Doral Tablets

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.

2.1       Special Populations

Elderly and debilitated patients may be more sensitive to benzodiazepines.

5.1       Risks from Concomitant Use with Opioids

Concomitant use of benzodiazepines, including DORAL, and opioids may result in profound sedation, respiratory depression, coma, and death. Because of these risks, reserve concomitant prescribing of these drugs for use 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 DORAL 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 DORAL than indicated in the absence of an opioid and titrate based on clinical response. If an opioid is initiated in a patient already taking DORAL, 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 DORAL 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), Patient Counseling (17)].

5.2       CNS-Depressant Effects and Daytime Impairment

DORAL 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 DORAL may develop, patients using DORAL 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 DORAL and concomitant CNS depressants should be considered. The potential for adverse drug interactions continues for several days following discontinuation of DORAL, until serum levels of both active parent drug and psychoactive metabolites decline.

Use of DORAL with other sedative-hypnotics is not recommended. Alcohol generally should not be used during treatment with DORAL. The risk of next-day psychomotor impairment is increased if DORAL 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)].

5.3       Benzodiazepine Withdrawal Syndrome

A withdrawal syndrome similar to that from alcohol (e.g., convulsions, tremor, abdominal and muscle cramps, vomiting, and sweating) can occur following abrupt discontinuation of DORAL. The more severe withdrawal effects are usually limited to patients taking higher than recommended doses over an extended time. Abrupt discontinuation should be avoided in such patients, and the dose gradually tapered. Prescribers should monitor patients for tolerance, abuse, and dependence.

Milder withdrawal symptoms (e.g., dysphoria and insomnia) can occur following abrupt discontinuation of benzodiazepines taken at therapeutic levels for short periods [See Drug Abuse and Dependence (9)].

5.4       Need to Evaluate for Co-morbid Diagnoses

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.

5.5       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 DORAL. 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 DORAL should not be rechallenged with the drug.

5.6       Abnormal Thinking and Behavior Changes

Abnormal thinking and behavior changes have been reported in patients treated with sedative-hypnotics including DORAL. 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 DORAL 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, DORAL 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.

5.7       Worsening of Depression

Benzodiazepines may worsen depression. Consequently, appropriate precautions (e.g., limiting the total prescription size and increased monitoring for suicidal ideation) should be considered.

DORAL contains DORAL, 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

DORAL has the empirical formula C17H11ClF4N2S, 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 DORAL. The inactive ingredients for Doral Tablets include cellulose, corn starch, FD&C Yellow No. 6 Al Lake, lactose, magnesium stearate, silicon dioxide, and sodium lauryl sulfate.

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

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 name (DORAL) on the other.

15 mg             Bottles of 100             NDC 61825-165-10

Store Doral Tablets at controlled room temperature 20°-25°C (68°-77°F).

See FDA-approved patient labeling (Medication Guide).

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)]

Inform patients about the benefits and risks of DORAL, stressing the importance of use as directed. Assist patients in understanding the Medication Guide and instruct them to read it with each prescription refill.

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.

Withdrawal

Instruct patients to contact you before stopping or decreasing the dose of DORAL, because withdrawal symptoms can occur.

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.

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.

Suicide

Tell patients that DORAL can worsen depression, and to immediately report any suicidal thoughts.

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

Instruct patients to inform you if they are nursing or pregnant, or may become pregnant while taking DORAL.

Tolerance, Abuse, and Dependence

Tell patients not to increase the dose of DORAL on their own, and to inform you if they believe the drug “does not work”.

Galt Pharmaceuticals, LLC.
Atlanta, GA 30339
Phone: (855) 965-2783
Fax (855) 276-4063

Manufactured by: Meda Pharmaceuticals,
Inc. Somerset, NJ 08873-4120

Printed in USA.                   IN-04052-02                         Rev. 08/2017

MEDICATION GUIDE

DORAL®

(quazepam tablets, USP) /CAPSULES C-IV

Read this Medication Guide before you start taking DORAL and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your doctor about your medical condition or treatment. You and your doctor should talk about DORAL when you start taking it and at regular checkups.

What is the most important information I should know about DORAL?

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”)
  
• making and eating food
  
• talking on the phone
  
• having sex
  
• walking

Important:

1. Take DORAL exactly as prescribed

• Do not take more DORAL than prescribed.
  
• Take DORAL right before you get in bed, not sooner.

2. Do not take DORAL if you:

• drink alcohol
  
• take other medicines that can make you sleepy. Talk to your doctor about all of your medicines. Your doctor will tell you if you can take DORAL with your other medicines
  
• cannot get a full night’s sleep

3. Call your doctor right away if you find out that you have done any of the above activities after taking DORAL.

What is DORAL?

DORAL is a sleep medicine. DORAL is used in adults for the short-term treatment of the symptom of trouble falling asleep from insomnia. DORAL does not treat other symptoms of insomnia which include waking up too early in the morning and waking up often during the night.

DORAL is not for children.

DORAL is a federally controlled substance (C-IV) because it 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 doctor if you have ever abused or been dependent on alcohol, prescription medicines or street drugs.

Who should not take DORAL?

Do not take DORAL if you are allergic to anything in it. See the end of this Medication Guide for a complete list of ingredients in DORAL.

DORAL may not be right for you. Before starting DORAL, tell your doctor about all of your health 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 kidney or liver disease
  
• have a lung disease or breathing problems
  
• are pregnant, planning to become pregnant, or breastfeeding

Tell your doctor about all of the medicines you take including prescription and nonprescription medicines, vitamins and herbal supplements. Medicines can interact, sometimes causing side effects. Do not take DORAL with other medicines that can make you sleepy.

Know the medicines you take. Keep a list of your medicines with you to show your doctor and pharmacist each time you get a new medicine.

How should I take DORAL?

• Take DORAL exactly as prescribed. Do not take more DORAL than prescribed for you.
  
• Take DORAL right before you get into bed. Or you can take DORAL after you have been in bed and have trouble falling asleep.
  
• Do not take DORAL with or right after a meal.
  
• Do not take DORAL unless you are able to get a full night’s sleep before you must be active again.
  
• 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.
  
• If you take too much DORAL or overdose, call your doctor or poison control center right away, or get emergency treatment.

What are the possible side effects of DORAL?

Serious side effects of DORAL include:

• getting out of bed while not being fully awake and do an activity that you do not know you are doing. (See “What is the most important information I should know about DORAL?”)
  
• abnormal thoughts and behavior. Symptoms include more outgoing or aggressive behavior than normal, confusion, agitation, hallucinations, worsening of depression, and suicidal thoughts or actions.
  
• memory loss
  
• anxiety
  
• severe allergic reactions. Symptoms include swelling of the tongue or throat, trouble breathing, and nausea and vomiting. Get emergency medical help if you get these symptoms after taking DORAL.

Call your doctor right away if you have any of the above side effects or any other side effects that worry you while using DORAL.

Common side effects of DORAL include:

• drowsiness
  
• headache
  
• fatigue
  
• dizziness
  
• dry mouth
  
• upset stomach
  
• You may still feel drowsy the next day after taking DORAL. Do not drive or do other dangerous activities after taking DORAL until you feel fully awake.
  
• You may have withdrawal symptoms for 1 to 2 days when you stop taking DORAL. Withdrawal symptoms include trouble sleeping, unpleasant feelings, stomach and muscle cramps, vomiting, sweating, shakiness, and seizures.

These are not all the side effects of DORAL. Ask your doctor or pharmacist for more information.

How should I store DORAL?

• Store DORAL at room temperature between 68° and 77° F (20° to 25°C).
  
• Protect from light.
  
• Keep DORAL and all medicines out of the reach of children.

General Information about DORAL

• Medicines are sometimes prescribed for purposes not mentioned 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 condition. It may harm them and it is against the law.

This Medication Guide summarizes the most important information about DORAL. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about DORAL that was written for healthcare professionals.

If you would like more information, contact Galt Pharmaceuticals at 1-855-965-2783 or visit http://www.doralrx.com

What are the ingredients in DORAL?

Active Ingredient: quazepam

Inactive Ingredients: cellulose, corn starch, FD&C Yellow No. 6 Al Lake, lactose, magnesium stearate, silicon dioxide, and sodium lauryl sulfate.

Rx only

Distributed by: Galt Pharmaceuticals, LLC
Marietta, GA 30339

This Medication Guide has been approved by the U.S. Food and Drug Administration.
IS-1500-01       Rev. 08/17

PRINCIPAL DISPLAY PANEL

NDC 61825-165-10
Doral (quazepam tablets, USP)
15 mg
100 Tablets
Rx Only