What medications can cause or exacerbate Raynaud's phenomenon?

Medications That Can Cause or Exacerbate Raynaud's Phenomenon

Beta-blockers are the most well-documented medication class that can cause or exacerbate Raynaud's phenomenon, followed by chemotherapeutic agents (particularly cisplatin and bleomycin), and various antidepressants. 1, 2

Common Medication Classes Associated with Raynaud's Phenomenon

Beta-Blockers

• Beta-adrenergic antagonists (e.g., atenolol) can aggravate peripheral arterial circulatory disorders 3
• These medications are among the most frequently implicated in drug-induced Raynaud's phenomenon 2
• The mechanism involves increased peripheral vasoconstriction due to unopposed alpha-adrenergic activity

Antidepressants

• Various antidepressants have been reported to cause RBD (REM sleep behavior disorder) and Raynaud's phenomenon, including:
  • Selective serotonin reuptake inhibitors (SSRIs) like paroxetine, fluoxetine 4, 1
  • Other antidepressants such as venlafaxine, mirtazapine, and imipramine 4

Stimulants and Sympathomimetics

• Methylphenidate has been reported to cause secondary Raynaud's phenomenon 5
• The mechanism involves increased sympathetic activation leading to vasoconstriction

Chemotherapeutic Agents

• Cisplatin and bleomycin are associated with the highest risk of drug-induced Raynaud's phenomenon 2
• Newer targeted therapies such as tyrosine kinase inhibitors (TKIs) have also been implicated 2

Other Medications

• Ergotamine derivatives
• Interferons
• Clonidine (particularly during withdrawal)
• Cyclosporine
• Bromocriptine

Mechanisms of Drug-Induced Raynaud's Phenomenon

1. Increased sympathetic activation - Beta-blockers, stimulants, sympathomimetics
2. Endothelial dysfunction - Chemotherapeutic agents
3. Neurotoxicity - Certain chemotherapy drugs
4. Decreased red blood cell deformability - Some medications affect blood viscosity

Clinical Implications and Management

• When prescribing potentially causative medications to patients with a history of Raynaud's phenomenon, careful monitoring is essential 2
• For patients who develop drug-induced Raynaud's phenomenon:
  • Consider alternative medications when possible
  • If the causative medication cannot be discontinued, implement standard treatments for Raynaud's phenomenon:
    • Calcium channel blockers (CCBs) are first-line therapy 1, 6
    • PDE5 inhibitors may be considered for those who fail or cannot tolerate CCBs 1
    • Intravenous prostacyclin analogues (e.g., iloprost) for severe cases 1, 6

Monitoring and Prevention

• Patients on high-risk medications should be educated about symptoms of Raynaud's phenomenon
• Regular assessment for complications, including digital ulcers, is necessary 1
• Implement non-pharmacological preventive measures:
  • Avoiding cold exposure
  • Wearing protective gloves
  • Smoking cessation
  • Stress management

Severity and Complications

• Drug-induced Raynaud's phenomenon can range from mild symptoms to severe complications
• Critical digital ischemia, though rare, has been reported with certain medications 2
• Digital ulcers associated with Raynaud's have a high risk of progression to gangrene (22.5%) and osteomyelitis (11%) 1

When a medication is suspected of causing or exacerbating Raynaud's phenomenon, the risk-benefit ratio of continuing the medication should be carefully evaluated, and alternative therapies should be considered whenever possible.