek medical help if they develop these signs and/or symptoms; and on the proper disposal of unused drug ( see warnings, abuse, misuse, and addiction and drug abuse and dependence ). withdrawal reactions inform patients that the continued use of restoril may lead to clinically significant physical dependence and that abrupt discontinuation or rapid dosage reduction of restoril may precipitate acute withdrawal reactions, which can be life-threatening. inform patients that in some cases, patients taking benzodiazepines have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months. instruct patients that discontinuation or dosage reduction of restoril may require a slow taper ( see warnings, dependence and withdrawal reactions and drug abuse and dependence ). “sleep-driving” and other complex behaviors there have been reports of people getting out of bed after taking a sedative-hypnotic and driving their cars while not fully awake, often with no memory of the event. if a patient experiences such an episode, it should be reported to his or her doctor immediately, since “sleep-driving” can be dangerous. this behavior is more likely to occur when restoril is taken with alcohol or other central nervous system depressants ( see warnings ). other complex behaviors (e.g., preparing and eating food, making phone calls, or having sex) have been reported in patients who are not fully awake after taking a sedative-hypnotic. as with “sleep-driving”, patients usually do not remember these events. advise patients that increased drowsiness and decreased consciousness may increase the risk of falls in some patients. pregnancy advise pregnant females that use of restoril late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in newborns ( see warnings, neonatal sedation and withdrawal syndrome and precautions, pregnancy ). instruct patients to inform their healthcare provider if they are pregnant. advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to restoril during pregnancy ( see precautions, pregnancy ). nursing instruct patients to notify their healthcare provider if they are breastfeeding or intend to breastfeed. instruct breastfeeding patients using restoril to monitor infants for excessive sedation, poor feeding and poor weight gain, and to seek medical attention if they notice these signs ( see precautions, nursing mothers ).