Doxofylline/Formoterol Fumarate 1209

only significant when they were given by nebulisation. 9 ··· • .· . Interactions • ·· .· · Also a working pany of the UK CSM considered10 that a asthma mortality and beta-agonist use As for Salbutamol, p. 1223.1. .CAS: · frlrpai:G te}. . ; . . · . could neither be confirmed nor refuted. < . . ATC ...... f/03Ati3.·• · • • \• · . · Not surprisingly there are different views on the cause of Pharmacokinetics .. . · A ' . • • •.• the increased asthma monality. The cardiotoxidty of the 'It Fenoterol is incompletely absorbed from the gastrointestinal Vel:.,_;;;i(.)/lt)3AC13. ·· W34SHF8.12K beta agonist ntight have to be considered, although UN/I . :- .· F'3]5()A S1?N terbutaline, salbutamol and fenoterol. Int J Clin Pharmacal Ther Toxicol 1992; 30: 342-62. 6.5. Protect from light. monality rates have fallen and current recommendations 3. Hildebrandt R, et al. Pharmacokinetics of fenoterol in pregnant and USP 36: (Formoterol Fumarate). A white or almost white or for the use of shon-acting beta agonists, which are nonpregnant women. Bur J Clin Pharmacol 1993; 45: 275-7. 2 slightly yellow powder. Slightly soluble in water and in generally more selective than fenoterol, are for them to be isopropyl alcohol; soluble in methyl alcohol; freely soluble taken as required rather than on a regular basis; indeed P..r�P.�.rc:'ti().".� ...... in acetic acid and in dimethyl sulfoxide; practically insoluble increasing use of such drugs is seen as an indication to Proprieklry Preparations (details are given in Volume B) in acetonitrile and in ether. A 0.1% solution in water has a amend the treatment schedule. Moreover, the dose of pH of 5.5 to 6.5. Protect from light. fenoterol has been reduced in recent years. However, Single-ingredient Preparations. Arg. : Alveofen; Asmopul; Berotec; Austria: Berotec; Belg. : Berotect; Braz.: Berotec; Bro­ controversy over regular use of short-acting beta2 agonists rnifen; Bromotec; Fenatec; Fenozant; Cz. : Berotec; Denm.: Stability. Nebuliser solution containing formoterol fumar­ continues to be fed by conflicting studies of their benefit. l Berotect; Ger.: Berotec; Partusisten; Gr. : Berotec; Ftagirol; ate 0 nticrograms/mL was found to be physically and che­ More recently 2 further observational studies have reported Hung. : Berotect; Indon.: Berotec; Irl.: Berotect; Ital.: Dosbero­ mically stable when ntixedwith the following solutions:1 an association between use of short-acting betaz agonists budesonide inhalation suspension 250 micrograms/mL tec; Jpn: Berotec; Malaysia: Berotec; Ferro; Mex. : Partusisten; • and adverse effects on mortality.I5•16 A cohort study, !' Neth.: Philipp. : Pol.: acetylcysteine solution 100 mg/mL Berotect; Partusisten; Berotect; Berotec; • designed to evaluate the effect of respiratory medications on Port. : Berotect; Rus.: Berotec (EeporeK); Partusisten ipratropium bromide inhalation solution 200 micro- • asthma death, found an association between the excessive (IIaprycHcTeH); S.Afr. : Berotec; Singapore: Berotec; Switz. : grams/mL use of short-acting beta2 agonists and an increased risk of Berotec; Thai. : Berotect; Iperol; Ukr. : Berotec (EeporeK); sodium cromoglicate inhalation solution 10 mg/mL • asthma death; no additional risk was found with fenoterol Venez. : Segamol. The authors of this study noted that when these solutions beyond the risk associated with beta agonists as a class. It 2 Multi-ingredient Preparations. Arg. : Berodual; Ipradual; Austria: were mixed and nebulised, or given sequentially, the was unknown whether excessive use was a symptom or a Berodual; Berodualin; Belg.: Duovent; Braz. : Duovent; Canad.: amount of drug delivered in vitro was increased compared cause of worsening asthma. A case-control study16 similarly Duovent; Chile: Berodual; Cz. : Berodual; Denm.: Berodual; with single-drug nebulisation. Additionally, sequential found a modestly increased risk of mortality associated with Duovent; Fin.: Atrovent Camp; Fr.: Bronchodual; Ger.: Bero­ nebulisation led to higher delivery of the first drug given. use of short -acting beta2 agonists in the previous l to 5 dual; Gr. : Berodual; Hung. : Berodual; India: Fenovent; Indon.: The clinical implications of these results were unclear. years. However, the study had insufficient power to come to Berodual; Irl.: Duoventt; Ital.: Duovent; Malaysia: Berodual; I. Akapo S, et a!. Compatibility and aerosol characteristics of formoterol any conclusions regarding the effects of fenoterol, which Duovent; Mex. : Berodual; Berosolvon; Neth.: Berodual; Phi­ fumarate mixed with other nebulizing solutions. Ann Phannacother was rarely prescribed alone, and concluded that evidence lipp.: Berodual; Pol. : Berodual; Port. : Berodual; Rus.: Berodual 2008; 42: 1416-24. (Eepo;zyaJI); Ditec ( eK)t; S.Afr. : Atrovent Beta; Berodualt; for a direct adverse effect of beta2 agonists was inconclusive; ):1m' other explanations might include lack of more appropriate Duovent; Sabax Nebrafen; Singapore: Berodual; Duovent; Uses and Administration Switz.: Thai.: asthma care, more severe disease or increasing severity of Berodual; Aeroduol; Berodual; Inhalex; Iprateral; Punol; UK: Duoventt; Ukr. : Berodual (Eepo;zyaJI); Venez : Hero­ Formoterol is a direct-acting sympathomimetic with mainly disease, or a tendency for patients whose disease was not dual; Duovent; Respidual. beta-adrenoceptor stimulant activity specific to beta responding to receive a wider range of treatments. 2 receptors (a beta agonist) . It has properties sintilar to For discussion of sintilar concerns about the use of long­ Pharmacopoeial Preparations 2 those of salbutamol (p. 1220.2), but like salmeterol acting beta agonists in asthma, see Salmeterol, p. 1224.3. BP 2014: Fenoterol Pressurised Inhalation. 2 (p. 1224.1) it has a prolonged duration of action of up to 12 1. Pearce N, et al. Beta agonists and asthma mortality: deja vu. Clin Exp hours; it is therefore not considered suitable for the Allergy 1991; 21: 401-10. 2. Crane J, et a!. Prescribed fenoterol and death from asthma in New Fenspiride Hydrochloride {USAN, r/NNM) symptomatic relief of acute attacks of bronchospasm. It is Zealand, 1981-83: case-control study. Lancet 1989; i: 917-22. used with regular inhaled corticosteroid when a regular 3. Pearce N, et al. Case-control study of prescribed fenoterol and death from .•. · .• •. long-acting beta2 agonist is needed for management of asthma in New Zealand, 1977-81. Thorax 1990; 45: 170-5. •1qidrq�iq(��.P �;�� �·��nspJr,i�e chronic asthma (p. 1195.2), or for prevention of exercise­ 4. Grainger J, et al. Prescribed fenoterol and death from asthma in New liltl£;42.8; induced asthma. It is also used in chronic obstructive Zealand, 1981-7: a further case-control study. Thorax 1991; 46: 105- · . $A; �ti.d!\1P'!AA 111. f14).1 p®1bp1i!.f!.· · i ...... (i ...... ; ( . pulmonary disease (p. 1199.1). 5. Pearce N, et al. End of the New Zealand asthma mortality epidemic. �Ptt�ii�thYf • • •• !0•• > ••.. • , • · �h!<;lr!d!)...... ••••• A usual dose for asthma is l inhalational capsule of asthma. Lancet 1990; 336: 139 1-6. ; · .· • , · . · ...... · > •· C,s!:J2o!'l202,8CI=�96,S . . 7. Spitzer WO, et al. The use of � -agonists and the risk of death and near 9\,9.:; :�o/J�� ;f��sfl(��.. );.. SIJS!.�Z:.·'·(fr!?s�lr!1Je •b�rp- formoterol fumarate 12 micrograms twice daily. In the death from asthma. N Bngl J Med 1992; 316: 501-6. UK, this may be increased to 2 inhalational capsules 8. Beasley R, et al. � -agonist therapy and asthma mortality in Japan. Lancet , ..•. • •••· . •• •• ,> , :cl'lton«li!J·• . . (24micrograms) twice daily if necessary for severe 1998; 351: 1406-7. · .· : : •,1lis ,.,.. RPJ�Ir·R03DXO$"\ . disease. In the USA. 1 inhalational capsule of l2 micr­ 9. Mullen M, et a/. The association between J3 -agonist use and death from ·t\iC: ; ()R()aDXIJ). . • · ··· ·· . .. . . ograms may be taken when required, at least 15 minutes asthma: a meta-analytic integration of case control studies. lAMA 1993; · · 270: 1842-5. . before exercise, to prevent exercise-induced broncho­ 10. CSM. Beta-agonist use in asthma: report from the CSM Working Party. '!J&d :£ constriction in those patients not taking regular doses; Current Problems 33 1992. Available at: http://www.mhra.gov.uk/home/ Profile additional doses should not be taken within 12 hours. idcplg?IdcService=GET_FILE&dDocName=CON2024451&RevisionS­ Metered doses from a dry powder inhaler may be electionMethod=LatestReleased (accessed 15/01/08) Fenspiride is reported to have bronchodilator and • 11. Sears MR, Taylor DR. The � 2-agonist controversy: observations, expressed as the amount delivered into the mouthpiece anti-inflammatory properties. It is given as the hydro­ explanations and relationship to asthma epidemiology. Drug Safety 1994; (multiples of 6micrograms per inhalation) or the amount ll: chloride in asthma (p. 1195.2) and other respiratory 259-8 3. delivered from the mouthpiece (corresponding to 12. Fuller RW. Use of � agonists in asthma: much ado about nothing? BMJ disorders in usual oral doses of 160 to 240 mg daily in 2 multiples of 4.5 micrograms per inhalation). Usual 1994; 309: 795-6. divided doses before meals. It has also been given rectally 13. Sears MR. Asthma deaths in New Zealand. Lancet 1995; 345: 655-6. doses, expressed as the amount delivered into the and by intramuscular or intravenous injection. 14. Tattersfield Use of � agonists in asthma: much ado about nothing? AE. 2 mouthpiece, are 6 or 12 micrograms once or twice daily, BMJ 1994; 309: 794-5. increased if necessary in severe disease to 24 micrograms 15. Lanes SF, et al. Respiratory medications and risk of asthma death. Thorax r r li twice daily. (In the UK, a dose of 12 micrograms may be 2002; 57: 683-6. P.. �P.�. �. ().".� ...... 16. Anderson HR, et al. Bronchodilator treatment and deaths from asthma: Proprieklry Preparations (details are given in Volume B) taken before exercise to prevent exercise-induced case-control study. Abridged version: BMJ 2005; 330: 117. Full version: Single-ingredient Preparations, Fr.: Pneumorel; Hong Kong: bronchoconstriction.) No more than 36micrograms http://www.bmj.com/cgi/reprint/330/7483/117 (accessed 15/01/08) Pneumorelt; Ita/. : Pneumorel; Pol. : Elofen; Eurespal; Fenspo­ should be inhaled as a single dose, with a maximum gal; Pulneo; Port. : Pneumorel; Rus.: Eurespal (3pecnaJI); Ukr. : daily dose of 72 nticrograms. (3pecnaJI); (llHcnapoH). Metered doses from an aerosol inhaler may also be Porphyria. The Drug Database for Acute Porphyria, com­ Erespal Inspiron • expressed as the amount delivered into the mouthpiece piled by the Norwegian Porphyria Centre (NAFOS) and (l2micrograms per inhalation) or the amount delivered the Porphyria Centre Sweden, classifies fenoterol as prob­ from the mouthpiece (corresponding to 10.1 micrograms ably not porphyrinogenic; it may be used as a drug of first Formoterol Fumarate per inhalation). Usual doses are l or 2 inhalations twice choice and no precautions are needed.1 (BANM, USAN, r/NNM) 0 daily. 1. The Drug Database for Acute Porphyria. Available at: http://www. · Treatment should be reassessed if this proves inadequate; in drugs-porphyria.org (accessed 17/l 0/11) A. · 8[4oA; CGI'-25,&27 Eformater'<:JI F:umarc�ti etaim Farinotero!i •ft.lnl� ili:• 1. Hawker F. Pulmonary oedema associated with rsympathomimetic �; � � £1 � the amount delivered into the mouthpiece, are 12 micr­ B � ; � treatment of premature labour. Anaesth IntensiveCare 1984; 12: 143-S l. m�ll!¥\!Jh�n!!fhyQal'(lln

The symbol t denotes a preparation no longer actively marketed The symbol 0 denotes a substance whose use may be restricted in certain sports (see p. viii) 1210 Bronchodilators and Anti-asthma

tion during high dose treatment with long acting agonists. Thorax inhaler are 12 micrograms twice daily; if required, improvement that persisted during 45 weeks of treat­ f) 2 2001; 56: 529-3 5. additional doses may be used for relief of symptoms. A ment.1 2. Jones SL, etal. Reversing acute bronchoconstriction in asthma: the dfect maximum of 24 micrograms may be inhaled as a single dose, with formoterol for the treatment of of bronchodilator toleran•e after treatment with fnrmoterol. Eur Respir J with a total maximum daily dose of 48 micrograms. 38: I323. 200I; 17: 368-73. Formoterol fumarate may also be inhaled via a nebuliser 3. in a dose of 20 micrograms twice daily. Adverse Effects and Precautions An oral formulation of formoterol fumarate is available in some countries for reversible airways obstruction; doses As for Salbutamol, p. 1221.3. Inhalation of formoterol may of SO micrograms have been given twice daily. be associated with paradoxical bronchospasm, and high Interactions For doses of formoterol fumarate used in children, see doses have been associated with an increase in severe exacerbations of asthma. It should not be used in patients Administration in Children, below. As for Salbutamol, p. 1223.1. who are not also receiving an inhaled corticosteroid. Reviews. Long-acting beta2 agonists such as formoterol are not appropriate for the treatment of acute bronchospasm. Pharmacokinetics Conjunctival irritation and eyelid oedema have been Inhaled formoterol is rapidly absorbed. It is largely reported in isolated cases. metabolised by glucuronidation and 0-demethylation, References. with about l 0% being excreted in the urine as unchanged 3. Sovani MP, et a!. A bendit-risk a�sessment of inhaled long-acting l. drug. The mean terminal elimination half-life after B 2- in the rnan<�gcment of obstructive pulmonary disease. Dmg inhalation is estimated to be 10 hours. 2004; 27: 689-715. 2. Pauwels RA, et al. Formoterol as relief medication in worldwide safety and effectiveness trial. Eur Respir 2003; 22: 787-94. Stereoselectivity. Formoterol occurs as a racemic mixture, Administration in children. Doses of formoterol fumarate .I in which arformoterol (p. 1202.3), the R,R-enantiomer, is inhaled from inhalational capsules in children aged 5 Asthma. A review of 3 controlled studies comparing the active form.1.2 It has been suggested that stereoselec· years or older are the same as those for adults, see Uses inhaled formoterol with placebo, concluded that regular tive metabolism and excretion may account for the indivi­ and Administration, p. 1209.3. use of high-dose formoterol (48 micrograms daily) may be dual variation in duration of effect seen with fornwterol, Fonnoterol fumarate may be given by metered-dose dry associated with more frequent serious asthma exacerba­ although the exact mechanism remains unclear. powder inhaler to children 6 years of age and over. The u tions. 1 The concomitant use of inhaled corticosteroids was et al. usual dose, expressed as the amount delivered into the l. Zhang M. Stereoselectivc glumronidation of formoterol by human allowed but not mandatory, and was not reported in the liver microsomcs. Br Clin Pharmacol 2000; 49: I '52-7. mouthpiece, is 6 to 12 micrograms once or twice daily. .I review, which led to debate on whether the results of the 2. Occasionally up to 48 micrograms daily may be required study would be applicable when current prescribing guide­ (maximum single dose should not exceed 12 micrograms). 3. Zhang M, et al. Stercosdectivc lines for asthma were followed. 2,3 In some countries, such as Japan, formoterol fumarate glucuronide con jugale in human. In contrast to this, a subsequent study,4 designed to test has been given orally to children from the age of 6 months at the hypothesis of a dose-related increase in serious astluna a dose of 4rnicrograms/kg daily, in 2 or 3 divided doses. Preparations exacerbations with formoterol therapy, did not show any ······················ increase in serious asthma exacerbations between different Proprietary Preparations (details are given in Volume B) Asthma. Formoterol is a long-acting beta agonist (dura­ 2 formoterol doses and placebo. Again, inhaled corticosteroid tion of action about 12 hours). Guidelines on the manage­ Single-ingredient Preparations. Arg. : Fordilen; Oxis; Xanol; Aus­ use was allowed but not mandatory, with 62.4% of patients ment of asthma. see p. 1195.2. generally recommend that tral. : Foradile; Oxis; Austria: Foradil; Oxis; Belg.: Foradil; For­ reported as receiving regular anti-inflammatory therapy. the use of long-acting beta agonists be reserved for magal; Formoair; Oxis; Braz. : Fluir; Foradil; Formare; Formo­ 2 A systematic review' firmly concluded that the addition patients with chronic asthma who have already progressed caps; Oxis; Canad. : Foradil; Oxeze; China: Atock (_'P.:lffi_ft);Oxis of a long-acting beta agonist (such as formoterol) to low or (�5/:¥Ji); to inhaled corticosteroids; they are not a substitute for cor­ 2 Pan De Xin (115ti':l'lik); Cz.: Atimos; Foradil; Forairt; high doses of inhaled corticosteroids reduced the risk of ticosteroids. Combinations of fornwterol with an inhaled Formano; Formovent; Oxist; Denm.: Delnil; E£ormaxt; Foradil; asthma exacerbations compared with ongoing treatment Formo; Fostair; Oxez: Oxis; Fin.: Cycloterol; Fomeda; Foradil; corticosteroid, used as both maintenance and reliever with similar doses of inhaled corticosteroids alone. The Formaxa; Oxis; Fr.: Asmelor; Atimos; Foradil; Formoair; Ger.: therapy. have been studied. Results are seemingly addition of a long-acting beta agonist reduced by 23% the Foradil; Forair; Formatris; Formolich; Formotop; Oxis; Gr.: encouraging, although what role such combinations 2 relative risk of patients requiring systemic corticosteroids for Broncoteril; Edufil; Foradil; Forair; Forcap; Pormaxa; Formo­ should play in therapy is not yet clearly defined. Formo­ an asthma exacerbation, over 4 to 54 weeks. There is no pen; Formotil; Imotec; Kinitron; Oxez; Hong Kong: Oxis; terol may also be useful in controlling persistent nocturnal evidence of a difference in safety between treatment with Hung.: Atimos; Diffumaxt; Foradil; Fortofant: Oxis; India: asthma or preventing exercise-induced attacks. There is formoterol plus a corticosteroid (typically budcsonide) and Deriform; Foratcc; Irl. : Foradil; Oxis; Israel: Foradil; Oxis; Ital.: some evidence that after prolonged use, protection against Aliterol; Atimos; Eolus; Evcrvent; Feronal; Foradil; Forotan; salmeterol plus a corticosteroid (fluticasone).6 However. for bronchoconstriction is reduced (see Tolerance, below), Fortasint; Kurovent; Levovent; Liferol; Oxis; Jp n: Atock; Oxis; concerns about serious adverse effects associated with long­ and high-dose therapy may be associated with an Malaysia: Oxis; Mex.: Foradil; Oxis; Neth.: Atimos; Foradil; For­ acting beta agonists in asthma, including systematic increased rate of severe exacerbations (see Asthma under 2 mocapst; Oxis; Norw. : Foradilt; Oxis; NZ: Foradil; Oxis; Phi­ reviews of largely asthma-related events with formoterol, Adverse Effects and Precautions. below). Although long­ lipp.: Atock; Foradil; Oxist; Pol.: Atimos; Diffumax; Foradil; see Increased Mortality. under Salmeterol p. 1224.3. acting bronchodilators should not be used for acute relief Forastmin; Oxis; Oxodil; Zafiron; Zomexil; Port. : Asmatec; Ati­ of asthma, formoterol has reportedly been used success­ 1. Mann M, et al. Serious asthma exacerbations in asthmatics treated with mos; Eforrnaxt; Foradil; Forair; Formaxat; Oxis; Rus.: Atimos high-dose formoterol. Chest 2003; 124: 70-4. (ATn:Moc); Foradil (ct>opa!U1n); Oxis (OKcn:c); S.Afr. : Foradil; For­ fully as part of the rnanagementof acute severe asthma in et al. Chest 2. Rissmiller RW, Asthma exacerbations and formoterol. 2004; atec; Oxis; Singapore: Foradil; Oxist; Spain: Broncoral; Foradil; hospital. 125: I590-l. 3. van der Molen T. Fonnoterol and asthma exacerbations. Chest 2004; 125: Formatris; Neblik; Oxis; Swed.: Foradil; Formatris; Oxis; Switz. : References. 1591. Foradil; Oxis; Thai.: Oxis; Turk. : Atimos; Foradil; Forast; For­ et al. 1. van der Molen T, Effects of the long acting f:l 4. Wolfe J, et al. Formoteroi, 24 1-l g bid, and serious asthma exacerbations: yxa; Oxis; Vcntofor; UK: Atimos Modulite; Foradil; Oxis; Ukr.: asthma control in asthmatic patients using similar rates compared with formoteroL I2l-l g bid. with and without Fortix (ct>opniKc); Zafiron (3a$n:poH); USA: Foradil; Perforomist; Thorax 1996; 52: '535-9. extra doses taken on demand. and placebo. Chest 2006; 129: 27-38. 2. Pauwels RA, et a!. Effect of inhaled formoterol and budesonide on Venez. : Fluir; Foradil; Formotec. 5 Ducharme FM, et al. Addition of long-acting beta2-agonists to inhaled N b'ngl Med 337: exacerbations of asthma. J 1997; 1405-1 1. Correction. corticosteroids versus same dose inhaled corticosteroids for chronic ibid.; 1998; 338: 139. MultHngredient Preparations. Arg. : Previa; Neumoterol; Symbi­ asthma in adults and children. Available in The Cochrane Database of 3. ()'ByrnePM, et a!. Low dose inhaled budesonidc and formoterol in mild cort; Austral.: Symbicort; Austria: Formodual; Foster; Symbi­ Systematic Reviews; Issue 5. Chichester: John Wiley; 20IO (accessed Am Respir Crit Care persistent asthma: the OPTIMA randomized trial. J 03/08/JO). cort; Belg. : Flutiform; Inuvair; Symbicort; Braz.: Alenia; Fora­ Med 2001; 164: I 392-7. 6. Cates CJ, Lasserson TJ. Regular treatment with formoterol and an seq; Fostair; Symbicort; Vannair; Canad.: Symbicort; Zenhale; 4. Goldsmith DR, Keating GM. Budesonide/fonnoterul: a review of its use inhaled corticosteroid versus regular treatment with salmeterol and an Chile: Symbicort; Vannair; China: Symbicort (1({:.16, PJ ); Cz, : in asthma. Drugs 2004; 64: I597-1618. inhaled corticosteroid for chronic asthma: serious adverse events. Budfor; Combair; Edoflo; Formodualt: Symbicort; Denm.: Assi­ 5. Pedersen S. Budesonide plus formoterol for reliever therapy in asthma. Avopa,IJ:n:JJ KoM6n:); Foster (ocTep); Simbicort II. Cates CJ, TJ. Combination formoterol and budesonide as Porphyria. The Drug Database for Acute Porphyria, com­ maintenance and reliever versus inhaled steroid maintenance piled by the Norwegian Porphyria Centre (NAPOS) and (CHM6HKOpT)t; Symbicort (CHM6HKOpT); S.Afr. : Symbicord; Sin­ for chronic asthma in adults children. Available in The Cochrane the Porphyria Centre Sweden, classifies formoterol as gapore: Symbicort; Spain: Formodual; Foster; RiJast; Symbicort; Database ot Systematic Reviews; Issue 2. Chichester: John Wiley; 2009 Swed. : Innovair; Symbicort; Switz. : Symbicort; Vannair; Thai. : 11/08/09). probably not porphyrinogenic; it may be used as a drug of Symbicort; Turk.: Combipack; Poradil Combi; Foster; Innovair; 12. CJ, T.asserson TJ. Combination fonnoterol and inhaled steroid first choice and no precautions are needed.1 versus betaragonist as relief medication for (·hronic asthma in adults Symbicort; Ventofor·Combi; UK: flutiform; Fostair; Symbicort; l. The Drug Database for Acute Porphyria. Available at: http://www. and children. Available in The Cochrane Database of Systematic Ukr.: Simbicort (CHM6rrKOpT); USA: Dulera; SJ'IDbicort; Venez. : drugs-porphyria.org (accessed 17I 1 0/1I) Reviews; Issue 1. Chichester: John Wiley; 2009 J 1 /08/09). Foraseq; Symbicort. 13. Rodrigo GJ, et al. Formoterol for acute in the emergency department: a systematic review with meta-analysis. Ann Allergy Asthma To lerance. Regular use of formoterol produced bronchodi­ lmmunol 2010; 104: 247-52. lator desensitisation, 1·3 and tachyphylaxis to bronchopro­ tection against methacholine, effects that have been noted Stuttering. Inhaled formoterol 12 micrograms daily was with other long-acting beta2 agonists (see Salmeterol. reported to improve stuttering (p. 1078.1) in 3 children p. 1225.2) and short-acting beta2 agonists (see Salbutamol, between 14 and 20 years old. In 2 males, the onset of p. 1222.3). effect was about 6 weeks, but long-term follow-up was I. van der Woude HJ, et al. Decreased bronchodilating effect of salbutamol not possible. In the female patient there was early in relieving methacholine indu•ed moderate to severe bronchoconstric-

All cross-references refer to entries in Volume A