Drug update: Long-term control of moderate to severe, persistent asthma. (Primary Care).

Inhaled corticosteroids are still considered the most important medications for treating persistent asthma. They have a long track record, and they are the only class of drugs that is proved to prevent death from asthma.

Recently, some experts have become more comfortable with the leukotriene modifiers. But the evidence suggests that leukotriene modifiers will work only in some cases of asthma. Many patients maintained on a corticosteroid and a leukotriene modifier will have clinically significant loss of control if the corticosteroid is stopped (and so this should be done gradually). The exact role of these drugs continues to evolve.

Most patients with mild to moderate, persistent asthma can be maintained with an inhaled corticosteroid alone. The recommendation is to start with a high dose to get inflammation under control and then step down the dose. If there are too many acute episodes or there is an inadequate peak flow rate, a possible first-line add-on drug is a long-acting, inhaled [[beta].sub.2]-adrenergic agonist. Leukotriene modifiers may be increasingly popular as the first-line add-on, but patients with nighttime episodes while on an inhaled corticosteroid can also be treated with an inhaled corticosteroid plus salmeterol. In addition, evidence suggests that a long-acting, inhaled [[beta].sub.2]-adrenergic agonist is more effective for overall asthma control than is a leukotriene modifier.

For the rare patients who don't respond to these drugs, options are limited, Cromolyn and nedocromil are usually used only in children. Theophylline is not a good option because of its side effects. A systemic corticosteroid is usually regarded as a final step, but in severe, acute asthma it can be life saving. (Theophylline, cromolyn, nedocromil, and systemic corticosteroids are not included in the chart below because of space limitations.)

In pregnancy, the consequences of uncontrolled asthma outweigh the risk from most medications. Zileuton and zafirlukast should be avoided during pregnancy because they are teratogenic or fetotoxic in animals. Short-acting [beta]-adrenergic agonists at high doses have been shown to be teratogenic in animals, but there is no evidence that animal data translate to human risk. Theophylline is teratogenic in animals but does not appear to be associated with fetal risk in humans. It can cross the placenta and cause tachycardia and vomiting in newborn infants. Clinical data indicate a possible association between use of oral corticosteroids in the first trimester and some birth defects and toxicity; therefore avoid these drugs during the first trimester, if possible.

 
INHALED CORTICOSTEROIDS 
 
Each corticosteroid is metabolized differently, and each has a different 
potency. The later-generation corticosteroids budesonide and fluticasone 
may have a better safety profile for systemic effects. Treatment 
guidelines suggest adding a long-acting, inhaled [[beta].sub.2] 
adrenergic agonist rather than using a high dose of corticosteroid. 
 
Drug              Dosage               Cost/Day 
 
fluticasone       88-264               $1.64 
 (Flovent)        [micro]/day          (176 [micro]g/day) (*) 
 
 
 
 
 
beclomethasone    up to 504            Beclovent: $1.84; 
 (Beclovent,      [micro]g/day         Vanceril: $1.76 
 Vanceril)                             (336 [micro]g/day) (*) 
 
 
beclomethasone    80-160               $1.04 
 (Qvar)           [micro]g/day         (160 [micro]g) (*) 
 
 
 
 
 
 
 
 
 
 
budesonide        200-400              $1.24 
 (Pulmicort)      [micro]g/day         (400 [micro]g) (*) 
 
 
 
 
 
flunisolide       500-1,000            $2.68 
 (Aerobid)        [micro]g/day         (1 mg) (*) 
 
 
fluticasone and   100 pg               $2.88 (**) 
 salmeterol       fluticasone 
 (Advair)         b.i.d., 50 [micro]g 
                  salmeterol 
                  b.i.d. 
 
 
 
 
 
 
 
 
 
triamcinolone     400 [micro]g/day      $1.00 (*) 
 (Azmacort) 
 
 
Drug              Comment (++) 
 
fluticasone       Most widely prescribed inhaled 
 (Flovent)        corticosteroid. Indicated dosage is low. 
                  Medium dosage is 264-660 [micro]g/day; 
                  high dosage is more than 660 [micro]g/ 
                  day. Available as metered-dose inhaler 
                  or dry powder inhaler. 
 
beclomethasone    Indicated dosage is low; labeled dosage 
 (Beclovent,      is 252-336 [micro]g/day. Medium dosage 
 Vanceril)        is 504-840 [micro]g/day; high dosage is 
                  more than 840 [micro]g/day. 
 
beclomethasone    Formulation with hydrofluoroalkane 
 (Qvar)           propellant. First approved 
                  corticosteroid that does not contain 
                  chlorofluorocarbons. The smaller 
                  particle size of this formulation leads 
                  to greater deposition ...