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The top third of sleeping-pill users had a 5.3-fold higher death risk."...
- Patient Information:
Details with Side Effects
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, including Sonata (zaleplon) . Because some of the important adverse effects of Sonata (zaleplon) appear to be dose-related, it is important to use the lowest possible effective dose, especially in the elderly (see DOSAGE AND ADMINISTRATION ).
A variety of abnormal thinking and behavior changes have been reported to occur in association with the use of sedative/hypnotics. Some of these changes may be characterized by decreased inhibition (eg, aggressiveness and extroversion that seem out of character), similar to effects produced by alcohol and other CNS depressants. Other reported behavioral changes have included bizarre behavior, agitation, hallucinations, and depersonalization.
Abnormal Thinking and Behavioral Changes
Complex behaviors such as "sleep-driving" (i.e., driving while not fully awake after ingestion of a sedative- hypnotic, with amnesia for the event) have been reported. These events can occur in sedative-hypnotic-naive as well as in sedative-hypnotic-experienced persons. Although behaviors such as sleep-driving may occur with Sonata (zaleplon) alone at therapeutic doses, the use of alcohol and other CNS depressants with Sonata (zaleplon) appears to increase the risk of such behaviors, as does the use of Sonata (zaleplon) at doses exceeding the maximum recommended dose. Due to the risk to the patient and the community, discontinuation of Sonata (zaleplon) should be strongly considered for patients who report a "sleep-driving" episode. Other complex behaviors (e.g., preparing and eating food, making phone calls, or having sex) have been reported in patients who are not fully awake after taking a sedative- hypnotic. As with sleep-driving, patients usually do not remember these events. Amnesia and other neuropsychiatric symptoms may occur unpredictably. In primarily depressed patients, worsening of depression, including suicidal thoughts and actions (including completed suicides), has been reported in association with the use of sedative/hypnotics.
It can rarely be determined with certainty whether a particular instance of the abnormal behaviors listed above is drug induced, spontaneous in origin, or a result of an underlying psychiatric or physical disorder. Nonetheless, the emergence of any new behavioral sign or symptom of concern requires careful and immediate evaluation.
Following rapid dose decrease or abrupt discontinuation of the use of sedative/hypnotics, there have been reports of signs and symptoms similar to those associated with withdrawal from other CNS-depressant drugs (see DRUG ABUSE AND DEPENDENCE).
Sonata (zaleplon) , like other hypnotics, has CNS-depressant effects. Because of the rapid onset of action, Sonata (zaleplon) should only be ingested immediately prior to going to bed or after the patient has gone to bed and has experienced difficulty falling asleep. Patients receiving Sonata (zaleplon) should be cautioned against engaging in hazardous occupations requiring complete mental alertness or motor coordination (eg, operating machinery or driving a motor vehicle) after ingesting the drug, including potential impairment of the performance of such activities that may occur the day following ingestion of Sonata (zaleplon) . Sonata (zaleplon) , as well as other hypnotics, may produce additive CNS-depressant effects when coadministered with other psychotropic medications, anticonvulsants, antihistamines, narcotic analgesics, anesthetics, ethanol, and other drugs that themselves produce CNS depression. Sonata (zaleplon) should not be taken with alcohol. Dosage adjustment may be necessary when Sonata (zaleplon) is administered with other CNS- depressant agents because of the potentially additive effects.
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 Sonata (zaleplon) . 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 Sonata (zaleplon) should not be rechallenged with the drug.
Timing of Drug Administration
Sonata (zaleplon) should be taken immediately before bedtime or after the patient has gone to bed and has experienced difficulty falling asleep. As with all sedative/hypnotics, taking Sonata (zaleplon) while still up and about may result in short- term memory impairment, hallucinations, impaired coordination, dizziness, and lightheadedness.
Use in the elderly and/or debilitated patients
Impaired motor and/or cognitive performance after repeated exposure or unusual sensitivity to sedative/hypnotic drugs is a concern in the treatment of elderly and/or debilitated patients. A dose of 5 mg is recommended for elderly patients to decrease the possibility of side effects (see DOSAGE AND ADMINISTRATION ). Elderly and/or debilitated patients should be monitored closely.
Use in patients with concomitant illness
Clinical experience with Sonata (zaleplon) in patients with concomitant systemic illness is limited. Sonata (zaleplon) should be used with caution in patients with diseases or conditions that could affect metabolism or hemodynamic responses.
Although preliminary studies did not reveal respiratory depressant effects at hypnotic doses of Sonata (zaleplon) in normal subjects, caution should be observed if Sonata (zaleplon) is prescribed to patients with compromised respiratory function, because sedative/hypnotics have the capacity to depress respiratory drive. Controlled trials of acute administration of Sonata (zaleplon) 10 mg in patients with mild to moderate chronic obstructive pulmonary disease or moderate obstructive sleep apnea showed no evidence of alterations in blood gases or apnea/hypopnea index, respectively. However, patients with compromised respiration due to preexisting illness should be monitored carefully.
The dose of Sonata (zaleplon) should be reduced to 5 mg in patients with mild to moderate hepatic impairment (see DOSAGE AND ADMINISTRATION ). It is not recommended for use in patients with severe hepatic impairment.
No dose adjustment is necessary in patients with mild to moderate renal impairment. Sonata (zaleplon) has not been adequately studied in patients with severe renal impairment.
Use in patients with depression
As with other sedative/hypnotic drugs, Sonata (zaleplon) should be administered with caution to patients exhibiting signs or symptoms of depression. Suicidal tendencies may be present in such patients and protective measures may be required. Intentional overdosage is more common in this group of patients (see OVERDOSE ); therefore, the least amount of drug that is feasible should be prescribed for the patient at any one time.
This product contains FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.
Information for Patients
Patient information is printed at the end of this insert. To assure safe and effective use of Sonata (zaleplon) , the information and instructions provided in the patient information section should be discussed with patients.
A patient Medication Guide is also available for Sonata (zaleplon) . The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions that they may have.
SPECIAL CONCERNS "Sleep-Driving" and other complex behaviors
There have been reports of people getting out of bed after taking a sedative hypnotic medicine and driving their cars while not fully awake, often with no memory of the event. If a patient experiences such an episode, it should be reported to his or her doctor immediately, since "sleep-driving" can be dangerous. This behavior is more likely to occur when Sonata (zaleplon) is taken with alcohol or other central nervous system depressants (see WARNINGS). Other complex behaviors (e.g., preparing and eating food, making phone calls, or having sex) have been reported in patients who are not fully awake after taking a sleep medicine. As with sleep-driving, patients usually do not remember these events.
There are no specific laboratory tests recommended.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Lifetime carcinogenicity studies of zaleplon were conducted in mice and rats. Mice received doses of 25 mg/kg/day, 50 mg/kg/day, 100 mg/kg/day, and 200 mg/kg/day in the diet for two years. These doses are equivalent to 6 to 49 times the maximum recommended human dose (MRHD) of 20 mg on a mg/m2 basis. There was a significant increase in the incidence of hepatocellular adenomas in female mice in the high dose group. Rats received doses of 1 mg/kg/day, 10 mg/kg/day, and 20 mg/kg/day in the diet for two years. These doses are equivalent to 0.5 to 10 times the maximum recommended human dose (MRHD) of 20 mg on a mg/m2 basis. Zaleplon was not carcinogenic in rats.
Zaleplon was clastogenic, both in the presence and absence of metabolic activation, causing structural and numerical aberrations (polyploidy and endoreduplication), when tested for chromosomal aberrations in the in vitro Chinese hamster ovary cell assay. In the in vitro human lymphocyte assay, zaleplon caused numerical, but not structural, aberrations only in the presence of metabolic activation at the highest concentrations tested. In other in vitro assays, zaleplon was not mutagenic in the Ames bacterial gene mutation assay or the Chinese hamster ovary HGPRT gene mutation assay. Zaleplon was not clastogenic in two in vivo assays, the mouse bone marrow micronucleus assay and the rat bone marrow chromosomal aberration assay, and did not cause DNA damage in the rat hepatocyte unscheduled DNA synthesis assay.
Impairment of Fertility
In a fertility and reproductive performance study in rats, mortality and decreased fertility were associated with administration of an oral dose of zaleplon of 100 mg/kg/day to males and females prior to and during mating. This dose is equivalent to 49 times the maximum recommended human dose (MRHD) of 20 mg on a mg/m2 basis. Follow-up studies indicated that impaired fertility was due to an effect on the female.
Pregnancy: Pregnancy Category C
In embryofetal development studies in rats and rabbits, oral administration of up to 100 mg/kg/day and 50 mg/kg/day, respectively, to pregnant animals throughout organogenesis produced no evidence of teratogenicity. These doses are equivalent to 49 (rat) and 48 (rabbit) times the maximum recommended human dose (MRHD) of 20 mg on a mg/m2 basis. In rats, pre- and postnatal growth was reduced in the offspring of dams receiving 100 mg/kg/day. This dose was also maternally toxic, as evidenced by clinical signs and decreased maternal body weight gain during gestation. The no-effect dose for rat offspring growth reduction was 10 mg/kg (a dose equivalent to 5 times the MRHD of 20 mg on a mg/m2 basis). No adverse effects on embryofetal development were observed in rabbits at the doses examined.
In a pre- and postnatal development study in rats, increased stillbirth and postnatal mortality, and decreased growth and physical development, were observed in the offspring of females treated with doses of 7 mg/kg/day or greater during the latter part of gestation and throughout lactation. There was no evidence of maternal toxicity at this dose. The no-effect dose for offspring development was 1 mg/kg/day (a dose equivalent to 0.5 times the MRHD of 20 mg on a mg/m2 basis). When the adverse effects on offspring viability and growth were examined in a cross-fostering study, they appeared to result from both in utero and lactational exposure to the drug. There are no studies of zaleplon in pregnant women; therefore, Sonata® (zaleplon) is not recommended for use in women during pregnancy.
Labor and Delivery
Sonata (zaleplon) has no established use in labor and delivery.
A study in lactating mothers indicated that the clearance and half-life of zaleplon is similar to that in young normal subjects. A small amount of zaleplon is excreted in breast milk, with the highest excreted amount occurring during a feeding at approximately 1 hour after Sonata (zaleplon) administration. Since the small amount of the drug from breast milk may result in potentially important concentrations in infants, and because the effects of zaleplon on a nursing infant are not known, it is recommended that nursing mothers not take Sonata (zaleplon) .
The safety and effectiveness of Sonata (zaleplon) in pediatric patients have not been established.
A total of 628 patients in double-blind, placebo-controlled, parallel-group clinical trials who received Sonata (zaleplon) were at least 65 years of age; of these, 311 received 5 mg and 317 received 10 mg. In both sleep laboratory and outpatient studies, elderly patients with insomnia responded to a 5 mg dose with a reduced sleep latency, and thus 5 mg is the recommended dose in this population. During short-term treatment (14 night studies) of elderly patients with Sonata (zaleplon) , no adverse event with a frequency of at least 1% occurred at a significantly higher rate with either 5 mg or 10 mg Sonata (zaleplon) than with placebo.
Last reviewed on RxList: 1/2/2008
This monograph has been modified to include the generic and brand name in many instances.
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