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Zaleplon

Pronunciation

Pronunciation

(ZAL e plon)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Sonata: 5 mg, 10 mg [contains tartrazine (fd&c yellow #5)]

Generic: 5 mg, 10 mg

Brand Names: U.S.

  • Sonata

Pharmacologic Category

  • Hypnotic, Miscellaneous

Pharmacology

Zaleplon is unrelated to benzodiazepines, barbiturates, or other hypnotics. However, it interacts with the benzodiazepine GABA receptor complex. Nonclinical studies have shown that it binds selectively to the brain omega-1 receptor situated on the alpha subunit of the GABA-A receptor complex.

Absorption

Rapid and almost complete; high-fat meal delays absorption

Distribution

Vd: ~1.4 L/kg

Metabolism

Extensive, primarily via aldehyde oxidase to form 5-oxo-zaleplon and, to a lesser extent, by CYP3A4 to desethylzaleplon; all metabolites are pharmacologically inactive

Excretion

Urine (~70% primarily metabolites, <1% as unchanged drug); feces (~17%)

Clearance: Plasma: Oral: 3 L/hour/kg

Onset of Action

Rapid

Time to Peak

Serum: ~1 hour

Half-Life Elimination

~1 hour

Protein Binding

~45% to 75%

Special Populations: Hepatic Function Impairment

Oral Cl was reduced 70% and 87% in compensated and decompensated cirrhotic patients, respectively.

Special Populations: Race

Cmax and AUC were increased 37% and 64%, respectively in Asian populations.

Use: Labeled Indications

Insomnia: Short-term treatment of insomnia.

Contraindications

Hypersensitivity to zaleplon or any component of the formulation

Dosing: Adult

Insomnia: Oral: Usual dosage 10 mg immediately before bedtime (range: 5 to 20 mg); 5 mg may be sufficient for certain low weight patients (maximum dose: 20 mg daily). Has been used for up to 5 weeks of treatment in controlled trial setting.

Debilitated patients: Oral: Usual dosage 5 mg immediately before bedtime (maximum dose: 10 mg daily)

Concomitant therapy: 5 mg initially should be given to patients concomitantly taking cimetidine.

Dosing: Geriatric

Insomnia: Oral: Usual dosage 5 mg immediately before bedtime (maximum dose: 10 mg daily).

Dosing: Renal Impairment

Mild to moderate impairment: No dosage adjustment necessary.

Severe impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Dosing: Hepatic Impairment

Mild to moderate impairment: 5 mg immediately before bedtime

Severe impairment: Use is not recommended.

Administration

Oral: Administer immediately before bedtime or when the patient is in bed and cannot fall asleep. Do not take with, or immediately following, a high-fat meal (may delay onset).

Dietary Considerations

Avoid taking with or after a heavy, high-fat meal; reduces absorption.

Storage

Store at 20°C to 25°C (68°F to 77°F). Protect from light.

Drug Interactions

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Cimetidine: May decrease the metabolism of Zaleplon. Consider therapy modification

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Levocabastine (Nasal). Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Zaleplon. Management: Consider the use of an alternative hypnotic that is not metabolized by CYP3A4 in patients receiving strong CYP3A4 inducers. If zalephon is combined with a strong CYP3A4 inducer, monitor for decreased effectiveness of zaleplon. Consider therapy modification

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification

Flumazenil: May diminish the sedative effect of Hypnotics (Nonbenzodiazepine). Monitor therapy

Hydrocodone: CNS Depressants may enhance the CNS depressant effect of Hydrocodone. Management: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

Metyrosine: CNS Depressants may enhance the sedative effect of Metyrosine. Monitor therapy

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: When oxycodone is combined with another CNS depressant, a dose reduction of one or both agents should be considered. The extended release oxycodone starting dose should be reduced 50% to 67% when initiated in patients already receiving CNS depressants. Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Sodium Oxybate: Hypnotics (Nonbenzodiazepine) may enhance the CNS depressant effect of Sodium Oxybate. Avoid combination

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Start tapentadol at a dose of one-third to one-half of the normal dose if being initiated in a patient who is taking another drug with CNS depressant effects. Monitor closely for evidence of excessive CNS depression. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

Adverse Reactions

>10%: Central nervous system: Headache (30% to 42%)

1% to 10%:

Cardiovascular: Chest pain (≥1%), peripheral edema (≤1%)

Central nervous system: Dizziness (7% to 9%), drowsiness (5% to 6%), amnesia (2% to 4%), paresthesia (3%), altered sense of smell (<1% to 2%), depersonalization (<1% to 2%), hyperacusis (1% to 2%), hypoesthesia (<1% to 2%), malaise (<1% to 2%), abnormality in thinking (≥1%), anxiety (≥1%), depression (≥1%), migraine (≥1%), nervousness (≥1%), hypertonia (1%), confusion (≤1%), hallucination (≤1%), vertigo (≤1%)

Dermatologic: Pruritus (≥1%), skin rash (≥1%), skin photosensitivity (≤1%)

Gastrointestinal: Nausea (6% to 8%), abdominal pain (6%), anorexia (<1% to 2%), constipation (≥1%), dysgeusia (≥1%), dyspepsia (≥1%), xerostomia (≥1%), colitis (≤1%)

Genitourinary: Dysmenorrhea (3% to 4%)

Neuromuscular & skeletal: Weakness (5% to 7%), tremor (2%), arthralgia (≥1%), arthritis (≥1%), back pain (≥1%), myalgia (≥1%)

Ophthalmic: Eye pain (3% to 4%), visual disturbance (<1% to 2%), conjunctivitis (≥1%)

Otic: Otalgia (≤1%)

Respiratory: Bronchitis (≥1%), epistaxis (≤1%)

Miscellaneous: Fever (≥1%)

<1% (Limited to important or life-threatening): Abnormal hepatic function tests, accommodation disturbance, ageusia, alopecia, anaphylaxis, anemia, angina pectoris, apathy, aphthous stomatitis, apnea, asthma, ataxia, bigeminy, blepharitis, blepharoptosis, bruxism, bundle branch block, bursitis, cataract, central nervous system stimulation, cerebral ischemia, cholelithiasis, conjunctival hyperemia (subconjunctival hemorrhage), corneal erosion, cyanosis, cystitis, deafness, decreased libido, delusions, diplopia, dry eye syndrome, duodenal ulcer, dysarthria, dysphagia, dyspnea, dystonia, dysuria, ecchymoses, edema, emotional lability, eosinophilia, esophageal achalasia, esophagitis, euphoria, facial paralysis, gastritis, gingivitis, glaucoma, glossitis, goiter, hangover effect, hemorrhage, hyperbilirubinemia, hypercholesterolemia, hyperesthesia, hyperglycemia, hyperkinesia, hyperreflexia, hypertension, hyperuricemia, hyperventilation, hypoglycemia, hypokinesia, hyporeflexia, hypotension, hypothyroidism, hypotonia, impotence, increased bronchial secretions, insomnia, intestinal obstruction, irregular menses, ketosis, lactose intolerance, laryngitis, leukocytosis, leukorrhea, lymphadenopathy, lymphocytosis, mastalgia, melanosis, melena, myasthenia, myoclonus, myositis, nephrolithiasis, neuropathy, nightmares, nystagmus, osteoporosis, palpitations, paradoxical central nervous system stimulation, peptic ulcer, pericardial effusion, photophobia, pleural effusion, pneumonia, psychomotor retardation, pulmonary embolism, purpura, renal pain, retinal detachment, sinus bradycardia, skin discoloration, skin hypertrophy, skin rash, sleep talking, slurred speech, snoring, somnambulism (complex sleep-related behavior [sleep-driving, sleep- cooking, sleep-eating, sleep-talking on the phone]), substernal pain, syncope, tenosynovitis, thrombophlebitis, tinnitus, tongue discoloration, tongue edema, transient perioral paresthesia, trismus, urethritis, urinary incontinence, urinary retention, urinary urgency, urticaria, vaginitis, vasodilatation, ventricular premature contractions, ventricular tachycardia, visual field defect, voice disorder, weight gain, weight loss, xeroderma

Warnings/Precautions

Concerns related to adverse effects:

• Abnormal thinking/behavioral changes: Hypnotics/sedatives have been associated with abnormal thinking and behavior changes including decreased inhibition, aggression, bizarre behavior, agitation, hallucinations, and depersonalization. These changes may occur unpredictably and may indicate previously unrecognized psychiatric disorders; evaluate appropriately.

• CNS depression: May cause CNS depression impairing physical and mental capabilities; patients must be cautioned about performing tasks which require mental alertness (operating machinery or driving); an increased risk of next-day psychomotor impairment may also occur. Additive CNS-depressant effects may also occur if a higher than recommended dose is taken and/or if coadministered with other CNS depressants. Dose adjustment may be necessary if taking concomitant CNS depressants; use with alcohol is not recommended.

• Hypersensitivity reactions: Hypersensitivity reactions, including anaphylaxis, as well as angioedema have been reported. Do not rechallenge patient if such reactions occur.

• Sleep-related activities: An increased risk for hazardous sleep-related activities such as sleep-driving, cooking and eating food, having sex, and making phone calls while asleep have been noted; amnesia may also occur. The use of alcohol, other CNS depressants, and exceeding the recommended maximum dose may increase the risk of these activities. Discontinue treatment in patients who report any sleep-driving episodes.

Disease-related concerns:

• Depression: Use with caution in patients with depression; worsening of depression, including suicide or suicidal ideation, has been reported with the use of hypnotics. Intentional overdose may be an issue in this population. The minimum dose that will effectively treat the individual patient should be used. Prescriptions should be written for the smallest quantity consistent with good patient care.

• Drug abuse: Use with caution in patients with a history of drug dependence, benzodiazepine abuse, or benzodiazepine-like hypnotic abuse.

• Hepatic impairment: Use with caution in patients with hepatic impairment; dosage adjustment recommended in mild to moderate impairment. Use is not recommended in patients with severe impairment.

• Respiratory disease: Use with caution in patients with respiratory compromise, COPD, or sleep apnea.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Debilitated: Use with caution in debilitated patients; potential for oversedation, impaired coordination, and confusion with use; dosage adjustment recommended.

• Elderly: Use with caution in elderly patients; dosage adjustment recommended. Monitor for impaired cognitive and/or motor performance, confusion, and potential for falling.

Dosage form specific issues:

• Tartrazine (FDC yellow #5): Capsules contain tartrazine; avoid in patients with sensitivity; reactions may be more frequently seen in patients with aspirin hypersensitivity; use caution in patients with asthma.

Other warnings/precautions:

• Appropriate use: Symptomatic treatment of insomnia should be initiated only after careful evaluation of potential causes of sleep disturbance. Failure of sleep disturbance to resolve after 7 to 10 days may indicate psychiatric and/or medical illness.

• Rapid onset: Because of the rapid onset of action, administer immediately prior to bedtime or after the patient has gone to bed and is having difficulty falling asleep.

• Withdrawal: Abrupt discontinuance or rapid dose decreases may lead to withdrawal symptoms.

Monitoring Parameters

Daytime alertness; respiratory rate (patients with compromised respiration); behavior profile; tolerance, abuse, and dependence

Pregnancy Risk Factor

C

Pregnancy Considerations

Teratogenic effects were not observed in animal reproduction studies. Adverse effects, including stillbirth, postnatal mortality, and decreased growth and physical development, were observed near the end of gestation. A small study of pregnant women did not show an increased risk of teratogenic effects when used early in pregnancy (Wiker, 2011). Use during pregnancy is not recommended by the manufacturer.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache, dizziness, fatigue, or nausea. Have patient report immediately to prescriber signs of depression (ie, suicidal ideation, anxiety, emotional instability, illogical thinking), insomnia, hallucinations, memory impairment, vision changes, change in balance, or considerable asthenia (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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