خواص دارویی و گیاهی
زفیرلوکاست Zafirlukast
قرص های 20 میلی گرمی
اکولیت محتوی دارویی به نام زفیرلوکاست است. این دارو متعلق به گروهی از داروها می باشد که اثرات بعضی مواد التهاب زا را کاهش می دهند. آن ها موادی طبیعی در ریه ها هستند که موجب آسم می شوند.
برای درمان حملات حاد آسم از این دارو استفاده نکنید. پزشک داروی مناسب برای درمان حملات حاد را تجویز خواهد کرد.
قرص accolate
در صورت وجود هرگونه تردید در موارد ذکر شده، قبل از مصرف اکولیت با پزشک یا داروساز مشورت نمایید.
در موارد زیر قبل از مصرف اکولیت با پزشک یا داروساز مشورت نمایید:
در صورت وجود هرگونه تردید در موارد ذکر شده، قبل از مصرف اکولیت با پزشک یا داروساز مشورت نمایید.
در صورت مراجعه به بیمارستان کارکنان درمانی را از مصرف اکولیت مطلع نمایید.
همواره اکولیت را دقیقاً مطابق توصیه پزشک مصرف کنید و در صورت هر گونه تردید در مورد نحوه مصرف، با پزشک یا داروساز مشورت کنید.
مصرف اکولیت در کودکان کمتر از 12 سال توصیه نمی شود.
در صورتی که برای درمان آسم از داروهای دیگری استفاده کرده اید، از قطع مصرف آن ها بدون توصیه پزشک اجتناب کنید.
در صورت تشدید آسم حین مصرف اکولیت، طبق توصیه پزشک در مورد حملات حاد آسم عمل کنید و در کمترین زمان ممکن به پزشک مراجعه کنید.
در صورت مصرف بیش از حد اکولیت با پزشک یا داروساز مشورت نمایید.
در صورت فراموش کردن مصرف یک دوز اکولیت در اولین فرصت آن را مصرف کنید و اگر به زمان مصرف دوز بعدی نزدیک شده اید دوز فراموش شده را حذف نمایید.
از 2 برابر کردن دوز دارو برای جبران دوز فراموش شده(مصرف دو دوز به صورت همزمان) خودداری نمایید.
مصرف اکولیت را حتی در صورت کنترل شدن علائم آسم ادامه دهید و با وجود احساس بهبودی از قطع مصرف دارو بدون توصیه پزشک خودداری کنید.
مانند هر دارویی مصرف اکولیت نیز ممکن است تعدادی عارضه ی جانبی در پی داشته باشد، اگرچه این عوارض در تمام افراد بروز نمی کنند.
علائم عبارتند از:
در صورت ایجاد این علائم، مصرف اکولیت را قطع کنید و فوراً به پزشک اطلاع دهید.
اکولیت ممکن است بر کبد اثرگذار باشد. این اثرات از افزایش نه چندان شدید آنزیم های کبدی تا نارسایی کبدی شدید متفاوت هستند.
پزشک قبل از درمان و حین درمان با اکولیت برای ارزیابی اختلالات کبدی آزمایشات لازم را درخواست خواهد کرد.
در صورت ایجاد این علائم، مصرف اکولیت را قطع کنید و فوراً به پزشک اطلاع دهید.
ماده فعال این دارو زفیرلوکاست است. هر قرص حاوی 20 میلی گرم زفیرلوکاست می باشد.
قرص های اکولیت سفید، گرد و پوشش دار هستند. این دارو در بسته بندی های محتوی 56 عدد قرص در دسترس می باشد.
Zafirlukast is an orally administered leukotriene receptor antagonist (LTRA) used for the chronic treatment of asthma. While zafirlukast is generally well-tolerated, headache and stomach upset often occur. Some rare side effects can occur, which can be life-threatening, such as liver failure. Churg-Strauss syndrome has been associated with zafirlukast, but the relationship isn’t thought to be causative in nature. Overdoses of zafirlukast tend to be self-limiting.
Zafirlukast, like other LTRAs, works by inhibiting the immune system. Through its action on inflammatory cells in the lungs, zafirlukast reduces the production of inflammatory mediators that are implicated in the pathogenesis of asthma. Zafirlukast is extensively hepatically metabolized by an enzyme called CYP2C9. Zafirlukast inhibits the action of CYP3A4, leading to drug-drug interactions with other drugs that are metabolized by CYP3A4. Genetic differences in LTC4 synthase and CYP2C9 may predict how a person reacts to zafirlukast treatment.
Zafirlukast (brand name Accolate) was the first cysteinyl leukotriene receptor antagonist approved in the United States. It is now approved in many other countries under other brand names.
Zafirlukast is FDA-approved for the prevention and treatment of asthma in adults and children older than 5 years old.[1] Like other leukotriene receptor antagonists, zafirlukast is thought to be useful for the long-term treatment of asthma, but it is generally less effective than inhaled glucocorticoids as monotherapy (which are the standard of care) or long-acting beta-2 agonists in combination therapy.[2] Notably, zafirlukast is ineffective in the event of an acute asthma attack.[1]
There are two dosage forms for zafirlukast, notable for their age-adjustments. The 20 mg tablet is for adults and children older than age 12, whereas the 10 mg tablet is for children between the ages of 5 and 12.[1] Tablets should be stored at room temperature, out of direct sunlight, and away from sources of moisture.[1]
قرص accolate
Tablets are for oral administration only.[1]
As a general rule, leukotriene receptor antagonists like zafirlukast are more effective in children that are younger and whose asthma is less atopic.[3] Atopy refers to a predisposition towards developing allergic conditions, including asthma, hay fever, and eczema.[4]
The hepatic clearance of zafirlukast is impaired in adults 65 years of age and older, resulting in a 2–3 fold increase in the maximum plasma concentration and the total area under the curve. Zafirlukast may increase the risk for infections (7.0% vs 2.9%, zafirlukast vs. placebo incidence respectively), especially lower respiratory tract infections, in older adults, though the infections noted were not severe.[1]
Zafirlukast is considered to be “pregnancy category B.” This is due, in part, to the wide safety margin of zafirlukast in animal studies investigating teratogenicity. No teratogenicity has been observed in doses up to 2000 mg/kg/day in cynomolgus monkeys, representing an equivalent 20x exposure of the maximum recommended daily oral dose in human adults. However, spontaneous abortions occurred in cynomolgus monkeys at 2000 mg/kg/day, though the dose itself was maternally toxic.[1]
There is limited research on the use of zafirlukast in women whom are breastfeeding.[5] Based on data from the manufacturer, it is expected that 0.6% of the maternal weight-adjusted dose would reach a breastfed infant, though the effects in the infant are unknown.[5]
Renal impairment does not appear to affect the pharmacokinetic profile of zafirlukast.[1]
The hepatic clearance of zafirlukast is impaired by significant hepatic impairment. Cirrhosis of the liver can result in an increase in the maximum plasma concentration and the total area under the curve (a measure of drug exposure) by 50–60%.[1]
Zafirlukast is contraindicated in people that are hypersensitive or allergic to it.[1]
Zafirlukast is generally well-tolerated, though headache and gastrointestinal (GI) upset can occur. The incidence of headache is between 12 and 20%, which is similar to the incidence of headache found in patients taking placebos in the studies that lead to zafirlukast’s approval. GI upset may include nausea, stomach discomfort/pain, and diarrhea. GI complaints can be lessened by taking zafirlukast with food, though this can dramatically impair the amount of drug that gets absorbed into the body (see the section on drug-food interactions below).[6]
Other common side effects include flu-like symptoms, sleep disturbances (abnormal dreams, insomnia), hallucinations, and daytime drowsiness.[6]
Neuropsychiatric side effects have been reported with the use of zafirlukast and other LTRAs. While some side effects are less severe (e.g. abnormal dreams), others are more serious (e.g. hallucinations, tremor, suicidality). These effects were discovered through post-marketing reports, as the initial trials were not designed to monitor for neuropsychiatric side effects.[7]
Zafirlukast can also cause rare but serious side effects like acute liver injury.[8] Zafirlukast-induced hepatotoxicity generally occurs within the first 2–6 months of initiating therapy, though cases have been reported up to 13 months after starting zafirlukast.[8] Zafirlukast-induced hepatotoxicity is characterized by a spectrum of liver damage symptoms, including fatigue, nausea, and right upper quadrant pain followed by dark urine, jaundice and pruritus.[8] Liver enzyme elevations are common, and the pattern usually reflects hepatocellular damage, resembling acute viral hepatitis.[8] It is unclear how the hepatotoxicity occurs, but it may be due to a metabolic intermediate of zafirlukast, since it is metabolized in the liver through the enzyme CYP2C9. When it does occur it can be fatal, and reexposure with zafirlukast may result in a worse injury.[8] Switching zafirlukast to another medication in the same class (e.g. montelukast) or in the related class of 5-lipoxygenase inhibitors can be attempted, but caution should be employed.[8]
According to the “Dear Health Care Provider” letter from AstraZeneca, zafirlukast-induced hepatotoxicity has occurred predominantly in females.[9]
Several cases of Churg-Strauss syndrome, also known as allergic angiitis and granulomatosis, have been reported with the use of zafirlukast, montelukast, pranlukast, and other asthma medications.[10] When Churg-Strauss syndrome occurs, it tends to occur in people with long-standing asthma and sinus inflammation, chronic oral corticosteroid use, and the recent initiation of a new anti-asthma therapy (like zafirlukast) in conjunction with tapering the corticosteroids.[10] While the exact etiology of the development of Churg-Strauss symptoms in proximity to initiating zafirlukast is unknown, it is thought that withdrawal of chronic corticosteroids “unmasks” the previously undetected disease.[10] Because corticosteroid withdrawal often happens while starting a new anti-asthma medication (like zafirlukast), this explains the rare but notable association.[10] These cases may represent misdiagnosed asthma, as Churg-Strauss syndrome can induce symptoms of airway obstruction that are akin to an acute asthma exacerbation.[10] As these asthma-like symptoms are reduced by zafirlukast, the symptoms of Churg-Strauss (e.g. neuropathy) increase due to the lack of the broader, anti-inflammatory coverage that the steroid was providing.[10]
The highest overdose reported with zafirlukast is 200 mg. All overdose patients have survived. Symptoms reported included rash and upset stomach.[1]
Zafirlukast is an inhibitor of the hepatic drug-metabolizing enzyme cytochrome P450 family 3 subfamily A member 4 (CYP3A4).[1] Zafirlukast may increase the concentration of drugs that are metabolized through CYP3A4, such as the anticoagulant medication warfarin and the antiepileptic drugs phenytoin and carbamazepine.[1]
The oral absorption (bioavailability) of zafirlukast is decreased by 40% when it is taken with high fat or high protein meals.[1] To avoid this interaction, zafirlukast should be taken on an empty stomach.[6] An empty stomach is classified as an hour before, or two hours after, consuming a meal.[1]
Zafirlukast is an antagonist of cysteinyl leukotriene receptor 1 (CysLT1), a receptor found throughout the smooth muscle of the lungs, within interstitial lung macrophages (white blood cells that operate in the interstitial space of the lungs), and rarely in epithelial cells.[11] CystLT1 is a receptor for a specific class of leukotrienes that contain the amino acid cysteine.[2] These cysteinyl leukotrienes include leukotriene C4, leukotriene D4, and leukotriene E4, all of which are produced by inflammatory cells like eosinophils, basophils, and macrophages in the lungs.[2] Through their action on CysLT1 these leukotrienes can trigger bronchoconstriction, a state in which the bronchial passages of the lungs constrict,[12] leading to the characteristic, reactive airway symptoms associated with bronchial asthma.[2] The other pro-inflammatory effects of leukotrienes, such as their inhibition of mucus clearance and their stimulation of mucus secretion and edema, are thought to play a role in the characteristic symptoms of allergic rhinitis (also called hay fever[13]).[2] By inhibiting the action of these specific leukotrienes, zafirlukast is thought to exert an anti-inflammatory effect against leukotriene-mediated inflammatory conditions.[2]
Zafirlukast is rapidly absorbed into the bloodstream following oral administration, reaching peak plasma levels within 3 hours of taking the dose.[1] The peak plasma level is the maximum concentration of zafirlukast in the blood.[14]
Zafirlukast is moderately distributed into the body’s tissues, with an apparent steady state volume of distribution of 70 liters.[1] Zafirlukast is highly plasma protein bound, 99% bound to albumin.[1] Albumin is the most abundant protein found in human plasma and is capable of carrying and transporting drugs (like zafirlkast) throughout the body.[15] In vivo research indicates that zafirlukast has low blood-brain barrier penetration.[1] The blood-brain barrier is a protective system that prevents many chemicals from entering the brain.[16]
Zafirlukast undergoes extensive hepatic metabolism into inactive metabolites.[1] Zafirlukast is primarily metabolized by the enzyme CYP2C9 to a hydroxylated metabolite.[1]
Zafirlukast is primarily cleared through biliary excretion at a rate of 20 liters/hour. Zafirlukast is undetectable in urine. The mean terminal half-life ranges 8–16 hours, following linear kinetics up to doses of 80 mg.[1]
Genetic polymorphisms in the LTC4 synthase promoter may predict response to zafirlukast. The single-nucleotide polymorphism (SNP) A444C (the wild-type DNA base adenine, at the 444th position on the gene, is mutated; cytosine is there instead), which is associated with a severe asthma phenotype, has been shown to decrease the clinical response to zafirlukast (both when the genetic alteration was heterozygous or homozygous).[17]
Zafirlukast is metabolized through the hepatic enzyme CYP2C9. SNPs that decrease the function of CYP2C9 (such as CYP2C9*3 and CYP2C9*13) may decrease the hepatic clearance of zafirlukast, leading to increased exposure of zafirlukast.[18] Notably, the CYP2C9*3 polymorphism is more commonly encountered in people of south/central Asian ancestry (10.165%) compared to people of Caucasian (7.083%), African American (1.170%), African (1.033%), middle eastern (9.312%), and east Asian (3.365%) ancestry.[19]
Zafirlukast can be synthesized by the following method:[20]
Pure zafirlukast is described as a fine, white to pale yellow, amorphous powder. It is practically insoluble in water, slightly soluble in methanol, and freely soluble in tetrahydrofuran, dimethylsulfoxide, and acetone.[1]
Zafirlukast was the first cysteinyl leukotriene receptor antagonist approved in the United States.[10] Zafirlukast was approved in 1996.[10]
While preliminary evidence suggests that zafirlukast may reduce healthcare costs, the cost-effectiveness of using zafirlukast has not been established.[21]
There is some research to suggest that zafirlukast actually acts as a partial inverse agonist at the CysLT1 receptor, though zafirlukast is still classified as an antagonist at this receptor. The possible clinical significance of this effect, if true, is unknown.[17]
There is some evidence that suggests that zafirlukast may be beneficial in the treatment of chronic urticaria (hives), whether due to a known cause such as cold-exposure or due to an unknown cause (idiopathic).[17] A pilot study indicated that zafirlukast may be of some benefit in cystic fibrosis.[17] In the setting of chronic obstructive pulmonary disorder (COPD), a disease characterized by chronic inflammation of the lungs, zafirlukast has been shown to improve lung function.[17]
Zafirlukast is sometimes used for the treatment of bronchial asthma in cats.[23]
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قرص accolate
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Kaiser Permanente health plans around the country: Kaiser Foundation Health Plan, Inc., in Northern and Southern California and Hawaii • Kaiser Foundation Health Plan of Colorado • Kaiser Foundation Health Plan of Georgia, Inc., Nine Piedmont Center, 3495 Piedmont Road NE, Atlanta, GA 30305, 404-364-7000 • Kaiser Foundation Health Plan of the Mid-Atlantic States, Inc., in Maryland, Virginia, and Washington, D.C., 2101 E. Jefferson St., Rockville, MD 20852 • Kaiser Foundation Health Plan of the Northwest, 500 NE Multnomah St., Suite 100, Portland, OR 97232 • Kaiser Foundation Health Plan of Washington or Kaiser Foundation Health Plan of Washington Options, Inc., 601 Union St., Suite 3100, Seattle, WA 98101
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چنانچه در خصوص “قرص آکولات 20 میلی گرم” سوالی دارید، عارضه خاصی مشاهده نموده اید و یا مطلب ویژه ای به نظرتان می رسد با دیگران به اشتراک بگذارید
Generic Name: zafirlukast
Dosage Form: tablet, coated
Medically reviewed by Drugs.com. Last updated on Dec 3, 2018.
Zafirlukast is a synthetic, selective peptide leukotriene receptor antagonist (LTRA), with the chemical name 4-(5-cyclopentyloxy-carbonylamino-1-methyl-indol-3-ylmethyl)-3-methoxy-N-o-tolylsulfonylbenzamide. The molecular weight of zafirlukast is 575.7 and the structural formula is:
The empirical formula is: C31H33N3O6S
Zafirlukast, a fine white to pale yellow amorphous powder, is practically insoluble in water. It is slightly soluble in methanol and freely soluble in tetrahydrofuran, dimethylsulfoxide, and acetone.
قرص accolate
Accolate is supplied as 10 and 20 mg tablets for oral administration.
Inactive Ingredients: Film-coated tablets containing croscarmellose sodium, lactose, magnesium stearate, microcrystalline cellulose, povidone, hypromellose, and titanium dioxide.
Zafirlukast is a selective and competitive receptor antagonist of leukotriene D4 and E4 (LTD4 and LTE4), components of slow-reacting substance of anaphylaxis (SRSA). Cysteinyl leukotriene production and receptor occupation have been correlated with the pathophysiology of asthma, including airway edema, smooth muscle constriction, and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma. Patients with asthma were found in one study to be 25-100 times more sensitive to the bronchoconstricting activity of inhaled LTD4 than nonasthmatic subjects.
In vitro studies demonstrated that zafirlukast antagonized the contractile activity of three leukotrienes (LTC4, LTD4 and LTE4) in conducting airway smooth muscle from laboratory animals and humans. Zafirlukast prevented intradermal LTD4-induced increases in cutaneous vascular permeability and inhibited inhaled LTD4-induced influx of eosinophils into animal lungs. Inhalational challenge studies in sensitized sheep showed that zafirlukast suppressed the airway responses to antigen; this included both the early- and late-phase response and the nonspecific hyperresponsiveness.
In humans, zafirlukast inhibited bronchoconstriction caused by several kinds of inhalational challenges. Pretreatment with single oral doses of zafirlukast inhibited the bronchoconstriction caused by sulfur dioxide and cold air in patients with asthma. Pretreatment with single doses of zafirlukast attenuated the early- and late-phase reaction caused by inhalation of various antigens such as grass, cat dander, ragweed, and mixed antigens in patients with asthma. Zafirlukast also attenuated the increase in bronchial hyperresponsiveness to inhaled histamine that followed inhaled allergen challenge.
Zafirlukast is rapidly absorbed following oral administration. Peak plasma concentrations are generally achieved 3 hours after oral administration. The absolute bioavailability of zafirlukast is unknown. In two separate studies, one using a high fat and the other a high protein meal, administration of zafirlukast with food reduced the mean bioavailability by approximately 40%.
Zafirlukast is more than 99% bound to plasma proteins, predominantly albumin. The degree of binding was independent of concentration in the clinically relevant range. The apparent steady-state volume of distribution (Vss/F) is approximately 70 L, suggesting moderate distribution into tissues. Studies in rats using radiolabeled zafirlukast indicate minimal distribution across the blood-brain barrier.
Zafirlukast is extensively metabolized. The most common metabolic products are hydroxylated metabolites which are excreted in the feces. The metabolites of zafirlukast identified in plasma are at least 90 times less potent as LTD4 receptor antagonists than zafirlukast in a standard in vitro test of activity. In vitro studies using human liver microsomes showed that the hydroxylated metabolites of zafirlukast excreted in the feces are formed through the cytochrome P450 2C9 (CYP2C9) pathway. Additional in vitro studies utilizing human liver microsomes show that zafirlukast inhibits the cytochrome P450 CYP3A4 and CYP2C9 isoenzymes at concentrations close to the clinically achieved total plasma concentrations (see Drug Interactions).
The apparent oral clearance (CL/f) of zafirlukast is approximately 20 L/h. Studies in the rat and dog suggest that biliary excretion is the primary route of excretion. Following oral administration of radiolabeled zafirlukast to volunteers, urinary excretion accounts for approximately 10% of the dose and the remainder is excreted in feces. Zafirlukast is not detected in urine.
In the pivotal bioequivalence study, the mean terminal half-life of zafirlukast is approximately 10 hours in both normal adult subjects and patients with asthma. In other studies, the mean plasma half-life of zafirlukast ranged from approximately 8 to 16 hours in both normal subjects and patients with asthma. The pharmacokinetics of zafirlukast are approximately linear over the range from 5 mg to 80 mg. Steady-state plasma concentrations of zafirlukast are proportional to the dose and predictable from single-dose pharmacokinetic data. Accumulation of zafirlukast in the plasma following twice-daily dosing is approximately 45%.
The pharmacokinetic parameters of zafirlukast 20 mg administered as a single dose to 36 male volunteers are shown with the table below.
Cmax
ng/ml
tmax*
h
AUC
ng•h/mL
t1/2
h
CL/f
L/h
326 (31.0)
2 (0.5 – 5.0)
1137 (34)
13.3 (75.6)
19.4 (32)
Gender: The pharmacokinetics of zafirlukast are similar in males and females. Weight-adjusted apparent oral clearance does not differ due to gender.
Race: No differences in the pharmacokinetics of zafirlukast due to race have been observed.
Elderly: The apparent oral clearance of zafirlukast decreases with age. In patients above 65 years of age, there is an approximately 2-3 fold greater Cmax and AUC compared to young adult patients.
Children: Following administration of a single 20 mg dose of zafirlukast to 20 boys and girls between 7 and 11 years of age, and in a second study, to 29 boys and girls between 5 and 6 years of age, the following pharmacokinetic parameters were obtained:
Parameter
Children age 5-6 years Mean (% Coefficient of Variation)
Children age 7-11 years Mean
(% Coefficient of Variation)
Cmax (ng/mL)
قرص accolate
756 (39%)
601 (45%)
AUC (ng•h/mL)
2458 (34%)
2027 (38%)
tmax (h)
2.1 (61%)
2.5 (55%)
CL/f (L/h)
9.2 (37%)
11.4 (42%)
Weight unadjusted apparent clearance was 11.4 L/h (42%) in the 7-11 year old children and 9.2 L/h (37%) in the 5-6 year old children, which resulted in greater systemic drug exposures than that obtained in adults for an identical dose. To maintain similar exposure levels in children compared to adults, a dose of 10 mg twice daily is recommended in children 5-11 years of age (see DOSAGE AND ADMINISTRATION).
Zafirlukast disposition was unchanged after multiple dosing (20 mg twice daily) in children and the degree of accumulation in plasma was similar to that observed in adults.
Hepatic Insufficiency: In a study of patients with hepatic impairment (biopsy-proven cirrhosis), there was a reduced clearance of zafirlukast resulting in a 50-60% greater Cmax and AUC compared to normal subjects.
Renal Insufficiency: Based on a cross-study comparison, there are no apparent differences in the pharmacokinetics of zafirlukast between renally-impaired patients and normal subjects.
Drug-Drug Interactions: The following drug interaction studies have been conducted with zafirlukast (see PRECAUTIONS, Drug Interactions).
Three U.S. double-blind, randomized, placebo-controlled, 13-week clinical trials in 1380 adults and children 12 years of age and older with mild-to-moderate asthma demonstrated that Accolate improved daytime asthma symptoms, nighttime awakenings, mornings with asthma symptoms, rescue beta2-agonist use, FEV1, and morning peak expiratory flow rate. In these studies, the patients had a mean baseline FEV1 of approximately 75% of predicted normal and a mean baseline beta2-agonist requirement of approximately 4-5 puffs of albuterol per day. The results of the largest of the trials are shown in the table below.
Accolate
20 mg twice daily
N=514
Placebo
N=248
Daytime Asthma symptom score
(0-3 scale)
-0.44*
-0.25
Nightime Awakenings
(number per week)
-1.27*
-0.43
Mornings with Asthma Symptoms
(days per week)
-1.32*
-0.75
Rescue β2-agonist use
(puffs per day)
-1.15*
-0.24
FEV1 (L)
+0.15*
+0.05
Morning PEFR (L/min)
+22.06*
+7.63
Evening PEFR (L/min)
+13.12
+10.14
In a second and smaller study, the effect of Accolate on most efficacy parameters was comparable to the active control (inhaled cromolyn sodium 1600 mcg four times per day) and superior to placebo at end point for decreasing rescue beta2-agonist use (figure below).
In these trials, improvement in asthma symptoms occurred within one week of initiating treatment with Accolate. The role of Accolate in the management of patients with more severe asthma, patients receiving antiasthma therapy other than as-needed, inhaled beta2-agonists, or as an oral or inhaled corticosteroid-sparing agent remains to be fully characterized.
Accolate is indicated for the prophylaxis and chronic treatment of asthma in adults and children 5 years of age and older.
Accolate is contraindicated in patients who are hypersensitive to zafirlukast or any of its inactive ingredients.
Accolate is contraindicated in patients with hepatic impairment including hepatic cirrhosis.
Cases of life-threatening hepatic failure have been reported in patients treated with Accolate. Cases of liver injury without other attributable cause have been reported from post-marketing adverse event surveillance of patients who have received the recommended dose of Accolate (40 mg/day). In most, but not all post-marketing reports, the patient’s symptoms abated and the liver enzymes returned to normal or near normal after stopping Accolate. In rare cases, patients have either presented with fulminant hepatitis or progressed to hepatic failure, liver transplantation and death. In extremely rare post-marketing cases, no clinical symptoms or signs suggestive of liver dysfunction were reported to precede the latter observations.
Physicians may consider the value of liver function testing. Periodic serum transaminase testing has not proven to prevent serious injury but it is generally believed that early detection of drug-induced hepatic injury along with immediate withdrawal of the suspect drug enhances the likelihood for recovery.
Patients should be advised to be alert for signs and symptoms of liver dysfunction (eg, right upper quadrant abdominal pain, nausea, fatigue, lethargy, pruritus, jaundice, flu-like symptoms, and anorexia) and to contact their physician immediately if they occur. Ongoing clinical assessment of patients should govern physician interventions, including diagnostic evaluations and treatment.
If liver dysfunction is suspected based upon clinical signs or symptoms (eg, right upper quadrant abdominal pain, nausea, fatigue, lethargy, pruritus, jaundice, flu-like symptoms, anorexia, and enlarged liver), Accolate should be discontinued.
Liver function tests, in particular serum ALT, should be measured immediately and the patient managed accordingly. If liver function tests are consistent with hepatic dysfunction, Accolate therapy should not be resumed. Patients in whom Accolate was withdrawn because of hepatic dysfunction where no other attributable cause is identified should not be re-exposed to Accolate (see PRECAUTIONS, Information for Patients and ADVERSE REACTIONS).
Accolate is not indicated for use in the reversal of bronchospasm in acute asthma attacks, including status asthmaticus. Therapy with Accolate can be continued during acute exacerbations of asthma.
Coadministration of zafirlukast with warfarin results in a clinically significant increase in prothrombin time (PT). Patients on oral warfarin anticoagulant therapy and Accolate should have their prothrombin times monitored closely and anticoagulant dose adjusted accordingly (see PRECAUTIONS, Drug Interactions).
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Patients should be told that a rare side effect of Accolate is hepatic dysfunction, and to contact their physician immediately if they experience symptoms of hepatic dysfunction (eg. right upper quadrant abdominal pain, nausea, fatigue, lethargy, pruritus, jaundice, flu-like symptoms, and anorexia). Liver failure resulting in liver transplantation and death has occurred in patients taking zafirlukast (see WARNINGS, Hepatotoxicity and ADVERSE REACTIONS).
Accolate is indicated for the chronic treatment of asthma and should be taken regularly as prescribed, even during symptom-free periods. Accolate is not a bronchodilator and should not be used to treat acute episodes of asthma. Patients receiving Accolate should be instructed not to decrease the dose or stop taking any other antiasthma medications unless instructed by a physician. Patients should be instructed to notify their physician if neuropsychiatric events occur while using Accolate (see PRECAUTIONS, Neuropsychiatric Events). Women who are breast-feeding should be instructed not to take Accolate (see PRECAUTIONS, Nursing Mothers). Alternative antiasthma medication should be considered in such patients.
The bioavailability of Accolate may be decreased when taken with food. Patients should be instructed to take Accolate at least 1 hour before or 2 hours after meals.
In rare cases, patients with asthma on Accolate may present with systemic eosinophilia, eosinophilic pneumonia, or clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition which is often treated with systemic steroid therapy. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. These events have usually, but not always, been associated with reductions and/or withdrawal of steroid therapy. The possibility that Accolate may be associated with emergence of Churg-Strauss syndrome can neither be excluded nor established (see ADVERSE REACTIONS).
Neuropsychiatric events have been reported in adult, adolescent and pediatric patients taking Accolate. Post-marketing reports with Accolate include insomnia and depression. The clinical details of some post-marketing reports involving Accolate appear consistent with a drug-induced effect. Patients and prescribers should be alert for neuropsychiatric events. Patients should be instructed to notify their prescriber if these changes occur. Prescribers should carefully evaluate the risks and benefits of continuing treatment with Accolate if such events occur (see ADVERSE REACTIONS).
In a drug interaction study in 16 healthy male volunteers, coadministration of multiple doses of zafirlukast (160 mg/day) to steady-state with a single 25 mg dose of warfarin resulted in a significant increase in the mean AUC (+ 63%) and half-life (+36%) of S-warfarin. The mean prothrombin time (PT) increased by approximately 35%. This interaction is probably due to an inhibition by zafirlukast of the cytochrome P450 2C9 isoenzyme system. Patients on oral warfarin anticoagulant therapy and Accolate should have their prothrombin times monitored closely and anticoagulant dose adjusted accordingly (see WARNINGS, Concomitant Warfarin Administration). No formal drug-drug interaction studies with Accolate and other drugs known to be metabolized by the cytochrome P450 2C9 isoenzyme (eg, tolbutamide, phenytoin, carbamazepine) have been conducted; however, care should be exercised when Accolate is coadministered with these drugs.
In a drug interaction study in 11 asthmatic patients, coadministration of a single dose of zafirlukast (40 mg) with erythromycin (500 mg three times daily for 5 days) to steady-state resulted in decreased mean plasma levels of zafirlukast by approximately 40% due to a decrease in zafirlukast bioavailability.
Coadministration of zafirlukast (20 mg/day) or placebo at steady-state with a single dose of sustained release theophylline preparation (16 mg/kg) in 16 healthy boys and girls (6 through 11 years of age) resulted in no significant differences in the pharmacokinetic parameters of theophylline.
Coadministration of zafirlukast (80 mg/day) at steady-state with a single dose of a liquid theophylline preparation (6 mg/kg) in 13 asthmatic patients, 18 to 44 years of age, resulted in decreased mean plasma levels of zafirlukast by approximately 30%, but no effect on plasma theophylline levels was observed.
Rare cases of patients experiencing increased theophylline levels with or without clinical signs or symptoms of theophylline toxicity after the addition of Accolate to an existing theophylline regimen have been reported. The mechanism of the interaction between Accolate and theophylline in these patients is unknown (see ADVERSE REACTIONS).
Coadministration of zafirlukast (40 mg/day) with aspirin (650 mg four times daily) resulted in mean increased plasma levels of zafirlukast by approximately 45%.
In a single-blind, parallel-group, 3-week study in 39 healthy female subjects taking oral contraceptives, 40 mg twice daily of zafirlukast had no significant effect on ethinyl estradiol plasma concentrations or contraceptive efficacy.
Coadministration of zafirlukast with fluconazole, a moderate CYP2C9 inhibitor, resulted in increased plasma levels of zafirlukast, by approximately 58% (90% CI:28, 95). The clinical significance of this interaction is unknown. Zafirlukast exposure is likely to be increased by other moderate and strong CYP2C9 inhibitors. Coadministration of zafirlukast with itraconazole, a strong CYP3A4 inhibitor, caused no change in plasma levels of zafirlukast.
No other formal drug-drug interaction studies between Accolate and marketed drugs known to be metabolized by the P450 3A4 (CYP3A4) isoenzyme (eg, dihydropyridine calcium-channel blockers, cyclosporin, cisapride) have been conducted. As Accolate is known to be an inhibitor of CYP3A4 in vitro, it is reasonable to employ appropriate clinical monitoring when these drugs are coadministered with Accolate.
In two-year carcinogenicity studies, zafirlukast was administered at dietary doses of 10, 100, and 300 mg/kg to mice and 40, 400, and 2000 mg/kg to rats. Male mice at an oral dose of 300 mg/kg/day (approximately 30 times the maximum recommended daily oral dose in adults and in children on a mg/m2 basis) showed an increased incidence of hepatocellular adenomas; female mice at this dose showed a greater incidence of whole body histocytic sarcomas. Male and female rats at an oral dose of 2000 mg/kg/day (resulting in approximately 160 times the exposure to drug plus metabolites from the maximum recommended daily oral dose in adults and in children based on a comparison of the plasma area-under the curve [AUC] values) of zafirlukast showed an increased incidence of urinary bladder transitional cell papillomas. Zafirlukast was not tumorigenic at oral doses up to 100 mg/kg (approximately 10 times the maximum recommended daily oral dose in adults and in children on a mg/m2 basis) in mice and at oral doses up to 400 mg/kg (resulting in approximately 140 times the exposure to drug plus metabolites from the maximum recommended daily oral dose in adults and in children based on a comparison of the plasma AUC values) in rats. The clinical significance of these findings for the long-term use of Accolate is unknown.
Zafirlukast showed no evidence of mutagenic potential in the reverse microbial assay, in 2 forward point mutation (CHO-HGPRT and mouse lymphoma) assays or in two assays for chromosomal aberrations (the in vitro human peripheral blood lymphocyte clastogenic assay and the in vivo rat bone marrow micronucleus assay).
No evidence of impairment of fertility and reproduction was seen in male and female rats treated with zafirlukast at oral doses up to 2000 mg/kg (approximately 410 times the maximum recommended daily oral dose in adults on a mg/m2 basis)
No teratogenicity was observed at oral doses up to 1600 mg/kg/day in mice (approximately 160 times the maximum recommended daily oral dose in adults on a mg/m2 basis), up to 2000 mg/kg/day in rats (approximately 410 times the maximum recommended daily oral dose in adults on a mg/m2 basis) and up to 2000 mg/kg/day in cynomolgus monkeys (which resulted in approximately 20 times the exposure to drug plus metabolites compared to that from the maximum recommended daily oral dose in adults based on comparison of the AUC values). At an oral dose of 2000 mg/kg/day in rats, maternal toxicity and deaths were seen with increased incidence of early fetal resorption. Spontaneous abortions occurred in cynomolgus monkeys at the maternally toxic oral dose of 2000 mg/kg/day. There are no adequate and well-controlled trials in pregnant women. Because animal reproductive studies are not always predictive of human response, Accolate should be used during pregnancy only if clearly needed.
Zafirlukast is excreted in breast milk. Following repeated 40 mg twice-a-day dosing in healthy women, average steady-state concentrations of zafirlukast in breast milk were 50 ng/mL compared to 255 ng/mL in plasma. Because of the potential for tumorigenicity shown for zafirlukast in mouse and rat studies and the enhanced sensitivity of neonatal rats and dogs to the adverse effects of zafirlukast, Accolate should not be administered to mothers who are breast-feeding.
The safety of Accolate at doses of 10 mg twice daily has been demonstrated in 205 pediatric patients 5 through 11 years of age in placebo-controlled trials lasting up to six weeks and with 179 patients in this age range participating in 52 weeks of treatment in an open-label extension.
The effectiveness of Accolate for the prophylaxis and chronic treatment of asthma in pediatric patients 5 through 11 years of age is based on an extrapolation of the demonstrated efficacy of Accolate in adults with asthma and the likelihood that the disease course, and pathophysiology and the drug’s effect are substantially similar between the two populations. The recommended dose for the patients 5 through 11 years of age is based upon a cross-study comparison of the pharmacokinetics of zafirlukast in adults and pediatric subjects, and on the safety profile of zafirlukast in both adult and pediatric patients at doses equal to or higher than the recommended dose.
The safety and effectiveness of zafirlukast for pediatric patients less than 5 years of age has not been established. The effect of Accolate on growth in children has not been determined.
Based on cross-study comparison, the clearance of zafirlukast is reduced in patients 65 years of age and older such that Cmax and AUC are approximately 2- to 3-fold greater than those of younger patients (see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY).
A total of 8094 patients were exposed to zafirlukast in North American and European short-term placebo-controlled clinical trials. Of these, 243 patients were elderly (age 65 years and older). No overall difference in adverse events was seen in the elderly patients, except for an increase in the frequency of infections among zafirlukast-treated elderly patients compared to placebo-treated elderly patients (7.0% vs. 2.9%). The infections were not severe, occurred mostly in the lower respiratory tract, and did not necessitate withdrawal of therapy.
An open-label, uncontrolled, 4-week trial of 3759 asthma patients compared the safety and efficacy of Accolate 20 mg given twice daily in three patient age groups, adolescents (12-17 years), adults (18-65 years), and elderly (greater than 65 years). A higher percentage of elderly patients (n=384) reported adverse events when compared to adults and adolescents. These elderly patients showed less improvement in efficacy measures. In the elderly patients, adverse events occurring in greater than 1% of the population included headache (4.7%), diarrhea and nausea (1.8%), and pharyngitis (1.3%). The elderly reported the lowest percentage of infections of all three age groups in this study.
The safety database for Accolate consists of more than 4000 healthy volunteers and patients who received Accolate, of which 1723 were asthmatics enrolled in trials of 13 weeks duration or longer. A total of 671 patients received Accolate for 1 year or longer. The majority of the patients were 18 years of age or older; however, 222 patients between the age of 12 and 18 years received Accolate.
A comparison of adverse events reported by ≥1% of zafirlukast-treated patients, and at rates numerically greater than in placebo-treated patients, is shown for all trials in the table below.
Accolate
PLACEBO
Adverse Event
N=4058
N=2032
Headache
12.9%
11.7%
Infection
3.5%
3.4%
Nausea
3.1%
2.0%
Diarrhea
2.8%
2.1%
Pain (generalized)
1.9%
1.7%
Asthenia
1.8%
1.6%
Abdominal Pain
1.8%
1.1%
Accidental Injury
1.6%
1.5%
Dizziness
1.6%
1.5%
Myalgia
1.6%
1.5%
Fever
1.6%
1.1%
Back Pain
1.5%
1.2%
Vomiting
1.5%
1.1%
SGPT Elevation
1.5%
1.1%
Dyspepsia
1.3%
1.2%
The frequency of less common adverse events was comparable between Accolate and placebo.
Rarely, elevations of one or more liver enzymes have occurred in patients receiving Accolate in controlled clinical trials. In clinical trials, most of these have been observed at doses four times higher than the recommended dose. The following hepatic events (which have occurred predominantly in females) have been reported from postmarketing adverse event surveillance of patients who have received the recommended dose of Accolate (40 mg/day): cases of symptomatic hepatitis (with or without hyperbilirubinemia) without other attributable cause; and rarely, hyperbilirubinemia without other elevated liver function tests. In most, but not all postmarketing reports, the patient’s symptoms abated and the liver enzymes returned to normal or near normal after stopping Accolate. In rare cases, patients have presented with fulminant hepatitis or progressed to hepatic failure, liver transplantation and death (see WARNINGS, Hepatotoxicity and PRECAUTIONS, Information for Patients).
In clinical trials, an increased proportion of zafirlukast patients over the age of 55 years reported infections as compared to placebo-treated patients. A similar finding was not observed in other age groups studied. These infections were mostly mild or moderate in intensity and predominantly affected the respiratory tract. Infections occurred equally in both sexes, were dose-proportional to total milligrams of zafirlukast exposure, and were associated with coadministration of inhaled corticosteroids. The clinical significance of this finding is unknown.
In rare cases, patients with asthma on Accolate may present with systemic eosinophilia, eosinophilic pneumonia, or clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition which is often treated with systemic steroid therapy. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. These events have usually, but not always, been associated with reductions and/or withdrawal of steroid therapy. The possibility that Accolate may be associated with emergence of Churg-Strauss syndrome can neither be excluded nor established (see PRECAUTIONS, Eosinophilic Conditions).
Neuropsychiatric adverse events, including insomnia and depression, have been reported in association with Accolate therapy (see PRECAUTIONS, Neuropsychiatric Events). Hypersensitivity reactions, including urticaria, angioedema and rashes, with or without blistering, have also been reported in association with Accolate therapy. Additionally, there have been reports of patients experiencing agranulocytosis, bleeding, bruising, or edema, arthralgia, myalgia, malaise, and pruritus in association with Accolate therapy.
Rare cases of patients experiencing increased theophylline levels with or without clinical signs or symptoms of theophylline toxicity after the addition of Accolate to an existing theophylline regimen have been reported. The mechanism of the interaction between Accolate and theophylline in these patients is unknown and not predicted by available in vitro metabolism data and the results of two clinical drug interaction studies (see CLINICAL PHARMACOLOGY and PRECAUTIONS, Drug Interactions).
Accolate has been evaluated for safety in 788 pediatric patients 5 through 11 years of age. Cumulatively, 313 pediatric patients were treated with Accolate 10 mg twice daily or higher for at least 6 months, and 113 of them were treated for one year or longer in clinical trials. The safety profile of Accolate 10 mg twice daily-versus placebo in the 4- and 6-week double-blind trials was generally similar to that observed in the adult clinical trials with Accolate 20 mg twice daily.
In pediatric patients receiving Accolate in multi-dose clinical trials, the following events occurred with a frequency of ≥ 2% and more frequently than in pediatric patients who received placebo, regardless of causality assessment: headache (4.5 vs. 4.2%) and abdominal pain (2.8 vs. 2.3%).
The post-marketing experience in this age group is similar to that seen in adults, including hepatic dysfunction, which may lead to liver failure.
No deaths occurred at oral zafirlukast doses of 2000 mg/kg in mice (approximately 210 times the maximum recommended daily oral dose in adults and children on a mg/m2 basis), 2000 mg/kg in rats (approximately 420 times the maximum recommended daily oral dose in adults and children on a mg/m2 basis), and 500 mg/kg in dogs (approximately 350 times the maximum recommended daily oral dose in adults and children on a mg/m2 basis).
Overdosage with Accolate has been reported in four patients surviving reported doses as high as 200 mg. The predominant symptoms reported following Accolate overdose were rash and upset stomach. There were no acute toxic effects in humans that could be consistently ascribed to the administration of Accolate. It is reasonable to employ the usual supportive measures in the event of an overdose; eg, remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring, and institute supportive therapy, if required.
Because food can reduce the bioavailability of zafirlukast, Accolate should be taken at least 1 hour before or 2 hours after meals.
The recommended dose of Accolate in adults and children 12 years and older is 20 mg twice daily.
The recommended dose of Accolate in children 5 through 11 years of age is 10 mg twice daily.
Based on cross-study comparisons, the clearance of zafirlukast is reduced in elderly patients (65 years of age and older), such that Cmax and AUC are approximately twice those of younger adults. In clinical trials, a dose of 20 mg twice daily was not associated with an increase in the overall incidence of adverse events or withdrawals because of adverse events in elderly patients.
Accolate is contraindicated in patients with hepatic impairment including hepatic cirrhosis (see Contraindications). The clearance of zafirlukast is reduced in patients with stable alcoholic cirrhosis such that the Cmax and AUC are approximately 50 – 60% greater than those of normal adults. Accolate has not been evaluated in patients with hepatitis or in long-term studies of patients with cirrhosis.
Dosage adjustment is not required for patients with renal impairment.
Accolate 10 mg Tablets, (NDC 49884-589-02) white, round, biconvex, film-coated tablets debossed with “P” on one side and “10” on the other, are supplied in opaque HDPE bottles of 60 tablets.
Accolate 20 mg Tablets, (NDC 49884-590-02) white, round, biconvex, film-coated tablets debossed with “P” on one side and “20” on the other, are supplied in opaque HDPE bottles of 60 tablets.
Store at controlled room temperature, 20-25°C (68-77°F) [see USP]. Protect from light and moisture. Dispense in the original air-tight container.
Accolate is a registered trademark of Par Pharmaceutical, Inc.
Manufactured by:
Par Pharmaceutical Companies, Inc.
Chestnut Ridge, NY 10977 U.S.A.
Accolate® (ak-o-late)
(zafirlukast) Tablets
Read the Patient Information leaflet before you start taking Accolate and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.
What is Accolate?
Accolate is a prescription medicine used to help prevent asthma attacks and for the long-term treatment of asthma symptoms in adults and children 5 years and older.
It is not known if Accolate is safe and effective when used in children under 5 years old. The effect of Accolate on growth in children has not been determined.
Do not take Accolate if you need relief right away for a sudden asthma attack. If you get an asthma attack, you should follow the instructions your healthcare provider gave you for treating asthma attacks.
Who should not take Accolate?
Do not take Accolate if you;
What should I tell my healthcare provider before taking Accolate?
Before you take Accolate, tell your healthcare provider if you:
Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.
Accolate may affect the way other medicines work, and other medicines may affect how Accolate works.
Especially tell your healthcare provider if you take:
Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.
How should I take Accolate?
What are the possible side effects of Accolate?
Accolate may cause serious side effects, including:
The most common side effects of Accolate in people 12 years and older include:
The most common side effects of Accolate in children 5 to 11 years include:
Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
These are not all of the possible side effects of Accolate. For more information, ask your healthcare provider or pharmacist.
Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
You may also report side effects to Par Pharmaceutical, Inc. at 1-800-828-9393.
How should I store Accolate?
General information about the safe and effective use of Accolate.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Accolate for a condition for which it was not prescribed. Do not give Accolate to other people, even if they have the same symptoms that you have. It may harm them.
This Patient Information leaflet summarizes the most important information about Accolate. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about Accolate that is written for healthcare professionals.
For more information, go to www.parpharm.com, or call 1-800-828-9393.
What are the ingredients in Accolate?
Active ingredient: zafirlukast
Inactive ingredients: croscarmellose sodium, lactose, magnesium stearate, microcrystalline cellulose, povidone, hypromellose, and titanium dioxide.
What do Accolate tablets look like?
PRINCIPAL DISPLAY PANEL – 10 mg
PRINCIPAL DISPLAY PANEL – 20 mg
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Accolate reviews
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Generic Name: zafirlukast (za FIR loo kast)Brand Name: Accolate
Medically reviewed by Drugs.com on Dec 28, 2018 – Written by Cerner Multum
Accolate is a leukotriene (loo-koe-TRY-een) inhibitor. Leukotrienes are chemicals your body releases when you breathe in an allergen (such as pollen). These chemicals cause swelling in your lungs and tightening of the muscles around your airways, which can result in asthma symptoms.
Accolate is used for chronic treatment of asthma, and to prevent asthma attacks in adults and children as young as 5 years old.
Do not give Accolate to a child younger than 5 years without a doctor’s advice.
قرص accolate
Accolate may also be used for purposes not listed in this medication guide.
You should not use this medicine if you have liver disease (including cirrhosis).
Accolate will not work fast enough to treat an asthma attack. Use only a fast acting inhalation medicine for an asthma attack. Tell your doctor if it seems like your asthma medications don’t work as well.
Do not give this medicine to a child younger than 5 years without a doctor’s advice.
You should not use Accolate if you are allergic to Accolate, or if you have liver disease (including cirrhosis).
To make sure Accolate is safe for you, tell your doctor if you have:
a history of liver disease;
if you also take erythromycin or theophylline; or
if you also take a blood thinner (warfarin, Coumadin, Jantoven).
The chewable tablet form of this medication may contain up to 0.842 milligrams of phenylalanine. Talk to your doctor before using this form of zafirlukast if you have phenylketonuria (PKU).
Accolate is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.
Zafirlukast can pass into breast milk and may harm a nursing baby. You should not breast-feed while using this medicine.
Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.
Accolate will not work fast enough to treat an asthma attack. Use only a fast acting inhalation medicine for an asthma attack. Tell your doctor if it seems like your asthma medications don’t work as well.
Take Accolate on an empty stomach, at least 1 hour before or 2 hours after a meal.
Your dose needs may change if you have surgery, are ill, are under stress, or have recently had an asthma attack. Do not change your medication dose or schedule without your doctor’s advice.
Keep using this medicine as directed, even if you have no asthma symptoms.
Asthma is sometimes treated with a combination of drugs. Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Every person with asthma should remain under the care of a doctor.
If you also use a steroid medication, do not stop using it suddenly or you may have unpleasant withdrawal symptoms. Talk with your doctor about tapering your steroid dose before stopping completely.
Store at room temperature away from moisture, heat, and light. Keep the bottle tightly closed when not in use.
Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.
Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.
Avoid situations or activities that may trigger an asthma attack.
Get emergency medical help if you have signs of an allergic reaction: hives, blisters, severe itching; difficult breathing; swelling of your face, lips, tongue, or throat.
Call your doctor at once if you have:
depressed mood, unusual thoughts or behavior;
severe sinus pain or congestion;
numbness or tingly feeling in your arms or legs;
worsening or no improvement in your asthma symptoms;
liver problems–nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or
high levels of certain white blood cells–skin rash, bruising, severe tingling, pain, muscle weakness, new or worsening cough, fever, trouble breathing.
Common side effects may include:
nausea, diarrhea, stomach pain;
headache; or
cold symptoms such as stuffy nose, sneezing, sore throat.
قرص accolate
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Accolate side effects (in more detail)
Other drugs may interact with zafirlukast, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.
Accolate drug interactions (in more detail)
Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
Copyright 1996-2018 Cerner Multum, Inc. Version: 11.01.
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Symbicort, Ventolin, Breo Ellipta, Ventolin HFA, Dulera, Dupixent
Accolate reviews
The easiest way to lookup drug information, identify pills, check interactions and set up your own personal medication records. Available for Android and iOS devices.
Subscribe to Drugs.com newsletters for the latest medication news, alerts, new drug approvals and more.
Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. Data sources include IBM Watson Micromedex (updated 1 July 2019), Cerner Multum™ (updated 1 July 2019), Wolters Kluwer™ (updated 29 June 2019) and others.
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Zafirlukast is an oral leukotriene receptor antagonist (LTRA) for the maintenance treatment of asthma, often used in conjunction with an inhaled steroid and/or long-acting bronchodilator. It is available as a tablet and is usually dosed twice daily. Another leukotriene receptor antagonist is montelukast (Singulair), which is usually taken just once daily.
Zafirlukast blocks the action of the cysteinyl leukotrienes on the CysLT1 receptors, thus reducing constriction of the airways, build-up of mucus in the lungs and inflammation of the breathing passages.
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
قرص accolate
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
For the prophylaxis and chronic treatment of asthma.
Zafirlukast is a synthetic, selective peptide leukotriene receptor antagonist (LTRA) indicated for the prophylaxis and chronic treatment of asthma. Patients with asthma were found in one study to be 25-100 times more sensitive to the bronchoconstricting activity of inhaled LTD4 than nonasthmatic subjects. In vitro studies demonstrated that zafirlukast antagonized the contractile activity of three leukotrienes (LTC4, LTD4 and LTE4) in conducting airway smooth muscle from laboratory animals and humans. Zafirlukast prevented intradermal LTD4-induced increases in cutaneous vascular permeability and inhibited inhaled LTD4-induced influx of eosinophils into animal lungs.
Zafirlukast is a selective and competitive receptor antagonist of leukotriene D4 and E4 (LTD4 and LTE4), components of slow-reacting substance of anaphylaxis (SRSA). Cysteinyl leukotriene production and receptor occupation have been correlated with the pathophysiology of asthma, including airway edema, smooth muscle constriction, and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma.
Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.
Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.
Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.
Rapidly absorbed following oral administration, reduced following a high-fat or high-protein meal.
99%
Hepatic
The most common metabolic products are hydroxylated metabolites which are excreted in the feces.
10 hours
Side effects include rash and upset stomach.
Extended description of the mechanism of action and particular properties of each drug interaction.
A severity rating for each drug interaction, from minor to major.
A rating for the strength of the evidence supporting each drug interaction.
An effect category for each drug interaction. Know how this interaction affects the subject drug.
Arie Gutman, “Process for the preparation of zafirlukast.” U.S. Patent US20040186300, issued September 23, 2004.
The date on which a patent was filed with the relevant government.
There is additional data available for commercial users including Adverse Effects, Contraindications, and Blackbox Warnings. Contact us to learn more about these and other features.
Drug created on June 13, 2005 07:24 / Updated on July 21, 2019 06:25
Es la nueva aplicación móvil (de pago) para los profesionales de la salud donde encontrará la Guía Farmacológica en español más consultada en el mundo, actualizada semanalmente.
Incluye los módulos de cálculo de Interacciones y de búsqueda de Equivalencias Internacionales con el objetivo de fomentar el uso racional del medicamento.
Gracias, pero no estoy interesado en este momento.
قرص accolate
Es la nueva aplicación móvil (de pago) para los profesionales de la salud donde encontrará la Guía Farmacológica en español más consultada en el mundo, actualizada semanalmente.
Incluye los módulos de cálculo de Interacciones y de búsqueda de Equivalencias Internacionales con el objetivo de fomentar el uso racional del medicamento.
Gracias, pero no estoy interesado en este momento.
Es la nueva aplicación móvil (de pago) para los profesionales de la salud donde encontrará la Guía Farmacológica en español más consultada en el mundo, actualizada semanalmente.
Incluye los módulos de cálculo de Interacciones y de búsqueda de Equivalencias Internacionales con el objetivo de fomentar el uso racional del medicamento.
Gracias, pero no estoy interesado en este momento.
Es la nueva aplicación móvil (de pago) para los profesionales de la salud donde encontrará la Guía Farmacológica en español más consultada en el mundo, actualizada semanalmente.
Incluye los módulos de cálculo de Interacciones y de búsqueda de Equivalencias Internacionales con el objetivo de fomentar el uso racional del medicamento.
Gracias, pero no estoy interesado en este momento.
Es la nueva aplicación móvil (de pago) para los profesionales de la salud donde encontrará la Guía Farmacológica en español más consultada en el mundo, actualizada semanalmente.
Incluye los módulos de cálculo de Interacciones y de búsqueda de Equivalencias Internacionales con el objetivo de fomentar el uso racional del medicamento.
Gracias, pero no estoy interesado en este momento.
Es la nueva aplicación móvil (de pago) para los profesionales de la salud donde encontrará la Guía Farmacológica en español más consultada en el mundo, actualizada semanalmente.
Incluye los módulos de cálculo de Interacciones y de búsqueda de Equivalencias Internacionales con el objetivo de fomentar el uso racional del medicamento.
Gracias, pero no estoy interesado en este momento.
Es la nueva aplicación móvil (de pago) para los profesionales de la salud donde encontrará la Guía Farmacológica en español más consultada en el mundo, actualizada semanalmente.
Incluye los módulos de cálculo de Interacciones y de búsqueda de Equivalencias Internacionales con el objetivo de fomentar el uso racional del medicamento.
Gracias, pero no estoy interesado en este momento.
Es la nueva aplicación móvil (de pago) para los profesionales de la salud donde encontrará la Guía Farmacológica en español más consultada en el mundo, actualizada semanalmente.
Incluye los módulos de cálculo de Interacciones y de búsqueda de Equivalencias Internacionales con el objetivo de fomentar el uso racional del medicamento.
Gracias, pero no estoy interesado en este momento.
قرص accolate
Antagonista del receptor de leucotrienos. Reduce la contracción del músculo liso, el edema de las vías respiratorias, la actividad celular inflamatoria, incluyendo la migración de eosinófilos en el pulmón; efectos relacionados con los signos y síntomas del asma.
Profilaxis y tto. crónico del asma como terapia adicional de mantenimiento cuando los ß-agonistas de acción corta “a demanda” no proporcionan suficiente control clínico, así como asma persistente leve-moderada no adecuadamente controlada con corticoides inhalados.
Para acceder a la información de posología en Vademecum.es debes conectarte con tu email y clave o registrarte.
Oral. Ads. y niños >= 12 años: 20 mg, 2 veces/día. Ancianos: iniciar con 20 mg, 2 veces/día y ajustar según respuesta. No administrar con alimentos.
No debe administrarse con alimentos.
Hipersensibilidad previa; daño hepático incluyendo cirrosis hepática.
Tomar continuadamente, incluso en períodos asintomáticos; no indicado para broncoespasmo agudo en ataque asmático; no debe sustituir a los corticoides inhalados u orales; interrumpir el tto. si aparece: alteración hepática (determinar las transaminasas séricas al comienzo y durante el tto.), condiciones eosinofílicas o síndrome de Churg-Strauss (no realizar prueba de reexposición ni reiniciar el tto.); experiencia limitada en I.R. leve-grave; no administrar en niños < 12 años (no se ha establecido seguridad y eficacia).
Contraindicado con daño hepático, incluyendo cirrosis.
Precaución. Experiencia limitada en I.R. leve-grave.
Niveles plasmáticos aumentados por: AAS, fluconazol.
Niveles plasmáticos disminuidos por: eritromicina, terfenadina.
Monitorizar tiempo de protrombina con: warfarina.
En animales no presentó efectos aparentes. Valorar beneficio/riesgo.
Zafirlukast es excretado en leche humana; por lo tanto, no deberá ser administrado a madres durante el periodo de lactancia.
Infecciones; nauseas, vómitos, diarrea, dolor abdominal; aumento de los niveles de transaminasas séricas; mialgia; cefaleas; erupciones.
Fuente: El contenido de esta monografía de principio activo según la clasificación ATC, ha sido redactado teniendo en cuenta la información clínica de todos los medicamentos autorizados y comercializados en España clasificados en dicho código ATC. Para conocer con detalle la información autorizada por la AEMPS para cada medicamento, deberá consultar la correspondiente Ficha Técnica autorizada por la AEMPS.
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(zafirlukast)
Zafirlukast belongs to a group of medications known as leukotriene receptor antagonists. It works by blocking chemicals produced by the body called leukotrienes. Leukotrienes cause the lining of the breathing passages of the lung to swell. When used regularly, zafirlukast helps to reduce inflammation in the lining of the airways to make breathing easier.
Zafirlukast is used for the prevention and chronic treatment of asthma in adults and children 12 years of age and older. It works over a long period of time to prevent asthma attacks but will not help to relieve an asthma attack when it is occurring. Asthma sufferers should always have their fast-acting asthma relief medication on hand to deal with attacks.
This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here.
Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor. Do not stop taking this medication without consulting your doctor.
قرص accolate
Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.
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Each white-to-off-white, round, biconvex, film-coated tablet, with surface markings, contains zafirlukast 20 mg. Nonmedicinal ingredients: croscarmellose sodium, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, and titanium dioxide.
The recommended dose for adults and children aged 12 years and over is 20 mg twice daily taken on an empty stomach (at least one hour before or 2 hours after a meal). Continue to take this medication regularly, even when you are not having symptoms of asthma.
Many things can affect the dose of medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here, do not change the way that you are taking the medication without consulting your doctor.
It is important to take this medication exactly as prescribed by your doctor. If you miss a dose, take it as soon as possible and continue with your regular schedule. If it is almost time for your next dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a missed one. If you are not sure what to do after missing a dose, contact your doctor or pharmacist for advice.
Store this medication at room temperature and keep it out of the reach of children.
Do not dispose of medications in wastewater (e.g. down the sink or in the toilet) or in household garbage. Ask your pharmacist how to dispose of medications that are no longer needed or have expired.
Do not take zafirlukast if you:
Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.
The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.
The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.
Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.
Although most of the side effects listed below don’t happen very often, they could lead to serious problems if you do not check with your doctor or seek medical attention.
Check with your doctor as soon as possible if any of the following side effects occur:
Stop taking the medication and seek immediate medical attention if any of the following occur:
Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.
Before you begin taking a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should take this medication.
Asthma attacks: Zafirlukast should not be used to try to relieve acute asthma attacks. Have your rescue medication ready in case of an acute attack. Do not stop taking zafirlukast without consulting your doctor.
Liver problems: Zafirlukast is not recommended for people with reduced liver function. It may also cause severe liver problems. If you develop jaundice (signs include yellowing of the skin or eyes); flu-like symptoms; nausea; fatigue; loss of appetite; itching; and pain on the right side of your abdomen, under the ribcage, stop taking this medication and contact your doctor immediately.
Warfarin interaction: Taking warfarin together with zafirlukast significantly increases the time it takes blood to clot. People taking warfarin and zafirlukast should have their bleeding times monitored closely and have their anticoagulant dose (warfarin) adjusted accordingly.
Pregnancy: This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.
Breast-feeding: Zafirlukast passes into breast milk. If you are a breast-feeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.
Children: The effectiveness and safety of zafirlukast for children under 12 years of age have not been established.
There may be an interaction between zafirlukast and any of the following:
If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:
An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.
Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.
All material copyright MediResource Inc. 1996 – 2019. Terms and conditions of use. The contents herein are for informational purposes only. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Source: www.medbroadcast.com/drug/getdrug/Accolate
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