From the FDA Drug Label
Case reports have demonstrated that pergolide increases the risk of fibrotic complications including pulmonary, pleural, and/or retroperitoneal fibrosis, pericarditis, pleuritis, and pericardial and/or pleural effusions. Cases of retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, pleural thickening, pericarditis, and cardiac valvulopathy have been reported in some patients treated with ergot-derived dopaminergic agents. There have been reports of pleural and retroperitoneal fibrosis in patients following prolonged daily use of injectable dihydroergotamine mesylate.
Medications that can cause retroperitoneal fibrosis include:
- Pergolide 1
- Ergot-derived dopaminergic agents, such as methysergide 2
- Ropinirole, although the evidence is not sufficient to establish a causal relationship 3 Key points to consider when prescribing these medications:
- Monitor patients for signs and symptoms of fibrotic complications
- Discontinue the medication if a patient is diagnosed with a specific fibrotic complication
- Consider alternative treatments for patients with a history of fibrotic conditions
From the Research
Medications that can cause retroperitoneal fibrosis include ergot derivatives, such as ergotamine and methysergide, as well as other drugs like dopamine agonists, analgesics, and certain antihypertensives, with the risk increasing with longer duration of use, particularly after 6-12 months of continuous use 4. The most commonly implicated medications are ergot derivatives, which have been associated with retroperitoneal fibrosis in several studies, including a study published in 2015 that highlighted the risk of retroperitoneal fibrosis with long-term use of ergot alkaloid derivatives 4. Other medications linked to retroperitoneal fibrosis include:
- Dopamine agonists like bromocriptine and pergolide, which have been shown to cause fibrotic reactions, including retroperitoneal fibrosis, in some patients 5
- Analgesics such as phenacetin and acetaminophen, which can cause retroperitoneal fibrosis when used chronically
- Methyldopa, an antihypertensive that has been implicated in retroperitoneal fibrosis
- Hydralazine, another antihypertensive that has been linked to retroperitoneal fibrosis The mechanism of retroperitoneal fibrosis involves drug-induced inflammatory reactions that trigger fibroblast proliferation and collagen deposition in the retroperitoneal space, leading to obstructive symptoms 6. Patients taking these medications who develop flank pain, lower extremity edema, or unexplained renal dysfunction should be evaluated for possible retroperitoneal fibrosis, and medication discontinuation is typically the first step in management 7. It is essential to weigh the benefits and risks of using these medications, particularly for prolonged periods, and to monitor patients closely for signs of retroperitoneal fibrosis 8.