The Salina Journal from Salina, Kansas on October 6, 1996 · Page 52
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The Salina Journal from Salina, Kansas · Page 52

Salina, Kansas
Issue Date:
Sunday, October 6, 1996
Page 52
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« „ BRIEFSUMMARY Serevent 1 * (itlnuteraliinaloite) Inhalation Aerosol Bronchodilator Aerosol For Oral Inhalation Only The following Is a brief summary only. Before prescribing, see complete prescribing Information In Serevent® Inhalation Aerosol product labeling. CONTRAINDICATIONS: Serevent® Inhalation Aerosol Is contralndlcated In patients with a history ot hypersensitivity to any of the components. WARNINGS* IMPORTANT INFORMATION: SEREVENT® INHALATION AEROSOL SHOULD NOT BE INITIATED IN PATIENTS WITH SIGNIFICANTLY WORSENING OR ACUTELY DETERIORATING ASTHMA, WHICH MAY BE A LIFE-THREATENING CONDITION. Seriouiicuteretpiritory events, including fatalltiei, turn been reported, both In Hi* US ami worldwide, wkin Serevent Inhslitlon Aerosol has been InrrlettdlnuiUsltuitlen. Although It Is not powlWe from these rtpertj to determine «hethtr Strtveni Inhalation Atrotol coalributid to Urn* adverse evtrrti or simply tilled to relieve the ditertoratlnfl. asthma, tht in* of Strevtnt Inhalation Atrostl In this stttlng Is Inapproprlit*. SEHEVENT INHALATION AEROSOL SHOULD NOT BE USED TO TREAT ACUTE SYMPTOMS. It Is crucial to Inform patients of this and prescribe I short-Ktirig, Inhaled betaj-aionltt lor thti purpou «s well a* warn them Hurt Increasing Inhaled bitaz-agonlsl UM Is * signal ol deteriorating atthrnt. SEREVENT INHALATION AEROSOL IS NOT A SUBSTITUTE FOR INHALED OH ORAL CORTICOSTEROIDS. CortlcodwoUs thoyW not btstopDit or reduced whtiSemtnl Inhalation Aerosol Is Initiated. (Ste PRECAUTIONS: IrrionnallM lor PMKnti ami PATIENTS INSTRUCTIONS FOR USE leifM.) 1. Do Not Introduce Serevent Inhalation Aerosol as a Treatment for Acutely OateriiiratlrK] Asthma: Serevent Inhalation Aerosol is intended for the maintenance treatment of asthma (see INDICATIONS AND USAGE section ot lull prescribing Information) and should not be introduced In acutely deteriorating asthma, which Is a potentially life-threatening condition. There are no data demonstrating that Serevent Inhalation Aerosol provides greater efficacy than or additional efficacy to short-acting, Inhaled betaz-agonists In patients with worsening asthma. Serious acute respiratory events, Including fatalities, have been reported, both in the US and worldwide, in patients receiving Serevent Inhalation Aerosol. In most cases, these have occurred In patients with severe asthma (e.g., patients with a history of corticoslerok) dependence, low pulmonary function, Intubation, mechanical ventilation, frequent hospttattzatlons, or previous lite-threatening acute asthma exacerbations) and/or In some patients In whom asthma has been acutely deteriorating (e.g., unresponsive to usual medications, Increasing need for Inhaled, short-acting betaz-agonists, increasing need for systemic corticosterolds, significant Increase in symptoms, recent emergency room visits, sudden or progressive deterioration In pulmonary function). However, they have occurred In a few patients with less severe asthma as well. It was not possible from these reports to determine whether Serevent Inhalation Aerosol contributed to these events or simply failed to relieve the deteriorating asthma. 2. Do Not Use Sary/ent Inhalation Aerosol to Treat Acute Symptoms: A short-acting inhaled betaz-agonist, not Serevent Inhalation Aerosol, should be used to relieve acute asthma symptoms. When prescribing Serevent Inhalation Aerosol, the physician must also provide the patient with a short-acting, Inhaled betaz-agonlst (e.g., albuterol) for treatment of symptoms that occur acutely, despite regular twice daily (morning and evening) use of Serevent Inhalation Aerosol. When beginning treatment with Serevent Inhalation Aerosol, patients who have been taking short-acting, inhaled betaz-agonists on a regular basis (e.g., q.i.d.) should be Instructed to discontinue the regular use of these drugs and use them only for symptomatic relief if they develop acute asthma symptoms while taking Serevent Inhalation Aerosol (see PRECAUTIONS: Information for Patients). 3. Watch for Increasing USB nt Short-Acting Inhaktd Balay- Aoonlate. Which Is a Marter ol Deteriorating A»th™ r AJitRina may deteriorate acutely over a period of hours or chronically over several days or longer. If the patient's short-acting, Inhaled betaz-agonist becomes less effective or the patient needs more inhalations than usual, this may be a marker of destabllization ot asthma. In this setting, the patient requires immediate re-evaluation with reassessment of the treatment regimen, giving special consideration to the possible need for corticosterolds. If the patient uses four or more Inhalations per day of a short-acting, Inhaled betaz-agonlst for 2 or more consecutive days, or if more than one canister (200 inhalations per canister) of short-acting, Inhaled betaz-agonist Is used in an 6-week period In conjunction with Serevent Inhalation Aerosol, then the patient should consult the physician for re-evaluation. Increasing the tally titan *J Serevtnl Itttutttloo A*fi*ottl bi this tltmtiM is BO! iBoiwiite Strtvtot WialaUoB Aerosol should eol be uwtmort IreqttosUy than twice dally (mortal aot tvtatn*) it ft* retenaeadet toe ol two Ipfcalttioas. 4. tatiofiAarosol as a Substitute tor itjng that Serevent Inhalation Aerosol has a clinical anti-Inflammatory effect and could be expected to take the place of, or reduce the dose of, corticosterolds. Patient) who already require oral or inhaled corticosterolds lor treatment ol asthma should be continued on this type of treatment even H they feel better as a result ol Initiating Serevent Inhalation Aerosol. Any change In corticosttroid dosage should be made ONLY after clinical evaluation (see PRECAUTIONS: Information for Patients). 5. Do Not ExcMd HKomityfKtod Dmun. As *lth olhur recommended. Fatalities have been reported in association with excessive use of Inhaled sympathomlmetic drugs. Large doses of inhaled or oral salmeterol (1 2 to 20 times the recommended dose) have been associated with clinically significant prolongation of the QT C Interval, which has the potential for producing ventricular arrhythmias. 6. Paradoxical Bronchnsnasm! As with other inhaled asthma medications, paradoxical bronchospasm (which can be life threatening) has been reported following the use of Serevent® (salmeterol xlnafoate) Inhalation Aerosol. It it occurs, treatment with Serevent Inhalation Aerosol should be discontinued Immediately and alternative therapy Instituted. 7. Immediate HvoerMnsltivltv Reactions: Immediate hypersensitivity reactions may occur after administration of Serevent Inhalation Aerosol, as demonstrated by rare cases of urticaria, angloedema, rash, and bronchospasm. 8. Uoner Airway Svmotoms: Symptoms of laryngeal spasm, Irritation, or swelling, such as strldor and choking, have been reported rarely In patients receiving Serevent Inhalation Aerosol. PRECAUTIONS: General: 1 . Use with Spacer or Other Devices: The safety and atfec- tiveness of Serevent® Inhalation Aerosol when used with a spacer or other devices have not been adequately studied. 2. Cardiovascular and Olhar Effects: No effect on the cardiovascular system Is usually seen after the administration of inhaled salmeterol In recommended doses, but the cardiovascular and central nervous system effects seen with all sympathomlmetic drugs (e.g., Increased blood pressure, heart rale, excitement) can occur after use of Serevent Inhalation Aerosol and may require discontinuation of the drug. Salmeterol, like all sympathomlmetic amines, should be used with caution In patients with cardiovascular disorders, especially coronary Insufficiency, cardiac arrhythmias, and hypertension; In patients with convulsive disorders or thyrotoxicosis; and In patients who are unusually responsive to sympathomimetic amines. As has been described with other beta-adrenerglc agonist bronchodllators, clinically significant changes In systolic and/or dlastolic blood pressure, pulse rate, and electrocardiograms have been seen Infrequently in Individual patients in controlled clinical studies with salmeterol. 3. Metabolic Effects: Doses of the related betaz-adrenoceptor agonist albuterol, when administered Intravenously, have been reported to aggravate preexisting diabetes mellitus and ketoacldosls. No effects on glucose have been seen with Serevent Inhalation Aerosol at recommended doses. Administration ot betaz-adrenoceptor agonists may cause a decrease In serum potassium, possibly through Intracellular shunting, which has the potential to Increase the likelihood ol arrhythmias. The decrease Is usually transient, not requiring supplementation. Clinically significant changes In blood glucose and/or serum potassium were seen rarely during clinical studies with long- term administration of Serevent Inhalation Aerosol at recommended doses. Information lor Patients: See Illustrated Pattern's Instructions for Use leaflet SHAKE WELL BEFORE USING. It is Important that patients understand how to use Serevent Inhalation Aerosol appropriately and how it should be used In relation to other asthma medications they are taking. Patients should be given the following information: 1. Shake well before using. 2. The recommended dosage (two inhalations twice dairy, morning and evening) should not be exceeded. 3. Serevent Inhalation Aerosol is not meant to relieve acute asthma symptoms and extra doses should not be used for that purpose. Acute symptoms should be treated with a short- acting, Inhaled betaz-agonlst such as albuterol (the physician should provide the patient with such medication and Instruct the patient in how It should be used). 4. The physician should be notified Immediately It any ol the following situations occur, which may be a sign of seriously worsening asthma. • Decreasing effectiveness of short-acting, Inhaled betaz- agonists • Need for more Inhalations than usual ot short-acting, Inhaled betaz-agonists • Use of four or more Inhalations per day of a short-acting betaz-ewiist for 2 or rwre days consecutively • Use ot more than one canister of a short-acting, Inhaled betaz-agonlst in an 8-week period (I.e., canister with 200 inhalations) 5. Serevent Inhalation Aerosol should not be used as « substitute tor oral or inhaled corticosteroids. The dosage of these medications should not be changed and they should not be Jtorjpsd without consulting the physician, even II the patient feels 6. Patients should be cautioned regarding potential adverse cardiovascular effects, such as palpitations or chest pain, related to the use of additional betaz-agonlst. 7. In patients receiving Serevent Inhalation Aerosol, other Inhaled medications should be wed only as directed by the physician. 8. When using Serevent Inhalation Aerosol to prevent exercise- Induced bronchospasm, patients should take the dose at least 30 to 60 minutes before exercise. Drug Weratttosa: MttMcttw MMmbtt.- In the two 3- month, repetitive-dose clinical trials (n.TM), the mean dally neeaforaooitlonaJMtez-agontjtusewasltol'/ilnhalallons per day, but some patients used more. Eight percent of patients used si least eight Inhalations per day at tot on one occasion. SU percent i^9 to 12lr&latlora it least orw.Therewere 1 5 patients (814) who averaged over toMr-halations per day. Four of these used an average of 8 to 11 Inhalations per day. In these 1 5 patients there was no observed Increase In frequency of cardiovascular adverse event*. The safety of concomttanl use ol more than eight Inhalations per day ol short-acting beUz-agonUU with Serevent Inhalation Aerosol has ratteen established. In ISpatierns who exporienced worsening o asthma while receiving Serevent Inhalation Aerosol, neb , albuterol (one dost In most) led to Improvement In FEV, and no Increase In occurrence ot cardiovascular adverse events. oxidase Inhibitors or tricycllc antidepressants because the action of salmeterol on the vascular system may be potentiated by these agents. Cottlwtt*nUt*a<ICnnailrcitt:\s\ clinical trials, Inhaled corticosterolds and/or Inhaled cromolyn sodium did not alter the safety profile of Serevent® (salmeterol xinafoate) Inhalation Aerosol when administered concurrently. Mettyfirutti/MtvThe concurrent use ol Intravenously or orally administered methylxanthines (e.g., amlnophylllne, theophylllne) by patients receiving Serevent Inhalation Aerosol has not been completely evaluated. In one clinical trial, 87 patients receiving Serevent Inhalation Aerosol 42 meg twice dally concurrently with a theophylllne product had adverse event rates similar to those in 71 patients receiving Serevent Inhalation Aerosol without theoprrylllne. Resting heart rates were slightly higher In the patients on theophylllne but were little affected by Serevent Inhalation Aerosol therapy. CimiogeiMsts, Mutaaentttj, Impilrment ol Fertility: In an 1 8-month oral carclnogenlcity study in CD mice, salmeterol xinafoate caused a dose-related increase In the incidence of smooth muscle hyperplasla, cystic glandular hyperplasia, and lelomyomas of the uterus and a dose-related Increase In the Incidence ol cysts in the ovaries. A higher Incidence of lelomyosarcomas was not statistically significant tumor findings were observed at oral doses of 1 .4 and 1 0 mg/kg, which gave 9 and 63 times, respectively, the human exposure based on rodenthuman AUC comparisons. Salmeterol caused a dose-related Increase In the incidence ol mesovarian lelomyomas and ovarian cysts In Sprague Dawley rats In a 24-month Inhalation/oral carcinogenlcity study. Tumors were observed In rats receiving doses of 0.68 and 2.58 mg/kg per day (about 55 and 21 5 times the recommended clinical dose Img/nfD.These findings In rodents are slmilartothose reported previously for other beta-adrenerglc agonist drugs. The relevance of these findings to human use Is unknown. No significant effects occurred in mice at 0.2 mg/kg (1 .3 times the recommended clinical dose based on comparisons of the AUCs) and In rats at 0.21 mg/kg (1 5 times the recommended clinical dose on a mg/m' basis). Salmeterol xinafoate produced no detectable or reproducible Increases in microbljl and mammalian gene mutation In vitro. No blastogenlc activity occurred /n vitro in human lymphocytes or In we In a rat mlcronucleus test. No effects on fertility were identified in male and female rats treated orally with salmeterol xinafoate at doses up to 2 mg/kg orally (about 1 60 times the recommended clinical dose on a mg/m- basis). ttMdrenerglc drugs, Serevent Inhalation Aerosol should not be used more often or at Mglwr doses than extreme caution to patients being treated with monoamlne No significant effects of maternal exposure to oral salmeterol xinafoate occurred In the rat at doses up to the equivalent of about 160 times the recommended clinical dose on a mg/m 1 basis. Dutch rabbit fetuses exposed to salmeterol xinafoate in utoro exhibited effects characteristically resulting from beta- adrenoceptor stimulation; these included precocious eyelid openings, deft palate, stemebral fusion, limb and paw flexures, and delayed ossification of the frontal cranial bones. No significant effects occurred at 0.6 mg/kg given orally (1 2 times the recommended clinical dose based on comparison of theAUCs). New Zealand White rabbits were less sensitive since only delayed ossification of the frontal bones was seen at 1 0 mg/kg given orally (approximately 1 ,800 times the recommended clinical dose on a mg/m- basis). Extensive use of other beta- agonists has provided no evidence that these class effects In animals are relevant to use In humans. There are no adequate and well-controlled studies with Serevent Inhalation Aerosol In pregnant women. Serevent Inhalation Aerosol should be used during pregnancy only If the potential benefit justifies the potential risk to the fetvs. Ust In Labor and Delivery: There are no wen-controlled human studies that have Investigated effects of salmeterol on preterm labor or labor at term. Because of the potential lor beta- agonist Interference with uterine contractility, use ot Serevent Inhalation Aerosol during labor should be restricted to those patients In whom the benefits clearly outweigh the risks. Nursing Methen: Plasma levels of salmeterol after Inhaled therapeutic doses are very low (85 to 200 pg/mL) In humans. In totaling rats dosed with radlolabeled salmeterol, levels ot radioactivity were similar in plasma and milk. In rats, concentrations of salmeterol In plasma and milk were similar. The xinafoate moiety Is also transferred to milk In rats at concentrations of about half the corresponding level In plasma. However, since there Is no experience with use ot Serevent Inhalation Aerosol by nursing mothers, a decision should be made whether to discontinue nursing or to discontinue the drug, taking Into account the Importance of the drug to the mother. Caution should be exercised when salmeterol xlnafoale Is administered to a nursing woman. Pedletrte Use: The safety and effectiveness ol Serevent Inhalation Aerosol In children younger than 12 years of age have not been established. Geriatric Us»: Of the total number ol patients who received Serevent inhalation Aerosol In all clinical studies. 241 were 65 years and older. Geriatric patients (65 years «nd older) with reversible obstructive ilrway disease were evaluated In four well-controlled studies Of 3 weeks' to 3 months' duration. Two placebo-controlled, crossover studies evaluated twice-daily dosing with salmeterol for 21 to 28 days in 45 patlertls. An additional 75 geriatric patients were treated with salmeterol for 3 months In two large parallel-group. mulUcenter studies. These 1 20 patients experienced Increases in AM and PM peak expiratory flow rate md decreases In diurnal variation In peak expiratory flow rale sknllv to responses teen In the total populations of the two latter studies. The adverse event type and frequency In geriatric patients were notrJMerent from thoseofthetotalpopglationsttudled. No apparent differences In the efficacy and safety ot Seievent Inhalation Aerosol were observed when geriatric patients were compared with younger patients In clinical trials. As with other betaz-agortsts, however, special caution should be observed when using Serevent Inhalation Aerosol in elderly patients who have concomitant cardiovascular disease that could be adversely affected by this class of drug. Based on available data, no adlustmentotsajnumoldowge In geriatric AOV1R»7(*ACTKH«: Adverse reartlow to «alm«terol are similar In nature to reactions to other Mtecttv«betjj- adrenoceptor agonists, i.e., tachycardia; palpitations; Immediate hypersensitivity reactions. Including urticaria, angloedema, rash, bronchospasm (see WARNINGS); headache; tremor nervousness; and paradoxical bronchospasm (seeWARNINGS). Two multicenter, 12-wtek, controlled studies have evaluated twice-daily doses of Serevent® (salmeterol xinafoate) inhalation Aerosol In patients 12 years of age and older with asthma. The following table reports the Incidence of adverse events in these two studies. Atars* Experience Incidence In Two Large 12-Week Clinical Trials- Adverse Event Type Ear, nose, and throat Upper respiratory tract Infection Nasopharyngitis Disease of nasal cavity/sinus Sinus headache Gastrointestinal Stomachache Neurological Headache Tremor Respiratory Cough Lower respiratory Infection Percent of Patients Placebo n.1B7 13 12 4 2 0 23 2 6 2 Serevent 42 meg b.l.d. na1R4 14 14 6 4 28 7 4 Albuterol 180 meg nlias 16' 11 1 <1 0 27 3 3 2 • The only adverse experience classified as serious was one case of upper respiratory tract Infection In a patient treated with albuterol. The table above includes all events (whether considered drug related or nondrug related by the Investigator) that occurred at a rate of over 3% In the Serevent Inhalation Aerosol treatment group and were more common In the Serevent Inhalation Aerosol group than In the placebo group, Pharyngitis, allergic rhinitis, dlzztness/giddlnesj. and Influenza occurred at 3% or more but were equally common on placebo. Other events occurring In the Serevent Inhalation Aerosol treatoiert group atafr^uencyof1%to3%v*m as follow CirtftomciiSar: Tachycardia, palpitations. tu, Hut, Mtf nmtr: Rhinitis, laryngitis. ButniatnOntl: Nausea, viral gastroenteritis, nausea and vomiting, diarrhea, abdominal pain. fc Urticaria. : Dental pain. f ft Pain In Joint, back pain, muscle cramp/contraction, myalgia/myositls, muscular soreness. NNratoffe": Nervousness, malaise/fatigue. J?«ii//Mwy:TrachetUs/broncnltis. Site Rash/skin eruption. Untulttl: Dysmenorrhea. In small dose-response studies, tremor, nervousness, and palpitations appeared to be dose related. Postmartujtlng Eip*rieM«: In extensive US and worldwide postmarketing experience, serious exacerbations of asthma. Including some that have been fatal, have been reported. In most cases, these have occurred In patients with severe asthma and/or In some patients In whom asthma has been acutely deteriorating (see WARNINGS no. 1), but they have occurred In a few patients with less severe asthma as well. It was not possible from these reports to determine whether Serevent Inhalation Aerosol contributed to these events or simply failed to relieve the deteriorating asthma. Postmarketing experience includes rare reports of upper airway symptoms of laryngeal spasm. Irritation, or swelling, such as stridorand choking. Hypertension and arrhythmias have been reported. OVEROOSAGE: Overdosage with salmeterol may be expected to result In exaggeration of Uiepharmacologlc adverse effects associated wittiBeta-adrenoceptoragonlsts, Including tachycardia and/or arrhythmia, tremor, headache, anif muscle cramps. Overdosage with satmeterol can lead to clinically significant prolongation of the QT C Interval, which can produce yentriculararrhythmlas. Other signsof overdosage may Include hypokalemla and hyperglycemla. In these cases, therapy with Serevent® inhalation Aerosol and all beta-adienerglc-stlmulant drugs should be stopped, supportive therapy provided, and Judicious us* of a beta- adrenjrgic blocking agent should be considered, bearing In mlndthepojslbilttythatsuchaoenujcanproduce bronchospasm. Cardiac monitoring Is recommended In cues of overdosage. As with ail •ympathomimettcpresiurrzed aerosol , maximum nonlethal oral doses In mice and rats were •wroxlrna tely 1 60 rag/kg and >1 ,000 mg/kg, respectively. DlilyslsrsnoUppropriaKtreatmenlforoverdosaoeof Serevent Inhalation Aerosol. GlaxoWellcome mo Inc. Printed In DBA September 1996

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