Is gynecomastia associated with OFEV (nintedanib)?

Gynecomastia and OFEV (Nintedanib): Association Assessment

No, gynecomastia is not associated with OFEV (nintedanib) based on available medical evidence. There are no documented cases or evidence linking nintedanib to gynecomastia in the current medical literature.

Understanding Gynecomastia and Medication Associations

Gynecomastia is the benign enlargement of male breast tissue resulting from an imbalance between estrogenic and androgenic effects on breast tissue, leading to increased or unopposed estrogen action 1. While medications account for approximately 10-25% of all gynecomastia cases 2, nintedanib is not among the documented causative agents.

Medications with Established Gynecomastia Associations:

Medications with strong evidence of association with gynecomastia include:

• Definite associations: Spironolactone, cimetidine, ketoconazole, hGH, estrogens, hCG, anti-androgens, GnRH analogs, and 5-α reductase inhibitors 2
• Probable associations: Risperidone, verapamil, nifedipine, omeprazole, alkylating agents, HIV medications (particularly efavirenz), anabolic steroids, alcohol, and opioids 2

Specific Documented Cases:

• Efavirenz (HIV medication) has multiple documented cases of gynecomastia, with regression occurring after drug withdrawal 3
• Digoxin and furosemide have been reported to cause gynecomastia, with potentially increased risk when co-administered 4

Differential Diagnosis for Breast Enlargement

When evaluating a patient with suspected gynecomastia while on OFEV, consider:

1. True gynecomastia vs. pseudogynecomastia:

   • True gynecomastia presents as a firm, rubbery mass directly under the nipple
   • Pseudogynecomastia is fatty tissue deposition without glandular proliferation 1

2. Other medications: Review the patient's complete medication list for known gynecomastia-inducing drugs

3. Underlying conditions: Gynecomastia can result from:

   • Hormonal changes
   • Chronic liver disease
   • Aging (physiologic gynecomastia)
   • Malignancy (rare but important to exclude) 1

Management Approach

If a patient on OFEV presents with breast enlargement:

1. Confirm true gynecomastia: Physical examination to differentiate from pseudogynecomastia

2. Medication review: Evaluate for other medications with known gynecomastia associations

3. Consider diagnostic imaging: If clinical examination is indeterminate, ultrasound may be appropriate, particularly in patients over 25 years of age 1

4. Look for alternative causes: Hormonal evaluation may be warranted if no medication cause is identified

Key Points for Clinicians

• Gynecomastia is common in men, often asymptomatic, and increases with age 5
• Medication-induced gynecomastia often presents as a painful/tender breast with enlargement (acute gynecomastia syndrome) and is typically transient 5
• When evaluating potential drug-induced gynecomastia, focus on medications with established associations rather than attributing it to medications like OFEV that have no documented link
• In patients with pulmonary fibrosis on OFEV who develop gynecomastia, investigate other medications or underlying conditions as the cause

In summary, there is no evidence supporting an association between OFEV (nintedanib) and gynecomastia. If gynecomastia occurs in a patient taking OFEV, other causes should be investigated.