(ZAL e plon)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Sonata: 5 mg, 10 mg [contains tartrazine (fd&c yellow #5)]
Generic: 5 mg, 10 mg
Brand Names: U.S.
- Hypnotic, Miscellaneous
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.
Rapid and almost complete; high-fat meal delays absorption
Vd: ~1.4 L/kg
Extensive, primarily via aldehyde oxidase to form 5-oxo-zaleplon and, to a lesser extent, by CYP3A4 to desethylzaleplon; all metabolites are pharmacologically inactive
Urine (~70% primarily metabolites, <1% as unchanged drug); feces (~17%)
Clearance: Plasma: Oral: 3 L/hour/kg
Onset of Action
Time to Peak
Serum: ~1 hour
~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.
Hypersensitivity to zaleplon or any component of the formulation
Adults: 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: Usual dosage: 5 mg immediately before bedtime (maximum dose: 10 mg daily)
Elderly: 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.
Dosage adjustment in 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).
Dosage adjustment in hepatic impairment:
Mild to moderate impairment: 5 mg immediately before bedtime
Severe impairment: Use is not recommended.
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).
Avoid taking with or after a heavy, high-fat meal; reduces absorption.
Store at 20°C to 25°C (68°F to 77°F). Protect from light.
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
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
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
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
>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
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.
• 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.
• 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. Avoid chronic use (>90 days) in older adults; adverse events, including delirium, falls, fractures, has been observed with nonbenzodiazepine hypnotic use in the elderly similar to events observed with benzodiazepines. Data suggests improvements in sleep duration and latency are minimal (Beers Criteria).
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.
• 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.
Daytime alertness; respiratory rate (patients with compromised respiration); behavior profile; tolerance, abuse, and dependence
Pregnancy Risk Factor
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.
• 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.
More about zaleplon
- Other brands: Sonata