Postgraduate Medicine
ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20
Correct use of metered-dose inhalers and spacer devices Timothy H. Self PharmD, Mark J. Rumbak MD & Tiffany M. Kelso PharmD To cite this article: Timothy H. Self PharmD, Mark J. Rumbak MD & Tiffany M. Kelso PharmD (1992) Correct use of metered-dose inhalers and spacer devices, Postgraduate Medicine, 92:3, 95-106, DOI: 10.1080/00325481.1992.11701442 To link to this article: http://dx.doi.org/10.1080/00325481.1992.11701442
Published online: 17 May 2016.
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Second of three articles on asthma
Correct use of metered-dose inhalers and spacer devices
Preview In the case of metered-dose inhalers, a picture or even a thousand words is not enough. Patients must be shown the proper technique, allowed to practice in the presence of their instructor, and receive follow-up review of their technique at each office visit. Medications can achieve long-term control of asthma symptoms but only if they are deposited in the lungs in adequate quantities. The authors summarize the problems and solutions of inhaler use among asthma patients.
Tunothy H. Self, PhannD Mark}. Rumbak, MD Tiffany M. Kelso, PhannD •:• Although long-term management of asthma should be successful in most patients with use of currently available drugs and other management strategies, treatment failures are still quite common. Because of rising morbidity and mortality from asthma, the National Institutes of Health initiated the National Asthma Education Program in
1991. 1 On the basis of results of recent research on asthma and its treatment, the expert panel has provided excellent guidelines for diagnosis and management of asthma. A critically important component of the National Asthma Education Program is patient education, especially in the correct use of medication. Without adequate patient education, longterm treatment is often suboptimal and may fail even though physicians prescribe the correct
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medications. This article summarizes the correct use of metereddose inhalers (MD Is) and spacer devices and describes approaches to successful patient education.
Effects of inadequate education Several studies2-5 have shown that many patients with asthma are poorly educated regarding their condition and its treatment. Patients often do not fully understand the concepts of asthma prevention and self-management or the role of different medications and their proper administration. Correct inhalation technique with MD Is and spacer devices is imperative. Without proper administration of inhalation therapy, management is not optimal. 1-5 Sometimes, even physicians lack adequate knowledge of asthma and how to prescribe for it. 2•6•7 Table 1 provides tips for educating patients on asthma and its treatment. Despite continuing debate on which technique is best, there is general agreement on most of the steps involved in inhalation therapy. Virtually all investigators agree that inhalation should be slow, approximating tidal breathing, and should be followed by breath holding, optimally for 10 seconds. 8' 9 Careful review of the literature reveals more than
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Patients with asthma should be taught to use inhaled anti-inflammatory therapy regularly, even when symptoms are absent.
Table 1. Tips for educating patients on asthma and its treatment
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Ensure patients, enthusiastically, that asthma attacks are preventable. Be a good listener. Demonstrate that you care about their well-being. Enlist the assistance of clinical pharmacists, respiratory therapists, and nurses whenever possible in all areas of patient education. Make educational videotapes and printed materials available. Emphasize the necessity of using inhaled anti-inflammatory agents (eg, corticosteroids, cromolyn sodium [lntal]) regularly, even when symptoms are absent. Stress that these agents are not for quick relief of shortness of breath. Warn patients who are also tak1ng sustained-release theophylline for nocturnal asthma to never exceed the prescribed dose. Clearly define the role of inhaled beta agonists for rescue treatment and for prevention of exercise-induced asthma. Provide a list of agents known to induce asthma (eg, aspirin, nonsteroidal anti-inflammatories, ophthalmic timolol maleate [Timoptic], oral beta blockers). Remind patients to mention their use of any medications, including over-the-counter products, so that drug-induced asthma and drug interactions can be prevented. Describe other asthma triggers and how to avoid them. Recommend vaccination against influenza every autumn. Demonstrate the correct use of metered-dose inhalers and spacer devices, and observe patients' technique as they practice. Offer the following tips as appropriate: • Use your fingers to count to 10 as you hold your breath. • For smokers or former smokers: pretend you are drawing on a cigarette to assist in slow inhalation. • For elderly patients who are very slow in putting the spacer in the mouth after exhaling: put the spacer in your mouth and then exhale. • Keep the dust cap on the inhaler when it is not in use. (A foreign body that drops into the device may be inhaled.) • Clean the inhaler actuator often. Review patients' technique with the inhaler at each clinic visit. Teach patients to use peak-flow meters. and emphasize self-monitoring.
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one correct way to use an MDI. For instance, even though lungdeposition studies show the open-mouth technique to be superior to the dosed-mouth technique,') most efficacy studies demonstrate that the two techniques are equal. 8' 10' 11 Studies showed that in beta-agonist therapy, the correctly performed closed-mouth technique is equal in efficacy to the use of a nebulizer12 and a spacer. 13 Another debate concerns whether exhalation before pressing down on the canister should be to residual volume or to functional residual capacity (resting volume). Package inserts and some researchers recommend exhaling fully, whereas other investigators argue for exhaling a tidal volume.') Either approach is probably acceptable as long as the patient exhales slowly through pursed lips. Despite the theoretical advantages of exhaling to resting volume, to our knowledge, no ?n~ has clearly proven its supenonty. Patients often have great difficulty using an MDF' In one srudy, 4 89% of patients could not perform all the steps correctly, and in another study, 3 14 (47%) of 30 patients had poor technique. Typical problems include failing to shake the canister before use, poor coordination between pressing down on the cancontinued
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Telling patients how to use a metered-dose inhaler or showing them pictures is clearly insufficient. Demonstration with observation of their technique is required.
ister and inhaling, breathing through the nose, and failing to hold the breath after inhaling. Some of these mistakes result in a clinically significant reduction of response to treatment. 23 ' 5 Table 2 lists steps in using an MDI correctly.8'9
Overcoming the problems of self-treatment for asthma In most patients, the cornerstone of long-term management of asthma is anti-inflammatory therapy delivered by an MDI. 1 Thus, correct use of these devices is critically important. Also, when patients use a beta agonist delivered by an MDI to prevent exercise-induced asthma or for rescue therapy, correct technique is of obvious significance. REPETITIVE DEMONSTRATION AND PATIENT OBSERVATION-
Patients must be taught to use an MDI by demonstration of the correct technique and observation of them as they practice. Telling patients how to use MD Is or showing them pictures is clearly insufficient. Placebo inhalers are available from several pharmaceutical manufacturers for use by health professionals to demonstrate proper technique. In the office setting, the most practical approach for most physicians is to have carefully trained nurses or other appropriate personnel educate patients.
Table 2. Patient instructions on use of metered-dose inhaler* 1. Remove the dust cap and shake the inhaler well. 2. Exhale slowly through pursed lips. 3. For the closed-mouth technique, hold the inhaler upright and place the mouthpiece between your lips. Do not block the opening with your tongue or teeth. For the open-mouth technique, open your mouth wide and hold the inhaler upright two fingerbreadths from your mouth, making sure the inhaler is properly aimed. 4. Press down on the inhaler once as you start a slow, deep inhalation. 5. Continue to breathe in slowly and deeply through your mouth. If a spacer device is used, inhale fully before removing it from your mouth (aerosol may remain in the spacer). 6. Hold your breath for 10 seconds (if 10 seconds is uncomfortable, hold at least 4 seconds). 7. Exhale slowly Exhaling through the nose may benefit rhinitis caused by the use of corticosteroids, cromolyn sodium (lntal), or ipratropium bromide (Atrovent). If preferred, you may exhale through pursed lips. 8. Wait at least 1 minute before inhaling the next puff of medication. 'See manufacturer's instructions for specific devices.
In the hospital setting, respiratory therapists or clinical pharmacists can be of great help. Physicians should be able to teach patients themselves, but studies have shown that many physicians lack knowledge and skill in using MDis. 6·7 Demonstrating once is not enough. The vast majority of patients need repeated instruction. Teaching by videotape is effec-
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tive, 14 and tapes are available to teach the use ofMDis, MDis plus spacer, and peak-flow meters. Also, several organizations (see box on page 100) are helpful in educating patients with asthma. USE OF SPACER DEVICES--In
one study, 9 (30%) of 30 patients had great difficulty learning to use an MDI even with careful instruction.3 Although such pacontinued
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Use of a spacer device dramatically reduces the risk of oropharyngeal candidiasis secondary to inhaled steroid therapy and enhances efficacy.
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Organizations that can provide information on asthma American Academy of Allergy and Immunology 611 E Wells St Milwaukee, WI 53202 800-822-ASMA
American College of Allergy and Immunology 800 E Northwest Hwy, Suite 1080 Palatine, IL 60067 800-842-7777
American Lung Association Call your local chapter
Asthma and Allergy Foundation of America 1717 Massachusetts Ave Nw, Suite 305 Washington, DC 20036 800-7 -ASTHMA
Mothers of Asthmatics 10875 Main St, Suite 210 Fairfax, VA 22030 703-385-4403
National Heart, Lung, and Blood Institute National Institutes of Health National Asthma Education Program 4733 Bethesda Ave, Suite 530 Bethesda, MD 20814-4820
National Institute of Allergy and Infectious Diseases National Institutes of Health Office of Communications 9000 Rockville Pike Bldg 31, Room 7A32 Bethesda, MD 20892 301-496-5717
Table 3. Situations in which a nebulizer is preferable over a spacer device for delivery of asthma medication Patient cannot learn to use a metered-dose inhaler and spacer device, even after careful instruction Patient received first dose of beta agonist in emergency department* Patient feels very strongly about response to medication with use of nebulizer Patient is seriously ill and not fully alert or incapable of using metered-dose inhaler and spacer device *First dose is important psychologically for many patients.
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tients are often preschoolers or the very elderly, patients of all ages can have trouble using MD Is correctly. Thus, use of spacer devices is extremely helpful. Devices such as the Aerochamber and InspirEase reduce coordination requirements, decrease oropharyngeal deposition of the aerosol, and enhance pulmonary deposition. The Optihaler is a recently released spacer device, and studies to document its clinical efficacy are needed. In most patients, aerosol delivery of beta agonists is as efficacious with a spacer device as with a nebulizer in the emergency departmene' and hospital 16 and at home. Spacer devices are also more convenient and less costly than nebulizers. Even though spacers make using MDis easier, the correct technique must still be demonstrated to patients. Observing patients' technique is absolutely essential. Also, some patients quit using their spacer because they cannot see or taste medicine when they use it (and they should not). Thus, it is important to teach patients what to expect and what not to expect. Most asthma experts agree that use of spacer devices should be routine when inhaled corticosteroids are prescribed. Spacers dramatically reduce the risk of oropharyngeal candidiasis seccontinued
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With careful demonstration and observation, young children may be able to use an MDI plus spacer device.
Timothy H. Self, PharrnD Mark J. Rumbak, MD Tiffany M. Kelso, PharrnD Dr Self (left) is professor of clinical pharmacy, division of pulmonary and critical care medicine, University of Tennessee, Memphis, College of Medicine. Dr Rumbak (right) is assistant professor of medicine, division of pulmonary, critical care, and occupational medicine, University of South Florida College of Medicine, Tampa. Dr Kelso (middle) is a resident in clinical pharmacy, UT Bowld Hospital, Memphis.
ondary to inhaled steroid therapy.17 Many clinicians are aware of this advantage of spacers, but fewer are aware that spacers enhance the efficacy of inhaled steroids, even in patients using optimal MDI technique. 17 How-
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ever, the same is not true for beta agonists: Spacers do not improve efficacy over optimal MD I technique.13 In our opinion, spacer devices should be used in all but the mildest cases of asthma. For ex-
ample, a patient who has exercise-induced asthma only and has excellent MDI technique does not need a spacer. In patients who have moderate or severe asthma, anti-inflammatory theraPY is essential for optimal treatment, and spacers should be used. Spacers are often of benefit with inhaled bronchodilators, because even patients who demonstrate correct inhalation technique to the health professional may not use the same technique at home. Some physicians believe that preschoolers are not candidates for MDI-plus-spacer therapy. However, with careful demonstration and observation, very young children can use this therapy. In fact, 2-year-old children have been shown to correctly use spacers by modeling after their mother. 18 Are there major differences among the several available spacer devices? Studies to date have not shown that any spacer is clearly superior to another in terms of clinical significance. 19 However, the design of some spacers facilitates optimal aerosol delivery. For example, the Aerochamber has a one-way inhalation valve and a "FLOWSIGnal" (ie, patient hear a whistle if inhalation is too fast). lnspirEase has a signaling sound as well as
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a visual component (patients can see the bag collapse as they breathe in). USE OF 01HER AEROSOL DEIJVERY ~In the United
States at present, there are no marketed alternatives to MDI plus spacer for delivery of inhaled corticosteroid therapy. For beta agonists, an inhaler (Rotahaler) is available for the dry-powder form of albuterol {Ventolin Rotacaps). Because it is breath-activated, this system is helpful for patients who cannot coordinate use of an MDJ.2° Nebulizer delivery is also available for beta agonists. Although it is not preferred in most patients, it can be quite helpful in selected situations (table 3). When an MDI or an MDI plus spacer is not preferred, cromolyn sodium (lntal) therapy may be administered via a nebulizer. The dry-powder form may be administered by inhaler (Spinhaler) but is irritating when inhaled and is rarely indicated. Although anticholinergic agents have a minimal role in asthma treatment, anticholinergic aerosol is useful with the first dose of beta agonist in the emergency depanmenr 1 and in psychogenic asthma. 22 Ipratropium bromide (Atrovent) administered by MDI plus spacer is the first choice. If it cannot be used, nebulized glycopyrrolate (Robinul)
is preferred over nebulized atropine sulfate (Dey-Dose) because it causes fewer side effects. 23 Other breath-activated devices are available outside the United States and are helpful for some patients.
Summary
In addition to prescribing an appropriate drug regimen, physicians must carefully educate asthmatic patients. For 10 million such patients in the United States as well as millions more around the world, successful education is critical to quality of life and can save
lives. Responsible patients who understand that asthma attacks are preventable and who use their medications correctly usually have a gratifying response to treatment. Of special importance is the optimal use of aerosolized drugs, most often given by a metered-dose inhaler plus spacer device. IVt'l
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Earn credit on this article. See CME Quiz.
Address for correspondence: Mark J. Rumbak, MD, James A Haley Veterans Affairs Medical Center, 13000 Bruce B. Downs Blvd (Ill C), Tampa, FL 33612-4799.
References 1. National Asrhma Education Program. Guidelines for the diagnosis and management of asthma. Bethesda: Dept of Health and Human Services, I 99I Aug; DHHS publication No. 9I-3042 2. Mayo PH, Richman], Harris Hw. Results of a program to reduce admissions for adult asrhma. Ann Intern Med I990;I I2(1 I):864-71 3. Shim C, Williams MH Jr. The adequacy of inhalation of aerosol from canister nebulizers. Am] Med I980;69(Dec):89I-4 4. Epstein SW, Manning CP, Ashley MJ, et al. Survey of the clinical use of pressurized aerosol inhalers. Can Med Assoc J I 979; I20(7): 8I3-6 5. Lindgren S, Bake 8, Larsson S. Clinical consequences of inadequate inhalation technique in asthma therapy. Eur J Respir Dis I 987; 70(2):93-8 6. Bunon AJ. Asthma inhalation devices:
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what do we know? BMJ (Clin Res Ed) I 984; 288(643I):I650-I 7. KellingJS, Strohl KP, Smith RL, et al. Physician knowledge in the use of canister nebulizers. Chest I 983;83(4):612-4 8. Newman SP, Pavia D, Clarke: SW. How should a pressurized beta-adrenergic bronchodilator be inhaled? Eur J Respir Dis I 98 I; 62(1):3-2I 9. Dolovich M, Ruffin RE, Roberts R, et al. Optimal delivery of aerosols from metered dose inhalers. Chest I98I;80(6 Suppi):9I I-5 10. Lawford P, McKenzie D. Pressurized bronchodilaror aerosol technique: influence of breath-holding rime and relationship of inhaler to the mouth. Br J Dis Chest I 982;76(3):22933 11. Unzeitig JC, Richards W, Church JA. Administration of metered-dose inhalers: comparison of open- and closed-mouth techniques
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~nil-sod~f~JL:sod~:~) ,ampiCI 1n
1um su uoclam
1um
1.5 or 3g q6h
Retennces: 1. Data available on request from Roerig. 2. Hemsell DL. Wendel GO, Hemsell PG: Combating beta-lactamase enzyme-principal defense mechanism of many pelvic infection pathogens. Presented as ascientific exhibit at the Thirty-Sixth Annual Climcal Meeting of the American College of Obstetricians and Gynecologists. Boston. May 2-4, 1988. 3. Senft H-H, Stiglmayer R. Eibach HW. et al· Sulbactam/ampicillin versus cefoxitin in the
treatment of obstetric and gynaecological infections. Drugs t986;31(suppl2):18-21. 4. Newton ER, Gibbs RS: Treatment of postpartum endometritis: A comparison of ampicillin/sulbactam vs. gentamicin plus clindamycin. Presented as a scientific exhibit at the Thirty-Sixth Annual Clinical Meeting of the Amencan College of Obstetricians and Gynecologists. Boston. May 2·4. 1988. 5. Gunning J: A comparison of parenteral sulbactam/ ampicillin versus clindamycin/gentamicin in the treatment of pelvic inflammatory disease. Drugs 1986:
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3t(suppl2):t4-17. 6. Ampicillintsulbactam (Unasyn). Mea Lett Drugs Ther1987;29(August 28):79-8t. IIIDICATIDNS AIID USAGE UNASYN is indicated for the treatment of infections due to susceptible strains of the designated microorganisms in the conditions listed below. Skin and Skin Structure Infections caused by beta-lactamase producing strains of Staphylococcus aureus, Escherichia coli, • Klebsiella spp. • (including K. pneumoniae•), Proteus mirabilis, • Bacteroides tragi/is, • Enterobacter spp., • and Acinetobacter ca/coaceticus. • Intra-Abdominal Infections caused by beta-lactamase producing strains of Escherichia coli, Klebsiella spp, (including K. pneumoniae*), Bacteroides spp. (including B. tragi/is), and Enterobacter spp. • Gynecolotlcal Infections caused by beta-lactamase producing strains of Escherichia coli, • and Bacteroides spp. • (including B. tragi/is•). *Efficacy for this organism in this organ system was studied in fewer than 10 infections. While UNASYN is indicated only for the conditions listed above, infections caused by ampicillinsusceptible organisms are also amenable to treatment with UNASYN due to its ampicillin content. Therefore, mixed infections caused by ampicillin-susceptible organisms and beta-lactamase producmg organisms susceptible to UNASYN should not require the addition of another antibiotic. COIITRAINDICATIONS The use of UNASYN is contraindicated in mdividuals with a history of hypersensitivity reactions to any of the penicillins. WARNINGS SERIOUS AND OCCASIONALLY FATAL HYPERSENSITIVITY (ANAPHYLACTIC) REACTIONS HAVE BEEN REPORTED IN PATIENTS ON PENICILLIN THERAPY. THESE REACTIONS ARE MORE APT TO OCCUR IN INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY AND/OR HYPERSENSITIVITY REACTIONS TO MULTIPLE ALLERGENS. THERE HAVE BEEN REPORTS OF INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY WHO HAVE EXPERIENCED SEVERE REACTIONS WHEN TREATED WITH CEPHALOSPORINS. BEFORE THERAPY WITH A PENICILLIN, CAREFUL INQUIRY SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY REACTIONS TO PENICILLINS, CEPHALOSPORINS, AND OTHER ALLERGENS. IF AN ALLERGIC REACTION OCCURS, UNASYN SHOULD BE DISCONTINUED AND THE APPROPRIATE THERAPY INSTITUTED. SERIOUS ANAPHYLACTOID REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE. OXYGEN, INTRAVENOUS STEROIDS, AND AIRWAY MANAGEMENT. INCLUDING INTUBATION, SHOULD ALSO BE ADMINISTERED AS INDICATED. PRECAUTIONS Saneral: A high percentage of patients with mononucleosis who receive ampicillin develop a skin rash. Thus, ampicillin class antibiotics should not be admin~stered to patients w1th mononucleosis. In pat1ents treated with UNASYN the possibility of supecinfectlons w1th mycoliC or bactenal pathogens should be kept in mind during therapy. If superinfections occur (usually involving Pseudomonas or Candida), the drug should be discontinued and/or appropnate therapy instituted. Dru1 Interactions: Probenecid decreases the renal tubular secretion of ampicillin and sulbactam. Concurrent use of probenecid with UNASYN may resuij in mcreased and prolonged blood levels of ampicillin and sulbactam. The concurrent adminostration of allopurinol and ampicillin increases substantially the incidence of rashes in patients receiving both drugs as compared to p_atients receiving ampicillin alone. It is not known whether this potentiation of ampicillin rashes is due to allopunnol or the hyperuricemia present in these. patients. There are no data with UNASYN and allopunnol administered concurrently. UNASYN and ammoglycosides should not be reconstituted together due to the m vitro inactivation of aminoglycosides by the ampicillin component of UNASYN. Drt~~/Laboratory Test Interactions: Administration of UNASYN will resuij in high urine concentrat~on of ampicillin. High urine concentrations of ampicillin may resuij in false positive reactions when testing for the presence of glucose in unne using Clin1test '", Benedict's Solut~on or Fehlmg's Solution. It is recommended that glucose tests based on enzymatic glucose oxidase react1ons (such as Climst1x '" or Testape '")be used. Following administration of ampicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriolglucuronide, conjugated estrone and estradiol has been noted. This effect may also occur with UNASYN. Carcinotenesis, Muta1enesis, Impairment of Fertility: Long-term studies m animals have not been performed to evaluate carcinogenic or mutagenic potential. l'nl1nancy Prepancy Catqory B: Reproduction studies haw been performed in mice, rats, and rabbits at doses up to ten 110) times the human dose and haw revealed no evidence of impaired fertility or harm to the fetus due to UNASYN. There are, however, no adequate and well controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. (See-Drug/Laboratory Test Interactions.) Labor and DeliYery: Studies in guinea pigs haw shown that intravenous administration of ampicillin decreased the uterine tone, frequency of contractions, height of contractions, and duration of contractions. However, it is not known whether the use of UNASYN in humans during labor or delivery has immediate or delayed adverse effects on the fetus, prolongs the duration of labor, or mcreases the likelihood that forceps delivery or other obstetrical intervention or resuscitat~on of the newborn w~ll be necessary. Nursiltl Mothers: Low concentrations of ampicillin and sulbactam are excreted in the m~lk: therefore, caution should be exercised when UNASYN is administered to a nursing woman. Pediatric Use: The efficacy and safety of UNASYN haw not been established m infants and children under the age of 12. ADVERSE REACTIONS UNASYN is generally well tolerated. The following adverse reactions haw been reported. Local Adverse Reactioas Pain at IM injection site-16% Pam at IV injection site-3% Thrombophlebitis-3% Systemic Adverse Reactions The most frequently reported adverse reactions were diarrhea m3% of the patients and rash in less than 2% of the patients. Additional systemic reactions reported in less than 1% of the patients were: itching, nausea. vomiting, candidiasis, fatigue, malaise, headache, chest pain, flatulence, abdominal distension, glossitis, urine retention, dysuria, edema. facial swelling, erythema. chills, tightness in throat. substernal pain. epistaxis and mucosal bleeding. Adverse Laboratory Chan1es Adverse laboratory changes without regard to drug relationship that were reported during clinical tnals were: Hepatic: Increased AST !SGOD. All ISGPD. alkaline phosphatase, and LDH. Hematologic: Decreased hemoglobin, hematocrit, RBC, WBC, neutrophils, lymphocytes, platelets and increased lymphocytes, monocytes, basophils, eosinophils, and platelets. Blood Chemistry: Decreased serum albumin and total proteins. Renal: Increased BUN and creatinine. Urinalysis: Presence of RBC's and hyaline casts in urine. The following adverse reactions haw been reported w~th ampicillin-class antibiotics and can also occur with UNASYN. Saslnlintestinal: Gastritis, stomatitis, black "hairy" tongue. enterocoUis and pseudomembranous colitis. Hypersensitivity Reactions: Urticaria, erythema muijiforme, and an occasional case of exfoliative dermatitis haw been reported. These reactions may be controlled with antihistamines and, if necessary, systemic corticosteroids. Whenever such reactions occur, the drug should be discontinued, unless the opinion of the physician dictates otherwise. Serious and occasiOnal fatal hypersensitivity (anaphylactic) reactions can occur with a penicillin (see WARNINGS). HematoiOiic: In addition to the adverse laboratory changes listed above for UNASYN, agranulocytos~s has been reported during therapy w1th penicillins. All of these reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena.
in childhood asthmatics. Ann Allergy 1983; 51(6):571-3 12. Mestitz H, Copland JM, McDonald CF. Comparison of outpatient nebulized vs metered dose inhaler terbutaline in chronic airflow obstruction. Chest 1989;96(6):1237-40 13. Rachelefsky GS, Rohr AS, Wo J, et al. Use of a tube spacer to improve the efficacy of a metered-dose inhaler in asthmatic children. Am J Dis Child 1986;140(11):1191-3 14. SelfTH, Brooks JB, Lieberman P, et al. The value of demonstration and role of the pharmacist in teaching the correct use of pressurized bronchodilators. Can Med Assoc J 1983; 128(2):129-31 15. Salzman GA, Steele MT, Pribble JP, et al. Aerosolized metaproterenol in the treatment of asthmatics with severe airflow obstruction: comparison of two delivery methods. Chest 1989; 95(5): 1017-20 16. Morley TF, Marozsan E, Zappasodi SJ, et al. Comparison of beta-adrenergic agents delivered by nebulizer vs metered dose inhaler with lnspirEase in hospitalized asthmatic patients. Chest 1988;94(6):1205-10 17. Salzman GA, Pyszczynski DR. Oropharyngeal candidiasis in patients treated with beclomethasone dipropionate delivered by metered-dose inhaler alone and with Aerochamber. J Allergy Clin lmmunol 1988;81 (2):424-8 18. Croft RD. 2 year old asthmatics can learn to operate a tube spacer by copying their mothers. Arch Dis Child 1989;64(5):742-3 19. Lee H, Evans HE. Evaluation of inhalation aids of metered dose inhalers in asthmatic children. Chest 1987;91(3):366-9 20. Bronsky E, Bucholtz GA, Busse WW, et al. Comparison of inhaled albuterol powder and aerosol in asthma. J Allergy Clin lmmunol 1987;79(5):741-7 21. O'Driscoll BR, Taylor RJ, Horsley MG, et al. Nebulised salbutamol with and without ipratropium bromide in acute airflow obstruction. Lancet 1989;1(8652):1418-20 22. Neild JE, Cameron IR. Bronchoconstriction in response to suggestion: its prevention by an inhaled anticholinergic agent. BMJ (Clin Res Ed) 1985;290(6469):674 23. Gilman MJ, Meyer L, Carter J, et al. Comparison of aerosolized glycopyrrolate and metaproterenol in acute asthma. Chest 1990; 98(5): 1095-8
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INHALERS
ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20
Correct use of metered-dose inhalers and spacer devices Timothy H. Self PharmD, Mark J. Rumbak MD & Tiffany M. Kelso PharmD To cite this article: Timothy H. Self PharmD, Mark J. Rumbak MD & Tiffany M. Kelso PharmD (1992) Correct use of metered-dose inhalers and spacer devices, Postgraduate Medicine, 92:3, 95-106, DOI: 10.1080/00325481.1992.11701442 To link to this article: http://dx.doi.org/10.1080/00325481.1992.11701442
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Date: 11 June 2016, At: 14:00
Symposium
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Second of three articles on asthma
Correct use of metered-dose inhalers and spacer devices
Preview In the case of metered-dose inhalers, a picture or even a thousand words is not enough. Patients must be shown the proper technique, allowed to practice in the presence of their instructor, and receive follow-up review of their technique at each office visit. Medications can achieve long-term control of asthma symptoms but only if they are deposited in the lungs in adequate quantities. The authors summarize the problems and solutions of inhaler use among asthma patients.
Tunothy H. Self, PhannD Mark}. Rumbak, MD Tiffany M. Kelso, PhannD •:• Although long-term management of asthma should be successful in most patients with use of currently available drugs and other management strategies, treatment failures are still quite common. Because of rising morbidity and mortality from asthma, the National Institutes of Health initiated the National Asthma Education Program in
1991. 1 On the basis of results of recent research on asthma and its treatment, the expert panel has provided excellent guidelines for diagnosis and management of asthma. A critically important component of the National Asthma Education Program is patient education, especially in the correct use of medication. Without adequate patient education, longterm treatment is often suboptimal and may fail even though physicians prescribe the correct
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medications. This article summarizes the correct use of metereddose inhalers (MD Is) and spacer devices and describes approaches to successful patient education.
Effects of inadequate education Several studies2-5 have shown that many patients with asthma are poorly educated regarding their condition and its treatment. Patients often do not fully understand the concepts of asthma prevention and self-management or the role of different medications and their proper administration. Correct inhalation technique with MD Is and spacer devices is imperative. Without proper administration of inhalation therapy, management is not optimal. 1-5 Sometimes, even physicians lack adequate knowledge of asthma and how to prescribe for it. 2•6•7 Table 1 provides tips for educating patients on asthma and its treatment. Despite continuing debate on which technique is best, there is general agreement on most of the steps involved in inhalation therapy. Virtually all investigators agree that inhalation should be slow, approximating tidal breathing, and should be followed by breath holding, optimally for 10 seconds. 8' 9 Careful review of the literature reveals more than
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Patients with asthma should be taught to use inhaled anti-inflammatory therapy regularly, even when symptoms are absent.
Table 1. Tips for educating patients on asthma and its treatment
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Ensure patients, enthusiastically, that asthma attacks are preventable. Be a good listener. Demonstrate that you care about their well-being. Enlist the assistance of clinical pharmacists, respiratory therapists, and nurses whenever possible in all areas of patient education. Make educational videotapes and printed materials available. Emphasize the necessity of using inhaled anti-inflammatory agents (eg, corticosteroids, cromolyn sodium [lntal]) regularly, even when symptoms are absent. Stress that these agents are not for quick relief of shortness of breath. Warn patients who are also tak1ng sustained-release theophylline for nocturnal asthma to never exceed the prescribed dose. Clearly define the role of inhaled beta agonists for rescue treatment and for prevention of exercise-induced asthma. Provide a list of agents known to induce asthma (eg, aspirin, nonsteroidal anti-inflammatories, ophthalmic timolol maleate [Timoptic], oral beta blockers). Remind patients to mention their use of any medications, including over-the-counter products, so that drug-induced asthma and drug interactions can be prevented. Describe other asthma triggers and how to avoid them. Recommend vaccination against influenza every autumn. Demonstrate the correct use of metered-dose inhalers and spacer devices, and observe patients' technique as they practice. Offer the following tips as appropriate: • Use your fingers to count to 10 as you hold your breath. • For smokers or former smokers: pretend you are drawing on a cigarette to assist in slow inhalation. • For elderly patients who are very slow in putting the spacer in the mouth after exhaling: put the spacer in your mouth and then exhale. • Keep the dust cap on the inhaler when it is not in use. (A foreign body that drops into the device may be inhaled.) • Clean the inhaler actuator often. Review patients' technique with the inhaler at each clinic visit. Teach patients to use peak-flow meters. and emphasize self-monitoring.
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one correct way to use an MDI. For instance, even though lungdeposition studies show the open-mouth technique to be superior to the dosed-mouth technique,') most efficacy studies demonstrate that the two techniques are equal. 8' 10' 11 Studies showed that in beta-agonist therapy, the correctly performed closed-mouth technique is equal in efficacy to the use of a nebulizer12 and a spacer. 13 Another debate concerns whether exhalation before pressing down on the canister should be to residual volume or to functional residual capacity (resting volume). Package inserts and some researchers recommend exhaling fully, whereas other investigators argue for exhaling a tidal volume.') Either approach is probably acceptable as long as the patient exhales slowly through pursed lips. Despite the theoretical advantages of exhaling to resting volume, to our knowledge, no ?n~ has clearly proven its supenonty. Patients often have great difficulty using an MDF' In one srudy, 4 89% of patients could not perform all the steps correctly, and in another study, 3 14 (47%) of 30 patients had poor technique. Typical problems include failing to shake the canister before use, poor coordination between pressing down on the cancontinued
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Telling patients how to use a metered-dose inhaler or showing them pictures is clearly insufficient. Demonstration with observation of their technique is required.
ister and inhaling, breathing through the nose, and failing to hold the breath after inhaling. Some of these mistakes result in a clinically significant reduction of response to treatment. 23 ' 5 Table 2 lists steps in using an MDI correctly.8'9
Overcoming the problems of self-treatment for asthma In most patients, the cornerstone of long-term management of asthma is anti-inflammatory therapy delivered by an MDI. 1 Thus, correct use of these devices is critically important. Also, when patients use a beta agonist delivered by an MDI to prevent exercise-induced asthma or for rescue therapy, correct technique is of obvious significance. REPETITIVE DEMONSTRATION AND PATIENT OBSERVATION-
Patients must be taught to use an MDI by demonstration of the correct technique and observation of them as they practice. Telling patients how to use MD Is or showing them pictures is clearly insufficient. Placebo inhalers are available from several pharmaceutical manufacturers for use by health professionals to demonstrate proper technique. In the office setting, the most practical approach for most physicians is to have carefully trained nurses or other appropriate personnel educate patients.
Table 2. Patient instructions on use of metered-dose inhaler* 1. Remove the dust cap and shake the inhaler well. 2. Exhale slowly through pursed lips. 3. For the closed-mouth technique, hold the inhaler upright and place the mouthpiece between your lips. Do not block the opening with your tongue or teeth. For the open-mouth technique, open your mouth wide and hold the inhaler upright two fingerbreadths from your mouth, making sure the inhaler is properly aimed. 4. Press down on the inhaler once as you start a slow, deep inhalation. 5. Continue to breathe in slowly and deeply through your mouth. If a spacer device is used, inhale fully before removing it from your mouth (aerosol may remain in the spacer). 6. Hold your breath for 10 seconds (if 10 seconds is uncomfortable, hold at least 4 seconds). 7. Exhale slowly Exhaling through the nose may benefit rhinitis caused by the use of corticosteroids, cromolyn sodium (lntal), or ipratropium bromide (Atrovent). If preferred, you may exhale through pursed lips. 8. Wait at least 1 minute before inhaling the next puff of medication. 'See manufacturer's instructions for specific devices.
In the hospital setting, respiratory therapists or clinical pharmacists can be of great help. Physicians should be able to teach patients themselves, but studies have shown that many physicians lack knowledge and skill in using MDis. 6·7 Demonstrating once is not enough. The vast majority of patients need repeated instruction. Teaching by videotape is effec-
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tive, 14 and tapes are available to teach the use ofMDis, MDis plus spacer, and peak-flow meters. Also, several organizations (see box on page 100) are helpful in educating patients with asthma. USE OF SPACER DEVICES--In
one study, 9 (30%) of 30 patients had great difficulty learning to use an MDI even with careful instruction.3 Although such pacontinued
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Use of a spacer device dramatically reduces the risk of oropharyngeal candidiasis secondary to inhaled steroid therapy and enhances efficacy.
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Organizations that can provide information on asthma American Academy of Allergy and Immunology 611 E Wells St Milwaukee, WI 53202 800-822-ASMA
American College of Allergy and Immunology 800 E Northwest Hwy, Suite 1080 Palatine, IL 60067 800-842-7777
American Lung Association Call your local chapter
Asthma and Allergy Foundation of America 1717 Massachusetts Ave Nw, Suite 305 Washington, DC 20036 800-7 -ASTHMA
Mothers of Asthmatics 10875 Main St, Suite 210 Fairfax, VA 22030 703-385-4403
National Heart, Lung, and Blood Institute National Institutes of Health National Asthma Education Program 4733 Bethesda Ave, Suite 530 Bethesda, MD 20814-4820
National Institute of Allergy and Infectious Diseases National Institutes of Health Office of Communications 9000 Rockville Pike Bldg 31, Room 7A32 Bethesda, MD 20892 301-496-5717
Table 3. Situations in which a nebulizer is preferable over a spacer device for delivery of asthma medication Patient cannot learn to use a metered-dose inhaler and spacer device, even after careful instruction Patient received first dose of beta agonist in emergency department* Patient feels very strongly about response to medication with use of nebulizer Patient is seriously ill and not fully alert or incapable of using metered-dose inhaler and spacer device *First dose is important psychologically for many patients.
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tients are often preschoolers or the very elderly, patients of all ages can have trouble using MD Is correctly. Thus, use of spacer devices is extremely helpful. Devices such as the Aerochamber and InspirEase reduce coordination requirements, decrease oropharyngeal deposition of the aerosol, and enhance pulmonary deposition. The Optihaler is a recently released spacer device, and studies to document its clinical efficacy are needed. In most patients, aerosol delivery of beta agonists is as efficacious with a spacer device as with a nebulizer in the emergency departmene' and hospital 16 and at home. Spacer devices are also more convenient and less costly than nebulizers. Even though spacers make using MDis easier, the correct technique must still be demonstrated to patients. Observing patients' technique is absolutely essential. Also, some patients quit using their spacer because they cannot see or taste medicine when they use it (and they should not). Thus, it is important to teach patients what to expect and what not to expect. Most asthma experts agree that use of spacer devices should be routine when inhaled corticosteroids are prescribed. Spacers dramatically reduce the risk of oropharyngeal candidiasis seccontinued
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With careful demonstration and observation, young children may be able to use an MDI plus spacer device.
Timothy H. Self, PharrnD Mark J. Rumbak, MD Tiffany M. Kelso, PharrnD Dr Self (left) is professor of clinical pharmacy, division of pulmonary and critical care medicine, University of Tennessee, Memphis, College of Medicine. Dr Rumbak (right) is assistant professor of medicine, division of pulmonary, critical care, and occupational medicine, University of South Florida College of Medicine, Tampa. Dr Kelso (middle) is a resident in clinical pharmacy, UT Bowld Hospital, Memphis.
ondary to inhaled steroid therapy.17 Many clinicians are aware of this advantage of spacers, but fewer are aware that spacers enhance the efficacy of inhaled steroids, even in patients using optimal MDI technique. 17 How-
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ever, the same is not true for beta agonists: Spacers do not improve efficacy over optimal MD I technique.13 In our opinion, spacer devices should be used in all but the mildest cases of asthma. For ex-
ample, a patient who has exercise-induced asthma only and has excellent MDI technique does not need a spacer. In patients who have moderate or severe asthma, anti-inflammatory theraPY is essential for optimal treatment, and spacers should be used. Spacers are often of benefit with inhaled bronchodilators, because even patients who demonstrate correct inhalation technique to the health professional may not use the same technique at home. Some physicians believe that preschoolers are not candidates for MDI-plus-spacer therapy. However, with careful demonstration and observation, very young children can use this therapy. In fact, 2-year-old children have been shown to correctly use spacers by modeling after their mother. 18 Are there major differences among the several available spacer devices? Studies to date have not shown that any spacer is clearly superior to another in terms of clinical significance. 19 However, the design of some spacers facilitates optimal aerosol delivery. For example, the Aerochamber has a one-way inhalation valve and a "FLOWSIGnal" (ie, patient hear a whistle if inhalation is too fast). lnspirEase has a signaling sound as well as
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a visual component (patients can see the bag collapse as they breathe in). USE OF 01HER AEROSOL DEIJVERY ~In the United
States at present, there are no marketed alternatives to MDI plus spacer for delivery of inhaled corticosteroid therapy. For beta agonists, an inhaler (Rotahaler) is available for the dry-powder form of albuterol {Ventolin Rotacaps). Because it is breath-activated, this system is helpful for patients who cannot coordinate use of an MDJ.2° Nebulizer delivery is also available for beta agonists. Although it is not preferred in most patients, it can be quite helpful in selected situations (table 3). When an MDI or an MDI plus spacer is not preferred, cromolyn sodium (lntal) therapy may be administered via a nebulizer. The dry-powder form may be administered by inhaler (Spinhaler) but is irritating when inhaled and is rarely indicated. Although anticholinergic agents have a minimal role in asthma treatment, anticholinergic aerosol is useful with the first dose of beta agonist in the emergency depanmenr 1 and in psychogenic asthma. 22 Ipratropium bromide (Atrovent) administered by MDI plus spacer is the first choice. If it cannot be used, nebulized glycopyrrolate (Robinul)
is preferred over nebulized atropine sulfate (Dey-Dose) because it causes fewer side effects. 23 Other breath-activated devices are available outside the United States and are helpful for some patients.
Summary
In addition to prescribing an appropriate drug regimen, physicians must carefully educate asthmatic patients. For 10 million such patients in the United States as well as millions more around the world, successful education is critical to quality of life and can save
lives. Responsible patients who understand that asthma attacks are preventable and who use their medications correctly usually have a gratifying response to treatment. Of special importance is the optimal use of aerosolized drugs, most often given by a metered-dose inhaler plus spacer device. IVt'l
-@
Earn credit on this article. See CME Quiz.
Address for correspondence: Mark J. Rumbak, MD, James A Haley Veterans Affairs Medical Center, 13000 Bruce B. Downs Blvd (Ill C), Tampa, FL 33612-4799.
References 1. National Asrhma Education Program. Guidelines for the diagnosis and management of asthma. Bethesda: Dept of Health and Human Services, I 99I Aug; DHHS publication No. 9I-3042 2. Mayo PH, Richman], Harris Hw. Results of a program to reduce admissions for adult asrhma. Ann Intern Med I990;I I2(1 I):864-71 3. Shim C, Williams MH Jr. The adequacy of inhalation of aerosol from canister nebulizers. Am] Med I980;69(Dec):89I-4 4. Epstein SW, Manning CP, Ashley MJ, et al. Survey of the clinical use of pressurized aerosol inhalers. Can Med Assoc J I 979; I20(7): 8I3-6 5. Lindgren S, Bake 8, Larsson S. Clinical consequences of inadequate inhalation technique in asthma therapy. Eur J Respir Dis I 987; 70(2):93-8 6. Bunon AJ. Asthma inhalation devices:
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what do we know? BMJ (Clin Res Ed) I 984; 288(643I):I650-I 7. KellingJS, Strohl KP, Smith RL, et al. Physician knowledge in the use of canister nebulizers. Chest I 983;83(4):612-4 8. Newman SP, Pavia D, Clarke: SW. How should a pressurized beta-adrenergic bronchodilator be inhaled? Eur J Respir Dis I 98 I; 62(1):3-2I 9. Dolovich M, Ruffin RE, Roberts R, et al. Optimal delivery of aerosols from metered dose inhalers. Chest I98I;80(6 Suppi):9I I-5 10. Lawford P, McKenzie D. Pressurized bronchodilaror aerosol technique: influence of breath-holding rime and relationship of inhaler to the mouth. Br J Dis Chest I 982;76(3):22933 11. Unzeitig JC, Richards W, Church JA. Administration of metered-dose inhalers: comparison of open- and closed-mouth techniques
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~nil-sod~f~JL:sod~:~) ,ampiCI 1n
1um su uoclam
1um
1.5 or 3g q6h
Retennces: 1. Data available on request from Roerig. 2. Hemsell DL. Wendel GO, Hemsell PG: Combating beta-lactamase enzyme-principal defense mechanism of many pelvic infection pathogens. Presented as ascientific exhibit at the Thirty-Sixth Annual Climcal Meeting of the American College of Obstetricians and Gynecologists. Boston. May 2-4, 1988. 3. Senft H-H, Stiglmayer R. Eibach HW. et al· Sulbactam/ampicillin versus cefoxitin in the
treatment of obstetric and gynaecological infections. Drugs t986;31(suppl2):18-21. 4. Newton ER, Gibbs RS: Treatment of postpartum endometritis: A comparison of ampicillin/sulbactam vs. gentamicin plus clindamycin. Presented as a scientific exhibit at the Thirty-Sixth Annual Clinical Meeting of the Amencan College of Obstetricians and Gynecologists. Boston. May 2·4. 1988. 5. Gunning J: A comparison of parenteral sulbactam/ ampicillin versus clindamycin/gentamicin in the treatment of pelvic inflammatory disease. Drugs 1986:
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3t(suppl2):t4-17. 6. Ampicillintsulbactam (Unasyn). Mea Lett Drugs Ther1987;29(August 28):79-8t. IIIDICATIDNS AIID USAGE UNASYN is indicated for the treatment of infections due to susceptible strains of the designated microorganisms in the conditions listed below. Skin and Skin Structure Infections caused by beta-lactamase producing strains of Staphylococcus aureus, Escherichia coli, • Klebsiella spp. • (including K. pneumoniae•), Proteus mirabilis, • Bacteroides tragi/is, • Enterobacter spp., • and Acinetobacter ca/coaceticus. • Intra-Abdominal Infections caused by beta-lactamase producing strains of Escherichia coli, Klebsiella spp, (including K. pneumoniae*), Bacteroides spp. (including B. tragi/is), and Enterobacter spp. • Gynecolotlcal Infections caused by beta-lactamase producing strains of Escherichia coli, • and Bacteroides spp. • (including B. tragi/is•). *Efficacy for this organism in this organ system was studied in fewer than 10 infections. While UNASYN is indicated only for the conditions listed above, infections caused by ampicillinsusceptible organisms are also amenable to treatment with UNASYN due to its ampicillin content. Therefore, mixed infections caused by ampicillin-susceptible organisms and beta-lactamase producmg organisms susceptible to UNASYN should not require the addition of another antibiotic. COIITRAINDICATIONS The use of UNASYN is contraindicated in mdividuals with a history of hypersensitivity reactions to any of the penicillins. WARNINGS SERIOUS AND OCCASIONALLY FATAL HYPERSENSITIVITY (ANAPHYLACTIC) REACTIONS HAVE BEEN REPORTED IN PATIENTS ON PENICILLIN THERAPY. THESE REACTIONS ARE MORE APT TO OCCUR IN INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY AND/OR HYPERSENSITIVITY REACTIONS TO MULTIPLE ALLERGENS. THERE HAVE BEEN REPORTS OF INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY WHO HAVE EXPERIENCED SEVERE REACTIONS WHEN TREATED WITH CEPHALOSPORINS. BEFORE THERAPY WITH A PENICILLIN, CAREFUL INQUIRY SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY REACTIONS TO PENICILLINS, CEPHALOSPORINS, AND OTHER ALLERGENS. IF AN ALLERGIC REACTION OCCURS, UNASYN SHOULD BE DISCONTINUED AND THE APPROPRIATE THERAPY INSTITUTED. SERIOUS ANAPHYLACTOID REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE. OXYGEN, INTRAVENOUS STEROIDS, AND AIRWAY MANAGEMENT. INCLUDING INTUBATION, SHOULD ALSO BE ADMINISTERED AS INDICATED. PRECAUTIONS Saneral: A high percentage of patients with mononucleosis who receive ampicillin develop a skin rash. Thus, ampicillin class antibiotics should not be admin~stered to patients w1th mononucleosis. In pat1ents treated with UNASYN the possibility of supecinfectlons w1th mycoliC or bactenal pathogens should be kept in mind during therapy. If superinfections occur (usually involving Pseudomonas or Candida), the drug should be discontinued and/or appropnate therapy instituted. Dru1 Interactions: Probenecid decreases the renal tubular secretion of ampicillin and sulbactam. Concurrent use of probenecid with UNASYN may resuij in mcreased and prolonged blood levels of ampicillin and sulbactam. The concurrent adminostration of allopurinol and ampicillin increases substantially the incidence of rashes in patients receiving both drugs as compared to p_atients receiving ampicillin alone. It is not known whether this potentiation of ampicillin rashes is due to allopunnol or the hyperuricemia present in these. patients. There are no data with UNASYN and allopunnol administered concurrently. UNASYN and ammoglycosides should not be reconstituted together due to the m vitro inactivation of aminoglycosides by the ampicillin component of UNASYN. Drt~~/Laboratory Test Interactions: Administration of UNASYN will resuij in high urine concentrat~on of ampicillin. High urine concentrations of ampicillin may resuij in false positive reactions when testing for the presence of glucose in unne using Clin1test '", Benedict's Solut~on or Fehlmg's Solution. It is recommended that glucose tests based on enzymatic glucose oxidase react1ons (such as Climst1x '" or Testape '")be used. Following administration of ampicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriolglucuronide, conjugated estrone and estradiol has been noted. This effect may also occur with UNASYN. Carcinotenesis, Muta1enesis, Impairment of Fertility: Long-term studies m animals have not been performed to evaluate carcinogenic or mutagenic potential. l'nl1nancy Prepancy Catqory B: Reproduction studies haw been performed in mice, rats, and rabbits at doses up to ten 110) times the human dose and haw revealed no evidence of impaired fertility or harm to the fetus due to UNASYN. There are, however, no adequate and well controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. (See-Drug/Laboratory Test Interactions.) Labor and DeliYery: Studies in guinea pigs haw shown that intravenous administration of ampicillin decreased the uterine tone, frequency of contractions, height of contractions, and duration of contractions. However, it is not known whether the use of UNASYN in humans during labor or delivery has immediate or delayed adverse effects on the fetus, prolongs the duration of labor, or mcreases the likelihood that forceps delivery or other obstetrical intervention or resuscitat~on of the newborn w~ll be necessary. Nursiltl Mothers: Low concentrations of ampicillin and sulbactam are excreted in the m~lk: therefore, caution should be exercised when UNASYN is administered to a nursing woman. Pediatric Use: The efficacy and safety of UNASYN haw not been established m infants and children under the age of 12. ADVERSE REACTIONS UNASYN is generally well tolerated. The following adverse reactions haw been reported. Local Adverse Reactioas Pain at IM injection site-16% Pam at IV injection site-3% Thrombophlebitis-3% Systemic Adverse Reactions The most frequently reported adverse reactions were diarrhea m3% of the patients and rash in less than 2% of the patients. Additional systemic reactions reported in less than 1% of the patients were: itching, nausea. vomiting, candidiasis, fatigue, malaise, headache, chest pain, flatulence, abdominal distension, glossitis, urine retention, dysuria, edema. facial swelling, erythema. chills, tightness in throat. substernal pain. epistaxis and mucosal bleeding. Adverse Laboratory Chan1es Adverse laboratory changes without regard to drug relationship that were reported during clinical tnals were: Hepatic: Increased AST !SGOD. All ISGPD. alkaline phosphatase, and LDH. Hematologic: Decreased hemoglobin, hematocrit, RBC, WBC, neutrophils, lymphocytes, platelets and increased lymphocytes, monocytes, basophils, eosinophils, and platelets. Blood Chemistry: Decreased serum albumin and total proteins. Renal: Increased BUN and creatinine. Urinalysis: Presence of RBC's and hyaline casts in urine. The following adverse reactions haw been reported w~th ampicillin-class antibiotics and can also occur with UNASYN. Saslnlintestinal: Gastritis, stomatitis, black "hairy" tongue. enterocoUis and pseudomembranous colitis. Hypersensitivity Reactions: Urticaria, erythema muijiforme, and an occasional case of exfoliative dermatitis haw been reported. These reactions may be controlled with antihistamines and, if necessary, systemic corticosteroids. Whenever such reactions occur, the drug should be discontinued, unless the opinion of the physician dictates otherwise. Serious and occasiOnal fatal hypersensitivity (anaphylactic) reactions can occur with a penicillin (see WARNINGS). HematoiOiic: In addition to the adverse laboratory changes listed above for UNASYN, agranulocytos~s has been reported during therapy w1th penicillins. All of these reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena.
in childhood asthmatics. Ann Allergy 1983; 51(6):571-3 12. Mestitz H, Copland JM, McDonald CF. Comparison of outpatient nebulized vs metered dose inhaler terbutaline in chronic airflow obstruction. Chest 1989;96(6):1237-40 13. Rachelefsky GS, Rohr AS, Wo J, et al. Use of a tube spacer to improve the efficacy of a metered-dose inhaler in asthmatic children. Am J Dis Child 1986;140(11):1191-3 14. SelfTH, Brooks JB, Lieberman P, et al. The value of demonstration and role of the pharmacist in teaching the correct use of pressurized bronchodilators. Can Med Assoc J 1983; 128(2):129-31 15. Salzman GA, Steele MT, Pribble JP, et al. Aerosolized metaproterenol in the treatment of asthmatics with severe airflow obstruction: comparison of two delivery methods. Chest 1989; 95(5): 1017-20 16. Morley TF, Marozsan E, Zappasodi SJ, et al. Comparison of beta-adrenergic agents delivered by nebulizer vs metered dose inhaler with lnspirEase in hospitalized asthmatic patients. Chest 1988;94(6):1205-10 17. Salzman GA, Pyszczynski DR. Oropharyngeal candidiasis in patients treated with beclomethasone dipropionate delivered by metered-dose inhaler alone and with Aerochamber. J Allergy Clin lmmunol 1988;81 (2):424-8 18. Croft RD. 2 year old asthmatics can learn to operate a tube spacer by copying their mothers. Arch Dis Child 1989;64(5):742-3 19. Lee H, Evans HE. Evaluation of inhalation aids of metered dose inhalers in asthmatic children. Chest 1987;91(3):366-9 20. Bronsky E, Bucholtz GA, Busse WW, et al. Comparison of inhaled albuterol powder and aerosol in asthma. J Allergy Clin lmmunol 1987;79(5):741-7 21. O'Driscoll BR, Taylor RJ, Horsley MG, et al. Nebulised salbutamol with and without ipratropium bromide in acute airflow obstruction. Lancet 1989;1(8652):1418-20 22. Neild JE, Cameron IR. Bronchoconstriction in response to suggestion: its prevention by an inhaled anticholinergic agent. BMJ (Clin Res Ed) 1985;290(6469):674 23. Gilman MJ, Meyer L, Carter J, et al. Comparison of aerosolized glycopyrrolate and metaproterenol in acute asthma. Chest 1990; 98(5): 1095-8
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