Lexuss

Öksürük ve Üst Solunum Alerjisi Belirtileri

Lexuss, 18 yaş ve üstü yetişkinlerde üst solunum alerjileri veya soğuk algınlığı ile ilişkili öksürük ve semptomların giderilmesi için endikedir.

Önemli Kullanım Sınırlamaları

18 yaşın altındaki pediatrik hastalar için endike değildir.

Yetişkinler 18 Yaş ve Üstü

Lexuss, 24 saatte 2 dozu (20 mL) aşmamak için her 12 saatte bir 10 mL'lik bir dozda oral yoldan uygulanmalıdır.

Yönetim Bilgileri

Lexuss'u sadece oral yoldan, yiyecek olsun veya olmasın yönetin. Kullanmadan önce iyice çalkalayın. Doğru bir mililitre ölçüm cihazı ile ölçün. Dozu ölçmek için bir çay kaşığı kullanmayın.

Lexuss kontrendikedir:

• 12 yaşından küçük tüm çocuklar.
• Bademcik ameliyatı ve / veya adenoidektomi sonrası 18 yaşından küçük çocuklarda postoperatif yönetim.
• Kodein, klorfeniramin veya Lexuss'un aktif olmayan bileşenlerinden herhangi birine karşı aşırı duyarlılığı olduğu bilinen hastalar. Diğer bazı opioidlere aşırı duyarlı olduğu bilinen kişiler kodeine karşı çapraz duyarlılık gösterebilir.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Ultra-Rapid Metabolism Of Codeine And Other Risk Factors For Life-threatening Respiratory Depression In Children

Life-threatening respiratory depression and death have occurred in children who received codeine. Codeine is subject to variability in metabolism based upon CYP2D6 genotype (described below), which can lead to an increased exposure to the active metabolite morphine. Based upon post-marketing reports, children younger than 12 years old appear to be more susceptible to the respiratory depressant effects of codeine, particularly if there are risk factors for respiratory depression. For example, many reported cases of death occurred in the post-operative period following tonsillectomy and/or adenoidectomy, and many of the children had evidence of being ultra-rapid metabolizers of codeine. Furthermore, children with obstructive sleep apnea who are treated with codeine for post-tonsillectomy and/or adenoidectomy pain may be particularly sensitive to its respiratory depressant effect. Because of the risk of life-threatening respiratory depression and death:

• Lexuss is contraindicated in all children younger than 12 years of age.
• Lexuss is contraindicated for post-operative management in pediatric patients younger than 18 years of age following tonsillectomy and/or adenoidectomy.
• Avoid the use of Lexuss in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of codeine. Risk factors include conditions associated with hypoventilation, such as postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression.
• When prescribing codeine for adolescents, healthcare providers should choose the lowest effective dose for the shortest period of time and inform patients and caregivers about these risks and the signs of morphine overdose.

Nursing Mothers

At least one death was reported in a nursing infant who was exposed to high levels of morphine in breast milk because the mother was an ultra-rapid metabolizer of codeine. Breastfeeding is not recommended during treatment with Lexuss.

CYP2D6 Genetic Variability: Ultra-Rapid Metabolizer

Some individuals may be ultra-rapid metabolizers because of a specific CYP2D6 genotype (e.g., gene duplications denoted as *1/*1xN or *1/*2xN). The prevalence of this CYP2D6 phenotype varies widely and has been estimated at 1 to 10% for Whites (European, North American), 3 to 4% for Blacks (African Americans), 1 to 2% for East Asians (Chinese, Japanese, Korean), and may be greater than 10% in certain ethnic groups (i.e., Oceanian, Northern African, Middle Eastern, Ashkenazi Jews, Puerto Rican).

These individuals convert codeine into its active metabolite, morphine, more rapidly and completely than other people. This rapid conversion results in higher than expected serum morphine levels. Even at labeled dosage regimens, individuals who are ultra-rapid metabolizers may have life-threatening or fatal respiratory depression or experience of signs of overdose (such as extreme sleepiness, confusion, or shallow breathing). Therefore, individuals who are ultra-rapid metabolizers should not use Lexuss.

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants

Concomitant use of opioids, including Lexuss, with benzodiazepines, or other CNS depressants, including alcohol, may results in profound sedation, respiratory depression, coma, and death. Because of these risks, avoid use of opioid cough medications in patients taking benzodiazepines, other CNS depressants, or alcohol.

Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. Because of similar pharmacologic properties, it is reasonable to expect similar risk with concomitant use of opioid cough medications and benzodiazepines, other CNS depressants, or alcohol.

Advise both patients and caregivers about the risks of respiratory depression and sedation if TUZISTRA XR is used with benzodiazepines, alcohol, or other CNS depressants.

Respiratory Depression

Codeine, one of the active ingredients in Lexuss, produces dose-related respiratory depression by directly acting on brain stem respiratory centers. Codeine affects the center that controls respiratory rhythm and may produce irregular and periodic breathing. Caution should be exercised when Lexuss is used postoperatively, in patients with pulmonary disease or shortness of breath, or whenever ventilator function is depressed.

Overdose of codeine in adults has been associated with fatal respiratory depression, and the use of codeine in children has been associated with fatal respiratory depression. Exercise caution when administering Lexuss because of the potential for respiratory depression. If respiratory depression occurs, discontinue Lexuss and use naloxone hydrochloride when indicated to antagonize the effect and other supportive measures as necessary.

Drug Dependence

Codeine can produce drug dependence of the morphine type and, therefore, has the potential for being abused. Psychological dependence, physical dependence, and tolerance may develop upon repeated administration of Lexuss. Prescribe and administer Lexuss with the same degree of caution appropriate to the use of other opioid drugs.

Head Injury And Increased Intracranial Pressure

The respiratory depression effects of opioids and their capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions, or a pre-existing increase in intracranial pressure. Furthermore, opioids produce adverse reactions that may obscure the clinical course of patients with head injuries. The use of Lexuss should be avoided in these patients.

Activities Requiring Mental Alertness

Codeine and chlorpheniramine, the active ingredients in Lexuss, may produce marked drowsiness and impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. Advise patients to avoid engaging in hazardous tasks requiring mental alertness and motor coordination after ingestion of Lexuss. Concurrent use of Lexuss with alcohol or other central nervous system depressants should be avoided because additional impairment of central nervous system performance may occur.

Obstructive Bowel Disease

Chronic use of opioids, including codeine, may result in constipation or obstructive bowel disease especially in patients with underlying intestinal motility disorders. Use with caution in patients with underlying intestinal motility disorders.

Acute Abdominal Conditions

Lexuss should be used with caution in patients with acute abdominal conditions since the administration of codeine may obscure the diagnosis or clinical course of patients with acute abdominal conditions. The concurrent use of other anticholinergics with codeine may produce paralytic ileus

Dosing

Patients should be advised to measure Lexuss with an accurate milliliter measuring device. Patients should be informed that a household teaspoon is not an accurate measuring device and could lead to overdosage, which can result in serious adverse reactions. Patients should be advised to ask their pharmacist to recommend an appropriate measuring device and for instructions for measuring the correct dose.

Special Risk Patients

As with other opioids, Lexuss should be used with caution in elderly or debilitated patients and those with asthma, persistent or chronic cough, hypothyroidism, Addison's disease, prostatic hypertrophy or urethral stricture. The usual precautions should be observed, and the possibility of respiratory depression should be kept in mind.

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Ultra-Rapid Metabolism Of Codeine And Other Risk Factors For Life-Threatening Respiratory Depression In Children

Advise patients of the risks of respiratory depression and death with Lexuss in children younger than 18 years of age. Advise patients that Lexuss should not be used in children younger than 12 years of age or in a child younger than 18 years of age for treatment after tonsillectomy and/or adenoidectomy.

Overdosage

Advise patients not to increase the dose or dosing frequency of Lexuss because serious adverse events such as respiratory depression may occur with overdosage.

Dosing

Administer Lexuss by the oral route only. Pharmacists and prescribers should ensure patients have an oral dosing dispenser that measures the appropriate volume in milliliters. Counsel patients on how to utilize an oral dosing dispenser and correctly measure the oral suspension as prescribed.

Lexuss should not be diluted with fluids or mixed together with other drugs.

Interactions With Benzodiazepines And Other Central Nervous System Depressants

Inform patients and caregivers that potentially fatal additive effects may occur if Lexuss is used with benzodiazepines or other CNS depressants, including, alcohol. Because of this risk, patients should avoid concomitant use of Lexuss with benzodiazepines or other CNS depressants, including alcohol.

Activities Requiring Mental Alertness

Caution patients that Lexuss may produce marked drowsiness and impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery

Controlled Substance Status/Potential For Abuse And Dependence

Caution patients that Lexuss contains codeine and can produce drug dependence.

Lactation

Advise women that breastfeeding is not recommended during treatment with Lexuss.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenicity, mutagenicity, and reproductive studies have not been conducted with Lexuss; however, published information is available for the individual active ingredients or related active ingredients.

Codeine

Carcinogenicity studies were conducted with codeine. In 2-year studies in F344/N rats and B6C3F1 mice, codeine showed no evidence of tumorigenicity at dietary doses up to 70 and 400 mg/kg/day, respectively (approximately 10 and 30 times, respectively, the MRHDD on a mg/m² basis).

Codeine was not mutagenic in the in vitro bacterial reverse mutation assay or clastogenic in the in vitro Chinese hamster ovary (CHO) cell chromosomal aberration assay.

Fertility studies with codeine have not been conducted.

Chlorpheniramine

In 2-year studies in F344/N rats and B6C3F1 mice, chlorpheniramine maleate showed no evidence of tumorigenicity when administered 5 days/week at oral doses up to 30 and 50 mg/kg/day, respectively (approximately 25 and 20 times, respectively, the MRHDD on a mg/m² basis).

Chlorpheniramine maleate was not mutagenic in the in vitro bacterial reverse mutation assay or the in vitro mouse lymphoma forward mutation assay. Chlorpheniramine maleate was clastogenic in the in vitro CHO cell chromosomal aberration assay.

Chlorpheniramine maleate had no effects on fertility in rats and rabbits at oral doses approximately 25 and 30 times the MRHDD on a mg/m² basis, respectively.

Use In Specific Populations

Pregnancy

Pregnancy Category C.

Teratogenic Effects

There are no adequate and well-controlled studies of Lexuss in pregnant women.

Reproductive toxicity studies have not been conducted with Lexuss; however, studies are available with individual active ingredients or related active ingredients. Because animal reproduction studies are not always predictive of human response, Lexuss should be used during pregnancy only if the benefit justifies the potential risk to the fetus.

Codeine

Codeine has embryolethal and fetotoxic effects in rats. In a study in which pregnant rats were dosed throughout organogenesis, a dose approximately 20 times the maximum recommended human daily dose (MRHDD; on a mg/m² basis at an oral maternal dose of 120 mg/kg/day) increased resorptions and decreased fetal weight; however, these effects occurred in the presence of maternal toxicity.

In studies in which rabbits and mice were dosed throughout organogenesis, codeine at doses approximately 9 and 45 times the MRHDD (on a mg/m² basis at 30 and 600 mg/kg/day, respectively) produced no adverse developmental effects.

Chlorpheniramine

A retrospective study found a small, but statistically significant, association between maternal use of chlorpheniramine and inguinal hernia and eye or ear anomalies in children. Other retrospective studies have found that the frequency of congenital anomalies, in general, was not increased among offspring of women who took chlorpheniramine during pregnancy. The significance of these findings to the therapeutic use of chlorpheniramine in human pregnancy is not known.

In studies with chlorpheniramine in which pregnant rats and rabbits were dosed throughout organogenesis, oral doses up to approximately 25 and 30 times the MRHDD on a mg/m² basis, respectively, produced no adverse developmental effects. However, when mice were dosed throughout pregnancy, a dose approximately 9 times the MRHDD (on a mg/m² basis at an oral maternal dose of 20 mg/kg/day) was embryolethal, and postnatal survival was decreased when dosing was continued after parturition. Embryolethality was also observed when male and female rats were dosed with approximately 9 times the MRHDD (on a mg/m² basis at an oral parental dose of 10 mg/kg/day) prior to mating.

Nonteratogenic Effects

Codeine

Babies born to mothers who have been taking opioids regularly prior to delivery will be physically dependent. The withdrawal signs include irritability and excessive crying, tremors, hyperactive reflexes, increased respiratory rate, increased stools, sneezing, yawning, vomiting, and fever. The intensity of the syndrome does not always correlate with the duration of maternal opioid use or dose.

Labor And Delivery

As with all opioids, administration of Lexuss to the mother shortly before delivery may result in some degree of respiratory depression in the newborn, especially if higher doses are used.

Nursing Mothers

Risk Summary

Codeine and its active metabolite, morphine, are present in human milk. There are published studies and cases that have reported excessive sedation, respiratory depression, and death in infants exposed to codeine via breast milk. Women who are ultra-rapid metabolizers of codeine achieve higher than expected serum levels of morphine, potentially leading to higher levels of morphine in breast milk that can be dangerous in their breastfed infants. In women with normal codeine metabolism (normal CYP2D6 activity), the amount of codeine secreted into human milk is low and dose-dependent.

There is no information on the effects of the codeine on milk production. Because of the potential for serious adverse reactions, including excess sedation, respiratory depression, and death in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with Lexuss.

Clinical Considerations

If infants are exposed to Lexuss through breast milk, they should be monitored for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped.

Chlorpheniramine is excreted in human milk. The clinical significance is unknown; however, the anticholinergic action of chlorpheniramine may suppress lactation if taken prior to nursing.

Pediatric Use

Safety and effectiveness of Lexuss in pediatric patients under 18 years of age have not been established.

Life-threatening respiratory depression and death have occurred in children who received codeine. In most of the reported cases, these events followed tonsillectomy and/or adenoidectomy, and many of the children had evidence of being ultra-rapid metabolizers of codeine (i.e., multiple copies of the gene for cytochrome P450 isoenzyme 2D6 or high morphine concentrations). Children with sleep apnea may be particularly sensitive to the respiratory depressant effects of codeine. Because of the risk of life-threatening respiratory depression and death:

• Lexuss is contraindicated in all children younger than 12 years of age.
• Lexuss is contraindicated for post-operative management in pediatric patients younger than 18 years of age following tonsillectomy and/or adenoidectomy.
• Avoid the use of Lexuss in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of codeine. Risk factors include conditions associated with hypoventilation, such as postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression.

Geriatric Use

Clinical efficacy and safety studies have not been conducted with Lexuss. Other reported clinical experience with the individual active ingredients of Lexuss did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be made with caution, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Renal Impairment

Pharmacokinetics of Lexuss has not been characterized in renal impairment subjects. Both codeine and chlorpheniramine are cleared substantially by the kidney. As such, impaired renal function could potentially lead to the risk of decreased clearance and thereby increased retention or systemic levels of both these drugs. Lexuss should be used with caution in patients with severe renal impairment.

Hepatic Impairment

Pharmacokinetics of Lexuss has not been characterized in hepatic impairment subjects. Both codeine and chlorpheniramine are extensively metabolized by the liver before elimination from the body. As such, impaired hepatic function could potentially lead to the risk of decreased metabolism and thereby increased systemic levels of both these drugs. TUZISTRA XR should be used with caution in patients with severe hepatic impairment.

Yarı sentetik bir opioid olan kodein kullanımı aşağıdakilere neden olabilir:

• Solunum depresyonu
• Uyuşturucu bağımlılığı
• Artan kafa içi basınç
• Zihinsel ve / veya fiziksel yeteneklerde zihinsel uyanıklığın azalması
• Paralitik ileus

Bir antihistamin olan klorfeniramin kullanımı aşağıdakilere neden olabilir:

• Zihinsel ve / veya fiziksel yeteneklerde zihinsel uyanıklığın azalması

Aşağıda listelenen advers reaksiyonlar, kodein ve klorfeniramin için literatürde bildirilmiştir ve Lexuss ile ortaya çıkması beklenebilir. Lexuss ile klinik farmakokinetik çalışmalar sırasında (tek veya çoklu doza maruz kalan toplam 66 sağlıklı yetişkin gönüllüde) meydana gelen ve araştırmacı tarafından çalışma tedavisi ile ilişkili olduğuna karar verilen olaylar da dahildir. Bu reaksiyonlar belirsiz büyüklükteki bir popülasyondan gönüllü olarak rapor edilebildiğinden, sıklıklarını güvenilir bir şekilde tahmin etmek veya ilaca maruz kalma ile nedensel bir ilişki kurmak her zaman mümkün değildir.

Alerjik

Alerjik laringospazm, burun tıkanıklığı, bronkospastik alerjik reaksiyon, kurdeşen, kaşıntı, yüzün şişmesi.

Bir Bütün Olarak Beden

Asteni, rahatlama hissi, yüzün kızarıklığı veya kızarması, olağandışı yorgunluk, halsizlik.

Kardiyovasküler

Hızlı veya yavaş kalp atışı, hipertansiyon, hipotansiyon, ortostatik hipotansiyon, çarpıntı, şok benzeri durum, senkop.

Dermatolojik Sistem

Deri döküntüsü, kaşıntı, eritem, ürtiker, aşırı terleme, dermatit.

Endokrin Sistem

Glikoz kullanımındaki değişiklikler, azalmış laktasyon, erken adet, glikozüri, jinekomasti, hipoglisemi, iştah artışı, libido artışı, feokromosito stimülasyonu.

Gastrointestinal Sistem

Bulantı ve kusma, kabızlık, karın şişliği, karın ağrısı, akut pankreatit, ağız kuruluğu, hazımsızlık, epigastrik sıkıntı, iştah kaybı, ishal, gastroözofageal reflü, gastrointestinal hipomotilite.

Genitoüriner Sistem

Üreteral spazm, idrar retansiyonu, dizüri, idrar sıklığı, idrar tereddütleri, tahriş edici mesane semptomu.

Sinir Sistemi

Bulanık görme, diplopi, görme bozuklukları, karışıklık, baş dönmesi, depresyon, uyuşukluk, sedasyon, baş ağrısı, öfori, yüz diskinezi, yanlış refah duygusu, baygınlık hissi, baş dönmesi, genel rahatsızlık veya hastalık hissi, uyarılabilirlik, sinirlilik, ajitasyon, huzursuzluk, uyku hali, uykusuzluk, diskinezi, sinirlilik, titreme.

Solunum

Farinks ve solunum pasajlarının kuruluğu, laringismus, atelektazi, hırıltılı solunum, sorunlu solunum, solunum depresyonu, hıçkırık.

Özel Duyular

labirentit, kulak çınlaması, baş dönmesi, hipermetropi, lakrimasyon arttı, midriyazis, fotofobi.

Lexuss için insan aşırı doz verisi mevcut değildir.

Codeine

Kodein ile aşırı doz, solunum depresyonu (solunum hızında ve / veya gelgit hacminde azalma, Cheyne-Stokes solunumu, siyanoz), stupor veya komaya ilerleyen aşırı uyku hali, iskelet kası sarkıklığı, soğuk ve rutubetli cilt ve bazen bradikardi ve hipotansiyon ile karakterizedir. . Şiddetli doz aşımı, apne, dolaşım çökmesi, kalp durması ve ölüm meydana gelebilir.

Kodein tamamen karanlıkta bile mioza neden olabilir. Pinpoint öğrencileri opioid doz aşımının bir işaretidir, ancak patognomonik değildir (ör.hemorajik veya iskemik kökenli pontin lezyonları benzer bulgular üretebilir). Aşırı doz durumlarında hipoksi ile miyoz yerine belirgin midriyazis görülebilir.

Klorfeniramin

Klorfeniramin doz aşımının belirtileri merkezi sinir sistemi depresyonundan stimülasyona kadar değişebilir. Merkezi toksik etkiler ajitasyon, anksiyete, deliryum, yönelim bozukluğu, halüsinasyonlar, hiperaktivite, sedasyon ve nöbetler ile karakterizedir. Şiddetli doz aşımı koma, medüller felç ve ölüm üretebilir. Periferik toksisite hipertansiyon, taşikardi, disitmiler, vazodilatasyon, hiperpireksi, midriyaz, idrar retansiyonu ve azalmış gastrointestinal motiliteyi içerir. Ağız kuruluğu, farinks, bronşlar ve burun pasajları görülebilir. Antikolinerjik yan etkileri olan toksik dozlarda ilaç sonrası ter bezlerinden bozulma salgısı hipertermiye yatkın olabilir.

Bir yetişkin, ciddi yan etkileri bildirilmeyen 400 mg klorfeniramin yuttu. Yanlışlıkla klorfeniramin doz aşımı ile sedasyon antihistaminlerin aşırı dozundan olası bir sınıf etkisi olan toksik psikoz bildirilmiştir.

Doz aşımı tedavisi, uygun tedavi kurumu ile birlikte Lexuss'un kesilmesinden oluşur.

Patentli bir hava yolu ve yardımlı veya kontrollü ventilasyon kurumu sağlayarak yeterli solunum değişiminin yeniden kurulmasına birincil dikkat edin. Opioid antagonist nalokson hidroklorür, aşırı dozdan veya kodein dahil opioidlere olağandışı duyarlılıktan kaynaklanabilecek solunum depresyonu için spesifik bir antidottur. Bu nedenle, tercihen intravenöz yolla, solunum resüsitasyon çabalarıyla eşzamanlı olarak uygun bir nalokson hidroklorür dozu uygulanmalıdır. Daha fazla bilgi için, nalokson hidroklorür için tam reçete bilgilerine bakın. Klinik olarak anlamlı solunum veya dolaşım depresyonu olmadan bir antagonist uygulanmamalıdır. Oksijen, intravenöz sıvılar, vazopresörler ve diğer destekleyici önlemler belirtildiği gibi kullanılmalıdır. Gastrik boşaltma, emilmemiş ilacın uzaklaştırılmasında yararlı olabilir.

Hemodiyaliz rutin olarak kodein veya klorfeniraminin vücuttan atılmasını arttırmak için kullanılmaz. İdrarın pH'ı asidik olduğunda idrar klorfeniramin atılımı artar; bununla birlikte, rabdomiyoliz hastalarında asidemi ve akut tübüler nekroz riskleri potansiyel faydalardan çok daha ağır bastığından, aşırı dozda eliminasyonu arttırmak için asit diürezi önerilmez.

Emilim

Açlık ve sağlıklı gönüllülerde Lexuss (kodine polistireks ve klorfeniramin polistireks) için farmakokinetik (PK) parametreleri (Ortalama ± SD) genişletilmiş salimli oral süspansiyon aşağıdaki tabloda gösterilmektedir.

Gıda Etkisi

Yüksek yağlı, yüksek kalorili bir yemeğin varlığı Lexuss farmakokinetiğini önemli ölçüde etkilemedi.

Dağıtım

Kodeinin, ilacın dokulara geniş dağılımını gösteren yaklaşık 3 ila 6 L / kg'lık bir görünür dağılım hacmine sahip olduğu bildirilmiştir. Kodeinin yaklaşık% 7 ila 25'inin plazma proteinlerine bağlı olduğu bildirilmektedir. Kodein kan beyin bariyerini ve plasenta bariyerini geçer. Az miktarda kodein ve metaboliti morfin anne sütüne aktarılır.

Klorfeniramin, merkezi sinir sistemi de dahil olmak üzere vücudun dokuları boyunca yaygın olarak dağılır. Yetişkinlerde ve çocuklarda yaklaşık 3.2 L / kg'lık bir kararlı durum dağılımına sahip olduğu ve plazma proteinlerine yaklaşık% 70 oranında bağlı olduğu bildirilmektedir. Klorfeniramin ve metabolitleri muhtemelen plasenta bariyerini geçer ve anne sütüne geçer.

Metabolizma

Uygulanan kodein dozunun yaklaşık% 70-80'i, glukuronik asit ile kodein-6glukuronide (C6G) konjügasyon ve morfine O-demetilasyon (yaklaşık% 5-10) ve norcodeine N-demetilasyon (yaklaşık% 10) yoluyla metabolize edilir. sırasıyla. UDP-glukuronosiltransferaz (UGT) 2B7 ve 2B4, kodeinin C6G'ye glukuronidinasyonuna aracılık eden başlıca enzimlerdir. CYP2D6 ve CYP3A4, sırasıyla kodeinin O-demetilasyonuna ve N-demetilasyonuna aracılık eden başlıca enzimlerdir. Morfin ve norcodein ayrıca glukuronik asit ile konjugasyon yoluyla metabolize edilir. Morfin ve M6 glukuronid konjugatı farmakolojik olarak aktiftir. C6G'nin farmakolojik aktiviteye sahip olup olmadığı bilinmemektedir. Morfinin norcodeine ve M3 glukuronid konjugatının genellikle farmakolojik olarak aktif olduğu düşünülmez.

Klorfeniramin, karaciğerde demetilasyon yoluyla hızlı ve yoğun bir şekilde metabolize edilir ve mono- ve didesmetil türevleri oluşur. Klorfeniraminin oksidatif metabolizması CYP2D6 tarafından katalize edilir.

Eliminasyon

Toplam kodein dozunun yaklaşık% 90'ı, yaklaşık% 10'u değişmemiş kodein olan böbrekler yoluyla atılır. Lexuss ile kodeinin plazma yarılanma ömrünün yaklaşık 5 saat olduğu gözlendi.

Klorfeniramin ve metabolitleri öncelikle büyük bireysel varyasyonlarla böbrekler yoluyla atılır. Üriner atılım idrar pH'ına ve akış hızına bağlıdır. TUZISTRA XR ile klorfeniraminin plazma yarılanma ömrünün yaklaşık 21 saat olduğu gözlenmiştir