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Revisión médica por Militian Inessa Mesropovna Última actualización de farmacia el 31.03.2022
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Los 20 mejores medicamentos con los mismos ingredientes:
El tratamiento a corto plazo del insomnio está indicado para el tratamiento a corto plazo del insomnio. Se ha demostrado que el Соната Адамед Адамед disminuye el tiempo de inicio del sueño hasta 30 días en estudios clínicos controlados (ver Ensayos clínicos debajo FARMACOLOGÍA CLÍNICA). No se ha demostrado que aumente el tiempo total de sueño o disminuya el número de despertares.
Los ensayos clínicos realizados en apoyo de la eficacia variaron de una sola noche a 5 semanas de duración. Las evaluaciones formales finales de la latencia del sueño se realizaron al final del tratamiento.
La dosis de Соната Адамед Адамед debe ser individualizada. La dosis recomendada de Соната Адамед Адамед para la mayoría de los adultos no mayores es de 10 mg. Para ciertos individuos de bajo peso, 5 mg pueden ser una dosis suficiente. Aunque el riesgo de ciertos eventos adversos asociados con el uso de Соната Адамед Адамед parece depender de la dosis, Se ha demostrado que la dosis de 20 mg se tolera adecuadamente y puede considerarse para el paciente ocasional que no se beneficia de un ensayo de una dosis más baja. Las dosis superiores a 20 mg no se han evaluado adecuadamente y no se recomiendan.
El Соната Адамед Адамед debe tomarse inmediatamente antes de acostarse o después de que el paciente se haya acostado y haya experimentado dificultades para conciliar el sueño (ver PRECAUCIONES). Tomar Соната Адамед Адамед con o inmediatamente después de una comida pesada y rica en grasas resulta en una absorción más lenta y se espera que reduzca el efecto de Соната Адамед Адамед en la latencia del sueño (ver. Farmacocinética debajo FARMACOLOGÍA CLÍNICA).
Poblaciones especiales
Los pacientes de edad avanzada y los pacientes debilitados parecen ser más sensibles a los efectos de los hipnóticos y responden a 5 mg de Соната Адамед Адамед. La dosis recomendada para estos pacientes es, por lo tanto, de 5 mg. No se recomiendan dosis superiores a 10 mg.
Insuficiencia hepática: Los pacientes con insuficiencia hepática leve a moderada deben ser tratados con Соната Адамед Адамед 5 mg porque el aclaramiento se reduce en esta población. No se recomienda el uso de Соната Адамед Адамед en pacientes con insuficiencia hepática grave.
Insuficiencia renal: No es necesario ajustar la dosis en pacientes con insuficiencia renal leve a moderada. El Соната Адамед Адамед no se ha estudiado adecuadamente en pacientes con insuficiencia renal grave.
Se debe administrar una dosis inicial de 5 mg a los pacientes que toman cimetidina concomitantemente porque el aclaramiento de zaleplón se reduce en esta población (ver INTERACCIONES DE DROGAS debajo PRECAUCIONES).
Hipersensibilidad al zaleplón o cualquier excipiente en la formulación (ver también PRECAUCIONES).
WARNINGS
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 Соната Адамед Адамед. Because some of the important adverse effects of Соната Адамед Адамед 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 (e.g., 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 Соната Адамед Адамед alone at therapeutic doses, the use of alcohol and other CNS depressants with Соната Адамед Адамед appears to increase the risk of such behaviors, as does the use of Соната Адамед Адамед at doses exceeding the maximum recommended dose. Due to the risk to the patient and the community, discontinuation of Соната Адамед Адамед 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).
Соната Адамед Адамед, like other hypnotics, has CNS-depressant effects. Because of the rapid onset of action, Соната Адамед Адамед 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 Соната Адамед Адамед should be cautioned against engaging in hazardous occupations requiring complete mental alertness or motor coordination (e.g., 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 Соната Адамед Адамед. Соната Адамед Адамед, 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. Соната Адамед Адамед should not be taken with alcohol. Dosage adjustment may be necessary when Соната Адамед Адамед 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 Соната Адамед Адамед. 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 Соната Адамед Адамед should not be rechallenged with the drug.
PRECAUTIONS
General
Timing Of Drug Administration
Соната Адамед Адамед 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 Соната Адамед Адамед 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 Соната Адамед Адамед in patients with concomitant systemic illness is limited. Соната Адамед Адамед 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 Соната Адамед Адамед in normal subjects, caution should be observed if Соната Адамед Адамед (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 Соната Адамед Адамед 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 Соната Адамед Адамед 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. Соната Адамед Адамед has not been adequately studied in patients with severe renal impairment.
Use In Patients With Depression
As with other sedative/hypnotic drugs, Соната Адамед Адамед 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 OVERDOSAGE); 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
A patient Medication Guide is also available for Соната Адамед Адамед. 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 “sleepdriving” can be dangerous. This behavior is more likely to occur when Соната Адамед Адамед 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.
Laboratory Tests
There are no specific laboratory tests recommended.
Carcinogenesis, Mutagenesis, And Impairment Of Fertility
Carcinogenesis
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.
Mutagenesis
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, Соната Адамед Адамед® (zaleplon) is not recommended for use in women during pregnancy.
Labor And Delivery
Соната Адамед Адамед has no established use in labor and delivery.
Nursing Mothers
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 Соната Адамед Адамед 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 Соната Адамед Адамед.
Pediatric Use
The safety and effectiveness of Соната Адамед Адамед in pediatric patients have not been established.
Geriatric Use
A total of 628 patients in double-blind, placebo-controlled, parallel-group clinical trials who received Соната Адамед Адамед 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 Соната Адамед Адамед, no adverse event with a frequency of at least 1% occurred at a significantly higher rate with either 5 mg or 10 mg Соната Адамед Адамед than with placebo.
El programa de desarrollo de premarketing para Соната Адамед Адамед incluyó exposiciones de zaleplón en pacientes y / o sujetos normales de 2 grupos diferentes de estudios: aproximadamente 900 sujetos normales en farmacología clínica / estudios farmacocinéticos; y aproximadamente 2,900 exposiciones de pacientes en estudios de efectividad clínica controlados con placebo, correspondientes a aproximadamente 450 años de exposición de pacientes. Las condiciones y la duración del tratamiento con Соната Адамед Адамед variaron mucho e incluyeron (en categorías superpuestas) fases abiertas y doble ciego de estudios, pacientes hospitalizados y ambulatorios, y exposición a corto o largo plazo. Las reacciones adversas se evaluaron mediante la recopilación de eventos adversos, resultados de exámenes físicos, signos vitales, pesos, análisis de laboratorio y ECG.
Los eventos adversos durante la exposición se obtuvieron principalmente mediante una investigación general y los investigadores clínicos los registraron utilizando la terminología de su elección. En consecuencia, no es posible proporcionar una estimación significativa de la proporción de individuos que experimentan eventos adversos sin agrupar primero tipos similares de eventos en un número menor de categorías de eventos estandarizados. En las tablas y tabulaciones que siguen, la terminología COSTART se ha utilizado para clasificar los eventos adversos informados.
Las frecuencias indicadas de eventos adversos representan la proporción de individuos que experimentaron, al menos una vez, un evento adverso emergente del tratamiento del tipo enumerado. Un evento se consideró emergente del tratamiento si ocurrió por primera vez o empeoró al recibir la terapia después de la evaluación inicial.
Hallazgos adversos observados en ensayos controlados con placebo a corto plazo
Eventos adversos asociados con la interrupción del tratamiento
En ensayos clínicos de fase 2 y fase 3 controlados con placebo previo a la comercialización, el 3,1% de 744 pacientes que recibieron placebo y el 3,7% de 2.149 pacientes que recibieron Соната Адамед Адамед interrumpieron el tratamiento debido a un evento clínico adverso. Esta diferencia no fue estadísticamente significativa. Ningún evento que resultó en la interrupción ocurrió a una tasa de ≥ 1%.
Eventos adversos que ocurren con una incidencia del 1% o más entre los pacientes tratados con 20 mg de Соната Адамед Адамед
La Tabla 1 enumera la incidencia de eventos adversos emergentes del tratamiento para un grupo de tres estudios controlados con placebo de 28 noches y uno de 35 noches de Соната Адамед Адамед a dosis de 5 mg o 10 mg y 20 mg. La tabla incluye solo aquellos eventos que ocurrieron en el 1% o más de los pacientes tratados con Соната Адамед Адамед 20 mg y que tuvieron una mayor incidencia en pacientes tratados con Соната Адамед Адамед 20 mg que en pacientes tratados con placebo.
El médico debe ser consciente de que estas cifras no pueden usarse para predecir la incidencia de eventos adversos en el curso de la práctica médica habitual, donde las características del paciente y otros factores difieren de los que prevalecieron en los ensayos clínicos. Del mismo modo, las frecuencias citadas no se pueden comparar con las cifras obtenidas de otras investigaciones clínicas que involucran diferentes tratamientos, usos e investigadores. Sin embargo, las cifras citadas proporcionan al médico que prescribe alguna base para estimar la contribución relativa de los factores farmacológicos y no farmacológicos a la tasa de incidencia de eventos adversos en la población estudiada.
Tabla 1: Incidencia (%) de eventos adversos emergentes del tratamiento a largo plazo (28 y 35 noches) Ensayos clínicos controlados por placebo de Соната Адамед Адамедa
Sistema del cuerpo Término preferido | Placebo | Соната Адамед Адамед 5 mg o 10 mg (n = 569) | Соната Адамед Адамед 20 mg (n = 297) |
Cuerpo en su conjunto | |||
Dolor abdominal | 3 | 6 | 6 |
Astenia | 5 | 5 | 7 |
Dolor de cabeza | 35 | 30 | 42 |
Malestar | <1 | <1 | 2 |
Reacción de fotosensibilidad | <1 | <1 | 1 |
Sistema digestivo | |||
Anorexia | <1 | <1 | 2 |
Colitis | 0 | 0 | 1 |
Náuseas | 7 | 6 | 8 |
Metabólico y nutricional | |||
Edema periférico | <1 | <1 | 1 |
Sistema nervioso | |||
Amnesia | 1 | 2 | 4 |
Confusión | <1 | <1 | 1 |
Despersonalización | <1 | <1 | 2 |
Mareo | 7 | 7 | 9 |
Alucinaciones | <1 | <1 | 1 |
Hipertonía | <1 | 1 | 1 |
Hipestesia | <1 | <1 | 2 |
Parestesia | 1 | 3 | 3 |
Somnolencia | 4 | 5 | 6 |
Temblor | 1 | 2 | 2 |
Vértigo | <1 | <1 | 1 |
Sistema respiratorio | |||
Epistaxis | <1 | <1 | 1 |
Sentidos especiales | |||
Visión anormal | <1 | <1 | 2 |
Dolor de oído | 0 | <1 | 1 |
Dolor de ojos | 2 | 4 | 3 |
Hiperacusia | <1 | 1 | 2 |
Parosmia | <1 | <1 | 2 |
Sistema urogenital | |||
Dismenorrea | 2 | 3 | 4 |
a Eventos para los cuales la incidencia de pacientes tratados con 20 mg fue al menos del 1% y mayor que la incidencia entre los pacientes tratados con placebo. La incidencia superior al 1% se ha redondeado al número entero más cercano. |
Otros eventos adversos observados durante la evaluación previa a la comercialización de Соната Адамед Адамед
A continuación se enumeran los términos COSTART que reflejan eventos adversos emergentes del tratamiento, tal como se definen en la introducción a la sección REACCIONES ADVERSAS. Estos eventos fueron reportados por pacientes tratados con Соната Адамед Адамед (zaleplon) a dosis en un rango de 5 mg / día a 20 mg / día durante los ensayos clínicos de fase 2 y fase 3 de precomercialización en los Estados Unidos, Canadá y Europa, incluidos aproximadamente 2,900 pacientes. Todos los eventos informados se incluyen, excepto los que ya figuran en la Tabla 1 o en otra parte del etiquetado, aquellos eventos para los cuales una causa de drogas fue remota y aquellos términos de eventos que fueron tan generales que no fueron informativos. Es importante enfatizar que aunque los eventos reportados ocurrieron durante el tratamiento con Соната Адамед Адамед, no fueron necesariamente causados por él.
Los eventos se clasifican aún más por sistema corporal y se enumeran en orden decreciente de frecuencia de acuerdo con las siguientes definiciones: frecuente los eventos adversos son los que ocurren en una o más ocasiones en al menos 1/100 pacientes; enfrecuente los eventos adversos son los que ocurren en menos de 1/100 pacientes pero al menos 1 / 1,000 pacientes; eventos raros son los que ocurren en menos de 1 / 1,000 pacientes.
Cuerpo en su conjunto - Frecuente: dolor de espalda, dolor en el pecho, fiebre ; Poco frecuente: dolor en el pecho subesternal, escalofríos, edema facial, edema generalizado, efecto de resaca, rigidez en el cuello.
Sistema cardiovascular - Frecuente: migraña ; Poco frecuente: angina de pecho, bloqueo de rama, hipertensión, hipotensión, palpitación, síncope, taquicardia, vasodilatación, extrasístoles ventriculares; Raro: bigeminia, isquemia cerebral, cianosis, derrame pericárdico, hipotensión postural, embolia pulmonar, bradicardia sinusal, tromboflebitis, taquicardia ventricular.
Sistema digestivo -Frecuente: estreñimiento, boca seca, dispepsia; Poco frecuente: eructos, esofagitis, flatulencia, gastritis, gastroenteritis, gingivitis, glositis, aumento del apetito, melena, ulceración bucal, hemorragia rectal, estomatitis; Raro: estomatitis aftosa, dolor biliar, bruxismo, cardiospasmo, queilitis, colelitiasis, úlcera duodenal, disfagia, enteritis, hemorragia de las encías, aumento de la salivación, obstrucción intestinal, pruebas de función hepática anormales, úlcera péptica, decoloración de la lengua, edema de la lengua, estomatitis ulcerosa.
Sistema endocrino -Rare: diabetes mellitus, bocio, hipotiroidismo.
Sistema hemico y linfático: infrecuente: anemia, equimosis, linfadenopatía; Raro: eosinofilia, leucocitosis, linfocitosis, púrpura.
Metabólico y nutricional -Infrecuente: edema, gota, hipercolesteremia, sed, aumento de peso; Raro: bilirrubinemia, hiperglucemia, hiperuricemia, hipoglucemia, reacción hipoglucemiante, cetosis, intolerancia a la lactosa, aumento de AST (SGOT), aumento de ALT (SGPT), pérdida de peso.
Sistema musculoesquelético - Frecuente: artralgia, artritis, mialgia ; Poco frecuente: artrosis, bursitis, trastorno articular (principalmente hinchazón, rigidez y dolor), miastenia, tenosinovitis; Raro: miositis, osteoporosis.
Sistema nervioso - Frecuente: ansiedad, depresión, nerviosismo, pensamiento anormal (principalmente dificultad para concentrarse); Poco frecuente: marcha anormal, agitación, apatía, ataxia, parestesia circunoral, labilidad emocional, euforia, hiperestesia, hipercinesia, hipotonía, incoordinación, insomnio, disminución de la libido, neuralgia, nistagmo; Raro: estimulación del SNC, delirios, disartria, distonía, parálisis facial, hostilidad, hipocinesia, mioclono, neuropatía, retraso psicomotor, ptosis, disminución de reflejos, aumento de reflejos, conversación del sueño, marcha del sueño, dificultad para hablar, estupor, trismus.
Sistema respiratorio - Frecuente: bronquitis; Poco frecuente: asma, disnea, laringitis, neumonía, ronquidos, alteración de la voz; Raro: apnea, hipo, hiperventilación, derrame pleural, aumento del esputo.
Piel y apéndices - Frecuentes: prurito, erupción cutánea ; Poco frecuente: acné, alopecia, dermatitis de contacto, piel seca, eccema, erupción maculopapular, hipertrofia de la piel, sudoración, urticaria, erupción vesiculobulosa; Raro: melanosis, psoriasis, erupción pustular, decoloración de la piel.
Sentidos especiales - Frecuentes: conjuntivitis, perversión del gusto ; Poco frecuente: diplopía, ojos secos, fotofobia, tinnitus, ojos llorosos ; Raro: anormalidad del alojamiento, blefaritis, cataratas especificadas, erosión corneal, sordera, hemorragia ocular, glaucoma, laberintitis, desprendimiento de retina, pérdida de sabor, defecto del campo visual.
Sistema urogenital -Infrecuente: dolor en la vejiga, dolor en los senos, cistitis, disminución del flujo de orina, disuria, hematuria, impotencia, cálculo renal, dolor renal, menorragia, metrorragia, frecuencia urinaria, incontinencia urinaria, urgencia urinaria, vaginitis; Raro: albuminuria, período menstrual retrasado, leucorrea, menopausia, uretritis, retención urinaria, hemorragia vaginal.
Informes de postmarketing
Reacciones anafilácticas / anafilactoides, incluidas reacciones graves y pesadillas.
Abuso de drogas y dependencia
Clase de sustancia controlada
La Адамед Адамед está clasificada como una sustancia controlada por el Anexo IV por la regulación federal.
Abuso, dependencia y tolerancia
El abuso y la adicción son separados y distintos de la dependencia física y la tolerancia. El abuso se caracteriza por el mal uso de la droga con fines no médicos, a menudo en combinación con otras sustancias psicoactivas. La dependencia física es un estado de adaptación que se manifiesta por un síndrome de abstinencia específico que puede producirse por cesación abrupta, reducción rápida de la dosis, disminución del nivel sanguíneo del medicamento y / o administración de un antagonista. La tolerancia es un estado de adaptación en el que la exposición a un medicamento induce cambios que resultan en una disminución de uno o más de los efectos del medicamento a lo largo del tiempo. La tolerancia puede ocurrir tanto a los efectos deseados como no deseados de los medicamentos y puede desarrollarse a diferentes tasas para diferentes efectos.
La adicción es una enfermedad primaria, crónica y neurobiológica con factores genéticos, psicosociales y ambientales que influyen en su desarrollo y manifestaciones. Se caracteriza por comportamientos que incluyen uno o más de los siguientes: control deteriorado sobre el uso de drogas, uso compulsivo, uso continuo a pesar del daño y antojo. La adicción a las drogas es una enfermedad tratable, que utiliza un enfoque multidisciplinario, pero la recaída es común.
Abuso
Dos estudios evaluaron la responsabilidad por abuso de Соната Адамед Адамед a dosis de 25 mg, 50 mg y 75 mg en sujetos con historias conocidas de abuso de drogas sedantes. Los resultados de estos estudios indican que Соната Адамед Адамед tiene un potencial de abuso similar a la benzodiacepina y los hipnóticos similares a las benzodiacepinas.
Dependencia
El potencial para desarrollar dependencia física de Соната Адамед Адамед y un síndrome de abstinencia posterior se evaluó en estudios controlados de duraciones de 14, 28 y 35 noches y en estudios abiertos de 6 y 12 meses de duración examinando la aparición de insomnio de rebote después de la interrupción del fármaco. Algunos pacientes (en su mayoría los tratados con 20 mg) experimentaron un insomnio leve de rebote la primera noche después de la abstinencia que parecía resolverse la segunda noche. El uso del Cuestionario del síntoma de abstinencia de benzodiacepinas y el examen de cualquier otro evento emergente de abstinencia no detectaron ninguna otra evidencia de un síndrome de abstinencia después de la interrupción abrupta de la terapia Адамед Адамед en estudios previos a la comercialización.
Sin embargo, los datos disponibles no pueden proporcionar una estimación confiable de la incidencia de dependencia durante el tratamiento a las dosis recomendadas de Соната Адамед Адамед. Otros sedantes / hipnóticos se han asociado con varios signos y síntomas después de una interrupción abrupta, que van desde disforia leve e insomnio hasta un síndrome de abstinencia que puede incluir calambres abdominales y musculares, vómitos, sudoración, temblores y convulsiones. Se han observado convulsiones en dos pacientes, uno de los cuales tuvo una convulsión previa, en ensayos clínicos con Соната Адамед Адамед. Se han observado convulsiones y muertes después de la retirada de zaleplón de animales a dosis muchas veces más altas que las propuestas para uso humano. Debido a que las personas con antecedentes de adicción o abuso de drogas o alcohol corren el riesgo de habituación y dependencia, deben estar bajo cuidadosa vigilancia al recibir Соната Адамед Адамед o cualquier otro hipnótico.
Tolerancia
La posible tolerancia a los efectos hipnóticos de Соната Адамед Адамед 10 mg y 20 mg se evaluó evaluando el tiempo hasta el inicio del sueño para Соната Адамед Адамед en comparación con placebo en dos estudios controlados con placebo de 28 noches y la latencia para un sueño persistente en un estudio de 35 noches noches 29 y 30. No se observó desarrollo de tolerancia a Соната Адамед Адамед durante el tiempo hasta el inicio del sueño durante 4 semanas.
Signos y síntomas
Se puede esperar que los signos y síntomas de los efectos de sobredosis de los depresores del SNC se presenten como exageraciones de los efectos farmacológicos observados en las pruebas preclínicas. La sobredosis generalmente se manifiesta por grados de depresión del sistema nervioso central que van desde la somnolencia hasta el coma. En casos leves, los síntomas incluyen somnolencia, confusión mental y letargo; En casos más graves, los síntomas pueden incluir ataxia, hipotonía, hipotensión, depresión respiratoria, rara vez coma y muy raramente la muerte.
La pérdida de conciencia, además de los signos y síntomas consistentes con los depresores del SNC como se describió anteriormente, se han informado después de una sobredosis de zaleplón. Las personas se han recuperado completamente de sobredosis de zaleplón de más de 200 mg (10 veces la dosis máxima recomendada de zaleplón). Se han informado casos raros de resultados fatales después de una sobredosis con zaleplón, más a menudo asociados con una sobredosis de depresores adicionales del SNC.
Tratamiento recomendado
Se deben usar medidas generales sintomáticas y de apoyo junto con lavado gástrico inmediato cuando corresponda. Los líquidos intravenosos deben administrarse según sea necesario. Los estudios en animales sugieren que el flumazenil es un antagonista del zaleplón. Sin embargo, no existe experiencia clínica previa a la comercialización con el uso de flumazenil como antídoto contra una sobredosis de Соната Адамед Адамед. Como en todos los casos de sobredosis de drogas, se debe controlar la respiración, el pulso, la presión arterial y otros signos apropiados y emplear medidas generales de apoyo. La hipotensión y la depresión del SNC deben controlarse y tratarse mediante una intervención médica adecuada.
Centro de control de venenos
Al igual que con el manejo de toda sobredosis, se debe considerar la posibilidad de ingestión múltiple de medicamentos. El médico puede considerar ponerse en contacto con un centro de control de intoxicaciones para obtener información actualizada sobre el manejo de la sobredosis de medicamentos hipnóticos.
Special Populations
Elderly patients and debilitated patients appear to be more sensitive to the effects of hypnotics, and respond to 5 mg of Соната Адамед Адамед. 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 Соната Адамед Адамед 5 mg because clearance is reduced in this population. Соната Адамед Адамед 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. Соната Адамед Адамед 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).
HOW SUPPLIED
Соната Адамед Адамед (zaleplon) capsules are supplied as follows:
5 mg: opaque green cap and opaque pale green body with “5 mg” on the cap and “Соната Адамед Адамед” on the body.
NDC 60793-145-01 Bottles of 100
10 mg: opaque green cap and opaque light green body with “10 mg” on the cap and “Соната Адамед Адамед” on the body.
NDC 60793-146-01 Bottles of 100
Storage Conditions
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.
Prescribing Information as of December 2007.
Distributed by: King Pharmaceuticals, Inc., Bristol, TN 37620 Manufactured by: Corepharma LLC, 215 Wood Avenue Middlesex, NJ 08846. Revised: April 2013
Side Effects & Drug InteractionsSIDE EFFECTS
The premarketing development program for Соната Адамед Адамед 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 Соната Адамед Адамед 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 listed. An event was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation.
Adverse Findings Observed In Short-Term, Placebo-Controlled Trials
Adverse Events Associated With Discontinuation Of Treatment
In premarketing placebo-controlled, parallel-group phase 2 and phase 3 clinical trials, 3.1% of 744 patients who received placebo and 3.7% of 2,149 patients who received Соната Адамед Адамед discontinued treatment because of an adverse clinical event. This difference was not statistically significant. No event that resulted in discontinuation occurred at a rate of ≥ 1%.
Adverse Events Occurring At An Incidence Of 1% Or More Among Соната Адамед Адамед 20 mg-Treated Patients
Table 1 enumerates the incidence of treatment-emergent adverse events for a pool of three 28night and one 35-night placebo-controlled studies of Соната Адамед Адамед at doses of 5 mg or 10 mg and 20 mg. The table includes only those events that occurred in 1% or more of patients treated with Соната Адамед Адамед 20 mg and that had a higher incidence in patients treated with Соната Адамед Адамед 20 mg than in placebo-treated patients.
The prescriber should be aware that these figures cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the adverse event incidence rate in the population studied.
Table 1 : Incidence (%) of Treatment-Emergent Adverse Events in Long-Term (28 and 35 Nights) Placebo-Controlled Clinical Trials of Соната Адамед Адамедa
Body System Preferred Term | Placebo | Соната Адамед Адамед 5 mg or 10 mg (n = 569) | Соната Адамед Адамед 20 mg (n = 297) |
Body as a whole | |||
Abdominal pain | 3 | 6 | 6 |
Asthenia | 5 | 5 | 7 |
Headache | 35 | 30 | 42 |
Malaise | < 1 | < 1 | 2 |
Photosensitivity reaction | < 1 | < 1 | 1 |
Digestive system | |||
Anorexia | < 1 | < 1 | 2 |
Colitis | 0 | 0 | 1 |
Nausea | 7 | 6 | 8 |
Metabolic and nutritional | |||
Peripheral edema | < 1 | < 1 | 1 |
Nervous system | |||
Amnesia | 1 | 2 | 4 |
Confusion | < 1 | < 1 | 1 |
Depersonalization | < 1 | < 1 | 2 |
Dizziness | 7 | 7 | 9 |
Hallucinations | < 1 | < 1 | 1 |
Hypertonia | < 1 | 1 | 1 |
Hypesthesia | < 1 | < 1 | 2 |
Paresthesia | 1 | 3 | 3 |
Somnolence | 4 | 5 | 6 |
Tremor | 1 | 2 | 2 |
Vertigo | < 1 | < 1 | 1 |
Respiratory system | |||
Epistaxis | < 1 | < 1 | 1 |
Special senses | |||
Abnormal vision | < 1 | < 1 | 2 |
Ear pain | 0 | < 1 | 1 |
Eye pain | 2 | 4 | 3 |
Hyperacusis | < 1 | 1 | 2 |
Parosmia | < 1 | < 1 | 2 |
Urogenital system | |||
Dysmenorrhea | 2 | 3 | 4 |
a Events for which the incidence for Соната Адамед Адамед 20 mg-treated patients was at least 1% and greater than the incidence among placebo-treated patients. Incidence greater than 1% has been rounded to the nearest whole number. |
Other Adverse Events Observed During The Premarketing Evaluation Of Соната Адамед Адамед
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 Соната Адамед Адамед (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 listed 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 Соната Адамед Адамед, they were not necessarily caused by it.
Events are further categorized by body system and listed 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.
Skin and 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.
Postmarketing Reports
Anaphylactic/anaphylactoid reactions, including severe reactions, and nightmares.
Drug Abuse And Dependence
Controlled Substance Class
Соната Адамед Адамед is classified as a Schedule IV controlled substance by federal regulation.
Abuse, Dependence, And Tolerance
Abuse and addiction are separate and distinct from physical dependence and tolerance. Abuse is characterized by misuse of the drug for non-medical purposes, often in combination with other psychoactive substances. Physical dependence is a state of adaption that is manifested by a specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug and/or administration of an antagonist. Tolerance is a state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug's effects over time. Tolerance may occur to both the desired and undesired effects of drugs and may develop at different rates for different effects.
Addiction is a primary, chronic, neurobiological disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving. Drug addiction is a treatable disease, utilizing a multidisciplinary approach, but relapse is common.
Abuse
Two studies assessed the abuse liability of Соната Адамед Адамед at doses of 25 mg, 50 mg, and 75 mg in subjects with known histories of sedative drug abuse. The results of these studies indicate that Соната Адамед Адамед has an abuse potential similar to benzodiazepine and benzodiazepine-like hypnotics.
Dependence
The potential for developing physical dependence on Соната Адамед Адамед and a subsequent withdrawal syndrome was assessed in controlled studies of 14-, 28-, and 35-night durations and in open-label studies of 6- and 12-month durations by examining for the emergence of rebound insomnia following drug discontinuation. Some patients (mostly those treated with 20 mg) experienced a mild rebound insomnia on the first night following withdrawal that appeared to be resolved by the second night. The use of the Benzodiazepine Withdrawal Symptom Questionnaire and examination of any other withdrawal-emergent events did not detect any other evidence for a withdrawal syndrome following abrupt discontinuation of Соната Адамед Адамед therapy in pre-marketing studies.
However, available data cannot provide a reliable estimate of the incidence of dependence during treatment at recommended doses of Соната Адамед Адамед. Other sedative/hypnotics have been associated with various signs and symptoms following abrupt discontinuation, ranging from mild dysphoria and insomnia to a withdrawal syndrome that may include abdominal and muscle cramps, vomiting, sweating, tremors, and convulsions. Seizures have been observed in two patients, one of which had a prior seizure, in clinical trials with Соната Адамед Адамед. Seizures and death have been seen following the withdrawal of zaleplon from animals at doses many times higher than those proposed for human use. Because individuals with a history of addiction to, or abuse of, drugs or alcohol are at risk of habituation and dependence, they should be under careful surveillance when receiving Соната Адамед Адамед or any other hypnotic.
Tolerance
Possible tolerance to the hypnotic effects of Соната Адамед Адамед 10 mg and 20 mg was assessed by evaluating time to sleep onset for Соната Адамед Адамед compared with placebo in two 28-night placebo-controlled studies and latency to persistent sleep in one 35-night placebo-controlled study where tolerance was evaluated on nights 29 and 30. No development of tolerance to Соната Адамед Адамед was observed for time to sleep onset over 4 weeks.
DRUG INTERACTIONS
As with all drugs, the potential exists for interaction with other drugs by a variety of mechanisms.
CNS-Active Drugs
Ethanol: Соната Адамед Адамед 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 Соната Адамед Адамед 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 Соната Адамед Адамед 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 Соната Адамед Адамед, reflecting the absence of a role of CYP2D6 in zaleplon's metabolism.
Thioridazine: Coadministration of single doses of Соната Адамед Адамед 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 Соната Адамед Адамед (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 (see DOSAGE AND ADMINISTRATION).
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 Соната Адамед Адамед 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:
Warfarin: Multiple oral doses of Соната Адамед Адамед (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.
Warnings & PrecautionsWARNINGS
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 Соната Адамед Адамед. Because some of the important adverse effects of Соната Адамед Адамед 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 (e.g., 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 Соната Адамед Адамед alone at therapeutic doses, the use of alcohol and other CNS depressants with Соната Адамед Адамед appears to increase the risk of such behaviors, as does the use of Соната Адамед Адамед at doses exceeding the maximum recommended dose. Due to the risk to the patient and the community, discontinuation of Соната Адамед Адамед 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).
Соната Адамед Адамед, like other hypnotics, has CNS-depressant effects. Because of the rapid onset of action, Соната Адамед Адамед 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 Соната Адамед Адамед should be cautioned against engaging in hazardous occupations requiring complete mental alertness or motor coordination (e.g., 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 Соната Адамед Адамед. Соната Адамед Адамед, 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. Соната Адамед Адамед should not be taken with alcohol. Dosage adjustment may be necessary when Соната Адамед Адамед 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 Соната Адамед Адамед. 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 Соната Адамед Адамед should not be rechallenged with the drug.
PRECAUTIONS
General
Timing Of Drug Administration
Соната Адамед Адамед 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 Соната Адамед Адамед 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 Соната Адамед Адамед in patients with concomitant systemic illness is limited. Соната Адамед Адамед 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 Соната Адамед Адамед in normal subjects, caution should be observed if Соната Адамед Адамед (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 Соната Адамед Адамед 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 Соната Адамед Адамед 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. Соната Адамед Адамед has not been adequately studied in patients with severe renal impairment.
Use In Patients With Depression
As with other sedative/hypnotic