DailyMed Label: Quazepam

DailyMed Label: Quazepam

2023

DailyMed Prescription

Quazepam

Quazepam

Atland Pharmaceuticals, LLC

NDC: 71993-265

NDC: 71993-265

Quazepam Tablets contain quazepam, a trifluoroethyl benzodiazepine hypnotic agent, having the chemical name 7-chloro-5- (o-fluoro-phenyl)-1,3-dihydro-1-(2,2,2- trifluoroethyl)-2H-1,4-benzodiazepine-2-thione and the following structural Quazepam has the empirical formula C 17 H 11 ClF 4 N 2 S, and a molecular weight of 386.8. It is a white crystalline compound, soluble in ethanol and insoluble in water. Each Quazepam Tablet contains 15 mg of quazepam. The inactive ingredients for Quazepam Tablets include cellulose, corn starch, FD&C Yellow No. 6, lactose, magnesium stearate, silicon dioxide, and sodium lauryl sulfate. structural formula

Quazepam Tablets are indicated for the treatment of insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings, and/or early morning awakenings. The effectiveness of Quazepam Tablets has been established in placebo-controlled clinical studies of 5 nights duration in acute and chronic insomnia. The sustained effectiveness of Quazepam Tablets has been established in chronic insomnia in a sleep lab (polysomnographic) study of 28 nights duration. Because insomnia is often transient and intermittent, the prolonged administration of Quazepam Tablets is generally not necessary or recommended. Since insomnia may be a symptom of several other disorders, the possibility that the complaint may be related to a condition for which there is a more specific treatment should be considered. Quazepam Tablets, a gamma-aminobutyric (GABAA) agonist, is indicated for the treatment of insomnia characterized by difficulty falling asleep, frequent nocturnal awakenings, and/or early morning awakenings. ( 1 )

Use the lowest dose effective for the patient: Recommended initial dose is 7.5 mg ( 2 ) Split the 15 mg tablet along the score line to achieve 7.5 mg dose ( 2 ) The elderly and debilitated may be more sensitive to benzodiazepines ( 2 ) Use the lowest dose effective for the patient, as important adverse effects of Quazepam Tablets are dose related. The recommended initial dose is 7.5 mg. The 7.5 mg dose can be increased to 15 mg if necessary for efficacy. The 7.5 mg dose can be achieved by splitting the 15 mg tablet along the score line. Elderly and debilitated patients may be more sensitive to benzodiazepines. To reduce the risk of withdrawal reactions, use a gradual taper to discontinue Quazepam Tablets or reduce the dosage. If a patient develops withdrawal reactions, consider pausing the taper or increasing the dosage to the previous tapered dosage level. Subsequently decrease the dosage more slowly [see Warnings and Precautions ( 5.3 ) and Drug Abuse and Dependence ( 9.3 )] .

Tablets, 15 mg, functionally scored, capsule-shaped, light orange, slightly white speckled tablets, impressed with the product identification number 15 on one side of the tablet, and the product name (DORAL) on the other. 15 mg functionally scored tablet, oral ( 3 )

Quazepam Tablets are contraindicated in patients with known hypersensitivity to quazepam or other benzodiazepines. Rare cases of angioedema involving the tongue, glottis or larynx have been reported in patients after taking the first or subsequent doses of Quazepam Tablets. Some patients have had additional symptoms such as dyspnea, throat closing, or nausea and vomiting that suggest anaphylaxis. Patients who develop such reactions should not be rechallenged with Quazepam Tablets. Contraindicated in patients with established or suspected sleep apnea, or with pulmonary insufficiency. Hypersensitivity to Quazepam Tablets or other benzodiazepines ( 4 ) Established or suspected sleep apnea, or chronic pulmonary insufficiency ( 4 )

CNS depressant effects: Impaired alertness and motor coordination, including risk of daytime impairment. Caution patients against driving and other activities requiring complete mental alertness ( 5.4 ) 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. ( 5.5 ) Severe anaphylactic/anaphylactoid reactions: Angioedema and anaphylaxis have been reported. Do not rechallenge if such reactions occur. ( 5.6 ) Sleep driving and other complex behaviors while not fully awake. Risk increases with dose and concomitant CNS depressants and alcohol. Immediately evaluate any new onset behavioral changes ( 5.7 ) Worsening of depression or suicidal thinking may occur: Prescribe the least number of tablets feasible to avoid intentional overdose ( 5.8 ) Concomitant use of benzodiazepines, including Quazepam Tablets, and opioids may result in profound sedation, respiratory depression, coma, and death. Because of these risks, reserve concomitant prescribing of these drugs in patients for whom alternative treatment options are inadequate. Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. If a decision is made to prescribe Quazepam Tablets concomitantly with opioids, prescribe the lowest effective dosages and minimum durations of concomitant use, and follow patients closely for signs and symptoms of respiratory depression and sedation. In patients already receiving an opioid analgesic, prescribe a lower initial dose of Quazepam Tablets than indicated in the absence of an opioid and titrate based on clinical response. If an opioid is initiated in a patient already taking Quazepam Tablets, prescribe 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 Quazepam Tablets 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 Drug Interactions ( 7 )] . The use of benzodiazepines, including Quazepam Tablets, 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 ( 9.2 )] . Before prescribing Quazepam Tablets and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction (e.g., using a standardized screening tool). Use of Quazepam Tablets, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of Quazepam Tablets 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. To reduce the risk of withdrawal reactions, use a gradual taper to discontinue Quazepam Tablets or reduce the dosage (a patient-specific plan should be used to taper the dose) [see Dosage and Administration ( 2.3 )] . 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 Quazepam Tablets, may lead to clinically significant physical dependence. Abrupt discontinuation or rapid dosage reduction of Quazepam Tablets 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 ( 9.3 )] . 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 ( 9.3 )] . Quazepam Tablet is a central nervous system (CNS) depressant and can impair daytime function in some patients even when used as prescribed. Prescribers should monitor for excess depressant effects, but impairment can occur in the absence of subjective symptoms, and may not be reliably detected by ordinary clinical exam (i.e. less than formal psychomotor testing). While pharmacodynamics tolerance or adaptation to some adverse depressant effects of Quazepam Tablets may develop, patients using Quazepam Tablets should be cautioned against driving or engaging in other hazardous activities or activities requiring complete mental alertness. Additive effects occur with concomitant use of other CNS depressants (e.g., other benzodiazepines, opioids, tricyclic antidepressants, alcohol), including daytime use. Downward dose adjustment of Quazepam Tablets and concomitant CNS depressants should be considered. The potential for adverse drug interactions continues for several days following discontinuation of Quazepam Tablets, until serum levels of both active parent drug and psychoactive metabolites decline. Use of Quazepam Tablets with other sedative-hypnotics is not recommended. Alcohol generally should not be used during treatment with Quazepam Tablets. The risk of next-day psychomotor impairment is increased if Quazepam Tablets is taken with less than a full night of sleep remaining (7 to 8 hours); if higher than the recommended dose is taken; if co-administered with other CNS depressants [see Dosage and Administration ( 2.1 )] . Because Quazepam Tablets can cause drowsiness and a decreased level of consciousness, patients particularly the elderly, are at higher risk of falls. Because sleep disturbances may be the presenting manifestation of a physical and/or psychiatric disorder, symptomatic treatment of insomnia should be initiated only after a careful evaluation of the patient. 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 or the emergence of new thinking or behavior abnormalities may be the consequence of an unrecognized psychiatric or physical disorder. Such findings have emerged during the course of treatment with sedative-hypnotic drugs. 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 Quazepam Tablets. 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 Quazepam Tablets should not be rechallenged with the drug. Abnormal thinking and behavior changes have been reported in patients treated with sedative-hypnotics including Quazepam Tablets. Some of these changes include decreased inhibition (e.g., aggressiveness and extroversion that seemed out of character), bizarre behavior, and depersonalization. Visual and auditory hallucinations have also been reported. Amnesia, and other neuro-psychiatric symptoms may occur. Paradoxical reactions such as stimulation, agitation, increased muscle spasticity, and sleep disturbances may occur unpredictably. Complex behaviors such as "sleep-driving" (i.e., driving while not fully awake, with amnesia for the event) have been reported with use of sedative-hypnotics. These behaviors can occur with initial treatment or in patients previously tolerant of Quazepam Tablets or other sedative-hypnotics. Although these behaviors can occur with use at therapeutic doses, risk is increased by higher doses or concomitant use of alcohol or other CNS depressants. Due to risk to the patient and community, Quazepam Tablets should be discontinued if "sleep-driving" occurs. 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. Benzodiazepines may worsen depression. Consequently, appropriate precautions (e.g., limiting the total prescription size and increased monitoring for suicidal ideation) should be considered. Use of Quazepam Tablets 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 Use in Specific Populations ( 8.1 )] . Monitor neonates exposed to Quazepam Tablets during pregnancy or labor for signs of sedation and monitor neonates exposed to Quazepam Tablets during pregnancy for signs of withdrawal; manage these infants accordingly.

The following serious adverse reactions are discussed in greater detail in other sections of the label:

The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. Benzodiazepines interact at GABAA sites and opioids interact primarily at mu receptors. When benzodiazepines and opioids are combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression exists. Limit dosage and duration of concomitant use of benzodiazepines and opioids, and monitor patients closely for respiratory depression and sedation. Benzodiazepines, including Quazepam Tablets, produce additive CNS depressant effects when co-administered with ethanol or other CNS depressants (e.g. psychotropic medications, anticonvulsants, antihistamines). Downward dose adjustment of Quazepam Tablets and/or concomitant CNS depressants may be necessary because of additive effects. CNS Depressants: downward dose adjustment may be necessary due to additive effects ( 7 )

Pregnancy Exposure Registry There is a pregnancy registry that monitors pregnancy outcomes in women exposed to psychiatric medications, including Quazepam Tablets, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Psychiatric Medications at 1-866-961-2388 or visiting on line at https://womensmentalhealth.org/pregnancyregistry/. Risk Summary Infants born to mothers using benzodiazepines late in pregnancy have been reported to experience symptoms of sedation and/or neonatal withdrawal [see Warnings and Precautions ( 5.9 ) 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) . 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 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 Quazepam Tablets during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems. Monitor neonates exposed to Quazepam Tablets during pregnancy for signs of withdrawal. Manage these neonates accordingly [see Warnings and Precautions ( 5.9 )] . 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 Developmental toxicity studies of Quazepam Tablets in mice at doses up to 400 times the human dose (15 mg) revealed no major drug-related malformations. Minor fetal skeletal variations that occurred were delayed ossification of the sternum, vertebrae, distal phalanges and supraoccipital bones, at doses approximately 70 and 400 times the human dose. A developmental toxicity study of Quazepam Tablets in New Zealand rabbits at doses up to approximately 130 times the human dose demonstrated no effect on fetal morphology or development of offspring. Risk Summary Quazepam and its metabolites 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 quazepam on milk production are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Quazepam Tablets and any potential adverse effects on the breastfed infant from Quazepam Tablets or from the underlying maternal condition. Clinical Considerations Infants exposed to Quazepam Tablets through breast milk should be monitored for sedation, poor feeding and poor weight gain. Safety and effectiveness in pediatric patients have not been established. Quazepam Tablets may cause confusion and over-sedation in the elderly. Elderly patients generally should be started on a low dose of Quazepam Tablets and observed closely. Elderly and debilitated patients may be more sensitive to benzodiazepines, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. A double-blind controlled sleep laboratory study (N=30) compared the effects of Quazepam Tablets 7.5 mg and 15 mg to that of placebo over a period of 7 days. Both the 7.5 mg and 15 mg doses appeared to be well tolerated. Caution must be used in interpreting this data due to the small size of the study.

Quazepam Tablets, 15 mg, functionally scored, capsule-shaped, light orange, slightly white speckled tablets, impressed with the product identification number 15 on one side of the tablet, and the product name (DORAL) on the other. 15 mg Bottles of 30 NDC 71993-265-30 Store Quazepam Tablets at controlled room temperature 20°-25°C (68°-77°F).

Quazepam Tablet, like other central nervous system agents of the 14-benzodiazepine class, presumably exerts its effects by binding to stereo-specific receptors at several sites within the central nervous system (CNS). The exact mechanism of action is unknown. Absorption Quazepam Tablet is rapidly (absorption half-life of about 30 minutes) and well absorbed from the gastrointestinal tract. The peak plasma concentration of quazepam is approximately 20 ng/mL after a 15 mg dose and occurs at about 2 hours. Metabolism Quazepam, the active parent compound, is extensively metabolized in the liver; two of the plasma metabolites are 2-oxoquazepam and N-desalkyl-2-oxoquazepam. All three compounds show CNS depressant activity. Distribution The degree of plasma protein binding for quazepam and its two major metabolites is greater than 95%. Elimination Following administration of 14C-quazepam, 31% of the dose appeared in the urine and 23% in the feces over five days; only trace amounts of unchanged drug were present in the urine. The mean elimination half-life of quazepam and 2-oxoquazepam is 39 hours and that of N-desalkyl-2-oxoquazepam is 73 hours. Steady-state levels of quazepam and 2-oxoquazepam are attained by the seventh daily dose and that of N-desalkyl-2-oxoquazepam by the thirteenth daily dose. Special Populations Geriatrics: The pharmacokinetics of quazepam and 2-oxoquazepam in geriatric subjects are comparable to those seen in young adults; as with desalkyl metabolites of other benzodiazepines, the elimination half-life of N-desalkyl-2-oxoquazepam in geriatric patients is about twice that of young adults. Drug Interactions Bupropion (a CYP2B6 substrate): Co-administration of a single dose of 150 mg Bupropion Hydrochloride XL with steady state quazepam did not significantly affect the AUC and Cmax of bupropion or its primary metabolite, hydroxybupropion.

Carcinogenesis Quazepam Tablet showed no evidence of carcinogenicity in oral carcinogenicity studies in mice and hamsters. Mutagenesis Quazepam Tablet was negative in the bacterial reverse mutation (Ames) assay and equivocal in the mouse lymphoma tk assay. Impairment of Fertility Reproduction studies in mice conducted with Quazepam Tablets at doses equal to 60 and 180 times the human dose of 15 mg produced slight reductions in fertility rate. Similar reductions in fertility rate have been reported in mice dosed with other benzodiazepines, and is believed to be related to the sedative effects of these drugs at high doses

The effectiveness of Quazepam Tablets was established in placebo-controlled clinical studies of 5 nights duration in acute and chronic insomnia. The sustained effectiveness of Quazepam Tablets was established in chronic insomnia in a sleep laboratory (polysomnographic) study of 28 nights duration. In the sleep laboratory study, Quazepam Tablets significantly decreased sleep latency and total wake time, and significantly increased total sleep time and percent sleep time, for one or more nights. Quazepam Tablets 15 mg was effective on the first night of administration. Sleep latency, total wake time and wake time after sleep onset were still decreased and percent sleep time was still increased for several nights after the drug was discontinued. Percent slow wave sleep was decreased, and REM sleep was essentially unchanged. No transient sleep disturbance, such as “rebound insomnia,” was observed after withdrawal of the drug in sleep laboratory studies in 12 patients using 15 mg doses. A double-blind, controlled sleep laboratory study (N=30) in elderly patients compared the effects of Quazepam Tablets 7.5 mg and 15 mg to that of placebo over a period of 7 days. Both the 7.5 mg and 15 mg doses appeared to be effective. Caution must be used in interpreting this data due to the small size of the study.

PRINCIPAL DISPLAY PANEL NDC 71993-265-30 Quazepam Tablets, USP 15 mg 30 Tablets Rx Only Label