Sonata^®
(zaleplon)
Capsules

CIV

RX only

Zaleplon is a nonbenzodiazepine hypnotic from the pyrazolopyrimidine class. The chemical name of zaleplon is N-[3-(3-cyanopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-N-ethylacetamide. Its empirical formula is C₁₇H₁₅N₅O, and its molecular weight is 305.34. The structural formula is shown below.

ZALEPLON

Zaleplon is a white to off-white powder that is practically insoluble in water and sparingly soluble in alcohol or propylene glycol. Its partition coefficient in octanol/water is constant (log PC = 1.23) over the pH range of 1 to 7.

Sonata^® capsules contain zaleplon as the active ingredient. Inactive ingredients consist of microcrystalline cellulose, pregelatinized starch, silicon dioxide, sodium lauryl sulfate, magnesium stearate, lactose, gelatin, titanium dioxide, D&C yellow #10, FD&C blue #1, FD&C green #3, and FD&C yellow #5.

While Sonata (zaleplon) is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties, it interacts with the gamma-aminobutyric acid benzodiazepine (GABA-BZ) receptor complex. Subunit modulation of the GABA-BZ receptor chloride channel macromolecular complex is hypothesized to be responsible for some of the pharmacological properties of benzodiazepines, which include sedative, anxiolytic, muscle relaxant, and anticonvulsive effects in animal models.

Other nonclinical studies have also shown that zaleplon binds selectively to the brain omega-1 receptor situated on the alpha subunit of the GABA_A/chloride ion channel receptor complex and potentiates t-butylbicyclophosphorothionate (TBPS) binding. Studies of binding of zaleplon to recombinant GABA_A receptors (α₁β₁γ₂ [omega-1] and α2β1γ2 [omega- 2]) have shown that zaleplon has a low affinity for these receptors, with preferential binding to the omega-1 receptor.

The pharmacokinetics of zaleplon have been investigated in more than 500 healthy subjects (young and elderly), nursing mothers, and patients with hepatic disease or renal disease. In healthy subjects, the pharmacokinetic profile has been examined after single doses of up to 60 mg and once-daily administration at 15 mg and 30 mg for 10 days. Zaleplon was rapidly absorbed with a time to peak concentration (t_max) of approximately 1 hour and a terminal-phase elimination half-life (t_1/2) of approximately 1 hour. Zaleplon does not accumulate with once-daily administration and its pharmacokinetics are dose proportional in the therapeutic range.

Because zaleplon is primarily metabolized by aldehyde oxidase, and to a lesser extent by CYP3A4, inhibitors of these enzymes might be expected to decrease zaleplon's clearance and inducers of these enzymes might be expected to increase its clearance. Zaleplon has been shown to have minimal effects on the kinetics of warfarin (both R- and S- forms), imipramine, ethanol, ibuprofen, diphenhydramine, thioridazine, and digoxin. However, the effects of zaleplon on inhibition of enzymes involved in the metabolism of other drugs have not been studied. (See Drug Interactions under PRECAUTIONS.)

Sonata (typically administered in doses of 5 mg, 10 mg, or 20 mg) has been studied in patients with chronic insomnia (n = 3,435) in 12 placebo- and active-drug-controlled trials. Three of the trials were in elderly patients (n = 1,019). It has also been studied in transient insomnia (n = 264). Because of its very short half-life, studies focused on decreasing sleep latency, with less attention to duration of sleep and number of awakenings, for which consistent differences from placebo were not demonstrated. Studies were also carried out to examine the time course of effects on memory and psychomotor function, and to examine withdrawal phenomena.

Sonata is indicated for the short-term treatment of insomnia. Sonata has been shown to decrease the time to sleep onset for up to 30 days in controlled clinical studies (see Clinical Trials under CLINICAL PHARMACOLOGY). It has not been shown to increase total sleep time or decrease the number of awakenings.

Hypnotics should generally be limited to 7 to 10 days of use, and reevaluation of the patient is recommended if they are to be taken for more than 2 to 3 weeks. Sonata should not be prescribed in quantities exceeding a 1-month supply (see WARNINGS).

Hypersensitivity to zaleplon or any excipients in the formulation (see also PRECAUTIONS).

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. Because some of the important adverse effects of Sonata 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. Amnesia and other neuropsychiatric symptoms may occur unpredictably. In primarily depressed patients, worsening of depression, including suicidal thinking, 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 uled 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, like other hypnotics, has CNS-depressant effects. Because of the rapid onset of action, Sonata 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 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. Sonata, 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 should not be taken with alcohol. Dosage adjustment may be necessary when Sonata is administered with other CNS-depressant agents because of the potentially additive effects.

Patient information is printed at the end of this insert. To assure safe and effective use of Sonata, the information and instructions provided in the patient information section should be discussed with patients.

There are no specific laboratory tests recommended.

As with all drugs, the potential exists for interaction with other drugs by a variety of mechanisms.

The aldehyde oxidase enzyme system is less well studied than the cytochrome P450 enzyme system.

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.

Sonata 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 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.

The safety and effectiveness of Sonata in pediatric patients have not been established.

A total of 628 patients in double-blind, placebo-controlled, parallel-group clinical trials who received Sonata 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, no adverse event with a frequency of at least 1% occurred at a significantly higher rate with either 5 mg or 10 mg Sonata than with placebo.

The premarketing development program for Sonata included zaleplon exposures in patients and/or normal subjects from 2 different groups of studies: approximately 900 normal subjects in clinical pharmacology/pharmacokinetic studies; and approximately 2,900 exposures from patients in placebo-controlled clinical effectiveness studies, corresponding to approximately 450 patient exposure years. The conditions and duration of treatment with Sonata varied greatly and included (in overlapping categories) open-label and double-blind phases of studies, inpatients and outpatients, and short-term or longer-term exposure. Adverse reactions were assessed by collecting adverse events, results of physical examinations, vital signs, weights, laboratory analyses, and ECGs.

Adverse events during exposure were obtained primarily by general inquiry and recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of events into a smaller number of standardized event categories. In the tables and tabulations that follow, COSTART terminology has been used to classify reported adverse events.

The stated frequencies of adverse events represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type uled. An event was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation.

Listed below are COSTART terms that reflect treatment-emergent adverse events as defined in the introduction to the ADVERSE REACTIONS section. These events were reported by patients treated with Sonata (zaleplon) at doses in a range of 5 mg/day to 20 mg/day during premarketing phase 2 and phase 3 clinical trials throughout the United States, Canada, and Europe, including approximately 2,900 patients. All reported events are included except those already uled in Table 1 or elsewhere in labeling, those events for which a drug cause was remote, and those event terms that were so general as to be uninformative. It is important to emphasize that although the events reported occurred during treatment with Sonata, they were not necessarily caused by it.

Events are further categorized by body system and uled in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring on one or more occasions in at least 1/100 patients; infrequent adverse events are those occurring in less than 1/100 patients but at least 1/1,000 patients; rare events are those occurring in fewer than 1/1,000 patients.

Body as a whole - Frequent: back pain, chest pain, fever; Infrequent: chest pain substernal, chills, face edema, generalized edema, hangover effect, neck rigidity.

Cardiovascular system - Frequent: migraine; Infrequent: angina pectoris, bundle branch block, hypertension, hypotension, palpitation, syncope, tachycardia, vasodilatation, ventricular extrasystoles; Rare: bigeminy, cerebral ischemia, cyanosis, pericardial effusion, postural hypotension, pulmonary embolus, sinus bradycardia, thrombophlebitis, ventricular tachycardia.

Digestive system - Frequent: constipation, dry mouth, dyspepsia; Infrequent: eructation, esophagitis, flatulence, gastritis, gastroenteritis, gingivitis, glossitis, increased appetite, melena, mouth ulceration, rectal hemorrhage, stomatitis; Rare: aphthous stomatitis, biliary pain, bruxism, cardiospasm, cheilitis, cholelithiasis, duodenal ulcer, dysphagia, enteritis, gum hemorrhage, increased salivation, intestinal obstruction, abnormal liver function tests, peptic ulcer, tongue discoloration, tongue edema, ulcerative stomatitis.

Endocrine system - Rare: diabetes mellitus, goiter, hypothyroidism.

Hemic and lymphatic system - Infrequent: anemia, ecchymosis, lymphadenopathy; Rare: eosinophilia, leukocytosis, lymphocytosis, purpura.

Metabolic and nutritional - Infrequent: edema, gout, hypercholesteremia, thirst, weight gain; Rare: bilirubinemia, hyperglycemia, hyperuricemia, hypoglycemia, hypoglycemic reaction, ketosis, lactose intolerance, AST (SGOT) increased, ALT (SGPT) increased, weight loss.

Musculoskeletal system - Frequent: arthralgia, arthritis, myalgia; Infrequent: arthrosis, bursitis, joint disorder (mainly swelling, stiffness, and pain), myasthenia, tenosynovitis; Rare: myositis, osteoporosis.

Nervous system - Frequent: anxiety, depression, nervousness, thinking abnormal (mainly difficulty concentrating); Infrequent: abnormal gait, agitation, apathy, ataxia, circumoral paresthesia, emotional lability, euphoria, hyperesthesia, hyperkinesia, hypotonia, incoordination, insomnia, libido decreased, neuralgia, nystagmus; Rare: CNS stimulation, delusions, dysarthria, dystonia, facial paralysis, hostility, hypokinesia, myoclonus, neuropathy, psychomotor retardation, ptosis, reflexes decreased, reflexes increased, sleep talking, sleep walking, slurred speech, stupor, trismus.

Respiratory system - Frequent: bronchitis; Infrequent: asthma, dyspnea, laryngitis, pneumonia, snoring, voice alteration; Rare: apnea, hiccup, hyperventilation, pleural effusion, sputum increased.

Skinand appendages - Frequent: pruritus, rash; Infrequent: acne, alopecia, contact dermatitis, dry skin, eczema, maculopapular rash, skin hypertrophy, sweating, urticaria, vesiculobullous rash; Rare: melanosis, psoriasis, pustular rash, skin discoloration.

Special senses - Frequent: conjunctivitis, taste perversion; Infrequent: diplopia, dry eyes, photophobia, tinnitus, watery eyes; Rare: abnormality of accommodation, blepharitis, cataract specified, corneal erosion, deafness, eye hemorrhage, glaucoma, labyrinthitis, retinal detachment, taste loss, visual field defect.

Urogenital system - Infrequent: bladder pain, breast pain, cystitis, decreased urine stream, dysuria, hematuria, impotence, kidney calculus, kidney pain, menorrhagia, metrorrhagia, urinary frequency, urinary incontinence, urinary urgency, vaginitis; Rare: albuminuria, delayed menstrual period, leukorrhea, menopause, urethritis, urinary retention, vaginal hemorrhage.

Anaphylactic/anaphylactoid reactions, including severe reactions.

Sonata is classified as a Schedule IV controlled substance by federal regulation.

There is limited pre-marketing clinical experience with the effects of an overdosage of Sonata. Two cases of overdose were reported. One was the accidental ingestion by a 2½ year old boy of 20 mg to 40 mg of zaleplon. The second was a 20 year old man who took 100 mg zaleplon plus 2.25 mg of triazolam. Both were treated and recovered uneventfully.

Signs and symptoms of overdose effects of CNS depressants can be expected to present as exaggerations of the pharmacological effects noted in preclinical testing. Overdose is usually manifested by degrees of central nervous system depression ranging from drowsiness to coma. In mild cases, symptoms include drowsiness, mental confusion, and lethargy; in more serious cases, symptoms may include ataxia, hypotonia, hypotension, respiratory depression, rarely coma, and very rarely death.

General symptomatic and supportive measures should be used along with immediate gastric lavage where appropriate. Intravenous fluids should be administered as needed. Animal studies suggest that flumazenil is an antagonist to zaleplon. However, there is no pre-marketing clinical experience with the use of flumazenil as an antidote to a Sonata overdose. As in all cases of drug overdose, respiration, pulse, blood pressure, and other appropriate signs should be monitored and general supportive measures employed. Hypotension and CNS depression should be monitored and treated by appropriate medical intervention.

As with the management of all overdosage, the possibility of multiple drug ingestion should be considered. The physician may wish to consider contacting a poison control center for up-to-date information on the management of hypnotic drug product overdosage.

The dose of Sonata should be individualized. The recommended dose of Sonata for most nonelderly adults is 10 mg. For certain low weight individuals, 5 mg may be a sufficient dose. Although the risk of certain adverse events associated with the use of Sonata appears to be dose dependent, the 20 mg dose has been shown to be adequately tolerated and may be considered for the occasional patient who does not benefit from a trial of a lower dose. Doses above 20 mg have not been adequately evaluated and are not recommended.

Sonata should be taken immediately before bedtime or after the patient has gone to bed and has experienced difficulty falling asleep (see PRECAUTIONS.). Taking Sonata with or immediately after a heavy, high-fat meal results in slower absorption and would be expected to reduce the effect of Sonata on sleep latency (see Pharmacokinetics under CLINICAL PHARMACOLOGY).

Elderly patients and debilitated patients appear to be more sensitive to the effects of hypnotics, and respond to 5 mg of Sonata. The recommended dose for these patients is therefore 5 mg. Doses over 10 mg are not recommended.

Hepatic insufficiency: Patients with mild to moderate hepatic impairment should be treated with Sonata 5 mg because clearance is reduced in this population. Sonata is not recommended for use in patients with severe hepatic impairment.

Renal insufficiency: No dose adjustment is necessary in patients with mild to moderate renal impairment. Sonata has not been adequately studied in patients with severe renal impairment.

An initial dose of 5 mg should be given to patients concomitantly taking cimetidine because zaleplon clearance is reduced in this population (see Drug Interactions under PRECAUTIONS).

Sonata (zaleplon) capsules are supplied as follows:

Sonata^® is a registered trademark of Jones Pharma Inc.^™, a wholly owned subsidiary of King Pharmaceuticals^®, Inc.

Store at controlled room temperature, 20°C to 25°C (68°F to 77°F).

Dispense in a light-resistant container as defined in the USP.

Your doctor has prescribed Sonata to help you sleep. The following information is intended to guide you in the safe use of this medicine. It is not meant to take the place of your doctor's instructions. If you have any questions about Sonata capsules, be sure to ask your doctor or pharmacist.

Sonata is used to treat difficulty in falling asleep. Sonata works very quickly and has its effect during the first part of the night, since it is rapidly eliminated by the body. You should take Sonata immediately before going to bed or after you have gone to bed and are having difficulty falling asleep. If your principal sleep difficulty is awakening prematurely after falling asleep, there is no evidence that Sonata will be helpful to you. For Sonata to help you fall asleep you should not take it with or immediately after a high-fat/heavy meal.

Sonata belongs to a group of medicines known as the “hypnotics”, or simply, sleep medicines. There are many different sleep medicines available to help people sleep better. Sleep problems are usually temporary, requiring treatment for only a short time, usually 1 or 2 days up to 1 or 2 weeks. Some people have chronic sleep problems that may require more prolonged use of sleep medicine. However, you should not use these medicines for long periods without talking with your doctor about the risks and benefits of prolonged use.

Who should not take Sonata

Do not take Sonata if you are hypersensitive to its active substance, zaleplon, or to any of its inactive ingredients, including tartrazine (FD&C Yellow No. 5).

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.

Side Effects

All medicines have side effects. The most common side effects of sleep medicines are:

• Drowsiness
• Dizziness
• Lightheadedness
• Difficulty with coordination

These side effects with Sonata occur most often within an hour after taking it, so it is especially important to take it only when you are about to go to bed or are already in bed.

Severe allergic reactions, sometimes with difficulty in breathing and possibly life threatening, have been reported and may require immediate medical care.

Sleep medicines can make you sleepy during the day. How drowsy you feel depends upon how your body reacts to the medicine, which sleep medicine you are taking, and how large a dose your doctor has prescribed. Daytime drowsiness is best avoided by taking the lowest dose possible that will still help you sleep at night. Your doctor will work with you to find the dose of Sonata that is best for you. Sonata generally does not cause next-day sleepiness but a few people have reported this.

To manage these side effects while you are taking this medicine:

• - When you first start taking Sonata or any other sleep medicine, until you know whether the medicine will still have some carryover effect in you the next day, use extreme care while doing anything that requires complete alertness, such as driving a car, operating machinery, or piloting an aircraft.
• - NEVER drink alcohol while you are being treated with Sonata or any sleep medicine. Alcohol can increase the side effects of Sonata or any other sleep medicine.
• - Do not take any other medicines without asking your doctor first. This includes medicines you can buy without a prescription. Some medicines can cause drowsiness and are best avoided while taking Sonata.
• - Always take the exact dose of Sonata prescribed by your doctor. Never change your dose without talking to your doctor first.

Special Concerns

There are some special problems that may occur while taking sleep medicines.

Memory Problems

Sleep medicines may cause a special type of memory loss or “amnesia.” When this occurs, a person may not remember what has happened for several hours after taking the medicine. This is usually not a problem since most people fall asleep after taking the medicine. Memory loss can be a problem, however, when sleep medicines are taken while traveling, such as during an airplane flight and the person wakes up before the effect of the medicine is gone. This has been called “traveler’s amnesia.” Memory problems are not common while taking Sonata. In most instances memory problems can be avoided if you take Sonata only when you are able to get 4 or more hours of sleep before you need to be active again. Be sure to talk to your doctor if you think you are having memory problems.

Tolerance

When sleep medicines are used every night for more than a few weeks, they may lose their effectiveness to help you sleep. This is known as “tolerance.” Development of tolerance to Sonata has not been observed in outpatient clinical studies of up to 4 weeks in duration; however, it is unknown if the benefits of Sonata in falling asleep more quickly persist beyond 4 weeks. Sleep medicines should, in most cases, be used only for short periods of time, such as 1 or 2 days and generally no longer than 1 or 2 weeks. If your sleep problems continue, consult your doctor, who will determine whether other measures are needed to overcome your sleep problems.

Dependence

Sleep medicines can cause dependence, especially when these medicines are used regularly for longer than a few weeks or at high doses. Some people develop a need to continue taking their medicines. This is known as dependence or “addiction.”

When people develop dependence, they may have difficulty stopping the sleep medicine. If the medicine is suddenly stopped, the body is not able to function normally and unpleasant symptoms (see Withdrawal) may occur. They may find they have to keep taking the medicine either at the prescribed dose or at increasing doses just to avoid withdrawal symptoms.

All people taking sleep medicines have some risk of becoming dependent on the medicine. However, people who have been dependent on alcohol or other drugs in the past may have a higher chance of becoming addicted to sleep medicines. This possibility must be considered before using these medicines for more than a few weeks. If you have been addicted to alcohol or drugs in the past, it is important to tell your doctor before starting Sonata or any sleep medicine.

Withdrawal

Withdrawal symptoms may occur when sleep medicines are stopped suddenly after being used daily for a long time. In some cases, these symptoms can occur even if the medicine has been used for only a week or two. In mild cases, withdrawal symptoms may include unpleasant feelings. In more severe cases, abdominal and muscle cramps, vomiting, sweating, shakiness, and rarely, seizures may occur. These more severe withdrawal symptoms are very uncommon. Although withdrawal symptoms have not been observed in the relatively limited controlled trials experience with Sonata, there is, nevertheless, the risk of such events in association with the use of any sleep medicines.

Another problem that may occur when sleep medicines are stopped is known as “rebound insomnia.” This means that a person may have more trouble sleeping the first few nights after the medicine is stopped than before starting the medicine. If you should experience rebound insomnia, do not get discouraged. This problem usually goes away on its own after 1 or 2 nights.

If you have been taking Sonata or any other sleep medicine for more than 1 or 2 weeks, do not stop taking it on your own. Always follow your doctor's directions.

Changes In Behavior and Thinking

Some people using sleep medicines have experienced unusual changes in their thinking and/or behavior. These effects are not common. However, they have included:

• - more outgoing or aggressive behavior than normal
• - loss of personal identity
• - confusion
• - strange behavior
• - agitation
• - hallucinations
• - worsening of depression
• - suicidal thoughts

How often these effects occur depends on several factors, such as a person’s general health, the use of other medicines, and which sleep medicine is being used. Clinical experience with Sonata (zaleplon) suggests that it is uncommonly associated with these behavior changes.

It is also important to realize that it is rarely clear whether these behavior changes are caused by the medicine, an illness, or occur on their own. In fact, sleep problems that do not improve may be due to illnesses that were present before the medicine was used. If you or your family notice any changes in your behavior, or if you have any unusual or disturbing thoughts, call your doctor immediately.

Pregnancy and Breastfeeding

Sleep medicines may cause sedation or other potential effects in the unborn baby when used during the last weeks of pregnancy. Therefore, Sonata is not recommended for use during pregnancy. Be sure to tell your doctor if you are pregnant, if you are planning to become pregnant, or if you become pregnant while taking Sonata.

In addition, a very small amount of Sonata may be present in breast milk after use of the medication. The effects of very small amounts of Sonata on an infant are not known; therefore, as with all other hypnotics, it is recommended that you not take Sonata if you are breastfeeding a baby.

Safe Use of Sleeping Medicines

To ensure the safe and effective use of Sonata or any other sleep medicine, you should observe the following cautions:

• Sonata is a prescription medicine and should be used ONLY as directed by your doctor. Follow your doctor's instructions about how to take, when to take, and how long to take Sonata.
• Never use Sonata or any other sleep medicine for longer than directed by your doctor.
• If you notice any unusual and/or disturbing thoughts or behavior during treatment with Sonata or any other sleep medicine, contact your doctor.
• Tell your doctor about any medicines you may be taking, including medicines you may buy without a prescription. You should also tell your doctor if you drink alcohol. DO NOT use alcohol while taking Sonata or any other sleep medicine.
• Do not take Sonata unless you are able to get 4 or more hours of sleep before you must be active again.
• Do not increase the prescribed dose of Sonata or any other sleep medicine unless instructed by your doctor.
• When you first start taking Sonata or any other sleep medicine, until you know whether the medicine will still have some carryover effect in you the next day, use extreme care while doing anything that requires complete alertness, such as driving a car, operating machinery, or piloting an aircraft.
• Be aware that you may have more sleeping problems the first night or two after stopping any sleep medicine.
• Be sure to tell your doctor if you are pregnant, if you are planning to become pregnant, if you become pregnant, or are breastfeeding a baby while taking Sonata.
• As with all prescription medicines, never share Sonata or any other sleep medicine with anyone else. Always store Sonata or any other sleep medicine in the original container and out of reach of children.
• Be sure to tell your physician if you suffer from depression.
• Sonata works very quickly. You should only take Sonata immediately before going to bed or after you have gone to bed and are having difficulty falling asleep.
• For Sonata to work best, you should not take Sonata with or immediately after a high-fat/heavy meal.
• Some people should start with the lowest dose (5 mg) of Sonata; these include the elderly (ie, ages 65 and over) and people with liver disease.

Prescribing Information as of July 2003

Distributed by: King Pharmaceuticals, Inc., Bristol, TN 37620
Manufactured by: Wyeth Pharmaceuticals Inc., Philadelphia, PA 19101