578 AeroBid® (flunisolide) Effective asthma control BID For oral inhalation only CONTRAINDICATIONS AeroBid Inhaler is contraindicated in the primarytreatment of status asthmaticus or other acute episodes of asthma where intensive measures are required. Hypersensitivity to any ofthe ingredients of this preparation contraindicates its use. WARNINGS Particularcare is needed in patientswhoare transferred from systemicallyactivecorticosteroids to AeroBid Inhaler be- causedeaths duetoadrenal insufficiency have occurred in asthmatic patients duringand aftertransfer from systemic corticosteroidsto aerosol corticosteroids. Afterwithdrawal from systemic corticosteroids, a number of monthsare re- quiredfor recoveryof hypothalamic-pituitary-adrenal (HPA) function. During this period of HPAsuppression, patients mayexhibit signsand symptomsofadrenal insufficiencywhen exposed to trauma, surgery or infections, particularly gastroenteritis. Although AeroBid Inhalermayprovidecontrol ofasthmatic symptomsduring theseepisodes, it does NOTprovidethesystemic steroidthat isnecessary for coping with theseemergencies. During periods ofstress orasevereasthmaticattack, patientswwho have been withdrawn from systemiccorticosteroids should be instructed to resumesystemic steroids (in large doses) immediatelyand to contact their physician forfurther instruction. These patients shouldalso be instructed tocarryawarning card indicating that they may need supplemen- tarysystemic steroids during periods of stressorsevere asthma attack.Toassessthe risk ofadrenal insufficiency in emergencysituations, routine tests ofadrenal cortical function, including measurement ofearly morning resting cortisol levels, should beperformed periodically in all patients. An earlymorning resting cortisol level may beaccepted as nor- mal if itfallsatornearthenormal mean level. Localized infections with Candidaalbicans orAspergillus niger have occurred in the mouth and pharynxand occasionally in the larynx. Positive culturesfor oral Candida may be present in upto 34% of patients. Although thefrequency of clinically apparent infection isconsiderably lower, these infections may requiretreatment withappropriate antifungal therapy or dis- continuancewithAeroBid Inhaler. AeroBid Inhaler is not to be regarded as a bronchodilatorand is not indicated for rapid relief of bronchospasm. Patients should be instructed to contact their physician immediately when episodes of asthmathat are not responsive to bronchodilators occur duringthe course of treatment. During such episodes, patients may requiretherapy with systemic corticosteroids. There is no evidence that control of asthma can beachieved byadministration of thedrug in amounts greaterthan the recom- mended doses, which appear to bethe therapeutic equivalent of approximately 10 mg/day of oral prednisone. Theoretically, the use of inhaled corticosteroids with altemate day prednisone systemic treatment should beaccompanied by more HPA right oi TARGET suppression than a therapeutically equivalent regimen of eitheralone. Transfer of patients from systemic steroid therapyto AeroBid Inhaler may unmask allergic conditions previously suppressed by the systemic steroid therapy, e.g., rhinitis, conjunctivitis, and eczema. Consider a few features of The Western Journal of Medicine: PRECAUTIONS Advances in Clinical Medicine General: Because of the relatively high molar dose of flunisolide per activation in this preparation, and because of the * Epitomes-Important evidence suggesting higher levels of systemic absorption with flunisolide than with othercomparable inhaled cortico- Each month this selection highlights the major advances in a steroids, patients treated should carefully for any with AeroBid be observed evidence of systemic corticosteroid effect, in- different with 15 or 20 brief cluding suppression of bone growth in children. Particular care should betaken in observing patients post-operatively or specialty epitomes by experts during periods of stress for evidence of a decrease in adrenal function. During withdrawal from oral steroids, some patients in the field. may experience symptoms of systemically active steroid withdrawal, e.g., joint and/or muscular pain, lassitudeand depres- sion, despite maintenance or even improvement of respiratory function. * Biomedical Science In responsive patients, flunisolide may permit control of asthmatic symptoms without suppression of HPAfunction. Since flunisolide is absorbed into the circulation and can be systemically active, the beneficial effects ofAeroBid Inhaler in Five major clinical research societies coordinate important minimizing or preventing HPA dysfunction may be expected only when recommended dosages are not exceeded. new research findings, emphasizing clinical value. The long-term effects of the drug in human subjects are still unknown. In particular, the local effects of the agent on develop- mental or immunologic processes in the mouth, pharynx, trachea, and lung are unknown. There isalso no information aboutthe possible long-term systemic effects oftheagent. * Socioeconomics The potential effects of the drug on acute, recurrent, or chronic pulmonary infections, including active or quiescenttuber- WJM is often the first to predict. examine, and evaluate culosis, are not known. Similarly, the potential effects of long-term administration of the drug on lung or othertissues are unknown. socioeconomic changes and trends. Pulmonary infiltrates with eosinophilia may occur in patients on AeroBid Inhaler therapy. Although it is possible that in some patients this state may become manifest because of systemicsteroid withdrawal when inhalational steroids are * Yearly Special Issue administered, a causative role for thedrug and/or its vehicle cannot be ruled out. Each devoted to a topic vital tf physicians: cross-cultural Carcinogenesis: A 22-month study was conducted in Swissderived mice toevaluate the carcinogenic potential of the drug. There wasan increase in the incidence of pulmonary adenomas within the range ofadenomas previously reported in mceclicine (1983). AIDS-a global perspective (1987). the literaturefor untreated or control Swissderived mice. An additional study is being conducted in a species with a lower women mnedicine (1988). addiction meedicinie and the incidence of spontaneous pulmonary tumors. andl hab add - Impairmentof ferlillty: Female rats receiving high doses of flunisolide (200 mcg/kg/day) showed some evidenceof pri mary Care phys ician ( 1990). re litation medicine: impaired fertility. Reproductive performance in the low (8 mcg/kg/day) and mid-dose (40 mcg/kg/day) groupswas compar- into lite to vears (1991). abIeto controls. Pregnancy: Pregnancy Category C. Aswith othercorticosteroids, flunisolide has been shown to beteratogenic in rabbits and rats at doses of 40 and 200 mcg/kg/day respectively. It was also fetotoxic in theseanimal reproductive studies. There Enclosed is $ to cover subscriptions. are no adequate and well-controlled studies in pregnantwomen. Flunisolide should be used during pregnancy only if the potential benefit justifiesthe potential riskto thefetus. Subscription renewal Regular subscription Nursing Mothers: It is not known whetherthisdrug is excreted in human milk. Becauseothercorticosteroids are excreted Ll LI. in human milk, caution should beexercised when flunisolide isadministered to nursingwomen. Foreign subscription Bill me [- ADVERSE REACTIONS Adverseevents reported in controlled clinical trialsand long-term open studies in 514 patients treatedwithAeroBidare Student Resident described below. Of those patients, 463 were treated for3 months or longer, 407 for6 months or longer, 287 for 1 yearor longer, and 122 for2 years or longer. Musculoskeletal reactions were reported in 35% of steroid-dependent patients in whom the dose of oral steroid was being TO: tapered. This is a well-known effect ofsteroid withdrawal. Incidence 10% or grater Gastrointestinal: diarrhea (10%), nausea and/orvomiting (25%), upset stomach (10%); General: flu (10%); Mouth and Street Throat: sore throat (20%); Nervous System: headache (25%); Respiratory: cold symptoms (15%), nasal congestion (15%), upper respiratory infection (25%); Special Senses: unpleasant taste (10%). Incidence 3-9% (^itv I tttP /7 in Cardiovascular: palpitations; Gastrointestinal: abdominal pain, heartburn; General: chest pain, decreased appetite, edema, fever; Mouthand Throat: Candida infection; NervousSystem: dizziness, irritability, nervousness, shakiness; Reproductive: menstrual disturbances; Respiratory: chest congestion, cough,* hoarseness, rhinitis, runnynose, sinus congestion, sinus Specialty (If applicable) drainage, sinus infection, sinusitis, sneezing, sputum, wheezing*; Skin: eczema, itching (pruritus), rash; Special Senses: ear infection, loss of smell ortaste. Incidence 1-3% Student/Resident Completion Date (Year) General: chills, increased appetite andweight gain, malaise, peripheral edema, sweating, weakness; Cardiovascular: hyper- tension, tachycardia; Gastrointestinal: constipation, dyspepsia, gas; Hemic/Lymph: capillaryfragility, enlarged Iymph Please mail this with enclosed to: nodes; Mouthand Throat: dry throat, glossitis, mouth irritation, pharyngitis, phlegm, throat irritation; Nervous System: coupon payment anxiety, depression, taintness, fatigue, hyperactivity, hypoactivity, insomnia, moodiness, numbness, vertigo; Respiratory: bronchitis, chest tightness,* dyspnea, epistaxis, head stuffiness, laryngitis, nasal irritation, pleurisy, pneumonia, sinus Circulation Department discomfort;