DORAL

6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the label: Risks from Concomitant Use with Opioids [see Warnings and Precautions ( 5.1 )] Abuse, Misuse, and Addiction [see Warnings and Precautions ( 5.2 )] Dependence and Withdrawal Reactions [see Warnings and Precautions ( 5.3 )] CNS-depressant effects and next-day impairment [see Warnings and Precautions ( 5.4 )] Abnormal thinking and behavior changes, and complex behaviors [see Warnings and Precautions ( 5.7 )] Worsening of depression [see Warnings and Precautions ( 5.8 )] Neonatal Sedation and Withdrawal Syndrome [see Warnings and Precautions ( 5.9 )] Most common adverse reactions (>1%): drowsiness, headache, fatigue, dizziness, dry mouth, dyspepsia ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Galt Pharmaceuticals at 1-844-416-4284 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . ( 6 ) 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The table shows adverse reactions occurring at an incidence of 1% or greater in relatively short-duration, placebo-controlled clinical trials of DORAL. DORAL 15 mg PLACEBO NUMBER OF PATIENTS 267 268 % OF PATIENTS REPORTING Central Nervous System Daytime Drowsiness 12 3 Headache 5 2 Fatigue 2 0 Dizziness 2 <1 Autonomic Nervous System Dry Mouth 2 <1 Gastrointestinal System Dyspepsia 1 <1 A double-blind, controlled sleep laboratory study (N=30) in elderly patients compared the effects of DORAL 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.

4 CONTRAINDICATIONS DORAL is contraindicated in patients with known hypersensitivity to DORAL 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 DORAL. 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 DORAL. Contraindicated in patients with established or suspected sleep apnea, or with pulmonary insufficiency. Hypersensitivity to DORAL or other benzodiazepines ( 4 ) Established or suspected sleep apnea, or chronic pulmonary insufficiency ( 4 )

11 DESCRIPTION DORAL contains 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 DORAL Tablet contains 15 mg of quazepam. The inactive ingredients for DORAL Tablets include cellulose, corn starch, FD&C Yellow No. 6, lactose, magnesium stearate, silicon dioxide, and sodium lauryl sulfate. structural formula

2 DOSAGE AND ADMINISTRATION 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 ) 2.1 Dosage Recommendations Use the lowest dose effective for the patient, as important adverse effects of DORAL 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. 2.2 Special Populations Elderly and debilitated patients may be more sensitive to benzodiazepines. 2.3 Discontinuation or Dosage Reduction of DORAL To reduce the risk of withdrawal reactions, use a gradual taper to discontinue DORAL 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 )] .

1 INDICATIONS AND USAGE DORAL is indicated for the treatment of insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings, and/or early morning awakenings. The effectiveness of DORAL has been established in placebo-controlled clinical studies of 5 nights duration in acute and chronic insomnia. The sustained effectiveness of DORAL 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 DORAL 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. DORAL, 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 )

9.1 Controlled Substance DORAL contains quazepam, a Schedule IV controlled substance.

9 DRUG ABUSE AND DEPENDENCE 9.1 Controlled Substance DORAL contains quazepam, a Schedule IV controlled substance. 9.2 Abuse DORAL is a benzodiazepine and a CNS depressant with a potential for abuse and addiction. Abuse is the intentional, nontherapeutic 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). 9.3 Dependence Physical Dependence DORAL 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 )] . To reduce the risk of withdrawal reactions, use a gradual taper to discontinue DORAL or reduce the dosage [see Dosage and Administration ( 2.3 ) and Warnings and Precautions ( 5.3 )] . Acute Withdrawal Signs and Symptoms Acute withdrawal signs and symptoms 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, 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 DORAL 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 may develop within days or weeks of the therapeutic effects of DORAL; however, little tolerance develops to the amnestic reactions and other cognitive impairments caused by benzodiazepines.

10 OVERDOSAGE Overdosage of benzodiazepines is characterized by central nervous system depression ranging from drowsiness to coma. In mild to moderate cases, symptoms can include drowsiness, confusion, dysarthia, lethargy, hypnotic state, diminished reflexes, ataxia, and hypotonia. Rarely, paradoxical or disinhibitory reactions (including agitation, irritability, impulsivity, violent behavior, confusion, restlessness, excitement, and talkativeness) may occur. In severe overdosage cases, patients may develop respiratory depression and coma. Overdosage of benzodiazepines in combination with other CNS depressants (including alcohol and opioids) may be fatal [see Warnings and Precautions ( 5.2 )] . Markedly abnormal (lowered or elevated) blood pressure, heart rate, or respiratory rate raise the concern that additional drugs and/or alcohol are involved in the overdosage. In managing benzodiazepine overdosage, employ general supportive measures, including intravenous fluids and airway management. Flumazenil, a specific benzodiazepine receptor antagonist indicated for the complete or partial reversal of the sedative effects of benzodiazepines in the management of benzodiazepine overdosage, can lead to withdrawal and adverse reactions, including seizures, particularly in the context of mixed overdosage with drugs that increase seizure risk (e.g., tricyclic and tetracyclic antidepressants) and in patients with long-term benzodiazepine use and physical dependency. The risk of withdrawal seizures with flumazenil use may be increased in patients with epilepsy. Flumazenil is contraindicated in patients who have received a benzodiazepine for control of a potentially life-threatening condition (e.g., status epilepticus). If the decision is made to use flumazenil, it should be used as an adjunct to, not as a substitute for, supportive management of benzodiazepine overdosage. See the flumazenil injection Prescribing Information. Consider contacting a poison center (1-800-222-1222) or medical toxicologist for additional overdosage management recommendations.

7 DRUG INTERACTIONS 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 DORAL, produce additive CNS depressant effects when co-administered with ethanol or other CNS depressants (e.g. psychotropic medications, anticonvulsants, antihistamines). Downward dose adjustment of DORAL 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 )

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action DORAL, 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. 12.3 Pharmacokinetics Absorption DORAL 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.

12.1 Mechanism of Action DORAL, 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.

12.3 Pharmacokinetics Absorption DORAL 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.

20230131

17

3 DOSAGE FORMS AND STRENGTHS 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 )

DORAL Quazepam POWDERED CELLULOSE STARCH, CORN FD&C YELLOW NO. 6 LACTOSE MAGNESIUM STEARATE SILICON DIOXIDE SODIUM LAURYL SULFATE QUAZEPAM QUAZEPAM light to medium orange 15;DORAL

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis DORAL showed no evidence of carcinogenicity in oral carcinogenicity studies in mice and hamsters. Mutagenesis DORAL 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 DORAL 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

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis DORAL showed no evidence of carcinogenicity in oral carcinogenicity studies in mice and hamsters. Mutagenesis DORAL 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 DORAL 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

NDA018708

DORAL

Quazepam

61825-165

HUMAN PRESCRIPTION DRUG

ORAL

PRINCIPAL DISPLAY PANEL NDC 61825-165-30 Doral (quazepam tablets, USP) 15 mg 30 Tablets Rx Only Label

RECENT MAJOR CHANGES Warnings and Precautions ( 5.9 ) 01/2023

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). Risks from Concomitant Use with Opioids Inform patients and caregivers that potentially fatal additive effects may occur if DORAL is used with opioids and not to use such drugs concomitantly unless supervised by a healthcare provider [see Warnings and Precautions ( 5.1 ), Drug Interactions ( 7 )] Abuse, Misuse, and Addiction Inform patients that the use of DORAL even at recommended dosages, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose and death, especially when used in combination with other medications (e.g., opioid analgesics), alcohol, and/or illicit substances. Inform patients about the signs and symptoms of benzodiazepine abuse, misuse, and addiction; to seek medical help if they develop these signs and/or symptoms; and on the proper disposal of unused drug [see Warnings and Precautions ( 5.2 ) and Drug Abuse and Dependence ( 9.2 )] . Withdrawal Reactions Inform patients that the continued use of DORAL may lead to clinically significant physical dependence and that abrupt discontinuation or rapid dosage reduction of DORAL may precipitate acute withdrawal reactions, which can be life-threatening. Inform patients that in some cases, patients have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months. Instruct patients that discontinuation or dosage reduction of DORAL may require a slow taper [see Warnings and Precautions ( 5.3 ) and Drug Abuse and Dependence ( 9.3 )] . CNS Depressant Effects and Next-Day Impairment Tell patients that DORAL can cause next-day impairment, even in the absence of symptoms. Caution patients against driving or engaging in other hazardous activities or activities requiring complete mental alertness when using DORAL. Tell patients that daytime impairment may persist for several days following discontinuation of DORAL. Advise patients that increased drowsiness and decreased consciousness may increase the risk of falls in some patients [see Warnings and Precautions ( 5.4 )] Severe Allergic Reactions Inform patients that severe allergic reactions can occur from DORAL. Describe the signs/symptoms of these reactions and advise patients to seek medical attention immediately if these occur [see Warnings and Precautions ( 5.6 )] . Abnormal Thinking and Behavior Change Instruct patients that sedative hypnotics can cause abnormal thinking and behavior change, including “sleep-driving” and other complex behaviors while not being fully awake (preparing and eating food, making phone calls, or having sex). Tell patients to call you immediately if they develop any of these symptoms [see Warnings and Precautions ( 5.7 )] . Suicide Tell patients that DORAL can worsen depression, and to immediately report any suicidal thoughts [see Warnings and Precautions ( 5.8 )] . Alcohol and Other Drugs Ask patients about alcohol consumption, medicines they are taking now, and drugs they may be taking without a prescription. Advise patients that alcohol generally should not be used during treatment with DORAL. Pregnancy Advise pregnant females that use of DORAL 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 and Precautions ( 5.9 ), Use in Specific Populations ( 8.1 )] . 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 DORAL during pregnancy [see Use in Specific Populations ( 8.1 )] . Nursing Instruct patients to notify their healthcare provider if they are breastfeeding or intend to breastfeed. Instruct breastfeeding patients using DORAL to monitor infants for excessive sedation, poor feeding and poor weight gain, and to seek medical attention if they notice these signs [see Use in Specific Populations ( 8.3 )] . Galt Pharmaceuticals, LLC. Atlanta, GA 30339 Printed in USA. 500494-12 Rev. 01/2023

Medication Guide DORAL ® (DOOR-al) (quazepam) tablets, C-IV What is the most important information I should know about DORAL? DORAL is a benzodiazepine medicine. Taking benzodiazepines with opioid medicines, alcohol, or other central nervous system (CNS) depressants (including street drugs) can cause severe drowsiness, breathing problems (respiratory depression), coma and death. Get emergency help right away if the following happens: shallow or slowed breathing breathing stops (which may lead to the heart stopping) excessive sleepiness (sedation) Do not drive or operate heavy machinery until you know how taking DORAL with opioids affects you. Risk of abuse, misuse, and addiction. There is a risk of abuse, misuse, and addiction with benzodiazepines, including DORAL which can lead to overdose and serious side effects including coma and death. Serious side effects including coma and death have happened in people who have abused or misused benzodiazepines, including DORAL. These serious side effects may include delirium, paranoia, suicidal thoughts or actions, seizures, and difficulty breathing. Call your healthcare provider or go to the nearest hospital emergency room right away if you get any of these serious side effects. You can develop an addiction even if you take Doral as prescribed by your healthcare provider Take DORAL exactly as your healthcare provider prescribed. Do not share your DORAL with other people. Keep DORAL in a safe place and away from children. Physical dependence and withdrawal reactions. DORAL can cause physical dependence and withdrawal reactions. Do not suddenly stop taking DORAL. Stopping DORAL suddenly can cause serious and life-threatening side effects, including unusual movements, responses, or expressions, seizures, sudden and severe mental or nervous system changes, depression, seeing or hearing things that others do not see or hear, an extreme increase in activity or talking, losing touch with reality, and suicidal thoughts or actions. Call your healthcare provider or go to the nearest hospital emergency room right away if you get any of these symptoms. Some people who stop benzodazepines have symptoms that can last for several weeks to more than 12 months, including, anxiety, trouble remembering, learning, or concentrating, depression, problems sleeping, feeling like insects are crawling under your skin, weakness, shaking, muscle twitching, burning or prickling feeling in your hands, arms, legs or feet, and ringing in your ears. Physical dependence is not the same as drug addiction. Your healthcare provider can tell you more about the differences between physical dependence and drug addiction. Do not take more DORAL than prescribed or take DORAL for longer than prescribed. After taking DORAL, you may get up out of bed while not being fully awake and do an activity that you do not know you are doing. The next morning, you may not remember that you did anything during the night. You have a higher chance for doing these activities if you drink alcohol or take other medicines that make you sleepy with DORAL. Reported activities include: driving a car (“sleep-driving”) having sex making and eating food sleep-walking talking on the phone Call your healthcare provider right away if you find out that you have done any of the above activities after taking DORAL. What is DORAL? DORAL is a prescription medicine used to treat certain types of insomnia including difficulty falling asleep, waking up often during the night, or waking up early in the morning. DORAL is a federal controlled substance (C-IV) because it contains quazepam that can be abused or lead to dependence. Keep DORAL in a safe place to prevent misuse and abuse. Selling or giving away DORAL may harm others, and is against the law. Tell your healthcare provider if you have ever abused or been dependent on alcohol, prescription medicines or street drugs. It is not known if DORAL is safe and effective in children. Do not take DORAL if you: are allergic to quazepam or any of the ingredients in DORAL. See the end of this Medication Guide for a complete list of ingredients in DORAL. have had an allergic reaction to other sleep medicines or sedatives such as benzodiazepines. Symptoms of a serious allergic reaction can include: swelling of your face, lips, and throat that may cause difficulty breathing or swallowing nausea and vomiting have sleep apnea, breathing or lung problems Before you take DORAL, tell your healthcare provider about all of your medical conditions, including if you: have a history of depression, mental illness or, suicidal thoughts have a history of drug or alcohol abuse or addiction have lung disease or breathing problems are pregnant or plan to become pregnant. Taking DORAL late in pregnancy may cause your baby to have symptoms of sedation (breathing problems, sluggishness, low muscle tone), and/or withdrawal symptoms (jitteriness, irritability, restlessness, shaking, excessive crying, feeding problems). Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment with DORAL. There is a pregnancy registry for women who take DORAL during pregnancy. The purpose of the registry is to collect information about the health of you and your baby. If you become pregnant during treatment with DORAL, talk to your healthcare provider about registering with the National Pregnancy Registry for Psychiatric Medications. You can register by calling 1-866-961-2388 or visiting https://womensmentalhealth.org/pregnancyregistry/. are breastfeeding, or plan to breastfeed. DORAL can pass through your breast milk. Breastfeeding during treatment with DORAL may cause your baby to have sleepiness, feeding problems, and decreased weight gain. Talk to your healthcare provider about the best way to feed your baby if you take DORAL. Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking DORAL with certain other medicines can cause side effects or affect how well DORAL or the other medicines work. Do not start or stop other medicines without talking to your healthcare provider. Do not take DORAL with other medicines that can make you sleepy unless your healthcare provider tells you to. How should I take DORAL? See “What is the most important information I should know about DORAL?” Take DORAL exactly as your healthcare providers tell you to take it. DORAL comes in 15 mg tablets. Your healthcare provider may start your DORAL dose at 7.5 mg which is half a tablet. Talk to your healthcare provider or pharmacist about your dose schedule. If you take too much DORAL or overdose, get emergency treatment right away. What are the possible side effects of DORAL? DORAL may cause serious side effects, including: See “What is the most important information I should know about DORAL?” Other conditions. Call your healthcare provider if your insomnia worsens or is not better within 7 to 10 days. This may mean that there is another condition causing your sleep problem. Severe allergic reactions. Symptoms include swelling of the tongue or throat, and trouble breathing. Other symptoms may include nausea and vomiting. Get emergency medical help right away if you have these symptoms after taking DORAL. Abnormal thoughts and behavior. Symptoms include more outgoing or aggressive behavior than normal, confusion, agitation, hallucinations, worsening of depression, and suicidal thoughts. DORAL can make you sleepy or dizzy and can slow your thinking and motor skills. Do not drive, operate heavy machinery, or do other dangerous activities until you know how DORAL affects you. Do not drink alcohol or take other drugs that may make you sleepy or dizzy while taking DORAL without first talking to your healthcare provider. When taken with alcohol or drugs that cause sleepiness or dizziness, DORAL may make your sleepiness or dizziness much worse Depression. Pre-existing depression may emerge or worsen during use of benzodiazepines including DORAL. Call your healthcare provider right away if you have any of the above side effects while taking DORAL. The most common side effects of DORAL include: drowsiness headache feeling very tired dizziness dry mouth upset stomach After you stop taking a sleep medicine, you may have symptoms for the next 1 to 2 days such as: trouble sleeping nausea flushing lightheadedness uncontrolled crying vomiting stomach cramps panic attack nervousness stomach area pain These are not all the possible side effects of DORAL. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store DORAL? Store at room temperature between 68°F to 77°F (20°C to 25°C). Keep DORAL and all medicines out of the reach of children. General information about the safe and effective use of Doral. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use DORAL for a condition for which it was not prescribed. Do not give DORAL to other people, even if they have the same symptoms that you have. It may harm them. You can ask your healthcare provider or pharmacist for information about DORAL that is written for healthcare professionals. What are the ingredients in DORAL? Active Ingredient: quazepam Inactive Ingredients: cellulose, corn starch, FD&C Yellow No.6, lactose, magnesium stearate, silicon dioxide, and sodium lauryl sulfate Distributed by Galt Pharmaceuticals, Atlanta, GA 30339 USA. If you would like more information, call Galt Pharmaceuticals at 1-855-965-2783 or visit www.doralrx.com . This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: 01/2023

14 CLINICAL STUDIES The effectiveness of DORAL was established in placebo-controlled clinical studies of 5 nights duration in acute and chronic insomnia. The sustained effectiveness of DORAL was established in chronic insomnia in a sleep laboratory (polysomnographic) study of 28 nights duration. In the sleep laboratory study, DORAL significantly decreased sleep latency and total wake time, and significantly increased total sleep time and percent sleep time, for one or more nights. DORAL 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 DORAL 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.

8.5 Geriatric Use DORAL may cause confusion and over-sedation in the elderly. Elderly patients generally should be started on a low dose of DORAL 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 DORAL 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.

8.3 Nursing Mothers 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 DORAL and any potential adverse effects on the breastfed infant from DORAL or from the underlying maternal condition. Clinical Considerations Infants exposed to DORAL through breast milk should be monitored for sedation, poor feeding and poor weight gain.

8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established.

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy registry that monitors pregnancy outcomes in women exposed to psychiatric medications, including Doral, 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 Doral during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems. Monitor neonates exposed to Doral 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 DORAL 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 DORAL in New Zealand rabbits at doses up to approximately 130 times the human dose demonstrated no effect on fetal morphology or development of offspring.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy registry that monitors pregnancy outcomes in women exposed to psychiatric medications, including Doral, 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 Doral during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems. Monitor neonates exposed to Doral 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 DORAL 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 DORAL in New Zealand rabbits at doses up to approximately 130 times the human dose demonstrated no effect on fetal morphology or development of offspring. 8.3 Nursing Mothers 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 DORAL and any potential adverse effects on the breastfed infant from DORAL or from the underlying maternal condition. Clinical Considerations Infants exposed to DORAL through breast milk should be monitored for sedation, poor feeding and poor weight gain. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use DORAL may cause confusion and over-sedation in the elderly. Elderly patients generally should be started on a low dose of DORAL 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 DORAL 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.

16 HOW SUPPLIED / STORAGE AND HANDLING DORAL ® 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 61825-165-30 Store DORAL Tablets at controlled room temperature 20°-25°C (68°-77°F).

WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS; ABUSE, MISUSE, AND ADDICTION; and DEPENDENCE AND WITHDRAWAL REACTIONS Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation [see Warnings and Precautions ( 5.1 ), Drug Interactions ( 7 )] . The use of benzodiazepines, including DORAL, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Abuse and misuse of benzodiazepines commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes. Before prescribing DORAL and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction [see Warnings and Precautions ( 5.2 )] . The continued use of benzodiazepines, including DORAL, may lead to clinically significant physical dependence. The risks of dependence and withdrawal increase with longer treatment duration and higher daily dose. Abrupt discontinuation or rapid dosage reduction of DORAL after continued use may precipitate acute withdrawal reactions, which can be life-threatening. To reduce the risk of withdrawal reactions, use a gradual taper to discontinue DORAL or reduce the dosage [see Dosage and Administration ( 2.3 ) and Warnings and Precautions ( 5.3 )] . WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS; ABUSE, MISUSE, AND ADDICTION; and DEPENDENCE AND WITHDRAWAL REACTIONS See full prescribing information for complete boxed warning. Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation ( 5.1 , 7 ). The use of benzodiazepines, including DORAL, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Before prescribing DORAL and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction ( 5.2 ). Abrupt discontinuation or rapid dosage reduction of DORAL after continued use may precipitate acute withdrawal reactions, which can be life-threatening. To reduce the risk of withdrawal reactions, use a gradual taper to discontinue DORAL or reduce the dosage ( 2.3 , 5.3 ).