Zalaplon
Zalaplon - General Information
Zalaplon is a sedative/hypnotic, mainly used for insomnia. It is known as a nonbenzodiazepine hypnotic. Zalaplon interacts with the GABA receptor complex and shares some of the pharmacological properties of the benzodiazepines. Zalaplon is a schedule IV drug in the United States.
Pharmacology of Zalaplon
Zalaplon is a nonbenzodiazepine hypnotic from the pyrazolopyrimidine class and is indicated for the short-term treatment of insomnia. While Zalaplon 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 (GABABZ) receptor complex. Subunit modulation of the GABABZ 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. Zalaplon binds selectively to the brain alpha subunit of the GABA A omega-1 receptor.
Zalaplon for patients
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 doctorís 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:
ó 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.
ó 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.
ó 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.
ó 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 "travelerís 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 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 doctorís 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:
ó more outgoing or aggressive behavior than normal
ó 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 personís 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:
1. Sonata is a prescription medicine and should be used ONLY as directed by your doctor. Follow your doctorís instructions about how to take, when to take, and how long to take Sonata.
2. Never use Sonata or any other sleep medicine for longer than directed by your doctor.
3. If you notice any unusual and/or disturbing thoughts or behavior during treatment with Sonata or any other sleep medicine, contact your doctor.
4. 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.
5. Do not take Sonata unless you are able to get 4 or more hours of sleep before you must be active again.
6. Do not increase the prescribed dose of Sonata or any other sleep medicine unless instructed by your doctor.
7. 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.
8. Be aware that you may have more sleeping problems the first night or two after stopping any sleep medicine.
9. 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.
10. 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.
11. Be sure to tell your physician if you suffer from depression.
12. 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.
13. For Sonata to work best, you should not take Sonata with or immediately after a high-fat/heavy meal.
14. 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.
Zalaplon Interactions
As with all drugs, the potential exists for interaction with other drugs by a variety of mechanisms.
CNS-Active Drugs
Ethanol: Sonata 10 mg potentiated the CNS-impairing effects of ethanol 0.75 g/kg on balance testing and reaction time for 1 hour after ethanol administration and on the digit symbol substitution test (DSST), symbol copying test, and the variability component of the divided attention test for 2.5 hours after ethanol administration. The potentiation resulted from a CNS pharmacodynamic interaction; zaleplon did not affect the pharmacokinetics of ethanol.
Imipramine: Coadministration of single doses of Sonata 20 mg and imipramine 75 mg produced additive effects on decreased alertness and impaired psychomotor performance for 2 to 4 hours after administration. The interaction was pharmacodynamic with no alteration of the pharmacokinetics of either drug.
Paroxetine: Coadministration of a single dose of Sonata 20 mg and paroxetine 20 mg daily for 7 days did not produce any interaction on psychomotor performance. Additionally, paroxetine did not alter the pharmacokinetics of Sonata, reflecting the absence of a role of CYP2D6 in zaleplonís metabolism.
Thioridazine: Coadministration of single doses of Sonata 20 mg and thioridazine 50 mg produced additive effects on decreased alertness and impaired psychomotor performance for 2 to 4 hours after administration. The interaction was pharmacodynamic with no alteration of the pharmacokinetics of either drug.
Venlafaxine: Coadministration of a single dose of zaleplon 10 mg and multiple doses of venlafaxine ER (extended release) 150 mg did not result in any significant changes in the pharmacokinetics of either zaleplon or venlafaxine. In addition, there was no pharmacodynamic interaction as a result of coadministration of zaleplon and venlafaxine ER.
Promethazine: Coadministration of a single dose of zaleplon and promethazine (10 and 25 mg, respectively) resulted in a 15% decrease in maximal plasma concentrations of zaleplon, but no change in the area under the plasma concentration-time curve. However, the pharmacodynamics of coadministration of zaleplon and promethazine have not been evaluated. Caution should be exercised when these 2 agents are coadministered.
Drugs That Induce CYP3A4
Rifampin: CYP3A4 is ordinarily a minor metabolizing enzyme of zaleplon. Multiple-dose administration of the potent CYP3A4 inducer rifampin (600 mg every 24 hours, q24h, for 14 days), however, reduced zaleplon Cmax and AUC by approximately 80%. The coadministration of a potent CYP3A4 enzyme inducer, although not posing a safety concern, thus could lead to ineffectiveness of zaleplon. An alternative non-CYP3A4 substrate hypnotic agent may be considered in patients taking CYP3A4 inducers such as rifampin, phenytoin, carbamazepine, and phenobarbital.
Drugs That Inhibit CYP3A4
CYP3A4 is a minor metabolic pathway for the elimination of zaleplon because the sum of desethylzaleplon (formed via CYP3A4 in vitro) and its metabolites, 5-oxo-desethylzaleplon and 5-oxo-desethylzaleplon glucuronide, account for only 9% of the urinary recovery of a zaleplon dose. Coadministration of single, oral doses of zaleplon with erythromycin (10 mg and 800 mg, respectively), a strong, selective CYP3A4 inhibitor produced a 34% increase in zaleplon's maximal plasma concentrations and a 20% increase in the area under the plasma concentration-time curve. The magnitude of interaction with multiple doses of erythromycin is unknown. Other strong selective CYP3A4 inhibitors such as ketoconazole can also be expected to increase the exposure of zaleplon. A routine dosage adjustment of zaleplon is not considered necessary.
Drugs That Inhibit Aldehyde Oxidase
The aldehyde oxidase enzyme system is less well studied than the cytochrome P450 enzyme system.
Diphenhydramine: Diphenhydramine is reported to be a weak inhibitor of aldehyde oxidase in rat liver, but its inhibitory effects in human liver are not known. There is no pharmacokinetic interaction between zaleplon and diphenhydramine following the administration of a single dose (10 mg and 50 mg, respectively) of each drug. However, because both of these compounds have CNS effects, an additive pharmacodynamic effect is possible.
Drugs That Inhibit Both Aldehyde Oxidase and CYP3A4
Cimetidine: Cimetidine inhibits both aldehyde oxidase (in vitro) and CYP3A4 (in vitro and in vivo), the primary and secondary enzymes, respectively, responsible for zaleplon metabolism. Concomitant administration of Sonata (10 mg) and cimetidine (800 mg) produced an 85% increase in the mean Cmax and AUC of zaleplon. An initial dose of 5 mg should be given to patients who are concomitantly being treated with cimetidine.
Drugs Highly Bound to Plasma Protein
Zaleplon is not highly bound to plasma proteins (fraction bound 60%±15%); therefore, the disposition of zaleplon is not expected to be sensitive to alterations in protein binding. In addition, administration of Sonata to a patient taking another drug that is highly protein bound should not cause transient increase in free concentrations of the other drug.
Drugs with a Narrow Therapeutic Index
Digoxin: Sonata (10 mg) did not affect the pharmacokinetic or pharmacodynamic profile of digoxin (0.375 mg q24h for 8 days).
Warfarin: Multiple oral doses of Sonata (20 mg q24h for 13 days) did not affect the pharmacokinetics of warfarin (R+)- or (S-)-enantiomers or the pharmacodynamics (prothrombin time) following a single 25-mg oral dose of warfarin.
Drugs That Alter Renal Excretion
Ibuprofen: Ibuprofen is known to affect renal function and, consequently, alter the renal excretion of other drugs. There was no apparent pharmacokinetic interaction between zaleplon and ibuprofen following single dose administration (10 mg and 600 mg, respectively) of each drug. This was expected because zaleplon is primarily metabolized and renal excretion of unchanged zaleplon accounts for less than 1% of the administered dose.
Zalaplon Contraindications
Hypersensitivity to zaleplon or any excipients in the formulation.
Additional information about Zalaplon
Zalaplon Indication: For the treatment of short-term treatment of insomnia in adults.
Mechanism Of Action: Zalaplon exerts its action through subunit modulation of the GABABZ receptor chloride channel macromolecular complex.Zalaplon binds selectively to the brain alomega-1 receptor situated on the alpha subunit of the GABA-A/chloride ion channel receptor complex and potentiates t-butyl-bicyclophosphorothionate (TBPS) binding.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Zaleplon
Synonyms: DEA No. 2781
Drug Category: Hypnotics and Sedatives; Anticonvulsants; Anxiolytics sedatives and hypnotics
Drug Type: Small Molecule; Illicit; Approved
Other Brand Names containing Zaleplon: Sonata; Zalaplon;
Absorption: Absorption Zaleplon is rapidly and almost completely absorbed following oral administration.
Toxicity (Overdose): Side effects include abdominal pain, amnesia, dizziness, drowsiness, eye pain, headache, memory loss, menstrual pain, nausea, sleepiness, tingling, weakness
Protein Binding: Approximately 60% (in vitro plasma protein binding).
Biotransformation: Zaleplon is primarily metabolized by aldehyde oxidase.
Half Life: Approximately 1 hour
Dosage Forms of Zalaplon: Capsule Oral
Chemical IUPAC Name: N-[3-(3-cyanopyrazolo[5,1-b]pyrimidin-7-yl)phenyl]-N-ethylacetamide
Chemical Formula: C17H15N5O
Zaleplon on Wikipedia: https://en.wikipedia.org/wiki/Zaleplon
Organisms Affected: Humans and other mammals
