Can Prolia (denosumab) cause or exacerbate a chronic cough?

Prolia (Denosumab) and Chronic Cough

Prolia (denosumab) is not listed as a cause of chronic cough in current clinical guidelines or its FDA label, and there is no established causal relationship between denosumab and chronic cough development or exacerbation.

Evaluating Medication-Induced Cough

When evaluating a patient with chronic cough who is taking Prolia, it's important to:

1. Review the FDA-approved drug label for Prolia (denosumab), which does not list chronic cough as a reported adverse effect 1
2. Consider more common causes of chronic cough as outlined in clinical practice guidelines 2, 3
3. Evaluate for potential respiratory infections, as denosumab has been associated with increased infection risk in some studies 4

Common Causes of Chronic Cough to Consider First

According to the ACCP evidence-based clinical practice guidelines, the most common causes of chronic cough that should be evaluated include:

• Upper airway cough syndrome (UACS)/postnasal drip
• Asthma
• Non-asthmatic eosinophilic bronchitis (NAEB)
• Gastroesophageal reflux disease (GERD)
• Chronic bronchitis
• ACE inhibitor use 2

Medication-Induced Cough Considerations

When evaluating medication-induced cough:

• ACE inhibitors are the most well-established medication cause of chronic cough 2, 5
• If a patient is taking an ACE inhibitor, the medication should be stopped and replaced 2
• For suspected drug-induced cough, resolution typically occurs within 1-4 weeks after drug withdrawal 5

Denosumab and Respiratory Effects

While denosumab has not been directly linked to chronic cough:

• Denosumab has been associated with increased infection risk, including pneumonia and influenza (aHR: 1.33) 4
• Infection risk appears highest in early treatment periods and attenuates after 2 years of therapy 4
• Serious adverse events reported in clinical trials included dyspnea (21% with denosumab vs. 18% with zoledronic acid) and cough (15% in both denosumab and zoledronic acid groups) 1

Diagnostic Approach for Chronic Cough in Patients on Prolia

1. Exclude common causes of chronic cough (UACS, asthma, GERD, chronic bronchitis) 2
2. Evaluate for respiratory infections, which may be more common in patients on denosumab 4
3. Consider bronchial provocation challenge (BPC) if asthma is suspected 2
4. Assess for GERD with appropriate testing if indicated 3
5. Consider induced sputum testing for eosinophilia if UACS and asthma have been excluded 2

Treatment Approach

1. Treat identified underlying causes according to guidelines 2, 3
2. For UACS, begin with an oral first-generation antihistamine/decongestant 2
3. For asthma, use appropriate bronchodilator and anti-inflammatory therapy 3
4. For GERD, implement dietary modifications and acid suppression therapy 3
5. If chronic cough persists despite addressing common causes, and there is strong temporal relationship with Prolia initiation, discuss with the prescribing physician about risk-benefit assessment of continuing Prolia

Important Considerations

• The benefits of denosumab in reducing fracture risk may outweigh potential respiratory side effects in patients with osteoporosis 6
• Denosumab discontinuation has been associated with multiple vertebral fractures, so treatment decisions should consider this risk 1
• Monitor for hypocalcemia, which is a known adverse effect of denosumab that can occur in up to 18% of patients and may require calcium supplementation 1, 7

If chronic cough persists despite evaluation and treatment of common causes, and there is strong temporal association with Prolia administration, consider consultation with both pulmonology and the prescribing physician to determine the best approach for the individual patient.