What medication can be prescribed for a patient on Xtandi (enzalutamide) and Xgeva (denosumab) experiencing wheezing that won't interfere with their current medications?

Management of Wheezing in a Patient on Xtandi and Xgeva

For a patient on enzalutamide (Xtandi) and denosumab (Xgeva) experiencing wheezing, prescribe an inhaled short-acting beta-2 agonist (SABA) such as albuterol 2-4 puffs (200-400 mcg) every 4-6 hours as needed, as there are no known drug interactions between SABAs and these cancer therapies. 1

Rationale for SABA Selection

• Albuterol (salbutamol) is the first-line treatment for acute wheezing and provides bronchodilation within minutes, with peak effect at 15-30 minutes and duration of 4-5 hours 1
• Standard dosing via metered-dose inhaler (MDI) is 200-400 mcg (2-4 puffs) every 4 hours for adults with wheezing 1
• Alternative SABA options include terbutaline 500-1000 mcg (2-4 puffs) every 4 hours 1

No Drug Interactions with Cancer Therapy

• Enzalutamide and denosumab have no documented interactions with inhaled bronchodilators 2, 3
• Enzalutamide is a CYP3A4 inducer, but inhaled SABAs are not significantly metabolized by this pathway, making them safe to use concurrently 3
• The primary concern with enzalutamide is fatigue (occurring in 55-62% of patients), which should not be confused with respiratory symptoms 4, 5

Alternative Bronchodilator Options

If SABA alone provides insufficient relief:

• Add ipratropium bromide (anticholinergic) 2-3 puffs every 4-6 hours, which can be combined with albuterol for additive bronchodilator effect 1
• Ipratropium has slower onset (30-90 minutes) but lasts 4-6 hours and is particularly effective in COPD-type bronchospasm 1
• Combination therapy (albuterol + ipratropium) provides greater benefit than either agent alone in moderate to severe bronchospasm 1

When to Consider Nebulized Therapy

Nebulized bronchodilators are indicated only if: 1

• Patient cannot use MDI correctly after proper instruction
• Wheezing is severe (respiratory rate >25/min, cannot complete sentences, peak flow <50% predicted) 1
• Nebulized albuterol dose: 2.5-5 mg in 3 mL saline every 4-6 hours 1
• Nebulized ipratropium: 250-500 mcg every 4-6 hours 1

Assessment of Wheezing Severity

Determine if this represents: 1

• Mild wheezing: Treat with MDI SABA 2-4 puffs every 4 hours
• Moderate wheezing: MDI SABA 4 puffs every 4 hours or consider nebulizer
• Severe wheezing (respiratory rate >25/min, cannot complete sentences, reduced activity): Consider hospital admission, nebulized bronchodilators, and systemic corticosteroids 1

Role of Inhaled Corticosteroids

• For persistent or recurrent wheezing, add inhaled corticosteroids (ICS) such as budesonide or fluticasone after establishing bronchodilator therapy 1
• ICS should be used as controller therapy for persistent symptoms, not for acute relief 1
• No drug interactions exist between ICS and enzalutamide/denosumab 3

Critical Safety Considerations

• Monitor for worsening respiratory symptoms that may indicate progression requiring systemic corticosteroids or hospitalization 1
• Beta-agonists may cause transient decrease in oxygen saturation due to pulmonary vascular effects, though this is rarely clinically significant 1
• In elderly patients (common with prostate cancer), first SABA treatment should be supervised as beta-agonists may rarely precipitate angina 1
• Avoid oral decongestants (pseudoephedrine) if patient has uncontrolled hypertension or cardiac disease, which is common in this population 6

When to Escalate Care

Seek immediate medical attention if patient develops: 6

• Inability to complete sentences in one breath
• Respiratory rate ≥25/min or heart rate ≥110/min
• Peak expiratory flow <50% predicted or personal best
• Silent chest, cyanosis, or confusion 1