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.
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.
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.
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.
The degree of plasma protein binding for quazepam and its two major metabolites is greater than 95%.
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.
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.
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.
DORAL showed no evidence of carcinogenicity in oral carcinogenicity studies in mice and hamsters.
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
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.
DORAL Tablets, 15 mg: A capsule shaped light orange, slightly white-speckled bisected tablet debossed “15″ on one side & “DORAL” on the other side.
|15 mg||Bottles of 30||NDC 61825-165-30|
|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. Advise patients that increased drowsiness and decreased consciousness may increase the risk of falls in some patients.
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.
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.
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
Printed in USA. 500494-07 Rev. 10/2019
What is the most important information I should know about DORAL?
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?
Do not take DORAL if you:
Before you take DORAL, tell your healthcare provider about all of your medical conditions, including if you:
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?
What should I avoid while taking DORAL?
What are the possible side effects of DORAL?
DORAL may cause serious side effects, including:
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:
After you stop taking a sleep medicine, you may have symptoms for the next 1 to 2 days such as:
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?
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: 04/2019|
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