What medications treat Raynaud’s phenomenon?

Medications for Raynaud's Phenomenon

Dihydropyridine-type calcium channel blockers, specifically oral nifedipine, should be used as first-line pharmacological therapy for Raynaud's phenomenon, with phosphodiesterase-5 inhibitors as second-line and intravenous iloprost reserved for severe cases unresponsive to oral therapies. 1

First-Line Treatment: Calcium Channel Blockers

• Nifedipine is the preferred first-line agent due to clinical benefit, low cost, and acceptable adverse effects 1
• Meta-analyses confirm nifedipine reduces both frequency and severity of Raynaud's attacks 1, 2
• In controlled trials, nifedipine decreased vasospastic episodes from 14.7 to 10.8 per two weeks (p<0.05), with 60% of patients reporting moderate to marked improvement versus only 13% on placebo 3
• Other dihydropyridine calcium channel blockers (amlodipine, felodipine, isradipine, nicardipine) can be considered if nifedipine lacks benefit or causes intolerable side effects 1, 2, 4
• Common adverse effects include headache, peripheral edema, hypotension, and flushing, which may limit use 5, 4

Second-Line Treatment: Phosphodiesterase-5 Inhibitors

• PDE5 inhibitors (sildenafil, tadalafil) should be considered when calcium channel blockers provide inadequate response 1
• A meta-analysis of six RCTs (224 patients) demonstrated significant improvements: Raynaud's condition score improved by mean difference -0.46 (95% CI -0.74 to -0.147; p=0.002), daily attack frequency decreased by -0.49 attacks (95% CI -0.71 to -0.28; p<0.0001), and daily attack duration reduced by -14.62 minutes (95% CI -20.25 to -9; p<0.0001) 1
• PDE5 inhibitors are effective for both treating attacks and healing/preventing digital ulcers 2, 6
• Cost and off-label use may limit utilization 2

Third-Line Treatment: Intravenous Prostacyclin Analogues

• Intravenous iloprost should be considered for severe Raynaud's phenomenon following failure of oral therapy 1
• Iloprost reduces frequency and severity of attacks in severe cases 1, 2
• This agent is particularly useful for patients with digital ulcers, as it has proven efficacy for healing existing ulcers 1

Digital Ulcer Prevention and Treatment

• Bosentan (endothelin receptor antagonist) should be considered specifically for reduction of new digital ulcers in systemic sclerosis, especially in patients with multiple digital ulcers despite use of calcium channel blockers, PDE5 inhibitors, or iloprost 1
• Two high-quality RCTs confirmed bosentan's efficacy in preventing new digital ulcers 1
• Important caveat: Bosentan prevents new ulcers but does not improve healing of existing ulcers 6, 5
• Macitentan (another endothelin receptor antagonist) showed negative results in two RCTs with >400 patients, so the recommendation remains specific to bosentan only 1
• PDE5 inhibitors and intravenous iloprost can be used for both healing and prevention of digital ulcers 1, 2

Treatment Algorithm by Severity

Mild Raynaud's:

• Non-pharmacological measures (cold avoidance, smoking cessation, proper warm clothing) 2, 6
• Add nifedipine if symptoms affect quality of life 2

Moderate to Severe or Inadequate Response to Calcium Channel Blockers:

• Add or switch to PDE5 inhibitors 2, 6

Severe Raynaud's with Frequent Attacks Despite Above Treatments:

• Consider intravenous iloprost 2, 6

Digital Ulcers Present:

• For prevention: bosentan, PDE5 inhibitors, or prostacyclin analogues 2, 6
• For healing: intravenous iloprost or PDE5 inhibitors 2, 6

Additional Pharmacological Options with Limited Evidence

• Fluoxetine (selective serotonin reuptake inhibitor) might be considered, though evidence is limited to small studies 1, 2
• Topical nitrates have been studied but are limited by adverse effects including flushing, headache, and hypotension 5

Critical Pitfalls to Avoid

• Avoid beta-blockers, ergot alkaloids, bleomycin, and clonidine as these can induce or worsen Raynaud's phenomenon 2, 6, 7
• Missing secondary causes (particularly systemic sclerosis) can lead to delayed treatment and poor outcomes including digital ulcers, gangrene, or amputation 6, 7
• Delaying pharmacological treatment in secondary Raynaud's increases risk of complications 6
• The treatment approach differs significantly between primary and secondary Raynaud's, with secondary forms potentially requiring more aggressive therapy 2

Monitoring and Escalation

• Reassess treatment efficacy at 3-6 months 6
• Escalate therapy if inadequate response 6
• Regular monitoring for digital ulcers, gangrene, and progression of underlying disease is essential in secondary Raynaud's 6