Avoiding Drug–Drug Interactions in Patients With Respiratory Diseases

An incredible number of diseases and infections warrant the use of respiratory medications. For example, in 2009, 1 in 12 people in the United States had asthma. Asthma has increased in prevalence annually across all ages, genders, and racial groups, costing billions of dollars in medical expenses and missed school and work days.^1,2According to the COPD Foundation, 6.3% of Americans have chronic obstructive pulmonary disease (COPD).³The prevalence of allergic diseases has also risen worldwide. In the United States, 7.8% and 13.0% of adults report having hay fever and sinusitis, respectively.⁴Retail health prescribers write prescriptions for numerous respiratory medications for this handful of disease states in diverse patient populations. With such widespread use of medications, how can prescribers avoid drug—drug interaction (DDI) incidents?

DDIs

An interaction is a reciprocal action or influence. All substances that people apply or consume, including drugs, food, and supplements, can potentially interact.⁵A DDI is the influence of drugs on each other, pharmacokinetically (ie, the body exerts effects on drugs), and pharmacodynamically (ie, drugs exert effects on the body). Major DDI categories involve the excretion and/or metabolism of 1 or all drugs in the relationship.⁶A major route of metabolism is cytochrome P450 (CYP) hepatic enzyme action.

RESPIRATORY DDIs

When respiratory medications are used appropriately, few DDIs occur. Many “major” interactions are magnified adverse events. Main interactions between many types of respiratory drugs are additive effects, commonly found with anticholinergic drugs and QTc interval—prolonging drugs.^7,8

Other DDIs produce antagonistic effects. For example, beta-agonists, found in many inhalers, cause bronchodilation, while beta-block- ers cause bronchoconstriction. Patients who take beta-blockers may require more inhaler doses to achieve desired outcomes because the drugs work against each other. Nonselective beta-blockers that influence both the cardiac and respiratory muscles are contraindicated with beta-agonist medications. Cardioselective beta-blockers work preferentially on cardiac muscles, with limited respiratory effects at low doses. Selective beta-blockers develop cardiac, nonselective, and respiratory effects as doses increase.⁹Table 1 lists noteworthy respiratory medication DDIs.^7,10-18

CONDITIONS REQUIRING RESPIRATORY MEDICATIONS

With a large portion of the population using respi- ratory medications, patients with comorbidities are common. Respiratory medications are also often used for secondary conditions. Subsequently, pre- scribers use respiratory medications in conjunction with many medication classes. Common medications include those for:

• Allergies, such as antihistamines and decongestants^11-14,18
• Asthma, such as antimuscarinics, beta-agonists, cromolyn, epinephrine, immune modulators, leukotriene-receptor modulators, steroids, and theophylline^11,20,21
• Bronchitis, such as antitussives, decongestants, expectorants, and mucolytics22,23
• COPD, such as antibiotics, antimuscarinics, beta-agonists, roflumilast, steroids, and theophylline²⁴
• Cystic fibrosis, such as antibiotics, cystic fibrosis trans- membrane regulator modulators, mucolytics, and nonsteroidal anti-inflammatory drugs^25,26
• Pneumonia, such as antibiotics, including β-lactams, doxycycline, fluoroquinolones, and macrolides;^27,28These medications are not ideal for all respiratory disease states and may be contraindicated.

Roflumilast is used for patients with COPD but not recommended for patients with asthma.¹⁴Leukotriene-receptor modulators and mast cell stabilizers are useful for asthma but not recommended for COPD.^11,20,21,24Corticosteroids should never be used in patients with cystic fibrosis.^25,26These considerations are important when treating patients with comorbidities, especially multiple respiratory diseases.

Smoking cigarettes can influence respiratory disease development and exacerbations. Smoking cessation is recommended for all patients but critical for those with respiratory diseases. Smoking cessation products also have the potential to create DDIs. Additionally, cigarette smoke induces several cytochrome P450 enzymes, notably CYP 1A2. Medications metabolized by CYP 1A2 will have shorter durations of action.^15,29,30

Table 2 notes specific DDIs that can occur in patients who use respiratory medications frequently.^{6,9-11,18,20,24,25,31-39}

Prevent medication errors and potential DDIs by building counseling and medication reconciliation into the practice.

Results from studies have shown that most patients use inhalers incorrectly.^40,41Review how to use respiratory medications such as inhalers with patients regularly. Educate them about proper use to prevent adverse reactions and errors.

Reassess all medications that patients take each visit to reduce additive or antagonistic reactions. Multiple prescribers may prescribe similar medications or make overlapping recommendations. Many patients must be prompted to disclose all prescription and OTC medications, supplements, and vitamins that they use. Patients may not consider vitamins important or share only the medications pertaining to a specific prescriber. As noted, all substances that patients put in or on their bodies have the potential to interact. Medication counseling and reconciliation can reduce the possibility of unknown interactions and adverse effects.

CONCLUSION

The potential for DDIs exists among all medications. The probability of interactions increases and decreases based on medication classes and the individual patient. Retail health providers can spot and prevent these interactions before they occur. Although respiratory medications are associated with few DDIs, patients who use respiratory medications may be on countless other drugs. Practicing medication reconciliation will help avoid DDIs, providing better care for patients.

Kelsey Fontneau is a PharmD candidate at the University of Connecticut School of Pharmacy in Storrs.

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